Human Anatomy and Physiology
 9789386202550

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AND

PHYSIOLOGY Ms. Vipula

|

Ms. Atula

ABOUT THE BOOK Learning and increasing knowledge in human anatomy and physiology has been a perennial need of undergraduate students of pharmacy, nursing, physiotherapy and other paramedical sciences. Though there are several books on this subject, the authors have made an appreciable attempt to write the book, Human Anatomy and Physiology to meet their ever-growing requirement in this faculty. The book, which has been presented in a simple, interesting and self-explanatory manner, has 17 chapters, each of them focusing and elucidating the points of studies in a way as demanded by those who want to increase their knowledge in the subject. ABOUT THE AUTHORS Ms. Vipula, who has M. Pharma besides having Diploma in Science writing from Stanford University, is well known for her writing diction and skills. As a co-author of the book, Human Anatomy and Physiology, she has proved her savvy in the subject. Armed with degrees of M.Sc, M. Phil and M.Ed., Ms. Atula has 20 years of successful experience of academic worth and skill of writing.

Ms. Vipula

teaching. As a co-author of the book, Human Anatomy and Physiology, she has proved her

HUMAN ANATOMY AND PHYSIOLOGY

HUMAN ANATOMY

| Ms. Atula

ISBN 978-93-86202-55-0

9789386202550- 0750

(An Imprint of Laxmi Publications Pvt. Ltd.) An ISO 9001:2015 Company

M.R.P. ` 750.00 UHA-9797-750-HUMAN ANA PHYSIOLOGY-VIP

HUMAN ANATOMY AND

PHYSIOLOGY FOR Undergraduate students of Pharmacy, Nursing, Physiotherapy and other Paramedical Sciences

Ms. Vipula

|

Ms. Atula

HUMAN ANATOMY AND

PHYSIOLOGY

HUMAN ANATOMY AND

PHYSIOLOGY FOR Undergraduate Students of Pharmacy, Nursing, Physiotherapy and other Paramedical Sciences

By

Ms. Vipula

Ms. Atula

M.Pharm, Diploma in Science

M.Sc. (Hons.), M.Phil., M.Ed.

Writing from Stanford University

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CONTENTS CHAPTER 1. NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY …

1–32

1.1

Introduction



1

1.2 1.3

Anatomy Physiology

… …

2 7

1.4  Need to Study Anatomy and Physiology 1.5  Relation to Other Subjects

… …

10 11

1.6   Exceptions 1.7   What Do Anatomists and Physiologists Study?

… …

12 12

1.8  Other Branches 1.9   Scope of Anatomy and Physiology

… …

12 13

1.10   Myths, Misconceptions and Disbeliefs 1.11   Misuse

… …

14 15

1.12   Contributions 1.13   Carriers in Anatomy and Physiology

… …

16 17

1.14   Basic Terminology 1.15   Directional Terms

… …

17 18

1.16   Planes of the Body 1.17   Body Cavities

… …

21 23

1.18   Sections 1.19   Levels of Organisation

… …

24 24

1.20   Body Plan 1.21   Body Symmetry

… …

24 25

1.22   Body Systems 1.23   Body Temperature

… …

25 32



32

Review Questions

CHAPTER 2. CHEMISTRY

OF

… 33–83

LIFE

2.1   Introduction



33

2.2  Atoms 2.3  Elements

… …

34 34

2.4  Molecules and Compounds 2.5  Chemical Bonds

… …

35 36

(v)

vi Contents 2.6  Biological Molecules



38

2.7   Analysis of Chemical Components 2.8   Carbohydrates

… …

39 40

2.9   Proteins 2.10   Lipids

… …

49 55

2.11   Nucleic Acids 2.12   Structure of DNA

… …

60 64

2.13   Structure of RNA 2.14   Enzymes

… …

69 72

2.15   Vitamins 2.16   Hormones

… …

80 81



82



84–137

Introduction



84

3.2  Cell Size and Shape 3.3  History

… …

85 85

3.4  Cell Theory 3.5 Prokaryotic Cell

… …

86 87

3.6   Eukaryotic Cell 3.7   Cytoplasm

… …

90 92

3.8   Cell Wall 3.9   Cell Membrane

… …

92 93

3.10   Nucleus 3.11   Mitochondria

… …

95 97

3.12   Ribosomes 3.13   Endoplasmic Reticulum

… …

99 101

3.14   Golgi Apparatus and Dictyosomes 3.15   Lysosomes

… …

102 104

3.16   Centrioles 3.17   Vacuoles

… …

105 106

3.18   Plastids 3.19   Microbodies

… …

107 108

3.20   Cilia and Flagella 3.21   Villi and Microvilli

… …

108 110

3.22   Chromosomes 3.23   Specialised Cells

… …

110 114

3.24   Components of the Cellular Environment



114

Review Questions

CHAPTER 3. CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 3.1

Contents

vii

3.25   Movement Across Membranes



115

3.26   Cell Division 3.27   Cell Cycle

… …

117 118

3.28   Mitosis 3.29   Cytokinesis

… …

120 125

3.30   Meiosis 3.31   Cell Division in Human Beings

… …

126 136

3.32   Significance of Cell Division 3.33   Karyotype

… …

136 137



137



138–169

4.1   Introduction



138

4.2   4.3   4.4  4.5   4.6  4.7  4.8   4.9  

… … … … … … … … …

139 146 151 151 155 158 163 167 169



170–203

5.1   Introduction



170

5.2   Human Skeleton 5.3   Axial Skeleton

… …

172 173

5.4   Skull 5.5   The Vertebral Column

… …

175 177

5.6   Ribs 5.7   Sternum

… …

185 186

5.8   Hyoid 5.9   Ear Ossicles

… …

187 187

5.10   Appendicular Skeleton 5.11   Pectoral Girdle

… …

187 188

5.12   Pelvic Girdle 5.13   Forelimbs

… …

189 190

5.14   Hindlimbs 5.15   Fractures

… …

193 196

Review Questions

CHAPTER 4. ELEMENTARY TISSUES OF HUMAN BODY Epithelial Tissues Muscle Tissues Connective Tissues Connective Tissue Proper Skeletal Connective Tissue Fluid Connective Tissue Nervous Tissues Membranes Review Questions

CHAPTER 5. THE OSSEOUS SYSTEM

viii Contents 5.16   Joints



196

5.17   Disorder of Bones and Joints Review Questions

… …

201 203



204–243

6.1   Introduction 6.2   Types of Muscles

… …

204 205

6.3   Muscular Function 6.4   Types of Muscle Fibres

… …

210 211

6.5   Structure of Muscle Cells 6.6 Structure of Skeletal Muscle

… …

212 213

6.7   Anatomy of a Sacromere 6.8   Contraction of Muscles

… …

216 217

6.9   The Neuromuscular Junction 6.10   Muscle Cell Depolarization

… …

223 226

6.11   Fueling Muscle Contraction 6.12   Muscle Metabolism

… …

227 228

6.13   Muscle Fatigue 6.14   Rigor Mortis

… …

229 229

6.15   Tendons 6.16   Muscle Tone

… …

229 230

6.17   Muscles in the Human Body 6.18   Development of the Muscles

… …

230 236

6.19   Machine Vs Muscles 6.20   Muscular System Disorders

… …

237 238

6.21   Healthy Muscular System 6.22   Muscles in Space

… …

242 242

6.23   Muscle Facts Review Questions

… …

243 243



244–290

7.1   Introduction 7.2   Components of Blood

… …

244 245

7.3   Plasma 7.4   Erythrocytes

… …

247 249

7.5   Leucocytes 7.6   Thrombocytes (Platelets)

… …

255 259

7.7   Haemopoeisis



261

CHAPTER 6. THE MUSCULAR SYSTEM

CHAPTER 7. HAEMOPOIETIC SYSTEM

Contents

ix

7.8   Hemostasis



262

7.9   Blood Clotting 7.10   Complete Blood Count

… …

263 268

7.11   Hemoglobin 7.12   Blood Groups

… …

269 271

7.13   Immune Response and Blood Transfusion 7.14   Hemolytic Disease of the Newborn (HDN)

… …

278 280

7.15   Blood Volume and Blood Pressure 7.16   Safety of Donated Blood

… …

284 288

7.17   Disorders Review Questions

… …

288 290

CHAPTER 8. LYMPH AND LYMPHATIC SYSTEM



291–330

8.1   Introduction 8.2   Lymph

… …

291 292

8.3   Functions of Lymphatic System 8.4   Components of Lymphatic System

… …

293 295

8.5   Thymus 8.6   Bone Marrow

… …

296 299

8.7   Lymphatic Vessels 8.8   Lymph Nodes

… …

300 301

8.9   Aggregated Lymphoid Tissue 8.10   Spleen

… …

307 309

8.11   The Lymphocytes 8.12   Lymph

… …

310 311

8.13   Lymphatic System 8.14   Movement of Lymph

… …

312 313

8.15   Working of Lymphatic System 8.16   The Development of the Lymphatic Vessels

… …

314 315

8.17   Lymphatic Capillaries 8.18   Drainage Areas

… …

316 318

8.19   Major Lymphatic Vessels 8.20   Role of the Lymphatic System in Immunity

… …

319 323

8.21   Role of Lymph in Human Health 8.22   Lymphatic System Disorders

… …

324 325

8.23   Care of Lymphatic System 8.24   Interesting Facts

… …

329 330



330

Review Questions

x Contents CHAPTER 9. THE CARDIOVASCULAR SYSTEM



331–375

9.1  Introduction



331

9.2   Transport of Materials 9.3   Transportation in Humans

… …

332 333

9.4   External Structure of Heart 9.5   Internal Structure of Heart

… …

335 336

9.6   Working of Heart 9.7   Heart Sounds and Murmurs

… …

340 344

9.8  Double Circulation 9.9   Portal Circulation

… …

344 346

9.10   Heart Beat 9.11   Blood Pressure

… …

348 349

9.12  Regulation of Heart Beat 9.13   Cardiac Output

… …

352 358

9.14   Electrocardiography (ECG) 9.15   Blood Vessels

… …

360 361

9.16   Arterial System 9.17   Venous System

… …

364 368

9.18   Common Heart Disorders 9.19   Common Methods of Treatment

… …

371 374



375



376–408

10.1   Introduction



376

10.2   Steps of Nutrition 10.3   Parts of the Digestive System

… …

377 377

10.4   Alimentary Canal 10.5   Digestive Glands

… …

378 388

10.6   Physiology 10.7   Glycogen

… …

394 404

10.8   Hormonal Control 10.9   The Gastrointestinal Immune System

… …

405 406

10.10 Digestive System Disorders Review Questions

… …

407 408

CHAPTER 11. THE RESPIRATORY SYSTEM



409–445

11.1  Introduction



409

11.2  Transportation of Gases—Diffusion



410

Review Questions

CHAPTER 10. THE DIGESTIVE SYSTEM

Contents

xi

11.3  Respiration and Breathing



410

11.4  Phases of Aerobic Respiration 11.5  Anaerobic Respiration

… …

414 424

11.6  Respiratory Organs 11.7  Physiology

… …

425 432

11.8  Factors Affecting Respiration 11.9  Lung Volumes and Capacities

… …

435 436

11.10  Respiratory Quotient 11.11  Transport of Oxygen

… …

438 438

11.12  Transport of Carbon Dioxide 11.13  Control of Respiration is Nervous and Chemical

… …

440 442

11.14  Respiratory Disorders Review Questions

… …

443 445



446–483

12.1   Introduction 12.2   Structure of Neuron

… …

446 448

12.3   Types of Neurons 12.4   Working of Neuron

… …

450 451

12.5   Transmission of Impulse at the Synapse 12.6   The Neuromuscular Junction

… …

455 459

12.7   Brain—Structure and Functions 12.8   Histology of Brain

… …

461 473

12.9   Ventricles of Brain 12.10  Meninges of Brain

… …

474 476

12.11  Spinal Cord 12.12  Histology of Spinal Cord

… …

477 479

12.13  Reflex Action 12.14  Devices for Testing Brain

… …

480 481

12.15  Central Nervous Disorders Review Questions

… …

482 483



484–521

13.1   Introduction 13.2   Excretory Products

… …

484 484

13.3   Organs of Excretion in Man 13.4   Human Urinary System

… …

485 487

13.5   Structure of Kidney



490

CHAPTER 12. THE CENTRAL NERVOUS SYSTEM

CHAPTER 13. THE EXCRETORY SYSTEM

xii Contents 13.6   Blood and Nerve Supply to Kidneys 13.7 Functions of Kidney 13.8   Structure of Nephron 13.9  Physiology of Excretion 13.10  Composition of Urine 13.11  Mechanism of Concentration of Filterate 13.12  Micturition 13.13  Osmoregulation 13.14  Haemodialysis/Artificial Kidney 13.15  Excretory Disorders 13.16  Keeping Kidneys Healthy Review Questions

… … … … … … … … … … … …

492 493 494 499 506 509 511 512 517 519 521 521



522–566

… … … … … … … … … … … … … … …

522 523 528 534 536 537 541 542 548 555 556 557 561 563 566



567–592

… … … … … …

567 572 586 589 589 592

CHAPTER 16. SENSE ORGANS



593–636

16.1   Introduction



593

16.2   Classification



594

CHAPTER 14. THE REPRODUCTIVE SYSTEM 14.1   Introduction 14.2   Male Reproductive System 14.3   Female Reproductive System 14.4   The Female Sexual Cycle 14.5   Hormonal Control 14.6   Gametogenesis 14.7   Fertilisation 14.8   Post Fertilisation Changes 14.9  Cleavage 14.10  Placenta 14.11  Assisted Reproductive Technology (“Art”) 14.12  Population Control 14.13  Sexually Transmitted Diseases 14.14  Disorders Review Questions

CHAPTER 15. THE ENDOCRINE SYSTEM 15.1   Introduction 15.2   The Structure of the Endocrine System 15.3   Other Chemical Messengers 15.4   Biological Cycles of Hormones 15.5   Endocrine-Related Problems Review Questions

Contents

xiii

16.3   Skin



595

16.4   Tongue 16.5   Nose

… …

601 602

16.6   Eyes 16.7   Ears — Statoacoustic Organs

… …

606 622



636



637–663

17.1  Introduction



638

17.2   History of Immunology 17.3   Defence Mechanisms

… …

638 639

17.4   Types of Immunity 17.5   Kinds of Defence Mechanisms

… …

642 642

17.6   The Organs of the Immune System 17.7   The Cells of the Immune System

… …

645 648

17.8   Antibodies 17.9   Types of Immune Systems

… …

650 654

17.10 The Immune Response 17.11 Complement System

… …

657 659

17.12 Hormones 17.13 Disorders

… …

660 660



663



664–666

Review Questions

CHAPTER 17. THE IMMUNE SYSTEM

Review Questions

INDEX

PREFACE The demand for a simple and standard book on Human Anatomy and Physiology for Undergraduate students has been felt since long time. We feel pleasure in presenting this book in a simple, interesting and self-explanatory manner. We hope that this book will cater to their needs on the subject. We have used our experience of teaching while writing this book. The book will be an asset for reference by students of pharmacy, nursing, physiotherapy and other paramedical sciences. Some important features of this book are: ∑ The language used is very simple and self-explanatory ∑ Numerous well-labelled and student-friendly diagrams make lessons simple and comprehensive ∑ Questions based on illustrations and topics have been given at the end of each chapter. We are sure that this book will create interest in the subject and will be appreciated and preferred by students in achieving their target of studies. Constructive suggestions for the improvement of this book are welcome and will be greatly acknowledged. —Authors

CHAPTER

1

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY

1.1

INTRODUCTION

To know various facts about living organisms along with the instinct to survive gave birth to the subject Biology. It is the science dealing with living organisms, which covers aspects of living organisms like origin, occurrence, external and internal organisation, life history and inheritance. This constitutes various branches of biology Physiology and Anatomy. Physiology such as the branch of biology which explains structures and functions of organisms. Galen (380–287 BC), was the most famous medical man who established the anatomy of human beings. Andreas Vesalius, a Belgian scientist, known as “Father of Anatomy” described structural aspects of human body in his book named ‘De Humanicorporis Fabrica’ (the structure of human body). In this book, he has mentioned that human body is composed of many complex sub-systems, each with its own 1 function. 11

2 HUMAN ANATOMY AND PHYSIOLOGY 1.2

ANATOMY

Anatomy is the branch of biology that is the consideration of the structure of living things. It is a general term that can include human anatomy, animal anatomy (zootomy) and plant anatomy (phytotomy). In some of its facts anatomy is closely related to embryology, comparative anatomy and comparative embryology, through common roots in evolution. Anatomy is subdivided into gross anatomy (or macroscopic anatomy) and microscopic anatomy. ∑ Gross anatomy is the study of anatomical structures that can be seen with naked eye. ∑ Microscopic anatomy is the study of minute anatomical structures assisted with microscope, which includes histology (the study of tissues), and cytology (the study of cells). The history of anatomy has been characterized, over time, by a continually developing understanding of the functions of organs and structures in the body. Methods have also advanced dramatically, advancing from examination of animals through dissection of cadavers (dead human bodies) to technologically complex techniques developed in the 20th century. ∑ Anatomy is the branch of biology which concerns with the study of body structure of various organisms, including humans. ∑ Comparative anatomy is concerned with the structural differences of plant and animal forms. The study of similarities and differences in anatomical structures forms the basis for classification of both plants and animals. ∑ Embryology deals with developing plants or animals until hatching or birth (or germination, in plants). ∑ Cell biology covers the internal anatomy of the cell, while Histology is concerned with the study of aggregates of similarly specialized cells, called tissues. ∑ Morphology is related to anatomy, which involves comparative study of the corresponding organs in humans and animals. There are four major types of tissue present in the human body—epithelial tissue, muscular tissue, connective tissue, and nervous tissue. ∑ Human anatomy is study of the individual systems composed of groups of tissues and organs. Such systems include the skeletal system, muscular system, cutaneous system, circulatory system, respiratory system, digestive system, reproductive system, urinary system, and endocrine system. Little was known about human anatomy in ancient times because dissection was strictly forbidden. ∑ In the 2nd century, Galen, largely on the basis of animal dissection, made valuable contributions to the field. His work remained authoritative until the 14th and 15th centuary, when a limited number of cadavers were made available to the medical schools. ∑ A better understanding of the science was soon reflected in the discoveries of Vesalius, William Harvey, and John Hunter. Various modern technologies have significantly refined the study of anatomy: X rays, CAT scans and Magnetic Resonance Imaging (MRI) are only several of the tools used today to obtain clear and accurate representations of the inner human anatomy. In 1994, for the first time, a detailed three-dimensional map of an entire human being was made available worldwide. This could be possible as an executed prisoner volunteered his body.

History The history of anatomy has developing understanding of the functions of organs and structures in the body. Methods have advanced from examination of animals and dissection of dead human bodies to technologically complex techniques developed in the beginning of 20th century.

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 3 India ∑ Indian Medical Science dates back to Vedic times when Dhanvantari and Susruta practised medicine known as God of Medicines and Father of Surgery respectively. ∑ Susruta is one of the earliest scientists who studied human anatomy using dead human bodies and carried out plastic surgery of human nose (rhinoplasty) and extraction of cataract (ophthalmic surgery). ∑ Non-poisonous live leeches were used for preventing clotting of blood in the post-operative cases. Leeches secrete heparin which is an anticoagulant. ∑ The two other ancient Indian medical practitioners were Atreya and Charaka. ∑ Agnivesha, a student of Atreya, wrote an encyclopaedic treatise under the guidance of Atreya. which was revised by Charaka and brought out as Charaka Samhita in 100 BC. ∑ Charaka gave the concept of digestion, metabolism and immunity. ∑ According to him, normal function of human body is governed by the three Doshas of the body, namely, pit, kaf and vayu. He even prescribed medicines for maintaining the balance among three. ∑ Charaka Samhita have formed the basis of Ayurveda (derived from Ayu meaning life, and veda, meaning knowledge) medicine in India. Ayurveda deals with the science of living and the origin of life. ∑ Charaka gave his view regarding origin and evolution of life, saying that a living creature is a replica of the universal spirit and that life is composed of six elements namely, prithvi (earth), ap (water or liquid), teja (fire), vayu (air), akasha (ether), and the spirit (or self) which is equivalent to Brahma in the universe. ∑ The observations on the evolution of life from space have been made in the Taittiriya Upanishad (7–8 BC), and Manu Samhita (200 AD).

Initial Contributions Aristotle (322-384 BC), a Greek philosopher attempted to explain the structure of living things. He gave the system of classification on the basis of his efforts of dissection and study of plants and animals remained acceptable for long.

Herophilus and Erasistratus ∑ Initial human dissections were carried out by Greek philosophers namely Herophilus (late fourth century B.C.) and his follower Erasistratus. Herophilus studied anatomy of the brain. ∑ He distinguished the cerebrum (larger portion) from the cerebellum (smaller portion) of brain and suggested that the brain was the seat of intelligence and identified and named several structures of the brain, some of which still carry the names he gave them. ∑ He also discovered that nerves originate in the brain and noted the difference between motor nerves (those concerned with motion) and sensory nerves (those related to sensation). He established the disciplines of anatomy and physiology (the science that deals with the function of the body parts and organs). ∑ His study on the heart and blood vessels, explained the working of circulatory system and also explained the function of the heart. Erasistratus theorized that the arteries and veins, both originate from the heart but wrongly believed that the arteries carried air instead of blood.

4 HUMAN ANATOMY AND PHYSIOLOGY Galen ∑ The final major anatomist of ancient times was Galen, active in the 2nd century. ∑ He compiled much of the knowledge obtained by previous writers, and furthered the inquiry into the function of organs by performing dissection on animals. ∑ His collection of drawings which are based mostly on dog anatomy became the anatomy text for 1500 years. ∑ The original text is long gone, and his work was only known to the Renaissance doctors through careful custody of Arabic medicine. ∑ Hampered by similar religious restrictions as anatomists for centuries after him, Galen assumed that anatomical structures in dogs were the same as for humans. ∑ He dissected and accurately observed all kinds of animals, at times erroneously applied on the human body. ∑ He was the first to observe that muscles work in opposing pairs: for every muscle that causes a joint to bend, there is an opposing muscle that restores the joint to its original position. His experiments described two anatomical events: 1. Paralysis resulting from the separating the spinal cord. 2. The process by which urine passes from the kidneys to the bladder. His observations about the heart and blood vessels, made critical errors acceptable for long and wrongly presumed that blood was formed in the liver and circulated through veins.

Andreas Vesalius ∑ Flemish anatomist and physician Andreas Vesalius (1514–1564) overturned the explanations of Galen. ∑ He reasoned that Galen’s errors resulted from only having done animal dissections, which often did not apply to human anatomy. ∑ In the middle of 15th century, Vesalius published only first book on the Structure of the Human Body. The book contains methods an dissections, thoroughly illustrated.

William Harvey ∑ The correct description of the circulation of blood was provided by English physician William Harvey (1578–1657). ∑ He established the existence of pulmonary circulation (blood flowing from heart to lungs and to heart). ∑ He also observed one-way flow of blood. ∑ He discovered that blood flows in a continuous circle from the heart to the arteries to the veins and back to the heart. ∑ Harvey published this new concept of blood circulation in early 16th century.

Marcello Malpighi The microscopic study of capillaries by Italian anatomist Marcello Malpighi (1628–1694) in 1661 confirmed Harvey’s theory of blood circulation.

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 5 Robert Hooke ∑ English physicist Robert Hooke (1635–1703) examined the porous structure of cork. His acceptance coined the term “cells” to describe the tiny rectangular holes observed by him. ∑ This led to the concept of cells, which of led to the discovery of the cell nucleus. ∑ This was the basis for the science of cytology.

Xavier Bichat ∑ Histology began in 1700s with the work of French scientist Xavier Bichat (1771–1802). ∑ He found that organs consisted of different types of simple structures. ∑ He also noted different tissues with different properties which are vulnerable to tissuespecific diseases. ∑ He adopted a systematic order for anatomy based on structure and function. ∑ He specified 21 tissues (or systems) in the human body based on what he saw with his naked eyes, distinguishing these different tissues by their composition and by the arrangement of their fibers. These include epithelial (skin and digestive), muscular, nervous, connective, and vascular (blood) types.

Edwin Smith Papyrus In 1550 BC, he noted that the heart is the engine of blood circulation, to different parts of the body through blood vessels.

Hippocrates (377–460 BC) His work demonstrates a basic understanding of musculoskeletal structure, and the beginnings of understanding of the function of certain organs, such as the kidneys. Much of his work, however, and much of that of his students and followers later, relies on speculation rather than empirical observation of the body.

Some other Initial Contributions ∑ The Persian physician Avicenna (980–1037) abserved the Galenic teachings on anatomy and explained it in The Canon of Medicine (1020s), which was very influential throughout the Islamic World and Christian Europe. ∑ The Canon remained the most authoritative book on anatomy in the Islamic world until lbn alNafis in the 13th century, though the book continued to dominate European medical education for even longer until the 16th century. ∑ The Arabian physician lbn Zuhr (Avenzoar) (1091–1161) was the first physician known to have carried out human dissections and postmortem autopsy. He proved that the skin disease scabies was caused by a parasite, a discovery which upset the theory of humorism supported by Hippocrates and Galen. ∑ The removal of the parasite from the patient’s body did not involve purging, bleeding, or any other traditional treatments associated with the fluids of the body. ∑ In the 12th century, Saladin’s physician lbn Jumay was also one of the first to undertake human dissections, and he made an explicit appeal to other physicians as well. ∑ During a famine in Egypt in 1200, Abd-el-latif observed and examined a large number of human skeletons.

6 HUMAN ANATOMY AND PHYSIOLOGY ∑ The Arabian physician lbn al-Nafis (1213–1288) was one of the earliest proponents of human dissection and postmortem autopsy, and in 1242, he was the first to describe the pulmonary circulation and coronary circulation of the blood, which form the basis of the circulatory system, for which he is considered the father of the theory of circulation. lbn al-Nafis also described the earliest concept of metabolism, and developed new systems of anatomy and physiology to replace the Avicennian and Galenic doctrines, while discrediting many of their erroneous theories on the four humours, pulsation, bones, muscles, intestines, sensory organs, bilious canals, esophagus, stomach, and the anatomy of almost every other part of the human body.

17th–19th Centuries ∑ The study of anatomy flourished between 17th to 18th centuries. ∑ The advent of the printing press facilitated the exchange of ideas. Because the study of anatomy concerned observation and drawings, the popularity of the anatomist was equal to the quality of his drawing talents, and one need not be an expert in Latin to take part. ∑ Only certified anatomists were allowed to perform dissections, and at times only yearly. ∑ These dissections were sponsored by the city councilors and often charged an admission fee. ∑ Though it was a risky business to perform dissections and unpredictable depending on the availability of fresh bodies. ∑ Many anatomy students travelled around Europe from dissection to dissection during the course of their study—they had to go where a fresh body was available (e.g., after a hanging) because before refrigeration, a body would decay rapidly and become unsuitable for examination. ∑ Many Europeans interested in the study of anatomy travelled to Italy, the then center of anatomy. ∑ Columbus, distinguished himself by rectifying and improving the anatomy of the bones, by giving correct accounts of the shape and also cavities of the heart, of the pulmonary artery and aorta and their valves, and tracing the course of the blood from the right to the left side of the heart, by a good description of the brain and its vessels, and by correct understanding of the internal ear, and the first good account of the ventricles of the larynx. ∑ Osteology at nearly the same time found an assiduous cultivator in Giovanni Filippo Ingrassias. ∑ During the 19th century, anatomists largely finalised and systematised the descriptive human anatomy of the previous century. ∑ It progressed to establish growing sources of knowledge in histology and developmental biology, not only of humans but also of animals.

Modern Anatomy ∑ Anatomical research in the past hundred years has taken advantage of technological developments and growing understanding of sciences such as evolutionary and molecular biology to create a thorough understanding of the body’s organs and structures. ∑ Disciplines such as endocrinology have explained the purpose of glands that anatomists previously could not explain; medical devices such as MRI machines and CAT scanners have enabled researchers to study the organs of living people or of dead ones. ∑ Progress today in anatomy is centered in the development, evolution, and function of anatomical features, as the macroscopic aspects of human anatomy have been largely catalogued.

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 7 ∑ The subfield of non-human anatomy is particularly active as modern anatomists seek to understand basic organizing principles of anatomy through the use of advanced techniques ranging from finite element analysis to molecular biology. ∑ Anatomy today makes use of knowledge from many fields of science to explore and understand how the structure of an oganism’s cells, tissues, and organs relates to their function. ∑ Human anatomy, a crucial element in the medical school curriculum, divides the body into separate functional systems. These consist of the skin, the muscles, the skeleton, the circulatory system (blood, blood vessels and heart), the digestive system, the urinary system, the respiratory system (lungs and breathing), the nervous system (brain, spinal cord, and nerves), the endocrine system (glands and hormones), and the reproductive system. ∑ The expression “the scientific revolution,” a fairly recent term, is generally employed to describe the great outburst in activity in the investigation of physical nature that took place in the sixteenth, seventeenth, and eighteenth centuries. ∑ At the beginning came the important books of Copernicus in astronomy and Vesalius in anatomy, both published in 1543. ∑ Although there had been much work done in the Middle Ages to prepare the way for achievements, the quality and impact of scientific discovery is taking place these days. ∑ That is to say, the modern world science had so profound and pervasive an impact on the way people live and think. ∑ We can even divide the history into a prescientific and a scientific phase. ∑ If we accept this system of periodization then the scientific revolution marks the point at which the change took place. To many, gross human anatomy is associated with Gray’s Anatomy, originally published by the English surgeon Sir Henry Gray in 1858. Since then the book has had several authors and has evolved into the current thirty-seventh edition in Great Britain and the thirtieth edition in the United States, each with its own character. Radiological advances in the twentieth century have allowed scientists to make remarkable connections between anatomy and physiology, and researchers are integrating the study of anatomy with other disciplines, including biochemistry, genetics, and biophysics. Physicians now have access to advanced technology such as CAT and PET scanners, and Magnetic Resonance Imaging (MRI), all of which go far beyond microscopy and x-rays. These techniques permit physicians to look inside the live body without performing surgery, yet another major breakthrough in the history of anatomy.

1.3

PHYSIOLOGY

Human physiology is the science of functions of various parts of the body. The body’s functions are ultimately its cells’ functions. Survival is the body’s most important business. Survival depends on the body’s maintaining or restoring homeostasis, a state of relative constancy, of its internal environment. More than a century ago, French physiologist, Claude Bernard (1813–1878), made a remarkable observation that body cells survived in a healthy condition only when the temperature, pressure, and chemical compositions of their environment remained relatively constant. Later, an American physiologist, Walter B. Cannon (1871–1945), suggested the name homeostasis for the relatively

8 HUMAN ANATOMY AND PHYSIOLOGY constant states maintained by the body. Homeostasis is a key word in modern physiology. It comes from two Greek words — “homeo,” meaning the same, and “stasis,” meaning standing. “Standing or staying the same” then is the literal meaning of homeostasis. However, as Cannon emphasized, homeostasis does not mean something set and immobile that stays exactly the same all the time. In his words, homeostasis “means a condition that may vary, but which is relatively constant”. Homeostasis depends on the body’s ceaselessly carrying on many activities. Its major activities or functions are responding to changes in the body’s environment, exchanging materials between the environment and cells, metabolizing foods, and integrating all of the body’s diverse activities. The body’s ability to perform many of its functions changes gradually over the years. In general, the body performs its functions least well at both ends of life — in infancy and in old age. During childhood, body functions gradually become more and more efficient and effective. During late maturity and old age the opposite is true. They gradually become less and less efficient and effective. During young adulthood, they normally operate with maximum efficiency and effectiveness. All living organisms have certain characteristics that distinguish them from non-living forms. The basic processes of life include organization, metabolism, responsiveness, movements, and reproduction. In humans, who represent the most complex form of life, there are additional requirements such as growth, differentiation, respiration, digestion, and excretion. All of these processes are interrelated. No part of the body, from the smallest cell to a complete body system, works in isolation. All function together, in fine-tuned balance, for the well being of the individual and to maintain life. Disease such as cancer and death represent a disruption of the balance in these processes. The following is a brief description of the life process:

Organization At all levels of the organizational scheme, there is a division of labour. Each component has its own job to perform in cooperation with others. Even a single cell, if it loses its integrity or organization, will die.

Metabolism Metabolism is a broad term that includes all the chemical reactions that occur in the body. One phase of metabolism is catabolism in which complex substances are broken down into simpler building blocks and by which energy is released.

Responsiveness Responsiveness or irritability is concerned with detecting changes in the internal or external environments and reacting to that change. It is the act of sensing a stimulus and responding to it.

Movement There are many types of movement within the body. On the cellular level, molecules move from one place to another. Blood moves from one part of the body to another. The diaphragm moves with every breath. The ability of muscle fibers to shorten and thus to produce movement is called contractility.

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 9 Reproduction For most people, reproduction refers to the formation of a new person, the birth of a baby. In this way, life is transmitted from one generation to the next through reproduction of the organism. In a broader sense, reproduction also refers to the formation of new cells for the replacement and repair of old cells as well as for growth. This is called cellular reproduction. Both types are essential to the survival of the human race.

Growth Growth refers to an increase in size either through an increase in the number of cells or through an increase in the size of each individual cell. In order for growth to occur, anabolic processes must occur at a faster rate than catabolic processes.

Differentiation Differentiation is a developmental process by which unspecialized cells change into specialized cells with distinctive structural and functional characteristics. Through differentiation, cells develop into tissues and organs.

Respiration Respiration refers to all the processes involved in the exchange of oxygen and carbon dioxide between the cells and the external environment. It includes ventilation, the diffusion of oxygen and carbon dioxide, and the transport of the gases in the blood. Cellular respiration deals with the cell’s utilization of oxygen and release of carbon dioxide in its metabolism.

Digestion Digestion is the process of breaking down complex ingested foods into simple molecules that can be absorbed into the blood and utilized by the body.

Excretion Excretion is the process that removes the waste products of digestion and metabolism from the body. It gets rid of by-products that the body is unable to use, many of which are toxic and incompatible with life. In addition to above processes, life also depends on certain physical factors of the environment like water, oxygen, nutrients, heat, and pressure. Mechanical, physical, and biochemical functions of humans are covered in physiology. The principal level of focus of physiology is at the level of organs and systems. Most aspects of human physiology are closely homologous to corresponding aspects of animal physiology, and animal experimentation has provided much of the foundation of physiological knowledge. Anatomy and physiology are closely related fields of study: anatomy, the study of form, and physiology, the study of function, are intrinsically tied and are studied in tandem as part of a medical curriculum. Physiology is the study of the mechanical, physical, and biochemical functions of living organisms. Physiology has traditionally been divided between plant physiology and animal physiology but the principles of physiology are universal, no matter what particular organism is being studied. For example, what is learned about the physiology of yeast cells may also apply to human cells.

10 HUMAN ANATOMY AND PHYSIOLOGY The field of animal physiology extends the tools and methods of human physiology/non-human animal species. Plant physiology also borrows techniques from both fields. Its scope of subjects is at least as diverse as the tree of life itself. Due to this diversity of subjects, research in animal physiology tends to concentrate on understanding how physiological traits changed throughout the evolutionary history of animals. Other major branches of scientific study that have grown out of physiology research include biochemistry, biophysics, paleobiology, biomechanics, and pharmacology.

History Physiology can trace its roots back more than two millennia to classical antiquity, to the Greek and Indian medical traditions. The critical thinking of Aristotle and his emphasis on the relationship between structure and function marked the beginning of physiology in Greece, while Claudius Galenus (c. 126–199), known as Galen, was the first to use experiments to probe the function of the body. The ancient Indian books of Ayurveda, the Sushruta Samhita and Charaka Samhita, also had descriptions on human anatomy and physiology. During the Middle Ages, the ancient Greek and Indian medical traditions were further developed by Muslim physicians, most notably Avicenna (980–1037), who introduced experimentation and quantification into the study of physiology in The Canon of Medicine. Many of the ancient physiological doctrines were eventually discredited by lbn al-Nafis (1213–1288), who was the first physician to correctly describe the anatomy of the heart, the coronary circulation, the structure of the lungs, and the pulmonary circulation, for which he is considered the father of circulatory physiology. He was also the first to describe the relationship between the lungs and the aeration of the blood, the cause of pulsation, and an early concept of capillary circulation. The middle ages brought an increase of physiological research in the Western world that triggered the modern study of anatomy and physiology. Anatomist William Harvey, described the circulatory system in the 17th century, demonstrating the fruitful combination of close observations and careful experiments to learn about the functions of the body, which was fundamental to the development of experimental physiology. Herman Boerhaave is sometimes referred to as a father of physiology due to his exemplary teaching in Leiden and textbook ‘Institutiones medicae’ (1708). In the 19th century, physiological knowledge began to accumulate at a rapid rate, most notably with Matthias Schleidan and Theodor Schwann’s “Cell theory” which radically stated in 1838 that organisms are made up of units called cells, along with Claude Bernards’ (1813–1878) many discoveries that ultimately led to his concept of, interieur (internal environment) which would later be taken up and championed as ‘Homeostasis’ by American physiologist Walter Cannon (1871–1945).

1.4

NEED TO STUDY ANATOMY AND PHYSIOLOGY ∑ Human anatomy, physiology and biochemistry are complementary basic medical sciences, which are generally taught to medical students. ∑ A thorough knowledge of anatomy is required by medical doctors, pharmacists and related medical scientists. ∑ Anatomy and physiology helps in studying various organ systems, like: – Circulatory system: pumping of blood from the heart to all parts of the body through blood vessels.

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 11 – Digestive system: digestion and processing food with salivary gland, esophagus, stomach, liver, gallbladder, pancreas, intestines, rectum and anus. – Endocrine system: communication within the body using hormones made by endocrine glands such as the hypothalamus, pituitary or pituitary gland, pineal body or pineal gland, thyroid, parathyroids, and adrenals or adrenal glands. – Integumentary systems: skin, hair and nails. – Lymphatic system: structures involved in the transfer of lymph between tissues and the blood stream, the lymph and the nodes and vessels that transport. – Immune system: With leukocytes, tonsils, adenoids, thymus and spleen defending against disease-causing agents. – Muscular system: movement with muscles. – Nervous system: collecting, transferring and processing information with brain, spinal cord, peripheral nerves and nerves. – Reproductive system: the sex organs, such as ovaries, fallopian tubes, uterus, vagina, mammary glands, testes, vas deferens, seminal vesicles, prostate, and penis. – Respiratory system: the organs used for breathing, the pharynx, larynx, trachea, bronchi, lungs and diaphragm. – Skeletal system: structural support and protection with bones, cartilage, ligaments, and tendons. – Urinary system: kidneys, ureters, bladder and urethra involved in fluid balance, electrolyte balance and excretion of urine.

1.5

RELATION TO OTHER SUBJECTS

Various disciplines are interrelated and cannot be studied in isolation. Knowledge of other subjects is also must for studying anatomy and physiology like chemistry, physics, biochemistry. ∑ Living organisms are composed of number of chemicals—organic and inorganic. Inorganic components mainly include water and minerals while organic ones include carbohydrates, proteins, fats, nucleic acids, etc. ∑ Inorganic compounds form ions on dissolving in water and play significant role in enzymatic action. ∑ Movement of molecules in and out of the cell occurs by physio-chemical processes like diffusion and osmosis. ∑ All metabolic activities of an organism involve chemical changes, degradation and transformation of biomolecules. ∑ Living organisms are not exceptions to physical laws governing energy changes. All activities in living-beings involve energy transfer and energy transformations. ∑ Cohesive and adhesive forces of liquids result in the phenomenon of surface tension and capillarity. The flow of blood in blood vessels is due to cohesion and capillarity. ∑ A sound knowledge of geography helps in understanding the distribution of organism which are intimately related to the climate of the area. ∑ Study of placeobiology helps in understanding human evolution. ∑ Science of mathematics is useful in data compilation and calculations.

12 HUMAN ANATOMY AND PHYSIOLOGY 1.6

EXCEPTIONS

Physical sciences are governed by a set of principles and laws, which are universal and exceptions to these are rare. While in life sciences there are very few principles and laws, but exceptions are numerous. Therefore, life-science is the science of exceptions. Some of the common examples are: 1. Mature erythrocytes of mammals are without nuclei while the RBCs of camel possess nuclei. 2. Blood of all vertebrates is red due to presence of haemoglobin, but a shark, carcharhinus, has colourless blood. 3. Mammals give birth to young ones and thus are viviparous but some primitive mammals like duck billed platypus and spiny ant eater are oviparous.

1.7

WHAT DO ANATOMISTS AND PHYSIOLOGISTS STUDY?

Anatomists and physiologists study∑ External form, structure and relative position of various organs of living beings which is called morphology. ∑ Internal morphology/anatomy—In an organism, external features show close resemblance to the gross internal structure. ∑ Histology—Every organ of the body is made up of large number of cells and tissues which are studied with the help of microscope. ∑ Physiologists study various processes and functions like digestion, respiration, etc., of the life that make an organism. ∑ Embryology—The life of an organism starts from a single cell—the zygote. The branch of biology that deals with the study of various events and changes that occur in the formation of zygote and then to transform it into an individual till the birth is called embryology. ∑ Molecular biology—It deals with the study of various complex organic molecules which the organism is made of like structure of various enzymes, hormones, carbohydrates, proteins, fats. Generally, pharmacists, medical students, physiotherapists, nurses, paramedics, radiographers, artists, and students of certain biological sciences, learn gross anatomy and microscopic anatomy from anatomical models, skeletons, textbooks, diagrams, photographs, lectures and tutorials. The study of microscopic anatomy (or histology) can be aided by practical experience examining histological preparations (or slides) under a microscope; and in addition, medical students generally also learn gross anatomy with practical experience of dissection and inspection of cadavers (dead human bodies). Human anatomy can be taught regionally or systemically. Studying anatomy by bodily regions such as the head and chest, or studying by specific systems, such as the nervous or respiratory systems.

1.8

OTHER BRANCHES ∑ Arthrology—Study of joints ∑ Angiology—Study of blood vessels

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 13 ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑





1.9

Chondrology—Study of cartilage Cardiology—Study of heart and related diseases Dermatology—Study of various aspects of skin Etnology—Study of human characters and animal behaviour Etiology—Study of the cause of diseases Haematology—Study of blood Kalology—The study of human beauty Myology—Study of muscles Nephrology—Study concerning excretory system Osteology—Study of bones Odontology—Study of teeth and gums Oncology—Study of cancer Protocology—Study of hind gut including rectum and anus Syndesmology—Study of joints and ligaments Traumatology—Study of tumours and wounds Tricology—Study of hairs Taxidermy—Study of the preservation of skin and stuffing of animals Comparative anatomy relates to the comparison of anatomical structures (both gross and microscopic) in different animals. Anthropological anatomy or physical anthropology relates to the comparison of the anatomy of different races of humans. Artistic anatomy relates to anatomic studies for artistic reasons. Human anatomy, physiology and biochemistry are complementary basic medical sciences, which are generally taught to medical students in their first year at medical school. Human anatomy can be taught regionally or systemically; that is, respectively, studying anatomy by bodily regions such as the head and chest, or studying by specific systems, such as the nervous or respiratory systems. Academic human anatomists are usually employed by universities, medical schools or teaching hospitals. They are often involved in teaching anatomy, and research into certain systems, organs, tissues or cells. Superficial anatomy or surface anatomy is important in anatomy being the study of anatomical landmarks that can be readily seen from the contours or the surface of the body. The knowledge of superficial anatomy, physicians or veterinary surgeons gauge the position and anatomy of the associated deeper structures.

SCOPE OF ANATOMY AND PHYSIOLOGY

A student of anatomy and physiology may like to know the benefit of studying these subjects. It’s scope and application is very vast as it provides a necessary knowledge and perfect understanding about almost everything about the individual. This enables to work on various problems that affect human health and lives. AIDs, cancer, population explosion, genetic engineering are some burning issues associated with human welfare. Some of the scopes are discussed below.

14 HUMAN ANATOMY AND PHYSIOLOGY 1. It helps us to understand ourselves in a better way by unfolding different queries of life and thus enables us to understand life in a better way. 2. It helps us to study present day problems and guides us for future directions of biotechnology, human welfare, medicine, etc. 3. It helps in acquiring knowledge regarding medicines and cure of diseases as anatomy and physiology helps people aware of the structure and functions of the human body. 4. A student of anatomy and physiology can develop the necessary skill to understand the cause of many hereditary diseases and genetic disorders. With this knowledge one can offer services to human causes by way of genetic counselling . 5. Moreover, knowledge of genetics can help in the improvement of reproductive health of humans and combat the problem of population growth. 6. Knowledge of anatomy and physiology is helpful in eradications of diseases like malaria, smallpox, polio, etc.

1.10

MYTHS, MISCONCEPTIONS AND DISBELIEFS

1. Amniocentesis aims at detecting the defect in foetus. It also tells us about the sex of the foetus based on presence of sex chromosomes (X, Y). As a consequence, some families go for abortion if the expected child happens to against the choice. Thus, the technique is used not to detect a disease but to get rid of the female child. 2. The most serious disbelief of people is related to the recently identified human disease called AIDS (Acquired Immuno Deficiency Syndrome) caused by a virus called HIV-III. A person suffering from this disease loses the immune system of his body and, ultimately dies. The people including the practitioners and the nurses are afraid of getting the disease if they even share food or clothes of a person having AIDS. Biological researches have revealed that HIV-III can be transmitted only by direct contact with body fluids of AIDS patient, that is, transfusion of blood from AIDS patient to a normal person; sharing of needle for drawing/ injecting blood; sexual contact; from mother having AIDS to the child through placenta and even through breast feeding of the child at the postnatal stage. 3. The people had a misconception that the snakes can hypnotise their prey. We now know that snake is a carnivore and it cannot blink its eyes. The myth developed because of the observation that the rats, birds and other preys become motionless when confronted with a snake. In fact, it happens because the prey is under fear of being eaten by snake and it appears as if it is being hypnotised due to non-blinking eyes of the snake. 4. The belief that a snake charmer can make a snake dance due to tune of his flute, is a myth. In fact, the snake does not have external ears to receive the sound and so no question of snake’s dance in response to the tune of flute. 5. That snakes suck milk from the teats of cattle, is also wrong. In fact, snakes do not have any mechanism to suck milk or water. They can drink only by submerging their mouth in liquid (or water) but do not have any taste or liking for milk. 6. Before 1897, malaria disease in man was believed to be caused by bad air. Sir Ronald Ross while working at Kolkata in 1897, discovered that the cause of malaria, i.e., Plasmodium (a protozoan) is transmitted by female mosquito, Anopheles. It has now been confirmed that Plasmodium needs two hosts for completing its life cycle. Its primary host is man and secondary host is female Anopheles.

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 15 Similarly, the dreaded disease smallpox was believed to be caused due to the anger of the Goddess, maata. Now, we know that it is caused by a virus and it has been eradicated from the world by use of the vaccine discovered by Edward Jenner in 1796.

1.11

MISUSE

Study of anatomy and physiology has enabled scientists to develop various techniques for the human welfare. But it is often seen that knowledge of these subjects is being wrongly used against the human race. 1. Amniocentesis. It is a technique by which a sample of amniotic fluid from the womb of a pregnant woman is taken out, using a special surgical syringe and the chromosomes of the foetal cells or amniocytes (cells of amniotic membrane and foetal skin) present in the amniotic fluid are analysed. Placenta

Syringe to obtain foetal cells

Chorion – Membrane of the foetus

Centrifugation of amniotic fluid Amniotic fluid with cells shed by growing foetus

Uterine wall

Fluid

Cells Alpha fetoprotein testing for neural tube defects Cell cultures analyzed for chromosomal or biochemical normalities

Fig. 1.1

Biochemical testing for genetic errors of metabolism

Steps of amniocentesis

In this technique, the cells present in the amniotic fluid are cultured and stimulated to divide. The dividing cells are then stained and observed under the microscope. The chromosomes of the cells are counted and compared with the 23 pairs of normal human chromosomes for detecting any possible chromosomal abnormalities in the developing foetus. The amniocentesis technique has been developed for detecting foetal abnormalities by analysing the chromosomal defect, if any of the foetus. But, with the realisation that the test could reveal the sex of the foetus, people are seen to take the test mostly for knowing the sex of the foetus instead of the possible genetic abnormalities. In many cases the women go or are forced to go for an abortion, if the expected child is a female. This is a clear case, where a biological technique developed for human welfare is being misused against the human race. 2. Bio-weapons and Bioterrorism. Our knowledge about microbes is also an outcome of researches in the modern biology. We have learnt that dangerous diseases are caused by viruses (e.g., rabies, conjunctivitis, polio, smallpox, chickenpox and influenza) and bacteria (e.g., anthrax and plague). A cloud of infective bacteria or viruses can be released at a location where large number of individuals can inhale these resulting in initiation and spread of these

16 HUMAN ANATOMY AND PHYSIOLOGY communicable diseases resulting in Biowar or Bioterrorism. Thus, employing these microbes as bioweapons would be a misuse of Biology. We have to train our future generation to create awareness that the techniques and the knowledge of biology are not to be misused to cause imbalance in nature and the living world. In the recent years biologists have developed techniques of producing genetically modified strains of microorganisms. But, these techniques are being increasingly misused to produce in proved variety of infective agents for using them as bioweapons. Such misuse includes the development of antibiotic resistant microorganisms with increased infectivity. For example, a spore forming bacterium Bacillus anthracis, causes an acute infectious disease—anthrax. The bacterium can be cultured and made to produce spores in laboratory. These spores can be kept viable for decades by storing them in dry form. A cloud of anthrax spores, if released at a strategic location will be inhaled by the individuals. Under attack such an agent may act as effective weapon of bioterrorism. The attack with bioweapons would initiate the incidence and spread of communicable diseases, such as anthrax, plague, etc., on either an endemic or epidemic scale. Biologists need to play an active role to fight against the misuse of biological techniques. They need to create awareness about the impact of the misuse of biology on the human society and the living world.

1.12

CONTRIBUTIONS

1. Andreas Vesalius described structural aspects of human body in his book named ‘De Humani Corporis Fabrica’ (The structure of human body). In this book, he has mentioned that human body is composed by many complex sub-systems, each with its own function. For his work, Andreas Vesalius is acknowledged as the ‘Father of Anatomy. 2. A British Scientist, William Harvey (1578–1657), for the first time demonstrated that the heart pumps the blood and the blood circulates in the body. He presented his findings on heart and the circulation of blood in a monograph namely ‘Anatomical Exercise on the Motion of the Heart and Blood.’ He has also worked on the reproduction and embryonic development of chick. 3. Antony Van Leeuwenhock (1632–1723) recorded the real living cells such as yeast, bacteria, blood corpuscles. 4. Cuvier made major contributions in comparative anatomy. He is known as ‘the father of comparative anatomy and palaentology’. 5. Karl Von Baer (1792–1876) discovered ovum in mammals and is regarded as Father of modern Embryology. 6. Alexander Fleming (1881–1955), a Scottish bacteriologist in 1928 discovered the antibiotic penicillin. 7. Ian Wilmut in 1996 was able to produce first boar calf clone from a frozen embryo (named as Frosty), Wilmut and Keith Campbell (1996) were able to create first live sheep clone— Dolly from differentiated adult mammary cells.

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 17 1.13

CARRIERS IN ANATOMY AND PHYSIOLOGY

To achieve a good carrier in biology, a student must study anatomy and physiology. After this one can enter various fields and carriers. 1. Anthropology: The science of man and mankind i.e., the study of physical and mental abilities of man, his cultural development, social conditions as exhibited both in the present and past. 2. Biomedical engineering: Designing and production of mechanical and electronic equipment for human beings for external use and implantation e.g., artificial limbs, heart, lung machines etc. 3. Computational biology: Systematic development, application and validation of computational hardware and software solutions for building simulation models of biological systems. 4. Dentistry: Care of teeth including cleaning and polishing, removal of spoiled teeth, filling and fitting of artificial teeth. 5. Forensic science: Application of scientific knowledge to questions of civil and criminal law in connection with identification of poisons and narcotics, blood types, finger prints, types of injuries etc. 6. Human reproductive biology: The science of understanding and regulating human reproduction. 7. Medicine: The science of treating diseases with drugs or curative substances. 8. Nursing: Caring of ill and injured person. 9. Dietetics: Study of nourishment of human beings or other organisms. 10. Ophthalmology: Practice connected with care, dignosis and cure of eye diseases. 11. Orthopaedics: Science dealing with diagnosis and repair of disorders of bones, joints and spine. 12. Paediatrics: Science dealing with diseases of children. 13. Pathology: Science dealing with nature of diseases, their causes, symptoms and effects. 14. Pharmacology: Science of drugs and preparing medicines. 15. Pharmacy: Preparing and compounding medicines and dispensing them according to the prescriptions of medical practitioners. 16. Physiotherapy: The treatment of diseases, bodily weaknesses or defects by physical remedies such as massage and exercise. 17. Psychology: The study of human mind, its behaviour and mental qualities. 18. Radiology: Use of X-rays, ultrasound and other imaging techniques for diagnosis of diseases and defects. 19. Radiotherapy: The treatment of cancerous growths and other defects with the help of radioactive substances. 20. Surgery: The branch of medicine, involving physical operations to cure diseases or injuries to the body.

1.14

BASIC TERMINOLOGY

Anatomical terms related location are the terms which help to identify positions or directions relative to a species. For example, the “top” of a human is generally considered to be the head, whereas it may not be in other organisms. Moreover anatomical terms of location are not standardized and can differ between different fields of biology.

18 HUMAN ANATOMY AND PHYSIOLOGY Thus, precise anatomical terms of location are necessary. Common language leads to two major problems: 1. Common words are language-specific, requiring translation into equivalent, or almostequivalent, terms in other languages. They are not universal terms that may be readily understood by zoologists speaking other languages. Differences in terminology remain a problem that, to some extent, still separates the fields of scientists anatomy (sometimes called zootomy) and human (medical) anatomy. 2. The second, and larger, problem is caused by the very nature of animals. Most animals are capable of moving relative to their environment. So while “up” might refer to the top of someone’s head when they are standing upright, the same term (“up”) would describe their belly while they are lying down. Therefore, standardized anatomical terms of location have been developed, usually based on Latin words, to enable all biological and medical scientists to precisely communicate information about animal and human bodies and their component organs.

Standard Anatomical Position Because animals can change orientation with respect to their environment, and because any appendages like arms and legs can change position with respect to the main body, it is important that any positional descriptive terms refer to the organism when it is in its standard anatomical position. Thus, all descriptions are with respect to the organism in its standard anatomical position, even when the organism in question has appendages in another position. However, a straight position is assumed when describing the proximo-distal axis. This helps avoid confusion in terminology when referring to the same organism in different postures. The position can be defined as the position in which the organism will usually be found when at rest. Thus, for most invertebrates, this would be the position in which they are normally found when not feeding, hiding, actively moving appendages are straight. For bilaterally-symmetrical organisms, such vertebrates or some invertebrates, this defined to include that the organisms are standing erect in a normal posture, and looking forward.

Human Anatomical Position Standard anatomical position is when the human body stands erect at rest. The body has its feet together and arms are outward so that the palms are forward, and the thumbs are pointed away from the body. The arms are usually moved slightly out from the body, so that the hands do not touch the sides. The positions of the limbs have important implications for directional terms in those appendages. In humans, the anatomical position of the skull has been agreed by international convention to be the Frankfurt plane.

1.15

DIRECTIONAL TERMS

All vertebrates including humans are bilaterally symmetrical i.e., and right halves are mirror images of each other when if divided down the centre. For these reasons the basic directional terms can be considered to be those used in vertebrates. The same terms are used for many other organisms as well.

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 19 First polar-opposite ends of the organism are chosen. Each pair of opposite points defines an axis.

Anterior and Posterior ∑ The most obvious end-points are the “nose” and “tail”. Anatomically, the nose is referred to as the anterior end. ∑ The polar opposite to the anterior end is the posterior end. Another term for posterior is caudal —a term which strictly applies only to vertebrates, and therefore less preferred, except in veterinary medicine where these terms are standard. ∑ Drawing a line connecting these two points, defines the anteroposterior axis. ∑ In veterinary medicine, caudo-cranial is preferred between head and tail, and rostro-caudal between nose and neck. ∑ The term anteroposterior is often abbreviated to read AP axis. ∑ As well as defining the anteroposterior axis, the terms “anterior” and “posterior” also define relative positions along the axis.

Dorsal and Ventral The next most obvious end-points are the back and belly. ∑ These are termed the dorsal end and the ventral end respectively by connecting the outermost points the dorsoventral axis is formed. ∑ This is commonly abbreviated to DV axis. ∑ The DV axis, by is perpendicular the AP axis.

Left, Right and Medial ∑ The last axis is at right angles to both the AP and DV axes. ∑ The left side and right side of the organism are the outermost points between the two “sides” of the organism. ∑ When connected, these points form the left-right axis (LR axis). ∑ This is also called the dextro-sinistral axis. ∑ The “left” and “right” sides are the sides of the organism, and not those of the observer. ∑ The directional term lateral is used for both sides, yielding the left lateral and right lateral sides. ∑ As an opposite to lateral, the term medial is used for a point in the centre of the organism. ∑ Thus, instead of “left-right” axis, the term mediolateral axis is frequently used, abbreviated as ML axis. ∑ Together, the AP, DV and LR (or ML) axes allow three-dimensional descriptions of location of while any bilaterally-symmetrical organism, whether vertebrate or invertebrate. ∑ While considering one segment, the dorsoventral axis is perpendicular to the AP axis. ∑ As a general rule of thumb, if the body is included in consideration, the AP axis of the main body would be used, as would the DV and ML axes perpendicular to it. ∑ However, if considering only one segment, the AP axis would shift to reflect the axes, with the DV and ML axes shifting correspondingly. ∑ Alternatively, to avoid confusion, AP, DV and ML terms are used strictly in relation to the main body, and the terms proximal and distal are used for body segments such as the head, neck and tail.

20 HUMAN ANATOMY AND PHYSIOLOGY ∑ In veterinary medicine, the terms anterior, posterior, superior, and inferior are generally avoided in quadrupeds except for certain structures within the head.

Proximal and Distal ∑ The term proximal describes the point where the appendage joins the body, and the term distal is used for the point farthest from the point of attachment to the body. ∑ Since appendages change position with respect to the main body, therefore other directional terms are used while describing them. ∑ The standard AP, DV and ML directional axes, can cause confusion while describing parts of the body which change position relative to the main body. ∑ This is particularly true when considering appendages. “Appendages” would include vertebrate fins and limbs, but properly apply to any structure that extends from the main body. ∑ Thus, “appendage” would also include such structures as external ears (pinnae) and hair (in mammals), feathers (in birds) and scales (fish, reptiles and birds). ∑ As well, varieties of tentacles or and other projections from the body in invertebrates and the male in many vertebrates and some invertebrates, would be included. ∑ By connecting the two points, the proximodistal axis. ∑ The terms “proximal” and “distal” can be used as relative terms to indicate where structures lie along the proximodistal axis. Thus, the “elbow” is proximal to the hoof, but distal to the “shoulder”. ∑ Choosing terms for the other two axes perpendicular to the proximodistal axis is variable, as it depends on the position of the limb. ∑ Therefore when considering any organism, the other two axes are considered to the relative to the appendage when in standard anatomical position. ∑ This is roughly defined for all organisms, as in the normal position when at rest and not moving.

Other Directional Terms In addition to the three primary axis namely AP, DV and the ML and the proximodistal axis of appendages, several directional terms can be used in bilaterally symmetrical animals. These terms are strictly relative, and as such cannot be used to define fixed axes. Some of these terms are : ∑ Ipsilateral: on the same side as another structure. Thus, the left arm is ipsilateral to the left leg. ∑ Contralateral: on the opposite from another structure. Thus, the left arm is contralateral to the right arm, or the right leg. ∑ Superficial: near the outer surface of the organism. Thus, skin is superficial to the muscle layer. ∑ Deep: further away from the surface of the organism. Thus, the muscular layer is deep to the skin, but superficial to the intestines. ∑ Intermediate: between two other structures. Thus, the navel is between the left arm and the right leg. ∑ Visceral: organs within the body’s cavities. The stomach is within the abdominal cavity, and is thus visceral. ∑ Superior or cranial: toward the head end of the body; upper e.g., the hand is part of the superior extremity.

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 21 ∑ ∑ ∑ ∑

Posterior or caudal: away from the head; lower e.g., the foot is part of the posterior extremity. Anterior or ventral: front e.g., the knee cap is located on the anterior side of the leg. Posterior or dorsal: back e.g., the shoulder blades are located on the posterior side of the body. Medial: toward the midline of the body the middle e.g., toe is located at the medial side of the foot. ∑ Lateral: away from the midline of the body e.g., the little toe is located at the lateral side of the foot. ∑ Proximal: toward or nearest the trunk or the point of origin of part e.g., the proximal end of the femur joins with the pelvic bone. ∑ Distal: away from or farthest from the trunk or the point or origin of a part e.g., the hand is located at the distal end of the forearm.

1.16

PLANES OF THE BODY

Sections of the body in terms of anatomical planes are imaginary lines—vertical or horizontaldrawn through an upright body. ∑ A sagittal plane/Lateral plane, this is the Anterior end vertical plane running from front to back and dividing the body or any of its parts into right and left sides, or sinister and Ventral side dexter (left and right) portions. Transverse ∑ A coronal or frontal plane divides the Dorsal plane or axial body into dorsal and ventral (back and side plane front, or posterior and anterior) portions. It is the vertical plane running from side to side dividing the body or any of its parts into anterior and posterior portions. Coronal plane or frontal plane ∑ A transverse plane, also known as an axial plane or cross-section, divides the Sagittal plane or total body into cranial and caudal i.e., head and Posterior end tail portions. A horizontal plane dividing d id the body or any of its parts into upper and Fig. 1.2 Body planes and sides lower parts is called axial plane. ∑ Median plane, it is the sagittal plane through the midline of the body dividing the body or any of its parts into right and left halves. Note down the following points: 1. For post-embryo humans a coronal plane is vertical and a transverse plane is horizontal, but for embryos and quadrupeds a coronal plane is horizontal and a transverse plane is vertical. 2. When describing anatomical motion, these planes describe the axis along which an action is performed. So by moving through the transverse plane, movement travels from head to toe. For example, if a person jumped directly up and then down, their body would be moving in the transverse plane. 3. A longitudinal plane is any plane perpendicular to the transverse plane. The coronal plane and the sagittal plane are examples of longitudinal planes.

22 HUMAN ANATOMY AND PHYSIOLOGY









∑ ∑ ∑

∑ ∑

4. Sometimes the orientation of certain planes needs to be distinguished, for instance in medical imaging techniques such as sonography, CT scans, MRI scans or PET scans. One imagines a human in the anatomical position, and an X-Y-Z coordinate system with the X-axis going from front to back, the Y-axis going from left to right, and the Z-axis going from up to down. The X-axis is always forward (Tait-Bryan angles) and the right-hand rule applies. A transverse (also known as axial or horizontal) plane is an X-Y plane, parallel to the ground, which (in humans) separates the superior from the inferior, or put another way, the head from the feet. A coronal (also known as frontal) plane is an Y-Z plane, perpendicular to the ground, which (in humans) separated the anterior from the posterior, the front from the back, the ventral from the dorsal. A sagittal (also known as median) plane is an X-Z plane, perpendicular to the ground, which separates left from right. The midsagittal plane is the specific sagittal plane that is exactly in the middle of the body. 5. The axis and the sagittal plane are the same for bipeds and quadrupeds, but the orientation of the coronal and transverse planes change. The axis on particular pieces of equipment may or may not correspond to axis of the body, especially since the body and the equipment may be in different relative orientations. 6. Occasionally, in medicine, abdominal organs may be described with reference to the trans-pyloric plane which is a transverse plane passing through the pylorus. 7. In the neuroanatomy of animals, particularly rodents used in neuroscience research, the convention has been to name the sections of the brain according to the homologous human sections. Hence, what is technically a transverse section with respect to the body of a rat may often be referred to in rat neuroanatomical coordinates as a coronal section, and likewise a coronal section with respect to the body in a rat brain is referred to as transverse. This preserves the comparison with the human brain which is rotated with respect to the body axis by 90 degrees in the ventral direction. It does mean that the planes of the rat brain are not necessarily the same as those of the body. 8. In humans, reference may be made to landmarks which are on the skin or visible underneath. As with planes, lines and points are imaginary. Examples include: The mid-axillary line, a line running vertically down the surface of the body passing through the apex of the axilla. Parallel are anterior axillary line, which passes through the anterior axillary skin fold and the posterior axillary line, which passes through the posterior axillary skin fold. The mid-clavicular line, a line running vertically down the surface of the body passing through the midpoint of the clavicle. The mid-pupillary line, a line running vertically down the face through the midpoint of the pupil when looking directly forwards. The mid-inguinal point, a pint midway between the anterior superior iliac spine and the pubic tubercle. 9. Mid-point of inguinal ligament = mid-point between anterior iliac spine and pubic tubercle. Tuffler’s line. Which is a transverse line passing across the lumbar spine between the posterior eliac creasts. Mid-ventral line. The intersection between the ventral skin and the median plane.

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 23 1.17

BODY CAVITIES

The cavities, or spaces, or the body contain the internal organs, or viscera. The two main cavities are called the ventral and dorsal cavities. The ventral is the larger cavity and is subdivided into thoracic and abdominopelvic cavities by the diaphragm.

Thoracic Cavity The upper ventral, thoracic, or chest cavity contains the heart, lungs, trachea, esophagus, large blood vessels, and nerves. The thoracic cavity is bound laterally by the ribs (covered by costal pleura) and the diaphragm caudally (covered by diaphragmatic pleura). Cranial cavity for brain

Diaphragm Dorssal cavity Spinal cavity for spinal cord Pelvic cavity

Thoracic cavity Ventral cavity Abdominal cavity

Abdominopelvic cavity

Fig. 1.3 Body cavities

Abdominal and Pelvic Cavity ∑ The lower part of the abdominopelvic cavity can be further divided into two portions: abdominal portion and pelvic portion. ∑ The abdominal cavity contains most of the gastrointestinal tract as well as the kidneys and adrenal glands. The abdominal cavity is bound cranially by the diaphragm laterally by the body wall, and caudally by the pelvic cavity. ∑ The pelvic cavity contains most of the urinogenital system as well as the rectum the pelvic cavity is bounded cranially by the abdominal cavity, dorsally by the sacrum, and laterally by the pelvis.

Dorsal Cavity ∑ Its name implies it contains organs lying more posterior in the body. ∑ The dorsal cavity can be divided into two portions. The upper portion or the cranial cavity, having the brain, and the lower portion, or vertebral canal having the spinal cord.

24 HUMAN ANATOMY AND PHYSIOLOGY Acoelom—No Body Cavity Coelomates—Organisms with true coelom, from mesoderm. Enterocoelom—Mesoderm arises from the wall of the embryonic gut or enteron as outgrowths or pouches. These pouches pinch off and enlarge until they squeeze out the blastocoel. Haemocoel—Coelom with blood. Pseudo-coelomates—False coelom, develops from the first formed embryonic body cavity called blastocoel. Schizocoelom—It develops as a split in the mesoderm sheet.

1.18

SECTIONS

Longitudinal section (L.S.) —Section is cut by passing the razor’s edge at right angles to the transverse axis. Transverse section (T.S.) — Section is cut by passing the razors edge at right angles to the longitudinal axis.

1.19

LEVELS OF ORGANISATION

Ambilysosome—lysosome in which both heteropophagy and autophagy go on simultaneously Apoplasm—Intercellular spaces with non living matter Desmotubules—SER tubules which help in the formation of plasmodesmata Episome—When plasmid becomes associated with nucleoid of bacterium Genophore—Nucleoid GERL—Golgi-endoplasmic reticulum-lysosome system Goblet cells—Cells secreting mucus Histogenesis—Process of differentiation of tissues Histology—Microscopic anatomy dealing with study of tissues Histolysis—Process of degeneration of tissues Palade particles—Ribosomes Protein trafficking—Process of directing proteins to their final sites. Ribophorin—A glycoproteins which binds ribosomes on protoplasmic face of ER. Sphaerosomes—Plant lysosomes Symplasm—Areas of cytoplasmic continuity between adjacent cells Zymogenic vesicles—when cellular secretions in the vesicles are highly concentrated

1.20

BODY PLAN

Blind sac plan—In this there is incomplete alimentary canal. Cell aggregate plan—In this, the body is just an aggregate of cells with no coordination between them.

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 25 Deuterostomous—During development anus is formed earlier than mouth. Protostomous—During development mouth is formed earlier than anus. Tube-within tube plan—In this organisms have complete alimentary canal in the body.

1.21

BODY SYMMETRY

Asymmetrical—The body cannot be divided into two equal halves in any plane. Bilateral symmetry—Body can be divided into two similar halves through one plane only. Radial symmetry—Body can be divided into two equal halves by cutting it in any plane passing through central axis.

1.22

BODY SYSTEMS

There are different types of body system. According to their functions, they are classified as follows:

Digestive System Bartholin’s duct—Duct of sublingual salivary duct Degluttition—Swallowing of food bolus Duct of santorini—Thin pancreatic duct which opens directly into duodenum Ductus choledochus—Bile duct Dysphagia—Difficulty in swallowing Paneth cells—Found in crypts of lieberkuhn and secrete enterocrinin hormone Peyer’s patches—lymphoid masses in submucosa of ileum and are involved in the production of B-lymphocytes. These are also called abdominal tonsils Philtrum—A depression on upper lip and below the nose Plicae circulares—Permanent circular folds of intestinal mucosa. These are best developed in the diaphragm. Sphincter of Boyden—Surrounds the bile duct before it joins with pancreatic duct Stenson’s duct—Duct of parotid salivary gland Wharton’s duct—Duct of sub-maxillary salivary gland Wirsung duct—Pancreatic duct which joins the bile duct

Respiratory System Acapnia—Stopping of respiration due to very low CO2 in blood Apnoea—Temporary stopping of respiration Atelactasis—Collapsing of lung alveoli Bohr effect—Effect of CO2 concentration on the dissociation of oxyhaemoglobin

26 HUMAN ANATOMY AND PHYSIOLOGY Chloride shift—Exchange of bicarbonate ions of erythrocytes and chloride ions of plasma is called chloride shift Dyspnoea—Painful respiration Eupnoea—Decreased rate of respiration Herrying-Breur Reflex—A defensive mechanism against overdilation of lungs Hypercapnia—Increased CO2 in blood Hyperpnoea—Increased rate of respiration Mediastinal—Space between two pleura Oxygen-dissociation curve—A graph which shows the percent saturation of hemoglobin with oxygen Pharyngeal chiasma—Gross of air passage and food passage in pharynx Polypnoea—Rapid deep breathing Spirogram—Graph showing pulmonary volumes and pulmonary capacities during different conditions of respiration Tachypnoea—Rapid shallow breathing

Circulatory System Angiogram—Film showing radio autograph Angiology—Study of blood cells Angioplasty—Removal of blockage of an artery by baloon surgery Aplastic anaemia—It is due to fall in rate of erythropoeisis in bone marrow Blood letting—Bleeding a person for treatment Cardiology—Study of heart Copraemia—Poisoning of blood from retained faeces Coronary angiography—Radio autograph of coronary arteries of heart Differential leucocyte count-DLC—Relative percentage of leucocytes Embolus—A moving foreign body in a blood vessel. Erythrocyte sedimentation rate-ESR—Rate of settling of RBCs and is calculated with either wintrobe’s tube or western blotting method Erythrocytopaenia—Decrease in the number of RBCs. Erythropoiesis—Formation of RBCs. Ferritin—Iron is stored in bone marrow in this form Fibrinolysis—Dissolution of blood clot by an enzyme called plasmin. Foramen ovale—An oval shape aperture in interauricular septum during the embryonic stage. Normally, it disappears before birth Fossa ovalis—An oval depression in inter-auricular septum and is vestige of foramen

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 27 Glycosuria—Sugar in urine in diabetes mellitus Haematocrit value—Also called Packed cell volume and is percentage of blood cells. It is about 40%–45% in man and 36% in woman but it may fall as low as 10% and may rise as high as 80% in diseased condition Haemodialysis—Separation of nitrogenous wastes from blood with the help of an artifical kidney Haemotology—Study of blood Haemotoma—Blood collected in an intercellular space Hypervolumia—Increased blood volume Hypovolumia—Decreased blood volume Hypoxia—Deficiency of oxygen supply Lymphatology—The study of lymphatic system Murmur—Abnormalities in the heart sounds due to defective heart valves Myeloblasts—Precursor cells of granulocytes found in the bone marrow Normovolemia—Normal blood volume Phonocardiogram—Instrument used to magnify and record the heart sounds Procoagulants—Blood substances which promote blood coagulation process Sphygmomanometer—An instrument used to measure blood pressure Stethoscope—An instrument used to hear heart sound. Thrombocytopencia—Decrease in number of thrombocytes Thrombocytosis—Increase in number of thrombocytes Thrombosis—Formation of blood clot inside the blood vessel Total leucoyte count-TLC—Total number of leucocytes per cubic mm Uraemia—Presence of more urea in blood Wintrobe tube—Instrument used to determine haematocrit value

Excretory System Anuria—Failure of formation of urine Compensatory hypertrophy—Enlargement of a kidney to compensate damaged other kidney. Cystometrogram—The graph showing the pressure changes in the urinary bladder Filtered load—Amount of a substance present in the glomerular filtrate per day e.g., 575 gms/ day for Na+ Filtration coefficents (Kf)—Glomerular filteration per mm Hg of GFP and is about 12.5 ml per mm Hg. Filtration fraction—Fraction of RPF which becomes glomerular filtrate and is about 19%

28 HUMAN ANATOMY AND PHYSIOLOGY Glomerular filtration pressures (GFP)—Pressure in glomerular capillaries which is responsible for ultra filtration and ranges from 10–25 mm Hg Glomerular filtration rate (GFR)—Amount of nephric filtrate formed in one minute and is about 125 ml/minute Haemodialysis—It separates small molecules called crystalloids from large molecules (colloids) Juxtaglomerular cells—smooth muscle cells of tunica media of afferent arteriole. These secrete renin enzyme Polyuria—Also called diuresis–Increased urine output Ptosis—Displacement of kidneys from proper place Renal plasma flow (RPF)—Amount of blood plasma which passes through glomerulas capillaries of all the nephrons of both the kidneys in one minute and is about 650 ml Renal threshold—Upper limit of the kidneys to reabsorb even high threshold compounds e.g., 180 mg/100 ml of nephric filtrate for glucose Trigone—A triangular area in urinary bladder between two openings of ureters and urethical orifice Uraemia—Excess of urea in blood Urigraphy—Radio x-ray photograph of urinary tract Urochrome—A light yellow-pigment which gives colour to urine

Nervous System and Sense Organs Agnosia—Failure to recognize Alexia—Failure to read Alfonso corti—Organ of corti Amnesia—Partial or complete loss of memory Analgesia—Loss of sensation of pain Anosomia—Lack of smelling power Aproxia—Inability to carry out purposeful movements. Audiology—Study of hearing power Auriscope—Instrument for examining the ear Broca’s area—Area of brain is motor speech area Cerebrospinal fluid—CSF, is similar to blood plasma except that it has less amount of proteins and cholesterol. Coma—Complete loss of consciousness Emmetropia—Normal vision of eye. Endoneurium—A thin sheath around a nerve fibre

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 29 Epineurium—White fibrous sheath on a nerve Insomnia—Inability to sleep Meningitis—Increased level of CSF causing inflammation of meninges Metencephalon—Cerebellum Myelencephalon—Medulla oblongata Neuralgia—Pain travelling along a nerve Neuritis—Inflammation of nerves Ophthalmology—Study of structure, working and disease of eye Otitis—Inflammation of ear. Otolagia—Ear pain Otology—Study of structure, working and disorder of ear Palpebrae—Eyelids. Perineurium—A sheath around a bundle of nerve fibres Rhinencephalon—Olfactory lobe Rhinology—Study of nose and its diseases Sty—Bacterial infection of gland of zeis Synaptic fatigue—Exhaustion of neurotransmitter at synapse due to repeated stimulation Telencephalon—Cerebral hemispheres Thalamen cephalan—Diencephelon Zonula of Zinn—Another name of suspensory ligaments

Skeletal System Arthrology—Study of joints Calcination—Process of burning of bone till it becomes white Chondrology—Study of cartilages Gristle—Hyaline cartilage Ligaments—Joins bone to bone Osteitis—Inflammation of bones Osteoid—Uncalcified matrix of bone Osteology—Study of bones Osteoporosis—Weakening of bone due to depressed activity of osteoplasts Pneumatic bones—Bones with air cavities

30 HUMAN ANATOMY AND PHYSIOLOGY Sprain—Excessive pulling of ligaments Synovitis—An inflammation leading to swelling at the joint Tendons—Joins muscle to bones

Muscular System Collagen—Most abundant protein of body and forms 40% of total body proteins. In old age rigidity of collagen decreases which causes wrinkles in the skin. Cori’s cycle—It shows relationship between muscle glycogen and liver glycogen Einthoven Galvanometer—Instrument used to measure electrical changes in a contracting muscle Endomysium—A connective tissue sheath covering a muscle fibre Epimysium—A sheath of connective tissue covering the whole muscle Hypertrophy—Increase in size of a muscle by increase in number of myofibrils, mitochondria and sarcoplasm. Hypotrophy—Decrease in size of a muscle by decrease in number of myofibrils, mitochondria and sarcoplasm. Kinesiology—Scientific study of body movements Myalagia—Pain in muscles Myoblasts—Muscle-forming embryonic cells Myoglobin—Muscle haemoglobin Myograph-or kymograph—Instrument used to record single muscle twitch while its record is called single muscle curve or myogram Myology—Study of muscles Myostasis—Inflammation of a muscle Oxygen debt—Amount of extra oxygen consumed during the recovery after an exercise. It is provided by faster breathing. Perimysium—A sheath of connective tissue covering a bundle (fasciculus) of muscle fibres. Rigor mortis—Rigidity of muscles, after death first seen in jaw muscles, starts second hour after death. Sarcosomes—Muscle mitochondria Thermopile—Instrument used to measure the heat produced during muscle contraction Vigor mortis—Rigidity of muscles due to deficiency of ATP in muscles

Reproductive System Amphimixis—It refers to mixing up of maternal and paternal chromosomal sets Capacitation—Activation of sperms

NATURE AND SCOPE OF ANATOMY, PHYSIOLOGY AND BASIC TERMINOLOGY 31 Castration—Removal of testes in the male, or of ovaries in the female Chryptorchidism—A condition in which testes do not descent into the scrotum. It causes sterility. Ectopicpregnancy—Impregnation of ovum out side the uterus (in fallopian tube, cervix, ovary) Gestation period—Term used for the period between fertilization and birth of young one Gestosis—Any disorder of pregnancy Hysterectomy—Surgical removal of the uterus Neonate—A new born baby upto one month old Oophoritis—Inflammation of the ovary Prostatectomy—Surgical removal of the prostate gland Teratogen—Agents which cause malformations in the developing embryo

Fertilization and Development Amniocentesis—The amniotic fluid contains foetal cells. These cells are the basis of prenatal test called amnicentesis for the sex of the foetus and for checking chromosomal defects. Amnionitis—Inflammation of amnion due to infection resulting from premature rupture of amnion, often leads to neonatal infection. Conceptus—Product of conception i.e., embryo and embryonic membranes together. Ontogeny—Development of the individual Phylogeny—Evolutionary history of a species

Endocrine System Apocrine glands—Whose apical part is discharged along with secretion e.g., mammary glands Endocrine glands—Glands which pour their secretion without duct e.g., thyroid Epicrineglands—Which secrete only their secretion eg. pancreas, liver, sweat, salivary glands Exocrine glands—Glands which pour their secretions with the help of ducts. e.g., Liver Heterocrine glands—Glands which can act as exocrine and endocrine gland e.g., pancreas Holocrine glands—Whole gland bursts along with the secretion e.g., oil glands Humulin—Genetically engineered human insulin Myosisthermia gravis—Abnormal neuromuscular excitation due to hypersecretion of thymosine. Nandrolone—Steroid used by sports people to improve their performance Parahormones—Hormone—like substances but are not produced by endocrine glands e.g., pheromones

32 HUMAN ANATOMY AND PHYSIOLOGY Pitnicytes—Endocrine cells of posterior pituitary Polydipsia—Increased thirst

1.23

BODY TEMPERATURE

Cold blooded—Organisms whose body temperatures changes with the change in the environment. Ectothermic—Cold blooded Endothermic—Warm blooded Homoeothermous—Warm blooded Poikilothermic—Cold blooded Warm blooded—Body temperature remains constant, it does not change with the change in the temperature.

REVIEW QUESTIONS 1. Briefly illustrate the role of anatomy and physiology in dispelling myths, misconceptions and disbelieves associated with various diseases. 2. Discuss in brief the contribution of Galen and Vesalius in the field of anatomy and physiology. 3. Explain the scope of studying anatomy and physiology. 4. Discuss in brief history of anatomy and physiology. 5. “The study of other basic sciences is useful in understanding biological processes”. Explain. 6. What do anatomists and physiologists study? 7. Discuss the need to study anatomy and physiology. 8. How is anatomy and physiology related to other subjects? 9. Explain contributions of any four scientists in the field of anatomy and physiology. 10. Explain various terms used in explaining directions and planes of the body in human anatomy and physiology.

CHAPTER

2

CHEMISTRY OF LIFE Cloud Rain

NH3 High + CN temperature CH4 H O 2 CH4

2.1

Lightning

N-bases (Purifies) (Pyrimidines) sugars Amino acids Glycerine Fatty acids

Radiations

Nucleotides Poly Saccarides Proteins Fats lipids

DNA (Replication) energy carriers coenzymes Construction materials enzymes energy sources

Biological evolution

Energy gases

INTRODUCTION

The study of living world reveals that there exist a hierarchy at the structural level, with each lower level emerging into a complex higher one. Every living organism is made of cells which form tissues, organs, organ systems and organism. Now various analytical techniques developed by physicists and chemists have made possible to analyse living things at the level even smaller than microscope. The basic chemical organisations of living things are complex but remarkably similar. Both living and non-living things are made up of same materials and are governed by the same physical laws i.e., life is chemically based on the universal physiochemical principles and obeys them. The basic unit of organisation in both living and non-living things is an atom. These atoms combine to form molecules by linking themselves through chemical bonds. The atoms aggregate to form elements. In this chapter, we are going to discuss chemistry of life covering atoms, elements, molecules and compounds, chemical bonds, various biological molecules like carbohydrates, proteins, fats and finally enzymes.

33

34 HUMAN ANATOMY AND PHYSIOLOGY 2.2

ATOMS

Atom is the smallest unit of matter. Matter is anything that takes up space and has a measurable amount of substance or mass. Every atom is made up of many smaller subunits. These subatomic particles are of three types: ∑ Electrons ∑ Protons ∑ Neutrons Neutrons = atomic number = number of protons Atomic mass = mass of protons + neutrons Mass number = number of protons + number of neutrons

Electrons ∑ These are integral part of all atoms which are negatively charged. ∑ The absolute charge on an electron is –1.6 ¥ 10–19 coulombs. ∑ Assuming the above charge equal to unit electric charge, we can say that relative charge on an electron is –1. ∑ The absolute mass of an electron is 9.1 ¥ 10-28 gm. However, if the above mass is compared with 1 atomic mass unit (amu), then relative mass of an electron is 1/1837 amu or 1/1837 times the mass of one atom of hydrogen. ∑ Electrons revolve around nucleus.

Protons ∑ Protons are positively charged particles present in the nucleus. ∑ The electric charge on a proton is +1.6 ¥ 10– 19 C. ∑ The mass of proton is 1.67 ¥ 10– 24 gm. It is estimated that a proton is 1837 times heavier than an electron. ∑ Atomic number = number of protons in the nucleus = number of electrons revolving around nucleus.

Neutrons ∑ These are neutral particles present in the nucleus. ∑ The total number of protons and neutrons present in the nucleus of an atom is called mass number. ∑ As the mass of one proton or one neutron is taken as 1 amu, therefore sum total of the number of protons and neutrons is equal to its atomic mass. ∑ Number of neutrons = mass number – atomic number

2.3

ELEMENTS ∑ These are pure substances that are made up of a single kind of atom (atoms with the same number of protons) and cannot be separated into different substances by ordinary chemical methods.

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∑ The identity of an atom is determined by its number of protons. E.g., an atom containing two protons is helium—a gas you have probably seen used to blow up balloons. ∑ The number of protons in each type of element is called the atomic number. ∑ The number of protons in an atom is the same as the number of electrons in that atom. ∑ Atoms are therefore electrically neutral; the positive charges of the protons are balanced by the negative charges of the electrons. ∑ The number of neutrons in an atom, may or may not equal to the number of protons. ∑ Atoms that have the same number of protons but different numbers of neutrons are called isotopes. ∑ Isotopes of an element differ in atomic mass but have similar chemical properties. ∑ Each isotope has a single proton in its nucleus but has different number of neutrons. E.g., isotopes of hydrogen, deuterium, tritium and hydrogen differ in their atomic masses but have the same chemical properties as one another because they all have the same number of electrons. ∑ In general, electrons determine the chemical properties of an element because atoms interact by means of their electrons (not their protons or neutrons). ∑ The energy of electrons increases as their distance from the attractive force of the nucleus increases, the various electron shells of atoms are also called energy levels. ∑ Electrons occupying increasingly distant shells from the nucleus have a stepwise increase in their levels of energy. ∑ The number of protons in the nucleus also influences the energy of electrons at the various energy levels, since the attractive force of the nucleus increases as its number of protons increases.

2.4

MOLECULES AND COMPOUNDS ∑ The atoms of most elements interact with each other. ∑ If the interaction is a sharing of electrons, the interacting atoms are called a molecule. ∑ Molecules are two or more atoms held together by shared electrons and can be made up of atoms of the same element or atoms of different elements. ∑ Molecules made up of atoms of different elements are called compounds. ∑ Compounds are also atoms of different elements held together by electrostatic attraction [ionic bonds]. ∑ The oxygen in the air consists of molecules made up of pairs of atoms of the same element-oxygen. ∑ These pairs are represented by the chemical formula O2. ∑ A chemical formula is a type of “shorthand” used to describe a molecule. ∑ The atoms are represented by symbols, such as O for oxygen. ∑ Three factors influence, whether an atom will interact with other atoms. ∑ In addition, these factors influence the types of interaction likely to take place. ∑ These factors are: 1. The tendency of electrons to occur in pairs. 2. The tendency of atoms to balance positive and negative charges, and 3. The tendency of the outer shell, or energy level, of electrons to be full. This third factor is often called the octet rule. ∑ The word octet means “eight objects” and refers to the fact that eight electrons are a stable number for an outer shell; the outer electron shell of many atoms contains a maximum of eight

36 HUMAN ANATOMY AND PHYSIOLOGY

∑ ∑ ∑ ∑ ∑

∑ ∑ ∑ ∑

2.5

electrons. (The first energy level is an exception to this rule because it contains a maximum of two electrons only). The octet rule states that an atom with an unfilled outer shell has a tendency to interact with another atom or atoms in ways that will complete this outer shell. Although the octet rule does not apply to all atoms, it does apply to all biologically important ones that are involved in the structure, energy needs, and information systems of living things. Atoms of elements that have equal number of protons and electrons and have full outerelectron energy levels are the only ones that exist as single atoms. Atoms with these characteristics are called noble gases, or inert gases, because they do not react readily with other elements. Many stories explain why they are called noble. They all center around the concept of nobility—have everything (in this case a full outer shell), need nothing, and interact little with others. Most of the noble gases—helium, neon, argon, krypton, xenon, and radon are rare. In addition, they are relatively unreactive and unimportant in living systems. Helium and radon are probably the best known and the least rare noble gases. Radon, in fact has gained more recognition in recent years. Formed in rock or soil particles from the radioactive decay of radium, radon gas can seep through cracks in basement walls and remain trapped in homes that are not well ventilated. Prolonged exposure to radioactive radon in levels greater than those normally found in the atmosphere may to lead to lung cancer.

CHEMICAL BONDS

An atom having an incomplete outer shell can satisfy the octet rule in one of three ways: 1. It can gain electrons from another atom. 2. It can lose electrons to another atom. 3. It can share one or more electron pairs with another atom. Such interaction among atoms results in chemical bonds, forces to hold atoms together. If the force is caused by the attraction of oppositely charged particles formed by the gain or loss of electrons, the bond is called ionic. If the force is caused by the electrical attraction created by atoms sharing electrons, the bond is called covalent. Other weaker kinds of bonds also occur. Thus outer electrons of one atom may interact with the outer electrons of other atoms producing forces of attraction or chemical bonds: ∑ Ionic or electrovalent bonds. ∑ Covalent bonds ∑ Hydrogen bonds

Ions and Ionic Bonds ∑ In ionic or electrovalent bonds electrons and are actually transferred from one atom to another. ∑ The atom gaining an electron becomes –vely charged while the one loosing electron becomes +vely charged. ∑ Negatively charged atom is called anion and positively charged one is called cation.

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∑ As oppositely charged particles attract each other and oppositely charged ions can be held together by their forces of attraction and form ionic bonds. For example, Na atom — Atomic number 11 (2, 8, 1–electronic configuration). When it looses one electron it becomes sodium ion (Na+) and its configuration changes to 2, 8. Cl atom—Atomic number 17 (2, 8, 7 – electronic configuration) To complete its octet, it gains an electron and becomes negatively charged (Cl–) Na+ and Cl– form ionic bonds. Cl

+

Na 11p 12n

17p 18n

11p 12n



17p 18n

Na atom Cl atom NaCl atom molecule ∑ The transfer of electrons between atoms is an important chemical event of one type of chemical reaction. ∑ When an atom loses an electron, it is oxidized. The process by which this occurs is called an oxidation meaning “to combine with oxygen.” ∑ The name reflects that in biological systems, oxygen which strongly attracts electrons, is the most frequent electron acceptor. ∑ Therefore, atoms that give up electrons to oxygen are “acted upon” by oxygen, or oxidized. ∑ For example, when iron combines with oxygen in the presence of moisture, it becomes oxidized. The product of this oxidation is commonly known as rust. ∑ Conversely, when an atom gains an electron, it becomes reduced. ∑ The process is called a reduction. ∑ This name reflects that the addition of an electron reduces the charge by one. ∑ For example, if a molecule had a charge of +2, the addition of an electron (–1) would reduce the molecule’s charge to +1. ∑ Oxidation and reduction always take place together because every electron that is lost by one atom (oxidation) is gained by some other atom (reduction). Together they are called redox reactions. ∑ In a redox reaction the charge of the oxidized atom is increased, and the charge of the reduced atom is lowered.

Covalent Bonds ∑ In covalent bonds, atoms share electrons in their outer shell. ∑ For example, in an H2 molecule two atoms share one pair of electrons. –

+ 1p H-atom

+

1p H-atom

p

+



e



e

p

H2-Molecule

∑ The attraction between electrons in the middle and the protons in the two nuclei holds the molecule strongly together.

38 HUMAN ANATOMY AND PHYSIOLOGY ∑ ∑ ∑ ∑ ∑

If one pair of electrons is shared, a single covalent bond is joined e.g., H2. Two pairs shared form a double bond e.g., O2. Three pairs shared form triple bond e.g., N2 Shared electrons are attracted equally to both atoms as in H2 and form non-polar covalent bond. However, if one atom attracts the shared electron more strongly than the other; the bond is a polar covalent bond and produces polar molecules with positive and negative areas. ∑ e.g., H2O is a polar molecule where oxygen attracts shared electrons more strongly and becomes somewhat negative. The hydrogen portion becomes somewhat positive. ∑ Polar bonds allow water to dissolve many molecules that are important to life. ∑ That is why water is called universal solvent.

Hydrogen Bond ∑ Oppositely charged regions of polar molecules can attract each other. ∑ Such a bond between hydrogen and other electronegative element like oxygen and nitrogen is called a hydrogen bond. ∑ These bonds occur in H2O, proteins and other large molecules. ∑ But these bonds are weak bonds. ∑ Large molecules like DNA may contain many hydrogen bonds, which can give strength and three dimensional shape to the molecules as seen in proteins and nucleic acids. – H + O H+

– H+ O H+

– H+ O H+

– H+ O H+

Fig. 2.1

– H+ O H+

Hydrogen bonding in water molecules

The structures and functions of all living systems are because of various organic molecules present in them. All these organic molecules contain carbon atoms in them as basic building blocks. Thus they are also called carbon compounds. In contrast to these complex carbon containing molecules, living systems also contain various inorganic molecules. An analysis of the cell shows the following composition of various molecules and atoms; Carbon, Hydrogen and Oxygen Non-metal elements (Nitrogen, Phosphorus, Chlorine and Sulphur) Metal elements (Calcium, Potassium, Sodium and Magnesium) Iodine, Fluorine, Boron, Selenium, Cobalt, Zinc, Molybdenum etc.

2.6

93 per cent 2 per cent Less than 5 per cent Traces

BIOLOGICAL MOLECULES ∑ Only six elements carbon, hydrogen, oxygen, nitrogen, phosphorus, and sulphur (sometimes called CHNOPS;) make up about 98% of the mass of all living organisms.

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∑ Carbon is a unique element with the remarkable ability to form strong, stable chemical bonds with other atoms. Each carbon atom can form four bonds with other atoms. (Sometimes, two atoms will form more than one bond between themselves making a double bond or even a triple bond.) ∑ This bonding ability allows carbon atoms to form chains of almost unlimited length. This property is called catenation. ∑ These chains can be closed on themselves to form rings or may branch wildly. ∑ This gives great variety to the kinds of molecules that carbon can form. Below are just a few examples of the many ways carbon chains can be arranged to form the skeleton for different molecules. ∑ Atoms of hydrogen and oxygen and less frequently nitrogen, sulphur, or phosphorous are bonded to the carbon skeleton to form giant molecules called macromolecules. ∑ A few other elements may occur in trace amounts. The four major types of macromolecules found in living cells: 1. Carbohydrates. 2. Lipids. 3. Proteins. 4. Nucleic acids. These are made of smaller, repeating subunits called monomers. The monomers are not always identical but they always have similar chemical structures. They are joined together by a series of chemical reactions in a process known as polymerization to form large, complex molecules called polymers. = Monomer 1

+

2

+

3

+

4

1

2

3

4

Polymer (4 monomers bonded together)

2.7

ANALYSIS OF CHEMICAL COMPONENTS

Organic Compounds Analysis ∑ Take a living tissue, grind it in trichloroacetic acid (Cl3 CCOOH) using pestle and mortar. ∑ Strain this thick slurry through a cheese cloth or cotton cloth. ∑ Two fractions are obtained. Two fractions

Acid soluble pool (Filtrate) – – – –

Contains compounds with molecular weight 18–800 Dalton These molecules can be separated and their chemical formula can be analyzed. These are called micromolecules or biomolecules. These are soluble in H2O.

Acid insoluble pellet (Retentrate) – –

– –

This is an acid insoluble fraction It contains ∑ Proteins ∑ Nucleic acids ∑ Polysaccharides ∑ Lipids Molecular weight is in the range of 10,000 Dalton and above. These are called macromolecules or macrobiomolecules.

All biomolecules present in the living tissues can be called metabolites. These include: (a) Carbohydrates—Monosaccharides, oligosaccharides, polysaccharides (b) Amino acids and proteins

40 HUMAN ANATOMY AND PHYSIOLOGY (c) Lipids—Fatty acids, oils, hard fats, waxes, cutin, suberin, phospholipids, steroids, tarpernes (d) Nucleotides and nucleic acids (e) Vitamins (f) Hormones Metabolites can be classified into two classes: ∑ Primary metabolites ∑ Secondary metabolites Animal tissues mostly contain primary metabolites while plants and microbes have both primary and secondary metabolites.

Inorganic Compounds Analysis Inorganic compounds analysis can be processed by the following steps: ∑ Take a small living tissue, weight it. This will be the wet weight. ∑ Dry it and let all H2O evaporate. ∑ Remaining material gives dry weight. ∑ Burn it. All carbon compounds get oxidized to CO2. ∑ Remaining material is ash which contains inorganic elements like—Ca, Mg etc. ∑ Ash or acid soluble fraction is subjected to elemental analysis. Various chemical compounds present in a cell constitute the cell pool or cellular pool. These chemical compounds are water; inorganic materials (salts, mineral ions); and organic compounds (carbohydrates, lipids, amino acids, proteins, nucleic acids, enzymes, nucleotides and vitamins.) Out of these, some organic compounds occur in colloidal form in the aqueous intracellular fluid; while others occur in non-aqueous phase like the cell membranes and cell walls. The semipermeable cell membrane maintains a required chemical composition of the cell. This makes the composition of cellular pool much different from the extracellular fluids. The specific consistency of the cell pool is maintained by the intake and elimination of specific molecules. The main function of the cell pool is to provide various materials for the structure and function of the cell.

2.8

CARBOHYDRATES ∑ Carbos means Sugars or Saccharides containing C, H, O in 1 : 2 : 1 ratio. ∑ Carbohydrate Monomers = Monosaccharides. ∑ Scientific names of all carbos end in – ose. Carbohydrates are carbon compounds that contain large quantities of hydroxyl groups. ∑ The simplest carbohydrates also contain either an aldehyde moiety (these are termed polyhydroxyaldehydes) or a ketone moiety (polyhydroxyketones). ∑ All carbohydrates can be classified as either monosaccharides, oligosaccharides or polysaccharides. ∑ Anywhere from 2 to 10 monosaccharide units, linked by glycosidic bonds, make up an oligosaccharide. ∑ Polysaccharides are much larger, containing hundreds of monosaccharide units. ∑ The presence of the hydroxyl groups allows carbohydrates to interact with the aqueous environment and to participate in hydrogen bonding, both within and between chains. ∑ Derivatives of the carbohydrates can contain nitrogen, phosphates and sulphur compounds. ∑ Carbohydrates also can combine with lipid to form glycolipids or with protein to form glycoproteins.

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∑ Chemically, the carbohydrates are either aldehyde or ketone derivatives of the polyhydroxic alcohols (more than one OH group) or as compounds that yield these derivatives on hydrolysis. It means they contain many hydroxyl (–OH) groups besides carbonyl or carbonoxygen groups. Carbohydrates containing aldehyde group is called aldose and with ketone group is called ketose. An aldose possesses this group (–CHO) at the end of its carbon chain, while the ketose has a ketone group (–C=O) in the middle position. The suffix –ose denotes a carbohydrate. The general formula of aldehyde and ketone are:

H

R

C

O

C

R

R

Aldhyde

Ketone

O

Here ‘R’ represents the hydrocarbon residue. In solution carbohydrates occur in two forms in equilibrium with each other—open and cyclic or ring form. Ring form is of two types: (a) Pyranose—Hexagonal, 5 carbon atoms and one oxygen atom in a ring (b) Furnanose—Pentagonal, 4 carbon atoms and one oxygen atom in a ring. ∑ The predominant carbohydrates encountered in the body are structurally related to the aldotriose glyceraldehydes and to the ketotriose dihydroxyacetone. ∑ All carbohydrates contain at least one asymmetrical (chiral) carbon and are, therefore, optically active. ∑ In addition, carbohydrates can exist in either of two conformations, as determined by the orientation of the hydroxyl group about the asymmetric carbon farthest from the carbonyl. ∑ With a few exceptions, those carbohydrates that are of physiological significance exist in the D-conformation. The mirror-image conformations, called enantiomers, are in the L-conformation.

Monosaccharides The monosaccharides commonly found in humans are classified according to the number of carbons they contain in their backbone structures. The major monosaccharides contain three to six carbon atoms.

H C HO

O

H

C C

H

H

OH

H

C

OH

C

O

C

OH

H

H

Glycerose or Glyceraldehyde

Dihydroxy acetone

C

O

H

C

OH

H

C

OH

H

C

OH

H Erythrose

42 HUMAN ANATOMY AND PHYSIOLOGY H

H

H

H

C

OH

H

C

O

H

C

H

C

C

O

H

C

OH

OH

H

C

OH

OH

H

C

H

C

H

Erythrulose

C

OH

C

O

H

C

H

OH

H

C

H

OH

H

C

H

H

H

H

Ribose

Ribulose

Structures of Some Carbohydrates Carbohydrate are classified as follows: Table 2.1. Carbohydrate Classification No. of Carbons 3

Category Triose

Examples Aldoses Glyceraldehyde/Glycerose

Examples Ketoses Dihydroxy-acetone

4

Tetrose

Erythrose

Erythrulose

5

Pentose

Ribose

Ribulose

6

Hexose

Glucose

Fructose

∑ The aldehyde and ketone moieties of the carbohydrates with five and six carbons will spontaneously react with alcohol groups present in neighboring carbons to produce intramolecular hemiacetals or hemiketals, respectively. ∑ This results in the formation of five-or six-membered rings. Because the five-membered ring structure resembles the organic molecule furan, derivatives with this structure are termed furanoses. ∑ Those with six-membered rings resemble the organic molecule pyran and are termed pyranoses. ∑ Such structures can be depicted by either Fischer or Haworth style diagrams. The numbering of the carbons in carbohydrates proceeds from the carbonyl carbon, for aldoses, or the carbon nearest the carbonyl, for ketoses. H

OH C

H

C

OH

HO

C

H

H

C

OH

H

C CH2OH

CH2OH OH

H

H OH H O

HO

OH H

OH

Cyclic Ficher Projection of Haworth Projection D-Glucose of D-Glucose Structure of D-Glucose

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∑ The rings can open and re-close, allowing rotation to occur about the carbon bearing the reactive carbonyl yielding two distinct configurations of the hemiacetals and hemiketals. ∑ The carbon about which this rotation occurs is the anomeric carbon and the two forms are termed anomers. ∑ Carbohydrates can change spontaneously between both configurations—a process known as mutarotation. ∑ When drawn in the Fischer projection, the configuration places the hydroxyl attached to the anomeric carbon to the right, towards the ring. ∑ When drawn in the Haworth projection, the configuration places the hydroxyl downward. ∑ The spatial relationships of the atoms of the furanose and pyranose ring structures are more correctly described by the two conformations identified as the chair form and the boat form. ∑ Constituents of the ring that project above or below the plane of the ring are axial and those that project parallel to the plane are equatorial. ∑ In the chair conformation, the orientation of the hydroxyl group about the anomeric carbon of D-glucose is axial and equatorial in D-glucose. H

CH2OH

O

H

HO HO

H

HO

OH

H

Chair form of D-Glucose

Examples of Monosaccharides: Simple Sugars (a) Glucose—Form of simple sugar used by all cells. From grapes and honey. (sweet !) (b) Fructose—Fruit sugar (sweet!) (c) Galactose—Less sweet. Dairy products and gums. Different 6-carbon monosaccharides can be made by switching positions of atoms on the carbon chains. H

H C

OH

C

O

HO

C

H

H

C

H H

H

H

C

O

H

C

OH

HO

C

OH

H

C

OH

C

OH

H

Fructose

Structural Isomer

C

O

H

C

OH

H

HO

C

H

C

OH

HO

C

H

H

C

OH

H

C

OH

H

C

OH

H

C

OH

Stereoisomer

H

Glucose

H

Galactose

44 HUMAN ANATOMY AND PHYSIOLOGY CH2OH

H C4 OH

H

C 5

C

O H

H H 2

3 C H

O

H

1C

C5

OH

OH

7

C

4 C

OH

OH

Glucose

3

Fructose

CH2OH 1 2C OH

C OH 5 C4

O

H

OH

H

C

3 C

H

H

2

1C OH

C

OH Galactose

Three types of hexose carbohydrates—glucose, fructose and galactose.

Structure of Ribose and Deoxyribose Sugars H

C

O

H

C

O

H

C

OH

H

C

H

H

C

OH

H

C

OH

H

C

OH

H

C

OH

C

H

C

OH

H

C

OH

H

H H

H Ribose open chain

Deoxyribose open chain

O

OH

HOCH2

H

C

C

C

C

H

H

OH

H

HOCH2

Deoxyribose closed chain

O

OH

H

H

C

C

OH

C H

OH

Ribose closed chain

Deoxyribose and ribose sugars present in DNA and RNA. (Note the difference of these two sugars at carbon atom number 2 position.)

Disaccharides: Double Sugars Formed by condensation synthesis (removal of water as the 2 monosaccharides bond)

Examples of Disaccharides: (a) Maltose (malt sugar) = glucose + glucose (b) Sucrose (table sugar) = glucose + fructose (c) Lactose (milk sugar) = glucose + galactose ∑ Covalent bonds between the anomeric hydroxyl of a cyclic sugar and the hydroxyl of a second sugar (or another alcohol containing compound) are termed glycosidic bonds, and the resultant molecules are glycosides. ∑ The linkage of two monosaccharides to form disaccharides involves a glycosidic bond. Several physiologically important disaccharides are sucrose, lactose and maltose. Sucrose: prevalent in sugar cane and sugar beets, is composed of glucose and fructose through an 1, 2 -glycosidic bond.

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O

O OH + OH

OH

HO C6H12O6 (Glucose)

H2O

(Glucose) C6H12O6

O

O O OH

OH Glycosidic bond Between C1 and C4 (1,2 glycosidic bond)

Disaccharide (Maltose) C12 O22 O11

Fig. 2.2

Formation of a disaccharide CH2OH

CH2OH

O

O H

H H OH

HO

H

H

H

O

HO H

CH2OH

OH OH Sucrose molecule

H

Lactose: It is found exclusively in the milk of mammals and consists of galactose and glucose in a 1, 4-glycosidic bond. CH2OH

CH2OH

O

HO H OH H

O OH

H O

H

H OH

H H

H OH Lactose molecule

H H OH

Maltose: The major degradation product of starch, is composed of 2 glucose monomers in an 1, 4-glycosidic bond.

46 HUMAN ANATOMY AND PHYSIOLOGY CH2OH

CH2OH O H

H H OH

O OH

H H OH

H O

HO H

H OH Maltose molecule

H H OH

Polysaccharides ∑ General formula—(C6 H10 O5)n ∑ Most of the carbohydrates found in nature occur in the form of high molecular weight polymers called polysaccharides. ∑ The monomeric building blocks used to generate polysaccharides can be varied; in all cases, however, the predominant monosaccharide found in polysaccharides is D-glucose. ∑ When polysaccharides are composed of a single monosaccharide building block, they are termed homopolysaccharides. ∑ Polysaccharides composed of more than one type of monosaccharide are termed heteropolysaccharides. ∑ Polysaccharides are also called glycans. ∑ These may be homopolysaccharide with one kind of monosaccharides (cellulose, starch, glycogen, insulin, agar, xylan, araban etc. ∑ Heteropolysaccharides consist of more than two or more types of monosaccharides as their derivatives. Like glucosamine, N-acetyl galactosamine, or sugar acids like glucoronic acid etc., e.g., chitin, Hyaluronic acid, peptidoglycans (murein).

Hyaluronic Acid ∑ ∑ ∑ ∑

It is a linear and acidic heteropolysaccharide. Mainly found in various lubricating fluids of body. For example, synovial fluid of limb joints. It is formed of alternatively arranged D-Glucoronic acid and N-acetyl glucosamino sugar molecules.

Peptidoglycans ∑ Found in the cell wall of bacteria and cyanobacteria. ∑ Formed of polysaccharide chain linked with tetrapeptide molecules. ∑ Prevents lysis and osmotic inflow of the cell wall.

Glycogen ∑ It is a storage homopolysaccharide. ∑ Glycogen is the major form of stored carbohydrate in animals and thus called animal starch. ∑ This crucial molecule is a homopolymer of glucose in 1, 4 linkage; it is also highly branched, with 1, 6 branch linkages occurring every 8 to 10 residues.

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∑ Glycogen is a very compact structure that results from the coiling of the polymer chains. ∑ This compactness allows large amounts of carbon energy to be stored in a small volume, with little effect on cellular osmolarity. ∑ It is branched, formed of 30,000 a-D-glucose molecules. ∑ It is the storage form of carbohydrate in animals and is often called “animal starch.” It is stored in the liver and muscles of animals. It can be broken down to glucose in liver to maintain the proper concentration of glucose in the blood. Glycogen resembles amylopectin in structure except that in amylopectin the molecular weight is lower and the chains are shorter. It has got large number of a-D glucose units. In glycogen, the chains of glucose units are joined by a 1-4 links and cross-linked by a 1-6 glycoside links.

Fig. 2.3

O O

Branching in glycogen molecule

O

O 1

O

O

O 6 CH2

O O

O Fig. 2.4

O 1

O

4 O Glycogen molecule structure

O O

Starch 6 CH2OH 5 H 4 C

C

O

H OH

H

C

C

OH

C 1 OH

3

2 H

Fig. 2.5

H

OH

Molecular structure of alpha-D glucose

O

48 HUMAN ANATOMY AND PHYSIOLOGY

O

H O

O A

O

n

CH2OH CH2OH CH2OH O H H O H H O H H H H H H H OH OH OH O O O H

OH

H

OH

H

OH

B

Fig. 2.6

Arrangement of alpha glucose units in starch. A–outline diagram, B–molecular diagram.

∑ It is a storage homopolysaccharide of plants. ∑ Starch is the major form of stored carbohydrate in plant cells. ∑ Its structure is identical to glycogen, except for a much lower degree of branching (about every 20 to 30 residues). ∑ Chemically it is formed of 2 glucose polymers — a amylose and amylopectin. Unbranched starch is called amylose while the branched starch is called amylopectin. The pentose sugar in DNA and ATP is a carbohydrate. a – amylose is unbranched but spiral chain of about 200 to 2000 a-glucose molecules interlinked by a-1, 4 glycosidic bonds and amylopectin is branched glucose of about 2000 to 20,000 a-glucose molecules so forming helical secondary structure.

Amylose Amylopectin

Fig. 2.7

Branching in amylose and amylopectin molecules

Cellulose ∑ It is a structural polysaccharide found is the cell wall of plants. ∑ It is linear, unbranched and homopolysaccharide. ∑ It consists of about 6000 to 10,000 b-D glucose molecules interlinked by b-1, 4 glycosidic linkage. ∑ It does not contain complex helices, so cannot hold iodine and does not give blue-black colour with iodine.

Inulin ∑ ∑ ∑ ∑

It is the polymer of fructose. It is also called fructane. It is found in roots and tubers of onion, garlic etc. It proves to be useful in determining the rate of ultra filtration.

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Xylon ∑ It is a polymer of xylose molecules. ∑ It is found in tertiary cell wall of gymnosperms.

Agar ∑ It is a polymer of glucose sugar. ∑ It is also called galactone. ∑ It is found in sea algae like Gracilaria and Gellidium.

Chitin ∑ ∑ ∑ ∑

It is heteropolysaccharide. Mainly found in exoskeleton of crustaceans (e.g., crabs, lobsters etc.) It is also found in cell wall of most of fungi. That is why it is also called fungal cellulose. It is a ploymer of N-acetyl galactosamine units interlinked by b- 1,4 glycosidic bonds.

Importance of Carbohydrates 1. Glucose – metabolic fuel 2. Animal Strarch (Glycogen)–long term energy storage for animal cells (stores the glucose molecules in a form that is not easily used!) 3. Plant Starch (Amylose) – long term energy storage for plant cells (stores the glucose molecules in a form that is not easily used!) 4. Cellulose – Structural polysaccharide of cell walls 5. Chitin – Structural polysaccharide of exoskeletons of insects and crustaceans.

2.9

PROTEINS

Proteins are organic molecules consisting of many amino acids bonded together.

Amino Acids ∑ Amino acids are monomers or building blocks of all proteins.

H O

H N

C

H

C O

H

R Amino Group

R - group

Carboxylic Group

50 HUMAN ANATOMY AND PHYSIOLOGY Some examples of amino acids are cysteine, cystine and methionine which also contain sulphur in them. A free amino group is basic; while a free carboxylic group is acidic in nature. Lysine and arginine are basic amino acids because they carry two amino groups and one carboxyl group. Glutamic acid (glutamate) and aspartic acid (aspartate) are acidic amino acids because they carry one amino group and two carboxyl groups. Alanine, glycine, valine, phenylalanine are neutral amino acids because they carry one amino group and one carboxyl group. There are total of 20 amino acids known to occur in plant and animal cells. These amino acids occur freely in the cytoplasm and constitute the so called amino acid pool. Following is the list of various amino acids: Glycine, alanine, serine, cysteine, aspartic acid, glutamic acid, asparagine, glutamine, methionine, threonine, valine, leucine, isoleucine, lysine, histidine, arginine, phenylanine, tyrosine, tryptophan and proline. ∑ Peptide bond is a bond formed when two amino acids bounded by condensation synthesis. H

H N H

C

O

N H

H

O

R

H

+

C

H2O

Amino Acid

H

O C O

R

H

Amino Acid

1

2

H N H

C



H

O

H

H

C

C

N

C

R

R

O C OH

Dipeptide

1

2

∑ Dipeptide: when two amino acids joined by peptide bond. ∑ Polypeptide: when many amino acids bonded together. All peptides and polypeptides are polymers of a-amino acids. ∑ There are 20 amino acids that are relevant to the make-up of mammalian proteins. ∑ Several other amino acids are found in the body as free or in combined states (i.e., not associated with peptides or proteins). ∑ These non-protein associated amino acids perform specialized functions. ∑ Several of the amino acids found in proteins also serve functions distinct from the formation of peptides and proteins, e.g., tyrosine in the formation of thyroid hormones or glutamate acting as a neurotransmitter. ∑ The amino acids in peptides and proteins (excluding proline) consist of a carboxylic acid (–COOH) and an amino (–NH2) functional group attached to the same tetrahedral carbon atom. ∑ Distinct R-groups, that distinguish one amino acid from another, are also attached to the a-carbon (except in the case of glycine where the R-group is hydrogen). ∑ The fourth substitution on the tetrahedral carbon of amino acids is hydrogen. The proteins in our bodies are made of 20 different amino acids strung together like beads on a string. ∑ All 20 amino acids have a part in common: a central carbon attached to a carboxyl, an amino and a hydrogen atom. ∑ The differences between the 20 types are in the side groups that can be designated as R.

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Functions 1. Enzyme Catalysis: Enzymes help reactions occur more easily. Example, Amylase (converts starch to simple sugar). 2. Defense: Antibodies-globular proteins that “recognize” foreign microbes. 3. Transport: Hemoglobin (red blood cell protein). 4. Structure: Support—collagen, which forms the matrix of skin, ligaments, tendons and bones. 5. Motion: Actin, a muscle protein responsible for muscle contraction. 6. Regulation: Hormones which serve as intercellular messengers. Example-Insulin (blood sugar regulation).

Protein Structure 1. Primary Structure: Single polypeptide chain with amino acids connected by peptide bonds. (No H-bonds between nearby amino acids) 2. Secondary Structure: Single polypeptide chain, H-bonding to side groups of amino acids several places away forms folded or coiled structure. 3. Tertiary Structure: Single polypeptide chain, 3-D shape due to H-bonds between amino acids that are nearby as well as. 4. Quaternary Structure: Two or more polypeptide chains linked. Denaturation: Using extremes of pH or temperature to alter the shape of a protein (breaks some of the H-bonds that hold the polypeptide chain in its original shape). C=O H3C

C

H N

H

O=C H H

C

C H2OH

Peptide bonds

N O CC==O

H

C

One amino acid

H N

H

C

C H2OH

O=C H H

N

Fig. 2.8 Primary structure of proteins

52 HUMAN ANATOMY AND PHYSIOLOGY H C H2N C O R1 H H C C H N R4 O 1 N H C C C H O N O R3 H H C N C O H H H R7 N N C C O R6 a-Helix

H N

Fig. 2.9

H C R2

R5 H C R8

Hydrogen Bond

C H Polypeptides

C O

b-Pleated (Diagrammatic)

C O

Secondary structure of proteins Alpha chain

Beta chain

Iron group

Alpha chain

Beta chain

A. Protein myoglobin

Fig. 2.10

B. Protein haemoglobin = 4 polypeptides (2 alpha chains, 2 Beta chains)

A. Tertiary structure of protein myoglobin. B. Quaternary structure of protein haemoglobin. Table 2.2. Chemistry of 20 Amino Acids

S.No.

Amino Acid

Symbol

Structure

Amino Acids with Aliphatic R-Groups

1.

Glycine

Gly

HO

CH2

CH

COOH

NH2 CH3 2.

Alanine

Ala

Valine

Val

COOH

NH2 H3C

3.

CH

H3C

CH

CH NH2

COOH

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54 HUMAN ANATOMY AND PHYSIOLOGY Basic Amino Acids

14.

Arginine

Agr

HN

CH2

C

NH

CH2 CH2 CH

COOH

NH2

NH2 H3C 15.

Lysine

Lys

CH

CH

HO

NH2 CH

CH2 16.

Histidine

His

HN

COOH

COOH

NH2

N:

Amino Acids with Aromatic Rings

17.

Phenylalanine

CH2

Phe

CH

COOH

NH2

18.

Trysoine

Tyr

HO

CH2

CH

COOH

NH2 CH2 19.

Tryptophan

Trp

CH

COOH

NH2 N H Imino Acids

20.

Proline

Pro

+ N

COOH

H H

Amino Acid Classification ∑ Each of the 20 amino acids found in proteins can be distinguished by the R-group substitution on carbon atom. ∑ There are two broad classes of amino acids based upon whether the R-group is hydrophobic or hydrophilic. ∑ The hydrophobic amino acids tend to repel the aqueous environment and, therefore, reside predominantly in the interior of proteins. ∑ This class of amino acids neither ionize nor participate in the formation of H-bonds.

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The hydrophilic amino acids tend to interact with the aqueous environment, are often involved in the formation of H-bonds and are predominantly found on the exterior surfaces proteins or in the reactive centers of enzymes.

Acid-base Properties of the Amino Acids ∑ The COOH and NH2 groups in amino acids are capable of ionizing (as are the acidic and basic R-groups of the amino acids). ∑ As a result of their ionizability, the following ionic equilibrium reactions may be written: R-COOH R-NH3+

R-COO– + H+ R-NH2+ H+

∑ The equilibrium reactions, as written, demonstrate that amino acids contain at least two weak acidic groups. ∑ However, the carboxyl group is a far stronger acid than the amino group. ∑ At physiological pH (around 7.4) the carboxyl group will be unprotonated and the amino group will be protonated. ∑ An amino acid with no ionizable R-group would be electrically neutral at this pH. This species is termed zwitterion. ∑ Like typical organic acids, the acidic strength of the carboxyl, amino and ionizable R-groups in amino acids can be defined by the association constant, Ka or more commonly the negative logarithm of Ka, the pKa. ∑ The net charge (the algebraic sum of all the charged groups present) of any amino acid, peptide or protein, will depend upon the pH of the surrounding aqueous environment. ∑ As the pH of a solution of an amino acid or protein changes so too does the net charge. ∑ We can synthesize about half of these amino acids in our body. The others are essential-that is, we must get them from our diet. As a practical matter, during periods of growth, we must get some of the non-essential ones from our diet as well-we cannot make them fast enough. ∑ Essential amino acids: Isoleucine, leucine, valine, lysine, metheonine, threonine, phenylalanine, tryptophan. ∑ Non-essential amino acids: Alanine, arginine, aspartic acid, asparagine, cysteine, glutamic acid, glutamine, histidine, glycine, proline, serine, tyrosine.

2.10

LIPIDS

Lipids are the organic compounds that are insoluble in water but soluble in organic solvents like ether, chloroform, benzene and petroleum ether. They have long chains of aliphatic hydrocarbons or benzene ring in them. Many substances like oil, butter, ghee, waxes, natural rubber and cholesterol are either lipids or rich in lipids. They also form an important constituent of cell membranes, plant pigments like carotene (in carrots) and lycopene (in tomatoes), menthol, eucalyptus oil, hormones and vitamins A, E and K of the body. Chemically, lipids are the compounds of carbon, hydrogen and oxygen. The number of oxygen atoms in a lipid molecule is always less as compared to the number of carbon atoms in carbohydrate. That is why they require more of oxygen for their oxidation and release of energy as compared to that of carbohydrates. Sometimes lipids may also contain small amounts of phosphorus, nitrogen and sulphur. They are the esters (alcohol and acid) of higher fatty acids.

56 HUMAN ANATOMY AND PHYSIOLOGY O ROH + HO alcohol

C acid

O R¢

– H2O

R

O

C



ester

∑ Fatty acids are long-chain hydrocarbon molecules containing a carboxylic acid moiety at one end. ∑ The numbering of carbons in fatty acids begins with the carbon of the carboxylate group. ∑ At physiological pH, the carboxyl group is readily ionized, rendering a negative charge onto fatty acids in bodily fluids. ∑ Fatty acids that contain carbon-carbon single bonds are termed saturated fatty acids; those that contain double bonds are unsaturated fatty acids. ∑ The numeric designations used for fatty acids come from the number of carbon atoms, followed by the number of sites of unsaturation (e.g., palmitic acid is a 16-carbon fatty acid with no unsaturation and is designated by 16:0) ∑ The site of unsaturation in a fatty acid is indicated by the symbol * and the number of the first carbon of the double bond (e.g., palmitoleic acid is a 16-carbon fatty acid with one site of unsaturation between carbons 9 and 10, and is designated by 16:1*9). ∑ Saturated fatty acids of less than eight carbon atoms are liquid at physiological temperature, whereas those containing more than ten are solid. ∑ The presence of double bonds in fatty acids significantly lowers the melting point relative to a saturated fatty acid. ∑ The majority of body fatty acids are acquired in the diet. However, the lipid biosynthetic capacity of the body (fatty acid synthase and other fatty acid modifying enzymes) can supply the body with all the various fatty acid structures needed. ∑ Two key exceptions to this are the highly unsaturated fatty acids known as linoleic acid and linolenic acid, containing unsaturation sites beyond carbons 9 and 10. ∑ These two fatty acids cannot be synthesized from precursors in the body, and are thus considered the essential fatty acids; essential in the sense that they must be provided in the diet. ∑ Since plants are capable of synthesizing linoleic and linolenic acid humans can acquire these fats by consuming a variety of plants or else by eating the meat of animals that have consumed these plant fats.

Types of Lipids 1. Simple lipids are the esters of alcohols or triglycerides containing fatty acids and alcohols. 2. Compound lipids are the simple lipids with a biologically active compound in them like glycolipids (carbohydrate + lipid), lipoproteins (protein + lipid) and phospholipids (phosphoric acid + lipid). 3. Derived lipids are hydrolysed products of simple lipids like fatty acids and alcohols (phytol, sterol, pyrrole). Fatty Acids. They are the organic acids with a long hydrocarbon chain ending in carboxyl group (–COOH). Following are the characteristics of a fatty acid: (i) It has a long chain of carbon atoms. (ii) It is insoluble in water. (iii) It is soluble in organic solvents. (iv) It should leave an oily spot on the piece of paper. Saturated fatty acids are those which do not have any double bond in between the carbon atoms of the molecular chain. Their examples are given below:

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1. Palmitic acid CH3 (CH2)14 COOH 2. Stearic acid CH3 (CH2)16 COOH Unsaturated fatty acids are those which have one or more double bonds in between the carbon atoms of the molecular chain. The unsaturated fatty acids have lower melting points as compared to the saturated fatty acids. Their examples are given below: 1. Oleic acid CH3 (CH2)7 CH=CH(CH2)7COOH 2. Linoleic acid CH3 (CH2)4 (CH=CHCH2)2(CH2)6COOH 3. Linolenic acid CH3 CH2 (CH=CHCH2)3 (CH2)6 COOH No animal is able to synthesize unsaturated fatty acids in their body that is why they are essential fatty acids and so must be present in the diet. A. Triglycerides (fats) = glycerol + three fatty acids ∑ They are nonpolar (don’t dissolve well in water). Only the ends of the fatty acids can be attracted to water. ∑ They tend to form circular blobs in water with the nonpolar glycerol inside the fatty parts facing to water.

O H2C

O

C

R

O HC

O

C

R’

O H2C

O

C

R”

Triglyceride

Saturated: All single bonds (many C–H bonds), hard, animal fats. Unsaturated: Some double bonds (less C–H bonds), liquid, plant oils. H

H

H

H

H

C

C

C

C

C

H

H

H

H

H

Saturated (max C – H bonds)

H

* C

C

C H

Unsaturated (fewer C – H bonds)

B. Phospholipids: Comprise cell membranes and soaps (Made of glycerol + 2 fatty acids + 1 phosphate). ∑ Polar PO4 faces outward. ∑ Nonpolar fatty acids face inward. C. Steroids: (a) lipid hormones (b) cholesterol (c) vitamins (Vit. D)

58 HUMAN ANATOMY AND PHYSIOLOGY Steroids have 4 rings, which make the molecule very flat and stiff. The best known steroid is cholesterol. Too much cholesterol causes clogging of the arteries, but in the right amount, it is very useful. It is essential for cell membranes (it keeps them from falling apart) and is a precursor for several hormones, including cortisone, aldosterone and both male and female sex hormones.The male and female sex hormones are very similar. They differ by only a hydroxyl group (OH) or a methyl group (CH3) and a couple of double bonds in the ring. D. Waxes: Waxes are the esters of saturated fatty acids with long chain alcohol other than glycerol. They are mainly protective in function. They form water insoluble coatings on hair and skin of animals; and stem, leaves and fruits of plants. Waxes are pliable and soft on warming but become hard and water resistant when cold e.g., paraffin. Another example of wax is bees wax.

Major Roles of Lipids Biological molecules that are insoluble in aqueous solutions and soluble in organic solvents are classified as lipids. The lipids of physiological importance for humans have following major functions: 1. They serve as structural components of biological membranes. 2. They provide energy reserves, predominantly in the form of triacylglycerols. 3. Both lipids and lipid derivatives serve as vitamins and hormones. 4. Lipophilic bile acids aid in lipid solubilization. 5. Energy storage-fats and oils store energy for long time periods. 6. Chemical messengers-Steroid hormones (testosterone and estrogen, etc). 7. Lipid bilayers of cell membranes (phospholipids). Fatty acids fill two major roles in the body: 1. As the components of more complex membrane lipids. 2. As the major components of stored fat in the form of triacylglycerols. Table 2.3.

Important Fatty Acids

Numerical Symbol 14:0

Common Name Myristic acid

Structure

16:0

Palmitic acid

CH3(CH2)14COOH

16:1*9

Palmitoleic acid

CH3(CH2)5C=C(CH2)7COOH

18:0

CH3(CH2)12COOH

(Often found attached to the N-term of plasma membrane— associated cytoplasmic proteins) (End product of mammalian fatty acid synthesis)

Stearic acid

CH3(CH2)16COOH

*9

Oleic acid

CH3(CH2)7C=C(CH2)7COOH

*9,12

18:2

Linoleic acid

CH3(CH2)4C=CCH2C=C(CH2)7COOH

18:3*9,12,15

Linolenic acid

CH3CH2C=CCH2C=CCH2C=C(CH2)7COOH (Essential fatty acid)

18:1

*5,8,11,14

20:4

Arachidonic acid CH3(CH2)3(CH2C=C)4(CH2)3COOH

(Essential fatty acid)

(Precursor for eicosanoid synthesis)

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Basic Structure of Phospholipids ∑ The basic structure of phospholipids is very similar to that of the triacylglycerides except that C-3 of the glycerol backbone is esterified to phosphoric acid. ∑ The building block of the phospholipids is phosphatidic acid which results when the X substitution in the basic structure shown in the figure below is a hydrogen atom. ∑ Substitutions include ethanolamine (phosphatidylethanolamine), choline (phosphatidylcholine, also called lecithins), serine (phosphatidylserine), glycerol (phosphatidylglycerol), myoinositol (phosphatidylinositol, these compounds can have a variety in the numbers of inositol alcohols that are phosphorylated generating polyphosphatidylinositols), and phosphatidylglycerol (diphosphatidylglycerol more commonly known as O H2C

O

C

R1

O HC

O

C

R2

O H2C

O

P

O

X

O– Phospholipid

Basic Structure of Plasmalogens ∑ Plasmalogens are complex membrane lipids that resemble phospholipids, principally phosphatidylcholine. ∑ The major difference is that the fatty acid at C-1 (sn1) of glycerol contains either an O-alkyl (–O–CH2–) or O-alkenyl ether (–O–CH=CH–) species. ∑ A basic O-alkenyl ether species is shown in the figure below. H2C

O

CH

CH

CH2

O HC

O

C



O H2C

O

P

O

O– Plasmalogen

X

CH3

60 HUMAN ANATOMY AND PHYSIOLOGY 2.11

NUCLEIC ACIDS

∑ Deoxyribonucleic acid: DNA, master molecule, stores hereditary information. ∑ Ribonucleic acid: RNA, template copy Nucleic acids Made of nucleotides

OH

Ribose Sugar

Nitrogen base

Deoxyribose

Purine (9 - membered double rings)

Adenine

Phosphate Phosphoric acid H3PO4

HO

P

O

OH

Pyrimidine (6-membered rings)

Guanine

Thymine

Cytosine

Uracil

∑ Nucleotides are found primarily as the monomeric units comprising the major nucleic acids of the cell, RNA and DNA. However, they also are required for numerous other important functions within the cell. These functions include: 1. Serving as energy stores for future use in phosphate transfer reactions. These reactions are predominantly carried out by ATP. 2. Forming a portion of several important coenzymes such as NAD+, NADP+, Nucleotides are the monomers (subunits) of all nucleic acids. Nucleotides consist of: (a) Phosphate group (PO4). (b) Five carbon sugar: deoxyribose- 1 less oxygen than ribose (RNA). (c) Nitrogen base consists of: Purines: adenine, guanine (double rings). Pyrimidines: thymine, cytosine, uracil-RNA (only single rings) O

NH2

O

C 6

C 6

C 6

H-N1

C2 O

5C-CH3

N1

5-CH

HN1

4CH

C2

4C-H

C2

3 N

O

3 N

O

5CH

4C-H 3 N

H

H

H

THYMINE (2-6-dihydroxy 5-methyl pyrimidine) (M.W. 126 .12 dalton)

CYTOSINE (2-dihydroxy 6-amino pyrimidine) (M.W. 111 .10 dalton)

URACIL (2-6 dihydroxy pyrimidine) (M.W. 112 .09 dalton)

CHEMISTRY NH2

5C

C 6

N 7

HN1

5C

N 7

9CH H-C

4C

2

LIFE 61

O

C 6 N1

OF

3 N

9 N

8CH 2

4C

C H2N

H

ADENINE (6-amino purine) (M.W. 135.13 dalton)

3 N

9 N H

GUANINE (2-amino 6-hydroxy purine) (M.W. 151.13)

∑ It is the chemical basicity of the nucleotides that has given them the common term “bases” as they are associated with nucleotides present in DNA and RNA. ∑ There are five major bases found in cells. ∑ The derivatives of purine are called adenine and guanine, and the derivatives of pyrimidine are called thymine, cytosine and uracil. ∑ The common abbreviations used for these five bases are, A, G, T, C and U. Table 2.4 Base Formula

Base (X=H)

Nucleoside X=ribose or deoxyribose

Nucleotide X=ribose phosphate

Cytosine, C

Cytidine, A

Cytidine monophosphate CMP

Uracil, U

Uridine, U

Uridine monophosphate UMP

Thymine, T

Thymidine, T

Thymidine monophosphate TMP

Adenine, A

Adenosine, A

Adenosine monophosphate AMP

Guanine, G

Guanosine, A

Guanosine monophosphate GMP

NH2 N

N X

O

O H

N

N X

O O H

CH3

N

O

N dx NH2 N

N

N

N

X

O H H2N

N

N

N

N X

62 HUMAN ANATOMY AND PHYSIOLOGY H O O

P

H N

N

O

N H

CH2

O

O

N

N Base (Adenine)

H

H H H OH H Sugar (Deoxyribose)

NUCLEOSIDE

NUCLEOTIDE

Fig. 2.11

Molecular formula of nucleoside and nucleotide

Nitrogen base + sugar Æ Nucleoside N-base + ribose sugar Æ ribonucleotide/riboside N-base + deoxyribose sugar Æ deoxyribonucleoside/deoxyriboside. Various nucleosides are– 1. Adenine + ribose Æ adenosine 2. Adenine + deoxyribose Æ deoxyadenosine 3. Guanine + ribose Æ guanosine 4. Guanine + deoxyribose Æ deoxyguanosine 5. Cytosine + ribose Æ cytidine 6. Cytosine + deoxyribose Æ deoxycytidene 7. Thyamine + deoxyribose Æ deoxythymidine 8. Uracil + ribose Æ Uradine R ibo n u cleotid es Nucleoside + phosphate group Æ Nucleotide Types D eo xy ribo n u cleotid es Various nucleotides are — 1. Adenylic acid or Adenosine monophosphate (AMP) 2. Guanylic acid or Guanosine monophosphate (GMP) 3. Cytidylic acid or Cytosine monophosphate (CMP) 4. Uridylic acid or Uridine monophosphate (UMP) 5. Deoxy adenylic acid or Deoxyadenosine monophosphate (dAMP) 6. Deoxyguanylic acid or Deoxyadenosine guanosine monophosphate (dGMP) 7. Deoxy citidylic acid or Deoxycytosine monophosphate (dCMP) 8. Deoxythymidylic acid or Deoxythymidine monophosphate (dTMP) O CH2OH

O

Adenine

HO

P

O

CH2

O

Adenine

OH OH

OH

Adenosine nucleoside

OH

OH

Adenylic acid nucleotide

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N-base A

Ribosides Adenosine

Ribotides Adenylic acid (AMP)

Deoxyribosides Deoxyadenosine

Deoxyribotides Deoxyadenylic acid (dAMP)

G

Guanosine

Guanylic acid (GMP)

Deoxyguanosine

Deoxy guanylic acid (dGMP)

C

Cytidine

Cytidylic acid (CMP)

Deoxy cytidine

Deoxy cytidylic acid (dCMP)

T



——

Deoxy thymidine

Deoxy thymidilic acid (dTMP)

U

Uridine

Uridylic acid (UMP)





∑ The purine and pyrimidine bases in cell are linked to carbohydrate and in this form are termed, nucleosides. ∑ The nucleosides are coupled to D-ribose or 2’-deoxy-D-ribose through a-N-glycosidic bond between the anomeric carbon of the ribose and the N9 of a purine or N1 of a pyrimidine. ∑ The base can exist in 2 distinct orientations about the N-glycosidic bond. ∑ These conformations are identified as, syn and anti. It is the anti conformation that predominates in naturally occurring nucleotides. NH2

NH2 N

N

HO

N

N

N

N

O

OH OH syn-Adenosine

HO

N

N

O

OH OH anti-Adenosine

∑ Nucleosides are found in the cell primarily in their phosphorylated form. These are termed nucleotides. ∑ The most common site of phosphorylation of nucleotides found in cells is the hydroxyl group attached to the 5’-carbon of the ribose. ∑ The carbon atoms of the ribose present in nucleotides are designated with a prime (‘) mark to distinguish them from the backbone numbering in the bases. ∑ Nucleotides can exist in the mono-, di-, or tri-phosphorylated forms. ∑ Nucleotides are given distinct abbreviations to allow easy identification of their structure and state of phosphorylation. ∑ The monophosphorylated form of adenosine (adenosine-5’-monophosphate) is written as, AMP. The di-and tri-phosphorylated forms are written as, ADP and ATP, respectively. ∑ The use of these abbreviations assumes that the nucleotide is in the 5’-phosphorylated form. ∑ The di-and tri-phosphates of nucleotides are linked by acid anhydride bonds. ∑ Acid anhydride bonds have a high G¢ for hydrolysis imparting upon them a high potential to transfer the phosphates to other molecules. ∑ It is the property of nucleotides that results in their involvement in group transfer reactions in the cell. ∑ The nucleotides found in DNA are unique from those of RNA in that the ribose exists in the 2’-deoxy form and the abbreviations of the nucleotides contain a “d” designation. ∑ The monophosphorylated form of adenosine found in DNA (deoxyadenosine-5’-monophosphate) is written as dAMP.

64 HUMAN ANATOMY AND PHYSIOLOGY ∑ The nucleotide uridine is never found in DNA and thymine is almost exclusively found in DNA. ∑ Thymine is found only in tRNAs but not in rRNAs and mRNAs. ∑ There are several less common bases found in DNA and RNA. ∑ The primary modified base in DNA is 5-methylcytosine. ∑ A variety of modified bases appear in the tRNAs. Many modified nucleotides are encountered outside of the context of DNA and RNA that serve important biological functions.

Polynucleotides ∑ Polynucleotides are formed by the condensation of two or more nycleotides. ∑ The condensation most commonly occurs between the alcohol of a 5’-phosphate of one nucleotide and the 3’-hydroxyl of a second, with the elimination of H2O, forming a phosphodiester bond. ∑ The formation of phosphodiester bonds in DNA and RNA exhibits directionality. ∑ The primary structure of DNA and RNA (the linear arrangement of the nucleotides) proceeds in the 5’ Æ 3’ direction. ∑ The common representation of the primary structure of DNA or RNA molecules is to write the nucleotide sequences from left to right synonymous with the 5’ Æ 3’ direction.

2.12

STRUCTURE OF DNA OH

OH 3

2

5 CH2

O 1

4

Base

5 CH2

O

3

H

4

1

Base Bond

2 OH

O O

P

O

P

O

O

O

OH CH2

H 1 Base

4 H

3

3

2

O Bond

Base

4

1 O

2

OH 3 end with free OH group

CH2OH 5

5 end with free OH group

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Polynucleotide chain formation Interlinking of nucleotides by 5-3 Phospho diester bonds i.e., 5-Carbon of sugar forms bond with 3-Carbon of pentose sugar of adjoining nucleotide Bond between sugar and phosphate is an ester bond Linking of phosphate gr oup to two sugar molecules in phosphodiester bond ∑ Each nucleo acid chain has two specific ends: (a) 5 end with free on group of 5-carbon of terminal nucleotide (b) 3 end with free on group of 3-carbon of terminal nucleotide ∑ Utilizing X-ray diffraction data, obtained from crystals of DNA, James Watson and Francis Crick proposed a model for the structure of DNA. ∑ This model predicted that DNA would exist as a helix of two complementary antiparallel strands, wound around each other in a rightward direction and stabilized by H-bonding between bases in adjacent strands. ∑ In the Watson-Crick model, the bases are in the interior of the helix aligned at a nearly 90 degree angle relative to the axis of the helix. ∑ Purine bases form hydrogen bonds with pyrimidines, in the crucial phenomenon of base pairing. ∑ Experimental determination has shown that, in any given molecule of DNA, the concentration of adenine (A) is equal to thymine (T) and the concentration of cytidine (C) is equal to guanine (G). ∑ This means that A will only base-pair with T, and C with G. ∑ According to this pattern, known as Watson-Crick base-pairing, the base-pairs composed of G and C contain three H-bonds, whereas those of A and T contain two H-bonds. This makes G-C base-pairs more stable than A-T base-pairs. ∑ The antiparallel nature of the helix stems from the orientation of the individual strands from any fixed position in the helix, one strand is oriented in the 5¢ Æ 3¢ direction and the other in the 3¢ Æ 5¢ direction. ∑ On its exterior surface, the double helix of DNA contains two deep grooves between the ribosephosphate chains. ∑ These two grooves are of unequal size and termed the major and minor grooves. ∑ The difference in their size is due to the asymmetry of the deoxyribose rings and the structurally distinct nature of the upper surface of a base-pair relative to the bottom surface. ∑ The double helix of DNA has been shown to exist in several different forms, depending upon sequence content and ionic conditions of crystal preparation.

66 HUMAN ANATOMY AND PHYSIOLOGY ∑ The B-form of DNA prevails under physiological conditions of low ionic strength and a high degree of hydration. Regions of the helix that are rich in pCpG dinucleotides can exist in a novel left-handed helical conformation termed Z-DNA. Table 2.5. Major DNA Helices and their parameters Parameters Direction of helical rotation

A-Form Right

B-Form Right

Left

Residues per turn of helix Rotation of helix per residue (in degrees) Base tilt relative to helix axis (in degrees) Major groove

11 33

10 36

12 base pairs 30

20

6

7

narrow and deep wide and shallow

wide and deep narrow and deep

Flat

Anti

Anti most prevalent within cells

Anti for Py, Syn for Pu occurs in stretches of alternating purine-pyrimidine base pairs

Minor groove Orientation of Nglycosidic Bond Comments

Z-Form

narrow and deep

Properties of DNA ∑ As cells divide it is a necessity that the DNA be copied (replicated), in such a way that each daughter cell acquires the same amount of genetic material. ∑ In order for this process to proceed the two strands of the helix must first be separated, in a process termed denaturation. This process can also be carried out in vitro. ∑ If a solution of DNA is subjected to higher temperature the H-bonds between bases become unstable and the strands of the helix separate in a process of thermal denaturation. ∑ The base composition of DNA varies widely from molecule to molecule and even within different regions of the same molecule. ∑ Regions of the duplex that have predominantly A-T base-pairs will be less thermally stable than those rich in G-C base-pairs. ∑ In the process of thermal denaturation, a point is reached at which 50% of the DNA molecule exists as single strands. This point is called the melting temperature (TM), and is characteristic of the base composition of that DNA molecule. The TM depends upon several factors in addition to the base composition.

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OH OH

O H2C5¢ H 3¢

H O

Adenine

O

H H H

O OH

P

20Å

O H2C5¢

Thymine

O

H H 3¢ O

H H

H O OH Phosphodiester bond

P

Shallow groove

34 Å

O

O

Guanine

O

H2C5¢ H H 3¢

H

P

O OH

H

H2C5¢

O

H

H 3¢

H

O OH O

P H2C5¢ H

10 Å

H H

Major axis

Deoxyribonucleotide Shallow groove

Guanine

H 3¢

H

OH

H

Fig. 2.12

34 Å

Cytosine

H O O

Deep groove

H

Molecular structure of DNA

Fig. 2.13

Double helical structure of DNA

68 HUMAN ANATOMY AND PHYSIOLOGY 5¢ End

3¢ End

P T

A

S

S P

P



G

S

C

P

P S





S

G

S

C

P

P S

T



S

A

P

P S

A

T

S

P 5¢ End

Fig. 2.14

3¢ End

Structure of DNA showing two strands which run antiparallel to each other

∑ These include the chemical nature of the solvent and the identities and concentrations of ions in the solution. ∑ When thermally melted DNA is cooled, the complementary strands will again form the correct base pairs, in a process is termed annealing or hybridization. ∑ The rate of annealing is dependent upon the nucleotide sequence of the two strands of DNA.

Analysis of DNA Structure Chromatography: Several of the chromatographic techniques available for the characterization of proteins can also be applied to the characterization of DNA. The most commonly used technique is HPLC (high performance liquid chromatography). Affinity chromatographic techniques can also be implied. One common affinity matrix is hydroxyapatite (a form of calcium phosphate), which binds double-stranded DNA with a higher affinity than single-stranded DNA. Electrophoresis: This procedure can serve the same function with regard to DNA molecules as it does for the analysis of proteins. However, since DNA molecules have much higher molecular weights than proteins, the molecular sieve used in electrophoresis of DNA must be different as well. The material of choice is agarose, a carbohydrate polymer purified from a salt water algae. It is a copolymer of mannose and galactose that when melted and re-cooled forms a gel with pores sizes dependent upon the concentration of agarose. The phosphate backbone of DNA is highly negatively charged, therefore DNA will migrate in an electric field. The size of DNA fragments can then be determined by comparing their migration in the gel to known size standards. Extremely large molecules of DNA (in excess of 106 base pairs) are effectively separated in agarose gels using pulsedfield gel electrophoresis (PFGE). This technique employs two or more electrodes, placed orthogonally with respect to the gel, that receive short alternating pulses of current. PFGE allows whole chromosomes and large portions of chromosomes to be analyzed.

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STRUCTURE OF RNA

O

P

O OH

O H2C5¢ H O

Uracil

O H 3¢

H H

P O OH O H2C5¢

OH Ribonucleotide

O

H 3¢ H

Adenine

H H OH

O

P O OH O H2C5¢ H

Fig. 2.15 ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

O H 3¢

Cytosine

H H

OH O A polynucleotide of RNA

Ribonucleic acid is found in the nucleus and cytoplasm. It is made up of single chain of nucleotides. A strand of RNA may contain 7–12,000. Each nucleotide consists of ribose sugar, phosphoric acid and nitrogen base. Nitrogen bases present in RNA are adenine, guanine, cytosine and uracil. The single chain of nucleotides sometimes form small helices by folding. In secondary helices, the bases are united together through hydrogen bonds. This gives various shapes to RNA molecules. RNA is generally involved in protein synthesis, but in some viruses it also serves as genetic material. ∑ Thus there are two types of RNA: – genetic RNA – Non genetic RNA

70 HUMAN ANATOMY AND PHYSIOLOGY ∑ Viruses having RNA as the genetic material are called riboviruses. ∑ Genetic RNA may be single stranded (e.g., tobacco mosaic virus) or double stranded (e.g., Rheovirus). ∑ Non genetic RNA is present in all cells, where DNA is a genetic material. ∑ Three types of nongenetic RNAs are ribosomal RNA (rRNA), transfer RNA (tRNA) and messenger RNA (mRNA). ∑ These three types of RNAs are transcribed from different regions of DNA template. ∑ Therefore, the sequence of nitrogen bases found on RNA strand is complementary to their sequence on DNA template. ∑ All types of RNAs are synthesized in the nucleus but moves into the cytoplasm. ∑ They play important role in protein synthesis.

Types of RNA There are three main types of RNA molecules: (i) messenger RNA (m-RNA) (ii) transfer RNA (t-RNA) (iii) ribosomal RNA (r-RNA) All the three types of RNAs are transcribed in both prokaryotes and eukaryotes by RNA polymerase as precursor molecules or primary transcripts. To become functionally competent, these primary transcripts must be modified by a series of chemical processing, known as post transcriptional processing. The processing of each major RNA species has its own peculiarities.

(i) Messenger RNA (mRNA) Methylated G - cap Initiating codon (AUG)

5’

Coding region

Termination cadon(UAA,UAG or UGA)

AUG

Poly A tail

Noncoding region

Fig. 2.16

Structure of mRNA strand

∑ The messenger RNA carries instructions from DNA for the synthesis of a particular protein in the cytoplasm. ∑ It is the longest of all RNAs and constitutes only 5% of the total RNA content of the cell. ∑ The information on mRNA is present in the base sequence of its nucleotides, which is called genetic code. ∑ The sequence of nitrogen bases on mRNA forms codons to specify amino acids in polypeptide chain. ∑ The 5¢ terminal of mRNA has a methylated region, which acts as cap for attachment with ribosome. ∑ An initiator or start codon (AUG) follows the cap either immediately or after a small non coding region. ∑ Then there is coding region. ∑ This is followed by terminator codon i.e., UAA, UAG or UGA, a small non-coding region and poly A area at the 3¢ termini.

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∑ One mRNA molecule normally specifies a single polypeptide chain and is said to be monocistronic. ∑ In some cases, mainly in prokaryotes, one mRNA can specify more than one polypeptide and is called polycistronic.

(ii) Transfer RNA (tRNA) ∑ It is also called soluble RNA or sRNA. ∑ Transfer RNA constitutes about 15% of the total RNA. tRNA is the smallest RNA consisting of 70–85 nucleotides. ∑ The nitrogen bases of some nucleotides get modified. ∑ This causes coiling of single stranded tRNA to form a clover leaf (in two dimension) or L-shaped (in three dimension) configuration (Fig. 2.17). tRNA has a site for binding amino acid. ∑ It lies at 3¢ ends and has CCA—OH group. ∑ Opposite to the amino acid or AA binding site, there is an anticodon made up of three nitrogen bases for recognising and attaching to mRNA. ∑ There are two loops, one for attaching to ribosome Amino acid A C C



5¢ T y C loop Amino acyl synthetase binding loop (8–12bases)

5

Ribosomal binding loop (7-bases)

DHU Loop

Anticodon stem

Lump Anticodon loop (7- bases) Anticodon (a)

Fig. 2.17

3CH CCA Aminoacyl acceptor

Anticodon loop A

A mG

Anticodon AA mG (Methylated G) (b)

Structure of tRNA (a) Clover leaf two dimensional (b) L-shaped three dimensional configuration

(T y C, loop) and the second for binding to an enzyme (DHU or dihydroxyuridine loop), tRNA is meant for transferring amino acids to ribosome for synthesis of polypeptide. ∑ There are different tRNA for different amino acids. Some amino acids can however, be picked up by 2–6 tRNAs. ∑ Thus, there are over 100 types of tRNA in a cell.

72 HUMAN ANATOMY AND PHYSIOLOGY (iii) Ribosomal RNA (rRNA) ∑ ∑ ∑ ∑

It is the constituent of ribosomes. It forms 70–80% of the total RNA contents of the cell. Ribosomal RNA lies coiled in between and over the protein molecules of the ribosome. It helps tRNA and mRNA in the synthesis of proteins over the ribosomes.

Functions of RNA ∑ ∑ ∑ ∑ ∑ ∑

2.14

RNA is the genetic material in some viruses. It is involved in the expression of genetic code of DNA by forming specific proteins. RNA primer is essential for DNA replication. Folding of prokaryotic DNA into a nucleoid needs the help of RNA. rRNA is a component of ribosomes, the site of protein synthesis. Some RNAs act as enzymes e.g., ribozyme, ribonuclease.

ENZYMES

The term enzyme is derived from Greek word En = in, zyme=yeast, which means “in yeast.” Enzymes are chemically proteins which act as biocatalysts and bring about various chemical changes in the cells. The term was first introduced by W. Kuhne in 1878, while studying the fermentation process in yeast.

Structure All enzymes are proteins but “all proteins are not enzymes”. Some enzymes also have non-protein part attached to it. Thus depending on the chemical composition enzyme is categorized into two categories. (i) Simple or Purely Proteinaceous Enzymes. These are made up of only proteins. Digestive enzymes such as pepsin and trypsin etc. (ii) Conjugated or Holoenzymes. These are made up of a protein molecule to which a non-protein group is also attached. These conjugated proteins are called holoenzymes. It may be dissociated into a protein component, termed as apoenzyme and a non-protein molecule, the cofactor. Cofactor is further divided into three groups — (a) prosthetic groups (b) co-enzymes (organic compounds) (c) metal-activators (inorganic compounds). (a) Prosthetic Groups. In a conjugated enzyme, if the non-protein moiety is tightly bound to the protein part of enzyme, it is called prosthetic group. Some of these prosthetic groups are metal compounds like iron porphyrine complexes of cytochrome and FAD of succinic dehydrogenase. (b) Co-enzyme. A co-enzyme is a small and heat stable organic molecule which generally acts as an acceptor or donor of a functional group or of an atom that are removed from or contributed to the substrate. A majority of co-enzymes are chemical derivatives of nucleotides and are loosely bound to the protein part of enzyme. In, most co-enzymes, the nitrogen base portion of nucleotides is replaced by another chemical unit. This unit is usually a derivative of vitamin-B. e.g., —NAD+, FAD, COQ, thiamine, pyrophosphate, biotin or cobalamin (B12) co-enzymes etc. (c) Metal-Activator. There are some enzymes which require metal ions (inorganic ions of metals) for their activation. The ions of Ca, Co, Cu, Mg, Mn, Mo, Na, K and Zn are known to participate in enzymatic reactions. For example, iron (Fe++) is a co-factor of enzyme catalase, manganese is a co-factor of peptidase. In some cases these activators function in combination with the protein and sometimes they form a compound with a substrate. These metal co-factors are also known as enzyme activators.

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Prosthetic group (metal compounds) Tightly bound Conjugated protein enzyme or Holoenzyme

Co-enzyme Apoenzyme + Non-protein ® Loosely ® (organic) bound Co-factor Metal activators (inorganic)

Free Energy

Enzymes and Activation Energy

S

Energy of activation with enzymes

A

Energy of activation without enzymes

Reactant

Substrate energy level

B Products Time

Fig. 2.18

Energy of activation of a non-catalysed and an enzyme catalysed reaction.

∑ Energy required to bring about a chemical reaction is called activation energy. ∑ Chemical reactions take place only when reactant molecules collide. ∑ In some reactions precise collisions fail to occur because of: – Mutual repulsion of reactant molecules due to presence of electrons on its surface. – Small active sites. ∑ An active site is an area of the enzyme which is capable of attracting and holding particular substrate molecules by its specific charge, size and shape, so as to allow the chemical change. ∑ Active site consists of a few amino acids and their side groups, which are brought together in a particular fashion due to secondary and tertiary folding of protein molecules and its association with the co-factor. ∑ Enzymes may have more than one active sites. ∑ Reactant molecules have on their surface specific areas, where active sites of the enzyme fits precisely. These areas are called reactive site or reaction sites. ∑ External input of energy called activation energy, is needed to initiate to the chemical reaction. ∑ Activation energy increases the kinetic energy of the system and brings about forceful collisions between the reactants. ∑ This much activation energy cannot be provided by the living system. ∑ Enzymes lower the activation energy required for a reaction. ∑ This can be achieved by two ways: – By bringing reactant molecules closer and favouring their precise collision. – By electrophilic and nucleophilic attack, developing strain in the bonds of the reactants.’

74 HUMAN ANATOMY AND PHYSIOLOGY Properties 1. All enzymes are chemically protein in nature but “all proteins are not enzymes.” 2. Enzymes lower the energy of activation of the substrate molecules so that the reaction can occur at normal body temperature. 3. Enzymes are very specific in their mode of action. Just as one key can open one lock only. Likewise enzyme acts on its specific substrate based on its chemical configuration. This is due to the configuration of proteins or the presence of “active sites” on the surface of the enzymes. Active sites on the surface of enzymes are formed by their three dimensional structure. An enzyme may have more than one active sites just as a lock has more than one lever. 4. Enzymes remain unchanged at the end of a reaction. Once the reaction is completed, the enzyme releases the products and is ready for the new substrate again. 5. Enzymes increase the rate of reaction. 6. They need optimum temperature to act. 7. Enzymes require specific pH for action.

Classification There are a large number of enzymes known in the living systems. So, to make their study easy and simple, they have been classified. This system of classification has been worked out by Ineternational Union of Biochemists and is popularly known a “IUB System of Nomenclature of Enzymes”. According to this system, all enzymes are grouped into classes; class into subclasses; subclass into division of subclasses; and division of subclass into subdivisions of divisions. There are a total of six classes as given below: Class 1. Oxidoreductases or Oxidases or Dehydrogenases. They bring about oxidation and reduction of their substrate by removing or adding electrons from or to the substrate e.g., cytochrome oxidase oxidises cytochromes. Class 2. Transferases. They transfer a specific group from one substrate to another substrate. The chemical group transferred is not in a free state e.g., glutamate pyruvate transminase transfer an amino group from the substrate glutamate to another substrate pruvate. Class 3. Hydrolases. They are known to break larger substrates into smaller substrates with the addition of water and by breaking of specific covalent bonds e.g., salivary amylase hydrolyses starch to maltose. Class 4. Lyases. They are known to break larger substrates into smaller substrates without the addition of water and by breaking of specific covalent bonds and removal of specific groups e.g., histidine decarboxylase breaks histidine to histamine and carbon dioxide. Class 5. Isomerases. They are known to bring about the rearrangement in the molecular organisation of the substrate to form isomers e.g., phosphohexose isomerase changes glucose-6-phosphate to fructose-6-phosphate. Class 6. Ligases or Synthatases. They are known to join smaller substrates into larger substrates by establishing covalent bonds between them e.g., pyruvic acid carboxylase combines pyruvate and carbon dioxide to form oxaloacetate. The energy for the reaction is derived from the hydrolysis of ATP.

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Mode of Action Two theories regarding mode of enzyme action are: 1. Lock and key theory 2. Induced fit theory

+

+

Active Site Key (Enzyme molecule)

Enzyme

Fig. 2.19

Enzyme Padlock (Substrate (Substrate molecule) complex)

Substrate

Key (Enzyme molecule)

Enzyme substrate complex

Products

End products

Lock and key mechanism showing breakdown reaction

Lock and Key Theory ∑ It was put forward by Emil Fischer in 1894. ∑ According to this both enzyme and substrate molecules have specific geometrical shapes. ∑ Enzyme, a protein, has on its surface a reactive site into which the substrate can fit so as to facilitate the formation of enzyme-substrate complex. ∑ Reactant or substrate fits like a key. ∑ Binding of substrate lowers the activation energy. ∑ Substrate molecule can be acted upon by a particular enzyme just as specific key can operate a particular lock. ∑ This forms enzyme-substrate complex. ∑ In the complexed state the molecules of the substrate undergo chemical change. ∑ After the action of enzyme is completed reaction products are released thus regenerating the original enzyme molecule. ∑ Thus we can say that enzymes catalyze the reaction of substrate but they definitely form intermediate enzyme substrate-complex which later on breaks up separating the products and the enzyme. ∑ Substrate + Enzyme Æ Substrate Enzyme Complex Æ Product + Enzyme ∑ In case it is a biosynthetic reaction, then new products are formed.

+

Enzyme molecule

+

Substrate Molecules (Reactant)

Enzyme Substrate complex (A transition state)

Enzyme

Product

Fig. 2.20 Lock and key mechanism showing biosynthetic reaction

76 HUMAN ANATOMY AND PHYSIOLOGY ∑ The enzyme molecules bring the reactant molecules into contact far faster than change collisions. The reactions are, therefore, accelerated. A single molecule of the fastest known enzyme, carbonic anhydrase found in RBCs, hydrates 36 million (36 ¥ 106) molecules of carbon dioxide per minute into carbonic acid. Carbonic anhydrase

CO 2 + H 2 O æææææææÆ H2 CO 3 The enzyme catalysed reaction is 10 million (107) times faster than the non-catalysed reaction.

Induced Fit Theory ∑ This theory was proposed by Daniel E. Koshland in 1959. ∑ According to this theory, the active site of the enzyme has two regions: buttressing and catalytic. ∑ The buttressing region holds the substrate at a correct position. ∑ The catalytic region weakens the bonds of the substrate by electrophilic or nucleophilic force. ∑ When the substrate binds to the buttressing region, the active site of the enzyme undergoes conformational changes to bring the catalytic region opposite to substrate bonds. This initiates the reactions. F

f

BU T

UP O

ENZYME S E SING GR TRD E F C G B

A

Catalytic group

H

A

Fig. 2.21

E

g

e

h

d

D

c

C B

b a

A

B

G efg d h H c b a

Catalytic group

C

Induced-fit theory of enzyme action. A. Active site of enzyme. B. Substrate molecule. C. Enzyme-substrate complex with conformational changes so as to bring the catalytic group against the substrate bonds to be broken.

Enzyme Inhibitors Enzyme action can be reduced or stopped due to internal or external factors in four different ways. 1. 2. 3. 4.

Denaturation of enzymes (proteins) Competitive inhibition Non-competitive inhibition Allosteric or feedback inhibition.

Denaturation of Enzymes ∑ Factors like heat, high energy radiations and salts of heavy metals destroy tertiary structure of enzymes. This is called denaturation of enzymes. This results in the inhibition of enzymatic activity.

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Competitive Inhibition ∑ It is brought about by a substance which closely resembles the substrate in molecular structure. ∑ Such a substance is called competitive inhibitor or substrate analogue. Due to its close structural similarity with the substrate, the inhibitor compete with the substrate for the active sites of the enzyme, forming enzyme inhibitor complex. ∑ As a result the enzyme cannot participate in catalytic change of the substrate, and the enzyme action declines. ∑ For example, the inhibition of succinate dehydrogenase by malonate which closely resembles succinate in structure. This may be compared to the jamming of a lock by a key similar to original one. Competitive inhibition is usually reversible since the addition of more substrate tends to reduce the effect of the inhibitor. Malonic acid (competitive inhibitor)

+

Succinic dehydrogenase (Enzyme)

+

Succinic acid (substrate)

Fig. 2.22

Active site of enzyme blocked by inhibitor

Substrate unused

Competitive inhibition of enzyme action

∑ Competitive inhibitors are often used in the control of bacterial pathogens. Sulpha durgs (e.g. sulphanilamide) inhibit the synthesis of folic acid in bacteria by competing with p-amino benzoic acid (PABA) for the active site of enzyme. ∑ Human beings are not harmed by sulpha drugs, because they get preformed folic acid through their diet. ∑ Competitive inhibition is important because (i) it supports the lock and key hypothesis of enzyme action and (ii) it shows that substrate analogues are not metabolised by a particular enzyme.

Non-competitive Inhibition ∑ It is inhibition of enzyme activity by the presence of a substrate that has no structural similarity with the substrate. ∑ The non-competitive inhibitor binds to the enzyme at some site other than the substrate binding site. ∑ This destroys the functional group of the enzyme that is essential for its catalytic function, and no product is formed. e.g., cyanide inhibits the mitochondrial enzyme, cytochrome oxidise which is essential for cellular respiration. ∑ This kills the animals. ∑ Here the inhibitor (cyanide) has no structural similarity with substrate of the enzyme, namely cytochrome C, and does not bind with the substrate binding site.

78 HUMAN ANATOMY AND PHYSIOLOGY Allosteric Modulation or Feedback Inhibition ∑ The activities of some enzymes particularly those which form a part of a chain of reaction or metabolic pathway are regulated internally. ∑ Some specific low molecular weight substance (such as the products of another enzyme of the metabolic pathway) act as modifier or modulator. ∑ Such a modulator substance binds with a specific site of the enzyme different from its substrate binding site. ∑ The sites where the modulator fits in is called allosteric site, and the enzyme is termed allosteric enzyme. ∑ The binding of the modulator with allosteric site increases or decreases the enzyme action. For example, glucose is changed to glucose 6 phosphate in glycolysis by the activity of enzyme hexokinase. ∑ Accumulation of glucose 6 phosphate beyond a threshold value, causes allosteric inhibition of hexokinase. This type of inhibition is also called feedback inhibition. ∑ Allosteric inhibition has a regulatory function as it stops the excess formation of a product. Glucose

ATP

Hexokinase

Inhibits

ADP

Fig. 2.23

Glucose 6-phosphate

Feedback allosteric inhibition

Factors Affecting Enzyme Activity (a) Temperature: Disrupts hydrogen bonds, alters protein shape (denature) (b) pH: Hydrogen ion concentration disrupts bonds between amino acids (c) Substrate Concentration: Increased substrate concentration increases reaction rate until all enzymes are involved, then reactions level out (d) Enzyme Concentration: Increased enzyme concentration increases reaction rate until all substrate is used up, then reactions decrease.

Effect of Temperature The activity of enzymes is mainly controlled by temperature. Enzymes generally function over a narrow range of temperature. Normally, it corresponds to the temperature of the body. Enzymes are sensitive to heat (higher temperature) and they coagulate on heating thus their catalytic effect is lost. When heated they get denatured because they are made up of proteins. At higher temperatures their physico-chemical properties are altered and they are not able to form a complex with the substrate molecule. In general, the rate of enzymatic reaction increases with the rise of temperature up to 37°C,

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Rate of Reaction

but it declines with the further increase of temperature (Fig. 2.24). 37°C is regarded as an optimum temperature for enzyme activity. Temperature sensitivity of enzymes also depends upon the degree of hydration. With 10 to 25% hydration, enzymes in the seeds may remain functional even up to 100–120°C. At low temperatures, the enzyme is preserved temporarily in an inactive state. This is the reason why foods are preserved for long in a frozen state. In a frozen state the enzymes of the microbes and that of the food do not act. At low temperatures, enzymes are deactivated.

37°C Temperature

Fig. 2.24

Effects of temperature on the rate of enzymatic reaction

Effect of pH Enzymes are sensitive to changes in the pH of the medium. Every enzyme requires a specific or optimum pH for their maximum activity. Activity of an enzyme declines both above or below this specific optimum pH. Most of the intracellular enzymes function best around neutral pH. pH affects the degree of dissociation of the enzyme that controls the formation of enzyme-substrate complex. Pepsin (a protein digesting enzyme in gastric juice) is most effective in acidic medium.

Rate of Reaction

Pepsin

Trypsin

0

2

4

6

8

10

pH

Fig. 2.25

Effect of pH in enzyme activity

Effect of Substrate Concentration The rate of an enzyme catalysed reaction steadily increases with an increase in the number of enzyme molecules till a saturation effect is attained.

Reaction velocity

80 HUMAN ANATOMY AND PHYSIOLOGY

Limiting Effect

Enzyme Concetration

Fig. 2.26

Effect of enzyme concentration on the rate of biochemical reaction

Substrate Concentration. Increase in substrate concentration increases the rate of enzymatic reaction. The rise in velocity is very high in the beginning but it decreases progressively with the increase in substrate concentration. The reaction ultimately reaches a maximum velocity which is not exceeded by any further rise in substrate concentration. At this stage the enzyme molecules become fully saturated and no active site is left free to bind additional substrate molecules. This saturation effect is shown by all enzymes.

Reaction velocity

Vmax

1 V 2 max V Km

[S]

Fig. 2.27 Effect of substrate concentration on the velocity of enzymatic reaction. Vmax. (maximum velocity). km (Michaelis constant). S. Substrate concentration.

2.15

VITAMINS

∑ In 1910, hopkins discovered some organic compounds of low molecular weight which are considered to be essential for the maintenance of the proper health of an organism. ∑ Funk in 1912 coined the term vitamins. ∑ As most of vitamins are chemically organic amines, they were named so. ∑ These are neither body builders nor energy releasers but they facilitate and regulate important chemical reactions. ∑ According to solubility in oil or water, vitamins are classified into two groups: (i) Water soluble — B, C, F, G, H, M, and P (ii) Fat soluble — A, D, E and K.

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HORMONES

∑ Hormones are chemical substances that are produced in minute quantities by some specialised tissue or organs, producing physiological and bio-chemical effects on the tissue remote from the source. ∑ In organisms most of the hormones are produced by the ductless organs called “endocrine glands. The hormones produced by these glands are mixed in the blood stream and transported to the target tissues. ∑ They normally stimulate some physiological functions, although some endocrine secretions have inhibitory actions and are called chalones. ∑ Animal hormones can be grouped into following three chemical classes: (i) Steroid hormones. These are composed of lipids of high molecular weight and are mostly produced by adrenal cortex, testis and ovary. (ii) Protein and peptide hormones. These are made up of proteins or peptide and are secreted by parathyroid, pituitary glands and pancreas. (iii) Amino acid derived hormones. These are derived from amino acids and produced by adrenal medulla and thyroid. ∑ Plant hormones are called phytohormones plant tissues do not contain cholesterol and their steroids are called phytosteroids.

Steroids ∑ These are insoluble in water, but are not typical lipids. ∑ Steroids are made up of large number of carbon atoms arranged in complex ring structures. ∑ Best known example of steroid is cholesterol, which when present in large amount can cause heart problems. ∑ Cholesterol can undergo rearrangements leading to formation of sex hormones and bite acids. ∑ Oestrogen, Aldosterone and Cortisol are steroid hormones.

CH2

CH3 CH CH3

CH2

CH2

CH2

CH CH3

CH3

HO Fig. 2.28

Structural formula of cholesterol

82 HUMAN ANATOMY AND PHYSIOLOGY ∑ Some important hormones present in human beings are: Organs Hormones Function 1. Gastro intestinal Gastrin Secretion of HCl by stomach. tract Cholecystokinin Stimulation of gall bladder. Secretin Stimulation of pancreas and liver to secrete fluid base of pancreatic juice.

2. Pancreas

Insulin Glucagon.

3. Adrenals

Epinephrine (Adrenalin) (Aldosterone) Cortisol.

Regulation of blood sugar. Glycogen breakdown. Stress hormone, Mineral balance, Na retention. Metabolism, gluconeogenesis.

4. Thyroid

Thyroxin Calcitonin

Increase of basal metabolic rate, development. Maintenance of Ca level in blood and bones.

5. Parathyroid

Parathormone.

Maintenance of Ca and P level.

Somatotropine Corticotropine Thyrotropine Follicle stimulating hormones Luteinising hormone Prolactin. Melanotropin.

Growth and metabolism. Stimulation of the adrenal cortex. Stimulation of mammary glands. Stimulation of maturing of gametes.

6. Pituitary (i) Anterior lobe

(ii) Middle lobe

(iii) Posterior lobe Vassopressin. Oxytocin. 7. Hypothalalmus

Corticotropin releasing hormone Thyrotropin releasing hormone Growth hormone releasing hormone Gonadotropin releasing hormone.

Stimulation of production of sex hormones. Stimulation of mammary glands. Dialation of melanophores. Renal reabsorption of water. Contraction of uterus and secretion of milk by lactating mammary gland. Release of corticotrophin. Release of thyrotropin. Release of somatotropin. Release of luteinizing and follicle stimulating hormones.

REVIEW QUESTIONS 1. 2. 3. 4. 5.

Discribe various structural levels of proteins. Explain glycosidic, peptide and phosphodiester bonds with the help of equations. Define structure of nucleotides in detail. Explain structure and functions of proteins. What are macromolecules? Discuss their chemical composition.

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Give detailed account of enzymes, their action and inhibition. Discuss various factors affecting enzymatic action. Write detailed note on steroids. Discuss chemistry of any ten amino acids. Explain carbohydrates and their biological significance. Write detailed note on nucleotides. All proteins are made up of amino acids linked by peptide bonds. How is then, one protein different from another? 13. Describe various properties of enzymes. 14. Explain and classify hormones and vitamins. 6. 7. 8. 9. 10. 11. 12.

CHAPTER

3

P S

T

A

S P

P S

A

T

S P

P S

C

G

S P

P S

G

C

3.4 Å

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION

S S T A P S G C S P S P T A S P S P C S G P

S P

3.1

INTRODUCTION

One of the basic tenets of biology is that all living things are composed of cells. Some organisms consist of a single cell, while others have multiple cells, organized into tissues and tissues organized into organs. In many living things, organs function together as an organ system. However, even in these complex organisms, the basic biology revolves around the activities of the cell. (a) The individual cell is the structural unit of all living things. An entire organism may consist of a single cell (unicellular) or many cells (multicellular). 84

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 85 (b) In human beings and other multicellular organisms, the cells tend to be organized in specific ways. A group of similar cells performing a particular function is referred to as a tissue. An organ is a discrete structure composed of several different tissues together. An organ system is a group of organs together performing an overall function. The individual organism is the combination of all of these things as a discrete and separate entity. (c) Although living matter is composed of cells, animal cells and plant cells yet are significantly different from each other. Not only plant cells contain chlorophyll, a green colouring matter; but also have a cell wall around them which is made up of a very complex carbohydrate known as cellulose. Neither chlorophyll nor a cell wall is present in animal cells.

3.2

CELL SIZE AND SHAPE

The shapes of cells are quite varied such as neurons, being longer than they are wide and others, such as parenchyma (a common type of plant cell) and erythrocytes (red blood cells) being equidimensional. Some cells are encased in a rigid wall, which constrains their shape, while others have a flexible cell membrane (and no rigid cell wall). The size of cells is also related to their functions. Eggs or ova are very large, often being the largest cells an organism produces. The large size of many eggs is related to the process of development that occurs after the egg is fertilized. The contents of the egg (termed zygote) are used in a rapid series of cellular divisions, each requiring tremendous amount of energy that is available in the zygote cells. Later in life the energy must be acquired, but at first a sort of inherited fund of energy is used. Cells range in size from small bacteria to large unfertilized eggs laid by birds and dinosaurs. In science we use the metric system for measuring. Here are some measurements and conversions that will aid in understanding of cell biology. 1 meter = 100 cm = 1 centimeter (cm) = 1 millimeter (mm) = 1 micrometer (mm) = 1 nanometer (nm) =

1,000 mm = 1,000,000 mm = 1,000,000,000 nm 1/100 meter = 10 mm 1/1000 meter = 1/10 cm 1/1,000,000 meter = 1/10,000 cm 1/1,000,000,000 meter = 1/10,000,000 cm

∑ Smallest cell, known so far measures 0.1 mm – 0.5 mm e.g., Pleuropneumonia. ∑ The largest cell known so far is that of an ostrich egg measuring 175 ¥ 135 mm. ∑ In mammals, nerve and muscle cells reach upto 900 mm in length.

3.3

HISTORY ∑ Cells were observed by Malphigi in 1661 and were called as saccules and utricles. ∑ One of the first scientists to observe cells was the Englishman Robert Hooke. In the mid 1600s, Hooke examined a thin slice of cork through the newly invented microscope. The microscopic compartments in the cork impressed him and reminded him of rooms in a monastery, known as cells. He therefore referred to the units as cells. The term cell was introduced by Robert Hooke in his book Micrographs, published in London in 1665.

86 HUMAN ANATOMY AND PHYSIOLOGY ∑ Later in that century, Anton Van Leeuwenhock, a Dutch merchant, made further observations of plant, animal and microorganism cells and observed bacteria, protozoa, red blood cells etc. ∑ In 1838, the German botanist Matthias Schleiden proposed that all plants are composed of cells. ∑ A year later, his colleague, the anatomist Theodore Schwann, concluded that all animals are also composed of cells. ∑ Living semi fluid material of cells was discovered by Dujardin in 1838. He called this material as sarcode. ∑ Sarcode was renamed as protoplasm by Purkinje in 1839. ∑ In 1858, the biologist Rudolf Virchow proposed that all living things are made of cells and that all cells arise from pre-existing cells. These premises have come down to us as the cell theory. ∑ First electron microscope was designed by Knoll and Ruska of Germany in 1932. ∑ Discovery of electron microscope made possible to observe and understand complex structures of the cell.

3.4

CELL THEORY

Schleiden in 1838, stated that all plants are composed of cells. Theodore Schwann in 1839, stated the same for animals and concluded that animal cells had nuclei and were enclosed by plasma membrane while plant cells in addition to it have cell wall. The cell theory as earlier stated, was put forward by Schleiden and Schwann (1839) which clearly states that: ∑ ∑ ∑ ∑ ∑

All living creatures are made up from one or more cells. All cells are produced from previously existing cells (no spontaneous generation). All cells appear to be descended from the first cell which existed about 4 billion years ago. For a species to exist its reproductive cells must be potentially immortal (no aging). Our bodies start from a single cell and contain about 100,000,000,000,000 cells at maturity.

Exceptions to Cell Theory Although cell theory applies to all living organisms yet there are some exceptions ∑ Viruses do not possess cellular machinery and consist of nucleic acid, DNA or RNA, core surrounded by a protein sheath. Thus they are without cells. ∑ Some fungi like Rhizopus and certain algae like Vaucheria consists of undivided mass of protoplasm with many scattered nuclei (syncytial mass). ∑ Bacteria and blue green algae do not have organised nucleus. Their genetic material lies directly in the cytoplasm. They also lack most of the cell organelles. ∑ RBCs are without nucleus and still continue to live. ∑ There is no mention of intercellular material in cell theory. ∑ Protoplasm gets replaced by non-living materials in the surface cells of skin and cork.

Modern Cell Theory This is the modified form of cell theory and is also known as cell doctrine or cell principle. ∑ All living organisms are made of cells and their products.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 87 ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

3.5

Cell is made of protoplasm having a nucleus, number of organelles and a covering membrane. A cell organelle cannot survive independently. Life exists only in cells because all activities of life are performed by cells. Each cell maintains its individuality and their specific internal environment and homeostasis. Cell is able to act independently in its growth, division, metabolism and even death. Cells are totipotent until they become specialized. Cells sometimes assume forms which no longer have all characteristics of cells e.g., loss of nucleus in RBCs or cytoplasm in outer skin cells. Genetic information is stored and expressed within cells. All cells have full genetic information coded in their DNA, but each type of cell uses only a part of information which is needed for its specialized structure and function. All present day organisms (Cells) have common ancestry because they are derived from the first cell that evolved on earth through continuous line of cell generation. Cells are produced from the preexisting cells by their division and daughter cells resemble the parent cell in every respect. Each cell to remain alive, maintains homeostasis.

PROKARYOTIC CELL

There are two basic types of cells: Prokaryotic and Eukaryotic. Characteristics of prokaryotes: Plasmid DNA Glycocalyx Plasma membrane Cell wall

Cell envelope 

Ribosomes

Nuclear region or chromosomal DNA

Pilli Cytoplasm Fimbrae Flagellum

Measome

Fig. 3.1 Structure of a bacterial cell (Prokaryotic) ∑ ∑ ∑ ∑ ∑ ∑ ∑

Antony Van Leewenhock (1632 – 1723), discovered bacteria. He called these as “little animalcules.” Ehrenberg (1838) was the first person to coin the word “bacteria” for these minute organisms. Prokaryotic cells are more primitive, small and without organelles. The cells of prokaryotes are simpler than those of eukaryotes. Prokaryotic cells lack nucleus, while eukaryotic cells have a nucleus. Prokaryotic cell lack internal cellular bodies (organelles), while eukaryotic cells possess them.

88 HUMAN ANATOMY AND PHYSIOLOGY ∑ Examples of prokaryotes are bacteria and cyanobacteria (formerly known as blue-green algae). ∑ Prokaryotes are classified into Archaebacteria and Eubacteria of which Archaebacteria are ancient. ∑ Most of archaebacteria are autotrophs but only few are able to photosynthesize. They mainly derive energy from the oxidation of chemical energy sources like NH3, CH4, H2S. ∑ Archaebacteria are of three types methanogens (manufacture methane, die in O2 and found in marshy areas), thermoacidophiles (favour hot and acidic environment) and halophiles (found in salty environment). ∑ There are four main forms of bacteria— Coccus (spherical), bacillus (rod shaped), vibrios (comma shaped) and spirilla (spiral).

Coccus

Diplococcus

Sarcina

Staphylococcus

Monobacillus

Vibrio

Fig. 3.2

Streptococcus

Tetracoccus

Diplobacillus

Spiral

Different forms of bacteria. Forms of bacteria

Cocus (Spherical)

Bacillus (Rods shaped)

Vibrio (Comma shaped)

Occur singly monococcus Single – Monobacillus Pairs – diplococcus Paire after dirision – Diplobacillus Tetrads – tetracoccus Chains – streptococcus Irregular grape like clustere – staphylococcus Clustered like a cuben sarcina

∑ Each bacterial cell consists of

Glycocaly – Cell envelope – Nucleoid – Plasmids – Flagella – Pili – Fimbrae – Spinae

Cell wall Plasma membrane

Spirilla (Spiral)

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 89 ∑ Cell envelope is the outer covering of cell wall consisting glycocalyx, cell wall and plasma membrane. – Glycocalyx, outermost layer may be in the form of loose sheath called slimy layer or thick and tough covering called capsule, made of polysaccharides and some proteins. – Cell wall lies inner to glycocalyx. It is chemically made of peptidoglycan or murein which consists of repeated frame work of long glycan strands (N-acetyl muramic acid and N-acetyl glucosamine). These are crosslinked by short peptide chains which can be inhibited by number of antibiotics namely penicillin and cephalosporin. Features of two types of bacteria (Classified on the basis of type of cell wall) Gram negative ∑ Shows two lagers-outer thin one of peptidoglycan and inner plasma membrane ∑ Outer face of outer membrane contains lipopoly saccharides, part of which is integrated into membrane lipids Inner face has number of proteins anchored into peptidoglycan ∑ Outer membrane of –ve bacteria also have proteins porins which function as channels for entry and exit of materials ∑ Do not retain gram’s stain









Gram Positive ∑ Cell wall is thick (20 – 80 nm) ∑ Primarily mode of peptidoglycan ∑ also contains tightly bound techoic acids ∑ As in My cobacterium, part of the wall is made of very long chain of after acids called my coir acid ∑ Bacteria stain blue with weak alkaline solution of crystal violet or gentian violet. ∑ When stained cells are treated with 0.5% KI solution and was had with absolute alcohol or a cetone, bacteria retain stain.

– Plasma membrane is the inner most layer of cell envelope. It’s structure is same as that of eukaryotes. Cytoplasm or cytosol contains various cell organelles like storage granules, gas vacuoles, inorganic inclusions, food reserves, ribosomes (70 S type). Ribosomes are of 70s type with two sub-units of 50s and 30s. ‘S’ stands for Suedberg unit which denotes sedimentation coefficient. Heavier the particle more will be the Suedberg number. Nucleoid or genophore is the genetic material of prokaryotes which lies directly in the cytoplasm. It has single and circular chromosome with no free ends. Nucleoid is connected to plasma membrane through mesosome which is formed by infolding of plasma membrane. Plasmids are additional rings of DNA molecules present in the prokaryotic cell. These may carry important genes like fertility factor, drug resistance factor or nitrogen fixing gene etc. At times plasmid get attached with nucleoid and is called episome. Flagella are locomotory organelles and consist of three parts — filament, hook and basal body depending on absence or presence, number and location of flagella bacteria which are classified into various categories: – Atrichous: No flagella – Monotrichous: One flagellum at one pole – Lophotrichous: Two or more flagella attached at one pole – Amphitrichous: One or more flagella on both ends – Peritrichous: Flagella distributed all over.

90 HUMAN ANATOMY AND PHYSIOLOGY

(a)

(b)

(d)

(c)

(e)

Fig. 3.3 Various types of bacteria (a) Atrichous (b) Monotrichous (c) Lophotrichous (d) Amphitrichous (e) Peritrichous ∑ Pili are tubular structures made of protein pilin and are helpful in forming conjugation tube resulting in transfer of DNA from the donor cell to the recepient cell. ∑ Fimbrae are small bristle like fibres coming out of the cell and meant to attach bacteria to solid surfaces like rocks, host tissues. ∑ Spinae are tubular structures made up of special protein called spinin. These have been reported in some gram –ve bacteria and are believed to help adjust cells to some environmental conditions like salinity, pH, temperature etc.

EUKARYOTIC CELL ∑ ∑ ∑ ∑

Eukaryotic cells have definite nuclear membrane around chromatin network. Eukaryotic cells are more advanced, larger and contain number of cell organelles. Examples of eukaryotes are protozoa, fungi, plants, and animals. Our cells are of the eukaryotic type. Microvilli

Microfilaments Phagosome

Pinosome

Secretory vesicle

Desmosome

Lysosome Plasma membrane Golgi apparatus

Centrioles Granular/Rough endoplasmic reticulum

Nucleolus Chromatin Nucleoplasm Nuclear envelope Agranular/smooth endoplasmic reticulum

Intercellular bridges

Nucleus

3.6

Cell gap junction Cytoplasmic matrix Glycogen particle Terminal bar Tight junction

Microtubules Mitochondrion

Sap Tonolplast

Ribosomes

Fig. 3.4

An Animal cell

Vacuole

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 91

Microfilaments Wall Middle lamella Plasma membrane Plasmodesma Chloroplast Tonoplast

Nucleus

Sap

Amyloplast (starch containing plastid) Pinosome Nucleopore Chromatin Nucleolus Nuclear envelope Rough endoplasmic reticulum Smooth endoplasmic reticulum Mitochondrion

Central vacuole

Dictyosome Secretory vesicle Cytoplasmic matrix

Microtubules

Fig. 3.5

Plant cell

Major Components of a “Typical” Cell (a) Cell Membrane and Cell Wall ∑ As its outer boundary, the animal cell has a special structure called the cell or plasma membrane. ∑ All substances that enter or leave the cell must in some way pass through this membrane. ∑ Plants have cell wall outside plasma membrane. (b) Protoplasm ∑ The major substance of the cell is known as protoplasm. ∑ It is a combination of water and a variety of materials dissolved in the water. ∑ Outside the cell nucleus, protoplasm is called cytoplasm. ∑ Inside the cell nucleus, protoplasm is called nucleoplasm. ∑ The contents (both chemical and organelles) of the cell are termed protoplasm, and are further subdivided into cytoplasm (all of the protoplasm except the contents of the nucleus) and nucleoplasm (all of the material, plasma and DNA etc., within the nucleus). (c) Nucleus ∑ Within the animal cell almost in the centre and at periphery is present the nucleus. ∑ This structure has a nuclear membrane separating it from the cytoplasm. ∑ Within the nucleus is the chromatin material, made up of deoxyribonucleic acid (DNA). ∑ At the time of cell division, this chromatin material is aggregated into individual structure known as chromosomes. ∑ Each chromosome has a set of specific genes, which determine all of the physical and chemical characteristics of the body, which represent its structure and function. (d) Organelles ∑ Within the cytoplasm, certain structures are called organelles. ∑ These organelles include structures such as the endoplasmic reticulum, ribosomes, various kinds of vacuoles, the Golgi apparatus, mitochondria and centrioles.

92 HUMAN ANATOMY AND PHYSIOLOGY 3.7

CYTOPLASM ∑ All prokaryote and eukaryote cells also have cytoplasm (or cytosol), a semiliquid substance that composes the foundation of a cell. ∑ Essentially, cytoplasm is the gel-like material enclosed by the plasma membrane. ∑ Within the cytoplasm of eukaryote cells are a number of membrane-bound bodies called organelles (“little organs”) that provide a specialized function within the cell.

Functions ∑ ∑ ∑ ∑

It contains all cell organelles. It helps in distribution of nutrients, metabolites and enzymes. It brings about exchange of materials between cells. It’s streaming movements prove to be useful in various ways like movement of organelles and food vacuoles, formation of pseudopodia etc. ∑ Breakdown of glucose (glycolysis), biosynthesis of fatty acids, nucleotides and proteins takes place in the cytoplasm.

3.8

CELL WALL

Many kinds of prokaryotes and eukaryotes contain a structure outside the cell membrane called cell wall. With only a few exceptions, all bacteria have thick, rigid cell walls that give them their shape. Among the eukaryotes, fungi and plants have cell walls. Cell walls are not identical in these organisms. In fungi, the cell wall contains a polysaccharide called chitin. Plant cells, in contrast, have no chitin; their cell walls are composed exclusively of the polysaccharide cellulose. The cell wall is formed by the endoplasmic reticulum at the time of cell plate formation during cell division at telophase stage; Nucleus Cytoplasm

Primary cell wall Plasma membrane Secondary cell wall

Vacuole

Middle lamella

(a)

(b)

Fig. 3.6 Cell wall showing various layers (a) Transverse section (b) Longitudinal section

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 93 ∑ It separates the cytoplasm from the external world. ∑ Cell membrane is made of phospholipids and proteins. ∑ It acts as barrier to movement of things in and out of the cell—Hydrophobic molecules pass through it more readily than hydrophilic ones. ∑ Specialized transport mechanisms selectively move materials across the membrane. ∑ It is supported on inside by protein filaments (cytoskeleton). ∑ Chemistry of the cell wall varies with the type of cell and its functions. Cell wall is made up of cellulose. The fungal cell walls are thick and made of polysaccharide fibres of either chitin or cellulose. Outside this, there is a layer of mixed glycans. Algae have cell walls with cellulose, galactans, mannans and minerals such as silicon dioxide and calcium carbonate. In higher plants cell wall fibres are made of cellulose which are embedded in highly cross linked matrix of polysaccharides such as pectin, lignin and hemicellulose. Other organic compounds like cutin, suberin, xylin, silicon minerals, waxes, resins etc. may also occur. ∑ Not all living things have cell walls, most notably animals and many of the more animal like protistans. ∑ Bacteria have cell walls containing the chemical peptidoglycan. ∑ Cell wall grows by addition of more wall material within the existing one. Such a growth is called intrussusception. ∑ Cellulose, a nondigestible (to humans anyway) polysaccharide is the most common chemical in the plant primary cell wall. ∑ Plasmodesmata are connections through which cells communicate chemically with each other through their thick walls.

Functions Cell walls provide support and help cells resist mechanical pressures, but they are not solid, so materials are easily able to pass through. Cell walls are not selective devices, as plasma membranes.

3.9

CELL MEMBRANE Carbohydrate chain with protein which acts as an antigen Hydrophilic heads of phospholipid molecules

Glycolipid Outer surface channel protein (Allows free movement of molecules across membrane) Water

Hydrophilic tails of phospholipid molecules

Inner surface

Completely embeded intrinsic protein molecule Cholesterol

Extrinsic protein molecule Lipid Molecules lying on the surface Pratially embeded intrinsic protein molecule

Fig. 3.7

(a) Fluid mosaic model of plasma membrane (b) Arrangement of phospholipid molecules in plasmalemma

Non - Polar Tails Polar Head Group Water

94 HUMAN ANATOMY AND PHYSIOLOGY Cell membrane is the outer mebrane of cell protoplasm. It is also called plasma membrane (Nageli and Cramer, 1855) or plasmalemma (Plowe, 1931). All prokaryote and eukaryote cells have plasma membranes. The plasma membrane (also known as the cell membrane) is the outermost cell surface, which separates the cell from the external environmemnt. The plasma membrane is composed primarily of proteins and lipids, especially phospholipids. The lipids occur in two layers (a bilayer). Proteins embedded in the bilayer appear to float within the lipid, so the membrane is constantly in flux. The membrane is therefore reffered to as a fluid mosaic structure. Within the fluid mosaic structure, proteins carry out most of the membrane’s functions. Microvilli (engaged in absorption), pores (continuous with endoplasma reticulum), intercellular junctions like inter cellulose bridges for rapid conduction of impulses, desmosomes which are circular areas where adjacent membranes possess disc shaped thickening on inerside and number of tono fibrils and trans membrane linkers, plasmodesmata are protoplasmic bridges amongst plant cells which occur in areas of pores. ∑ The cell membrane functions as a semi-permeable barrier, allowing a very few molecules across it while fencing the majority of organically produced chemicals inside the cell. ∑ Electron microscopic examination, of cell membranes have led to the development of the lipid bilayer model (also referred to as the fluid-mosaic model). ∑ The most common molecule in the model is the phospholipid, which has a polar (hydrophilic) head and two nonpolar (hydrophobic) tails. ∑ These phospholipids are aligned, tail to tail, so the nonpolar areas form a hydrophobic region between the hydrophilic heads on the inner and outer surfaces of the membrane. ∑ This layering is termed a bilayer since an electron microscopic technique known as freezefracturing is able to split the bilayer Cholesterol is another important component of cell membranes embedded in the hydrophobic areas of the inner (tail-tail) region. ∑ Most bacterial cell membranes do not contain cholesterol. ∑ Cholesterol aids in the flexibility of a cell membrane. ∑ Proteins are suspended in the inner layer, although the more hydrophilic areas of these proteins “stick out” into the cells interior as well as outside the cell. ∑ These proteins function as gateways that will allow certain molecules to cross into and out of the cell by moving through open areas of the protein channel. ∑ These integral proteins are sometimes known as gateway proteins. ∑ The outer surface of the membrane will tend to be rich in glycolipids, which have their hydrophobic tails embedded in the hydrophobic region of the membrane and their heads exposed outside the cell. ∑ These, along with carbohydrates attached to the integral proteins, are thought to function in the recognition of self, a sort of cellular identification system. ∑ Integral proteins extend through the bilipid layer and among the fatty acid tails of the phospholipids–though not necessarily all the way through the plasma membrane. ∑ Peripheral proteins are loosely attached to (either the interior or exterior) surface of the plasma membrane. ∑ Cell membrane may get modified to serve special functions.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 95 Functions ∑ Protection from injury ∑ Flow of materials and information between two cells ∑ It has carrier proteins for active transport.

3.10

NUCLEUS Ribosomes Rough endoplasmic reticulum Nucleolus Nuclear Pores Chromatin network Heterochomatin

Smooth endoplasmic reticulum Euchromatin Outer membrane Nuclear wall Inner membrane envelope Perinuclear space Ribosomes Nucleoplasm/karyoplasm

Fig. 3.8 ∑ ∑ ∑ ∑ ∑

Nucleus in Interphase

It was first discovered by Robern Brown (1831) in plant cell. It is present in all cells except red blood cells of mammals. Usually it occupies the central position in the cell. A nucleus in the non-dividing cell is called interphase nucleus. Structure – Nucleus is differentiated into five main parts nuclear wall, nuclear pores, nucleoplasm, nucleolus and chromatin network. Nuclear envelop is a double membrane which surrounds the nucleus and separates it from cytoplasm. Space between two membrane, which is filled with fluid is called perinuclear space. Inner membrane is smooth while outer may bear ribosomes and is often connected to endoplasmic reticulum. Nuclear envelope has number of perforation called nuclear pores. Transparent, semifluid ground substances of nucleus is called nucleoplasm. Chromatin stores genetic material of the cell. Nucleolus is naked, round irregular body attached to the chromatin at specific region called nuclear organiser region (NOR). This was first discovered by Fontane (1781) and present name was given by Bowman (1840). Nucleolus is main site for development of rRNAs and is the centre for the formation of ribosomes, RNA synthesis and storage i.e., protein synthesis (established by Caperson in 1939). ∑ It contains the DNA (genetic information). DNA does not leave nucleus, it is an archival copy of the genes.

96 HUMAN ANATOMY AND PHYSIOLOGY ∑ DNA is organized into chromosomes. Deeply stained area of chromosome is called heterochromatic region while lightly stained one is called euchromatic region. ∑ Genes are encoded in the DNA; many genes are present on each chromosome. ∑ DNA associated with protein turns genes on and off. ∑ Many repair mechanisms for DNA are there. ∑ Nucleus may contain one or more nucleoli (for making ribosomes). ∑ RNA copy of gene is made in nucleus (transcription): messenger RNA. ∑ Nucleus is surrounded by a membrane (the nuclear envelope) with special pores that let RNA out. ∑ Most cells contain one nucleus, but a few have more. Such as: – Some liver cells have multiple nuclei (polyploidy) – Muscle cells are very long and have hundreds of nuclei – Mature red blood cell has lost its nucleus. A distinguishing feature of a living thing is that it reproduces independent of other living things. This reproduction occurs at the cellular level. In certain parts of the body, such as along the gastrointestinal tract, the cells reproduce often. In other parts of the body, such as in the nervous system, the cells reproduce less frequently. With the exception of only a few kinds of cells, such as red blood cells (which lack nuclei), all cells of the human body reproduce. In eukaryotic cells, the structure and contents of the nucleus are of fundamental importance to an understanding of cell reproduction. The nucleus contains the hereditary material of the cell assembled into chromosomes. In addition, the nucleus usually contains one or more prominent nucleoli (dense bodies that are the site of ribosome synthesis). The nucleus is surrounded by a nuclear envelope consisting of a double membrane that is continuous with the endoplasmic reticulum. Transport of molecules between the nucleus and cytoplasm is accomplished through a series of nulear pores lined with proteins that facilitate the passage of moleules out of and into the nucleus. The proteins provide a certain measure of selectivity in the passage of molecules across the nuclear membrane. The nuclear material consists of deoxyribonucleic acid (DNA) organized into long strands. The strands of DNA are composed of nucleotides bonded to one another by covalent bonds. DNA molecules are extremely long relative to the cell; indeed, the length of a chromosome may be hundreds of times the diameter of its cell. However, in the chromosome, the DNA is ondensed and packaged with protein into manageable bodies. The mass of DNA material and its associated protein is chromatin. To form chromatin, the DNA molecule is wound around globules of a protein called histone. The units formed in this way are nucleosomes. Millions of nucleosomes are connected by short stretches of histone protein much like beads on a string. The configuration of the nucleosomes in a coil causes additional coiling of the DNA and the eventual formation of the chromosome.

Functions ∑ It contains all the genetic material of the individual. ∑ It is the control centre of the cell and controls all metabolic activities of the cell. ∑ It takes part in the formation of ribosomes.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 97 ∑ With the help of RNAs, nucleus direct the synthesis of specific proteins required by the cell for its growth and maintenance. ∑ It develops genetic variation that contributes to evolution.

3.11

MITOCHONDRIA Intermembrane space or outer chamber Inner membrane (electron transport chain) Intracristal Space Outer Membrane

Oxysome Ribosomes (70 S) Crista

Central cavity

Crista Matrix with enzymes for protein synthesis, lipid synthesis and krebs cycle

Circular DNA

Fig. 3.9

LS of Mitochondrion

F1 Particles Crista

Matrix

F1 Subunit

Inter membranous space

Inner membrane Outer membrane

Fig. 3.10

Inner membrane

F0 Subunit

(a) Structure of a crista; (b) F1 – F0 subunit of a mitochondrion.

During the 1980s, Lynn Margulis proposed the theory of endosymbiosis to explain the origin of mitochondria and chloroplasts from permanent resident prokaryotes. According to this idea, a larger prokaryote (or perhaps early eukaryote) engulfed or surrounded a smaller prokaryote some 1.5 billion to 700 million years ago. Instead of digesting the smaller organisms the large one and the smaller one entered into a type of symbiosis known as mutualism, wherein both organisms benefit and neither is harmed. The larger organism gained excess ATP provided by the “protomitochondrion” and excess sugar provided by the “protochloroplast”, while providing a stable environment and the raw materials the endosymbionts required. This is so strong that now eukaryotic cells cannot survive without mitochondria (likewise photosynthetic eukaryotes cannot survive without chloroplasts), and the endosymbionts can not survive outside their hosts. Nearly all eukaryotes have mitochondria.

98 HUMAN ANATOMY AND PHYSIOLOGY Mitochondria contain their own DNA (termed mDNA) and are thought to represent bateria-like organisms incorporated into eukaryotic cells over 700 million years ago (perhaps even as far back as 1.5 billion years ago). They function as, the sites of energy release (following glycolysis in the cytoplasm) and ATP formation (by chemiosmosis). The mitochondrion has been termed the powerhouse of the cell. Mitochondria are bounded by two membranes. The inner membrane folds into a series of cristae, which are the surfaces on which adenosine triphosphate (ATP) is generated. The matrix is the area of the mitochondrion surrounded by the inner mitochondrial membrane. Ribosomes and mitochondrial DNA are found in the matrix. Mitochondria were first observed by Kolliker (1880) and named mitochondria by Benda (1897)

Structure ∑ They have a double-membrane: outer membrane & highly convoluted inner membrane. Fluid filled space between them is called outer chamber or perimitochondrial space. It has some enzymes. ∑ Inner membrane has folds or shelf-like structures called cristae that contain elementary particles; these particles contain enzymes important in ATP production. ∑ Ground material is called matrix or inner compartment which contains circular double stranded DNA, many small ribosomes (55s to 70s type) enzymes and carrier proteins. ∑ Cristae present on the inner membrane bear elementary particles or oxysomes. Each such particle has a head, a stalk and a base. The head piece (F1 subunit) is spherical and is projected into the matrix from the membrane. It is connected by a stalk to a base piece (F0 subunit). ∑ F1 subunit is an integral protein embedded in lipid membrane. ∑ F0 – F1 combination functions as ATP synthase an enzyme that catylase ATP synthesis during oxidative phosphorylation. ∑ Enzymes of ETC are located in the inner membrane in contact with oxysomes.

Functions ∑ The mitochondria are the powerhouses of the cell and are sites of cell respiration (Krebs cycle and Electron transport). ∑ It requires oxygen to produce 36 ATPs or glucose molecule, which is the major source of energy. Krebs cycle is located in the internal matrix where, NADH and FADH (produced by glycolysis and the Krebs cycle) deliver their hydrogens and electrons to the electron transport chain (ETC). ∑ The ETC pumps hydrogen ions into the intramembrane space; this sets up a pH gradient-pH 8 in the matrix and pH 7 in the intramembrane space. ∑ Hydrogen ions flow through a channel in the enzyme ATP synthase from the intramembrane space to the matrix. This causes a shaft to rotate, and generates ATP in the matrix ∑ Mitochondria provide intermediates for synthesis of biomolecules like chlorophyll, cytochromes, steroids etc. ∑ Matrix of mitochondria contains enzymes for the synthesis of fatty acids. ∑ Mitochondria regulate calcium ion concentration in the cell by storing and releasing calcium ions as required.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 99 3.12

RIBOSOMES

∑ Ribosomes were discovered in plant cells by Robinson and Brown (1953). The present name was given by Palade (1955), who observed them in animal cells. ∑ It is found in both prokaryotes and eukaryotes except in RBCs of mammals. ∑ Ribosomes may lie freely in cytoplasm or attached with endoplasmic reticulum or nuclear membrane. ∑ Each ribosome consists of two subunits one of which is larger than the other. ∑ Depending on their sedimentation rate, there are two types of ribosomes – 70s and 80s. ∑ 70s is found in prokaryotes and chloroplasts and mitochondria of eukaryotes while 80s is characteristic feature of eukaryotes. PROKARYOTIC RIBOSOME

EUKARYOTIC RIBOSOME

50 S Subunit

60 S Subunit

30 S Subunit

40 S Subunit

Fig. 3.11 ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

Structure of ribosomes

‘S’ is a Svedberg unit and is a measure of sedimentation rate. Larger subunit is dome shaped while smaller one is oblate and ellipsoid. Large subunit has a protuberance, a ridge and a stalk. The smaller subunit possesses a platform, cleft, head and bases. It is almost half the size of the larger subunit. Smaller subunit can fit over the larger one like a cap. This needs magnesium ions for binding. Chemically each ribosome is a ribonucleoprotein i.e., RNA and protein. The two subunits of 80s ribosomes are 60s and 40s. The two subunits of 70s ribosomes are 50s and 30s. There is a groove between two subunits for passage of messenger RNA (mRNA). From this groove tunnel extends through large subunit and open into the cisternae of endoplasm reticulum. The large subunit has two reactive sites, P and A, a binding site for t-RNA and enzymes involved in protein synthesis. An aggregation of ribosomes attached to mRNA forms polysome or polyribosome In 80s ribosome, 60s subunit has 40 protein molecules and three types of rRNA (28s, 5.8s and 5s), while in 40s subunit there are 33 protein molecules and single 18s rRNA. In 70s ribosome, 50s subunit has 34 protein molecules and two types of rRNA (23s and 5s), while it's 30S subunit contains 21 protein molecules and 16S rRNA.

100 HUMAN ANATOMY AND PHYSIOLOGY Ribosomes Types

80 S (Eukaryotes subunits)

70 S (Prokaryotes, mitochondria and chloroplasts subunits)

60 S

40 protein molecules

40 S

r RNA 33 protein molecules

50 S

r RNA

34 protein molecules

30 S

r RNA 21 protein molecules

18S 28S

5.8S

r RNA 16S

5S

23S

5S

∑ In eukaryotic cells synthesis of ribosomes occur inside the nucleolus. ∑ Ribosomal RNAs, except 5s one, are synthesised in nucleolus while 5s is synthesised elsewhere in the nucleus. ∑ Ribosonal proteins are synthesized in the cytoplasm and later transported to the nucleolus for the formation of subunits along with rRNA. ∑ Later subunits are passed out to the cytoplasm through nuclear pores. ∑ In prokaryotes, both ribosomal RNAs and proteins are synthesized in the cytoplasm while in mitochondria and chloroplast, they are formed in their cell organelles.

Central Protuberance Cleft

Stalk

Valley

RNA Smaller subunit

Head Platform

Ridge

Proteins RNA Base

Large subunit

Larger subunit

Small subunit Larger subunit

Smaller subunit Proteins

A

B

C

Fig. 3.12 Structure of ribosome, A. Larger subunit, B. Smaller subunit, C. Complete ribosome. Smaller subunit mRNA 3¢ end 5¢ end Larger subunit

Fig. 3.13

Polyribosome

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 101 200–204 Å

18S RNA

170–210 Å 16S RNA

40S

30S

5S RNA

5S RNA

300–340 Å 60S

200–290 Å 50S 23S RNA

28S RNA 5.8S RNA A

2.7 – 3.0 ´ 106 Dalton 70S Ribosome

6

4.0 – 4.5 ´ 10 Dalton 80S Ribosome

Fig. 3.14

B

Ribosomes A-80s, B-70s

Functions ∑ Ribosomes help in protein synthesis and thus are also known as protein factories of the cell. ∑ They also provide enzymes required for formation of proteins. ∑ They provide sites for the attached tRNA and mRNA which help in protein synthesis.

3.13

ENDOPLASMIC RETICULUM

es

m

o os

b

Ri

Cisternae

Fig. 3.15A

Vesicles

Tubules

Various forms of Endoplasmic reticulum

Rough endoplasmic reticulum Cytosolic space

Cisternae

Ribosomes Tubules

Vesicle of ER Smooth endoplasmic reticulum

Fig. 3.15B Endoplasmic reticulum

102 HUMAN ANATOMY AND PHYSIOLOGY ∑ Endoplasmic reticulum (ER) was first discovered independently by Porter (1945) and Thompson (1945). ∑ It was named as ER by Porter in 1953. ∑ It is also known as ergastoplasm. ∑ It is found in all cells except in prokaryotic cells and RBCs of mammals. ∑ It is well developed in those cells which are actively involved in the synthesis of proteins, lipids, hormones etc. e.g., cells of liver and pancreas. ∑ ER occurs in three morphological forms-cisternae (long flattened sacs), vesicles (round or oval) and tubular (tube like irregular or branched structures). ∑ Depending on the presence or absence of ribosomes on its surface ER is named as rough endoplasmic reticulum and smooth endoplasmic reticulum respectively.

Functions ∑ ∑ ∑ ∑

It acts as endokeleton of the cell. It provides surface area for synthesis of protein molecules. It helps in transport of materials within the cell. Membranes of ER are the source of nuclear membrane and the membranes of some other organelles like mitochondria and Golgi apparatus. ∑ It’s membrane contains number of enzymes like ATPase, dehydrogenases, phosphatases for carrying out various metabolic activities.

3.14

GOLGI APPARATUS AND DICTYOSOMES

Golgi complexes are flattened stacks of membrane-bound sacs. Italian biologist Camillo Golgi discovered these structures in the late 1890s, although their precise role in the cell was not deciphered until the mid-1900s. The structure of golgi apparatus was studied by Dalton and Felix (1954). ∑ It occurs in all cells except in prokaryotic cells and some eukaryotic cells such as sieve tubes of plants, spermatocytes of bryophytes and pteridophytes and RBCs of mammals. ∑ In plants it occurs as golgi bodies and called as dictyosomes. ∑ Golgi apparatus has four components – cisternal – tubules – vesicles – vacuoles ∑ Cisternal, flattened sacs are in continuities of their lumen and also with smooth endoplasmic tubules. Cisterne are curved and thus give polarity to the golgi apparatus. Convex side is called forming face or cis-face and lies towards the cell membrane. Concave side is called maturing or trans-face and lies towards nucleus. Forming face receives secretory materials through vesicles, which are pinched from SER.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 103 Plasma membrane

Lysosome Secretory vesicle

Maturing face

Dictyosome Forming face E.R. Vesicle Endoplasmic reticulum

Fig. 3.16

Corelation between golgi apparatus ER, lysosomes and plasma membrane

∑ Tubules are short and branched structures which enlarge at their ends to form vesicles. These inter connect with cisternae. ∑ Vesicles are small sacs attached to the tubules. They carry materials to or from the cisternae. ∑ Vacuoles are pinched off from maturing side of the apparatus. Some of these contain hydrolysing enzymes and act as lysosomes. Golgian vacuoles Vesicles reaching the forming face

Cis Face or forming face

Cisternae Swollen End Golgi Ground Substance Tubules Trans Face or matering Secretory vesicles face leaving mature face

Fig. 3.17

Coated Vesicles

Golgi apparatus

Functions ∑ Functions include: synthesis (of substances likes phospholipids), packaging of materials for transport (in vesicles) and production of lysosomes.

104 HUMAN ANATOMY AND PHYSIOLOGY ∑ Proteins are synthesized at the surface of the endoplasmic reticulum with the help of ribosomes and RNA. These proteins later enter ER and send to golgi apparatus for complexing either to lipoproteins, glycoproteins and their packaging vacuoles are budded out through mature face. ∑ Membranes of vesicles produced by dictyosomes join at the time of cytokinesis and produce new plasma membrane. ∑ Golgi complex gives rise to primary lysosomes. ∑ Production of hormones by endocrine glands is mediated through golgi apparatus. ∑ Acrosome an important part of animal sperm is synthesised by golgi apparatus. Acrosome helps in digesting outer covering of ovum at the time of fertilization.

3.15 ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

∑ ∑ ∑ ∑

LYSOSOMES Lysosomes, are relatively large vesicles formed by the Golgi complexes. They contain hydrolytic enzymes that could destroy the cell. Lysosomes contents function in the extracellular breakdown of materials. Lysosomes also digest materials within the cell. Lysosomes contain digestive enzymes that break down proteins, lipids, etc. Lysosomes show polymorphism Lysosomes thus consist of number of enzymes mainly hydrolases bound by a single membrane. These enzymes are in their inactive form only in this form they are called primary lysosomes. When primary lysosome gets fused with food containing vacuole called phagosome then it is called secondary lysosome. This has enzymes in active form. Digestion occurs in the secondary lysosome and such a lysosome with undigested materials is called residual body. Under some conditions, lysosomes act of their own on cytoplasmic organelles. This process is called vacuole autolysis and lysosomes are called autophagic or autophagosomes or autolysosomes. Lysosomes are also known as suicide bags because of their autolytic role. These are also called scavengers of the cell as they destroy dead cells or debris at the site of injury. Lysosomes can also be called as disposal unit of the cell as it can digest food materials and removes wastes. They can even be called as recycling centres as they breakdown worn out cells and its organelles to various molecules which can be further used to build new organelles and cells.

Functions ∑ Lysosomes digest food contents of phagosomes as it contains hydrolysing enzymes. ∑ Lysosomes are also involved in intracellular digestion of the cells. ∑ In case of any disease, lysosomes burst and release all hydrolysing enzymes which digest cell itself. This is called autolysis or apoptosis. ∑ Lysosome of WBCs take part in natural defence of the body. ∑ Lysosomes also help in extracellular digestion as they release enzymes outside by the process of exocytosis.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 105 ∑ Dead cells accumulated at the site of injury are destroyed by lysosomes of WBCs. This is called natural scavenging of the body. Foreign particle Endocytic Invagination Endoplasmic reticulum

Phagosome Secondary lysosome (digestive vacuole) Primary lysosome Exocytosis

Golgi apparatus Residual body

Smooth endoplasmic reticulum

Fig. 3.18

3.16

Plasma membrane

Autophagic vacuole

Various polymorphic forms and formation of lysosomes

CENTRIOLES

∑ Centrioles are non membranous structure. These are either cylinderical or rod shaped which have ability to duplicate. ∑ Centrioles mainly occur in pairs and at right angle to each other. ∑ Pair of centrioles is called diplosome. ∑ Area of cytoplasm in which diplosome lies is called centrosphere. ∑ Complex formed by centrosphere and centrioles forms centrosome. Triplet Microtubules

Hub

Fig. 3.19 Structure of a centriole ∑ Centrioles are a pair of granular bodies present in all eukaryotic cells except Amoeba, red algae, pines and flowering plants. They always occur in pairs at right angles to one another near one pole of the nucleus.

106 HUMAN ANATOMY AND PHYSIOLOGY Structure Each centriole consists of a nine sets of microtubules arranged in a circular fashion. These tubules are equally spaced. Each microtubule has three submicrotubules and so is a triplet. This struture is often described as 9+0 arrangement of tubules. Triplets are embedded in the matrix. From outside to inside they are named as, B and A. ∑ ∑ ∑ ∑

Proteinaceious linkers connect C to A of adjacent microtubules. Centre of the centriole is occupied by a rod like proteincaeous mass called hub. Each triplet sends fine fibril made of protein towards hub, called spokes. Microtubules of centrioles are further surrounded outside by 9 amorphous spheres called percentriolar satellites or massules. Massule or pericentriolar satellite C-A linker C

B Y

Hub C

C B A

A

C B A

X

C

B A

A

B

Matrix

A B C

Fig. 3.20

A B C A B C

A

B

C

Spoke

Ultra structure of a centriole

Functions ∑ At the time of cell division it forms spindle fibres which help in the movement of chromosomes. ∑ It helps in the formation of cilia or flagella by forming their basal bodies. ∑ Out of two centrioles in sperm, distal one forms axial filament or tail.

3.17

VACUOLES

Vacuoles are single-membrane organelles that are essentially part of the outside that is located within the cell. The single membrane in plant cells is known as a tonoplast. Many organisms use vacuoles as storage areas. Vesicles are much smaller than vacuoles and function in transporting materials both within and to the outside of the cell. Vacuoles are of four types—sap vacuoles, contractile vacuoles, food vacuoles and gas vacuoles.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 107 Functions ∑ Sap vacuoles store and concentrate mineral salts and some other nutrients and thus maintain osmotic pressure in the cell. These also store wastes, tannins, latex alkaloids, water soluble pigments like anthocyanins (red, blue, purple) and anthoxanthins (deep yellow) which provide colouration in various plant parts. ∑ Contractile vacuoles help in osmoregulation and excretion. ∑ Food vacuoles are formed by fusion of phagosome and lysosome. ∑ Gas vacuoles also called pseudovacuoles contain metabolic gases and provide buyoncy to the cell. It also provides mechanical support and protects the cell from harmful radiations.

3.18

PLASTIDS

∑ Term plastid was given by E. Hackel in 1866. They are of three types — chloroplasts (green), chromoplasts (coloured) and leucoplast (colourless). ∑ Plastids are also membrane-bound organelles that only occur in plants and photosynthetic eukaryotes. ∑ Leucoplasts, also known as amyloplasts store starch, as well as sometimes protein or oils. ∑ Chromoplasts store pigments associated with the bright colors of flowers and/or fruits. ∑ Chloroplasts, are the sites of photosynthesis in eukaryotes. They contain chlorophyll, the green pigment necessary for photosynthesis to occur, and associate accessory pigments (carotenes and xanthophylls) in photosystems embedded in membranous sacs, thylakoids (collectively a stack of thylakoids are a granum [plural = grana]) floating in a fluid termed the stroma. Chloroplasts contain many different types of accessory pigments, depending on the taxonomic group of the organism being observed. ∑ Like mitochondria, chloroplasts have their own DNA, termed cpDNA. ∑ Chloroplasts of Green Algae (protista) and Plants (descendants of some of the Green Algae) are thought to have originated by endosymbiosis of a prokaryotic alga similar to living Prochloron (the sole genus present in the Prochlorobacteria. ∑ Chloroplasts of Red Algae (Protista) are very similar biochemically to cyanobacteria (also known as blue-green bacteria. ∑ Endosymbiosis is also invoked for this similarity, perhaps indicating more than one endosymbiotic event occurred.

Structure Each chloroplast consists of two membranes enclosing inter membrance space. Ground material is called stroma which contains disc like structures thylakoids occurring singly or piled up as grana. Matrix also contains ribosomes, DNA and RNA.

108 HUMAN ANATOMY AND PHYSIOLOGY

Outer DNA membrane

Fret-membrane or lamellae

Intermembrane space

Granum Stroma

Inner Membrane Granum

Thylakoid containing chloropyll Globule Ribosomes

RNA

Fig. 3.21 Structure of chloroplast

Functions ∑ ∑ ∑ ∑

3.19

Chloroplasts help in photosynthesis. Chloroplasts change to chromoplast to provide colour to flowers, fruits etc. Leucoplasts store food. Chloroplasts may synthesise some amino acids and fatty acids.

MICROBODIES

∑ ∑ ∑ ∑

Microbodies are extremely small cell organelles. These are membrane bound and have single membrane. These utilize oxygen. There are two types of microbodies: – Peroxisomes – Glycoxysomes ∑ Peroxisomes found in both plant and animal cells contains enzyme for peroxide biosynthesis. These develop from ER and are found in association with ER, mitochondria and chloroplast. Peroxisomes contain peroxide producing enzymes (oxidases) and peroxide destroying enzyme (catalase). Oxidases catalyse oxidation of substrates like amino acids and uric acid and produce hydrogen peroxide (H2 O2), while catalase degrades H2O2 to H2O and O2. Since H2O2 is harmful to cells, its destruction is good for the cell. ∑ Glycoxysomes contain enzymes for B-oxidation of fatty acids and glyoxylate cycle. Enzymes catalyse B-oxidation of fatty acid to produce acetyl to A which is converted to carbohydrates through glyoxylate cycle.

3.20

CILIA AND FLAGELLA

Cilia are short, usually numerous, hairlike projections that can move in an undulating fashion (e.g., the protozoan Paramecium the cells lining the human upper respiratory tract). Flagella are longer, usually fewer in number, projections that move in whip-like fasion (e.g., sperm cells). Cilia and flagella are similar except for length, cilia being much shorter. Both of them have the characteristic 9 + 2 arrangement of microtubules.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 109 Cilia and flagella move when the microtubules slide past one another. Both of these locomotion structures have a basal body at base with the same arrangement of microtubule triples as centrioles. Cilia and flagella grow by the addition of tubulin dimers to their tips. Flagella work as whips pulling (as in Chlamydomonas or Halosphaera) or pushing (dinoflagellates, a group of single-celled Protista) the organism through the water. Cilia works like oars. Paramecium has 17,000 such oars covering its outer surface. Both cilia and flagella consist of four parts—basal body, rootlets, basal plate and shaft. ∑ Basal body: This is also known as blepheroplast. It’s structure is similar to that of centriole. ∑ Rootlets arise from the lower part of the basal body. ∑ Basal plate lies above the basal body. One mirotubuls of each triplet disappears here but the central microtubules appear. ∑ Shaft is the projecting part which is covered by a sheath. Semifluid matrix has supporting axoneme which has 9 + 2 arrangement. Central two mirotubules are covered by proteinaceous central sheath. Nine pairs of microtubules occur at periphery and are named as A and B. ‘A ’ is comparatively narrower and has two bent arms, of which outer one has a hook. Each ‘A’ microtubule sends proteinaceous spoke to the centre. Movement of cilia and flagella occurs by sliding of the doublet microtubuls against one another. Beating of cilia shows power and recovery strokes which can be compared to the rowing of a boat. Movement of flagellum shows various symmetrical undulatory waves and drives the organism in the direction opposite to that of the flagellum. 4

5

3

14

2

6

13 12 11

7 10 8 9 Power Stroke (Maximum Resistance)

Return Stroke (Minimum Resistance)

Ciliary Movements Simple undulations

Return stroke

Power stroke

B

A

Fig. 3.22

Movements of cilia (A) and flagella (B).

110 HUMAN ANATOMY AND PHYSIOLOGY Functions ∑ ∑ ∑ ∑

3.21

Cilia and flagella are locomotory organelles. When present in the respiratory tract, cilia helps in eliminating dust particles. Cilia present in urinary and genital tracts helps in driving out urine and gametes. These help in circulation of the material.

VILLI AND MICROVILLI

Villi Villi are projections of cell membrane that serve to increase surface area of a cell (which is important, for cells that line the intestine).

Microvilli ∑ Microvilli increase the surface area of cells. ∑ Projections of cell surface: form the brush borders of cells. ∑ Sometimes confused with cilia, but much smaller (1 micron length) and with a different structure. ∑ Projections are supported by cytoskeletal filaments-mostly the protein actin. ∑ Used to increase the surface area for faster absorption or secretion of materials – Absorptive cells with microvilli: intestinal epithelium. – Secretory cells with microvilli: choroid plexus cells of brain-secrete cerebrospinal fluid. ∑ Specialized microvilli, called stereocilia are found on the surface of the hair cells of the inner ear. The stereocilia respond to sound vibrations and are involved in hearing.

3.22

CHROMOSOMES

Chromosomes in Prokaryotes In prokaryotes, there is no true chromosome present. There, it is known as Nucleoid and is not enclosed in a nuclear envelope. It does not divide by regular mitosis. Bacterial chromosome consists of a single DNA molecule called nucleoid in the form of circle without any free ends. DNA is not associated with histone proteins. DNA is attached to the plasma membrane at a point known as mesosome (outgrowth of plasma membrane). Viral chrormosome consists of proteins and one of the nuclei acids i.e., DNA or RNA. Nucleic acids may be single or double stranded, may be linear or circular. A virus with RNA as a genetic material is knwon as retrovirus. e.g., HIV (Human Immuno Deficiency Virus) is a retrovirus.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 111 Chromosomes in Eukaryotes Chromosomes are thread like structures present in the nuclei of all living cells,. When the cell is not dividing or during interphase it is in the form of very long and thin threads which appear as a network called chromatin network. As cells division proceeds they become short and thick. Structure of chromosome can be studied during metaphase stage when they are the shortest and thickest. During this stage each chromosome is doubled or replicated and consists of two thread like structures called chromatids attahced to each other at centromere or primary constriction. Each chromatid has a number of dense areas arranged linearly which are known as chromomeres. They represent the areas of active genes. Internally each chromosome has two spirally coiled threads called chromonemata.

Matrix

Chromonemata

Centromere

Matrix

Chromonema Centromere

Pellicle Chromatids

Matrix (a)

Fig. 3.23

(b)

(a) Structure of chromosome (b) Metaphase chromosome

(Sing. Chromonema) embedded in matrix. These are DNA molecules. DNA is the carrier of the genetic information from one generation to another. It was experimentally established by Giriffith in 1928, Avery, McLeod and McCarty in 1944. Frederick Meisher was the first person to isolate DNA in 1869 from the nucleus of pus cells. Chromonemal coiling is not there in the region of centromere. Centromere (kintetochore) Short arm

Long arm

Satellites Primary constriction Secondary constriction

Chromosome consisting of two chromatids

Fig. 3.24

Sat-chromosome

112 HUMAN ANATOMY AND PHYSIOLOGY Sometimes chromosomes bear a secondary constriction near one end. The swollen end of such a chromosome is called satellite. Chromosomes which bear satellites are known as sat-chromosomes. Chromosomes can be classified into different types, depending on the position of centromere : 1. 2. 3. 4.

Metacentric. Centromere is present in the centre Submetacentric. Centromere is subterminal Acrocentric. Centromere closer to the terminal end Telocentric. Centromere at the terminal end METACENTRIC

SUBMETACENTRIC

ACROCENTRIC

TELOCENTRIC

Fig. 3.25

Types of chromosomes

During anaphase, chromosomes move toward opposite poles. During this movement centomere moves first giving different shapes to the chromosomes. Telocentric chromosomes appear rod shaped, acrocentric rod shaped with tip bend, submetacentric L-shaped and metacentric V-shaped.

(a)

(b)

Fig. 3.26

(c)

(d)

(a) Rod shaped telocentric chromosome (b) Rod shaped with bend tip in acrocentric (c) L-shaped submetacentric chromosome (d) V-shaped metacentric chromosome

Chromosome number is fixed in a species. All body cells consist of two sets of chromosomes and are diploid i.e., 2n. During formation of gametes meiosis takes place and chromosome number is reduced to half or haploid i.e., n. Chromosome number of some of the organisms are given here as under:

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 113 Living Organism Man Rhesus monkey Rabbit Frog Pea Cotton Potato Corn

Scientific Name Homo sapiens Maccaca mulatta Oryctolagus cunniculus Rana tigrina Pisum sativum Gossypium hirsutum Solanum tuberosum Zea mays

Chromosome Number 46 48 44 24 14 52 48 20

DNA double helix (2-nm diameter) Eight - histone molecules Chromatid (¢¢beads on a string¢¢) structure

Nucleosome (10-nm diameter)

Solenoid [Tight Supercoiled helical fibre structure (30-nm (200-nm diameter)] diameter)] Chromatin

Chromatin Fibres Further looping and supercoiling 700 nm Chromatid 700 nm Metaphase chromosome

Fig. 3.27

Diagram showing condensation of chromatin network starting from DNA to Metaphase chromosome

114 HUMAN ANATOMY AND PHYSIOLOGY Shape and size of the chromosome change during the cell cycle. When cell is not dividing i.e., during interphase, chromosomes are in the form of long thread like structures known as chromatin network. As cell division proceeds this chromatin network starts condensing. By the end of prophase, chromosomes become distinct in shape. Metaphase chromosomes are thickest and shortest and therefore have definite shape and size. This is the best stage to count the number of chromosomes present in the cell. During anaphase chromosomes move towards opposite poles. As centromere moves first, chromosomes acquire different shapes. They appear rod shaped, like a bend rod, J-shaped or V-shaped. In telophase chromosomes again change to long thread like structures.

3.23

SPECIALISED CELLS

There are about 250 types of specialized cells in the body. Cells specialize by turning genes on and off and by structural modifications. Examples of specialized cells: ∑ Red blood cells: § Specialized for carrying O2 to the tissues. § Loaded with haemoglobin - O2 carrying protein. § Have lost their nuclei and mitochondria. ∑ Nerve cells § Specialized for transmitting electrical impulses. § Have long axons - may be a meter or more in length. § Have specialized Na and K channels for generating electricity. § Only a single nucleus in the cell body- requires a special axonal transport mechanism to deliver proteins made in the cell body to the ends of the cell. ∑ Muscle cells § Specialized for producing force by contraction. § Have special contractile proteins- actin & myosin, arranged in a sarcomere. § Very long cells: often attached to 2 bones. § Formed by fusion of many small cells; contain many nuclei. ∑ Insulin-secreting cells (beta cells of pancreas). § Gene for making the insulin hormone is turned on. § Contain large amounts of rough endoplasmic reticulum- needed for secretion.

3.24

COMPONENTS OF THE CELLULAR ENVIRONMENT

Water ∑ Comprises 60 – 90% of most living organisms (and cells). ∑ Important because it serves as an excellent solvent & enters into many metabolic reactions. Ions = atoms or molecules with unequal numbers of electrons and protons: ∑ Found in both intra and extracellular fluid. ∑ Examples of important ions include sodium, potassium, calcium, and chloride.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 115 Carbohydrates ∑ ∑ ∑ ∑

About 3% of the dry mass of a typical cell. Composed of carbon, hydrogen and oxygen atoms (e.g., glucose is C6H12O6). An important source of energy for cells. Types include: o Monosaccharides (e.g., glucose) — most contain 5 or 6 carbon atoms. o Disaccharides – Two monosaccharides linked together. – Examples include sucrose (a common plant disaccharide is composed of the monosaccharides glucose and fructose) and lactose (or milk sugar; a disaccharide composed of glucose and the monosaccharide galactose). o Polysaccharides – Several monosaccharides linked together. – Examples include starch (a common plant polysaccharide made up of many glucose molecules ) and glycogen (commonly stored in the liver).

Lipids ∑ ∑ ∑ ∑

About 40% of the dry mass of a typical cell. Composed largely of carbon and hydrogen. Generally insoluble in water. Involved mainly with long-term energy storage; other functions are as structural components (as in the case of phospholipids that are the major building block in cell membranes) and as “messengers” (hormones) that play roles in communications within and between cells. ∑ Subclasses include: o Triglycerides - consist of one glycerol molecule + 3 fatty acids. Fatty acids typically consist of chains of 16 or 18 carbons (plus lots of hydrogens). o Phospholipids - a phosphate group (–PO4) substitutes for one fatty acid and these lipids are an important component of cell membranes o Steroids - include testosterone, estrogen and cholesterol

Proteins ∑ About 50 – 60% of the dry mass of a typical cell. ∑ Subunit is the amino acid and amino acids are linked by peptide bonds. ∑ There are two functional catagories of proteins. Such as structural (proteins part of the structure of a cell like those in the cell membrane) and enzymes. o Enzymes are catalysts. Enzymes bind temporarily to one or more of the reactants of the reaction they catalyze. In doing so, they lower the amount of activation energy needed and thus speed up the reaction.

3.25

MOVEMENT ACROSS MEMBRANES

1. Passive Processes: require no expenditure of energy by a cell. ∑ Simple Diffusion = net movement of a substance from an area of high concentration to an area of low concentration. The rate of diffusion is influenced by:

116 HUMAN ANATOMY AND PHYSIOLOGY o

concentration gradient o cross-sectional area through which diffusion occurs o temperature o molecular weight of a substance o distance through which diffusion occurs. ∑ Osmosis ∑ Facilitated Diffusion: movement of a substance across a cell membrane from an area of high concentration to an area of low concentration. This process requires the use of ‘carriers’ (membrane proteins). A ligand molecule (e.g., acetylcholine) binds to the membrane protein. This causes a conformational change or, in other words, an ‘opening’ in the protein through which a substance (e.g., sodium ions) can pass. 2. Active Processes ∑ It is the movement of a substance across a cell membrane from an area of low concentration to an area of high concentration using energy molecules ∑ This energy is required to counter act the forces of diffusion which bring about equilibrium. ∑ During this process plasma membrane pumps ions against the concentration gradient i.e., it is working as ionic pump. ∑ This process uses energy rich molecules called ATP molecules. ∑ For the process of active transportation some carrier molecules are required which forms complex of activated carrier molecule and transport ions. ∑ Some enzymes like phosphatase, ATP are, pinase etc. help in the process. ∑ One very important example of active transport is sodium-potassium pump. ∑ Proteins which are involved in active transport are called pumps as they use energy to move molecules against concentration gradient. ∑ Sodium-potassium pump is associated with nerve and muscle cells. ∑ This pump moves sodium ions (not) to the outside of the cell and potassium ions to the inside of the cell. ∑ This requires carrier protein and ATP molecule. ∑ Three sodium ions are carried outwards for every two potassium ions carried inward. ∑ Therefore inward of the cell is negatively charged as compared to outside. ∑ Protein carrier has a shape that it allows it to take up three sodium ions. ∑ ATP is split and phosphate group attaches to carrier ∑ Change in shape results and causes carrier to release three Na+ outside the cell. ∑ Carrier now has a shape that allows it to take up 2K+. ∑ Then phosphate group is released from carrier. ∑ Change in shape results and causes carrier to release 2K+ inside the cell. ∑ Transport of salt (NaCl) consisting of ions Na+ and Cl– across plasma membrane is also very important for the cell. ∑ Cl– crosses plasma membrane as they get attracted by Na+. ∑ First Na+ are pumped across the membrane and this is followed by simple diffusion of Cl– through channels which allow their passage.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 117 3.26

CELL DIVISION

Formation of new cells is important for growth and development. This was first suggested by Rudolf Virchow in 1958 as ‘omnis cellulae cellula’ meaning every cell is derived from a cell. Formation of new cells by division of new cells is called cell reproduction. Despite differences between prokaryotes and eukaryotes, there are several common features in their cell division processes. Replication of DNA must occur. Segregation of the “original” and its “replica” follows, cytokinesis at the end of the cell division process. Whether the cell was eukaryotic or prokaryotic, these basic events must occur. Flemming in 1880 studied somatic cell division and coined the term meiosis. The term meiosis was given by Former and Moore (1905).

Prokaryotic Cell Division ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

Prokaryotes are much simpler in their organization than eukaryotes. There are a many organelles in eukaryotes, also more chromosomes. The usual method of prokaryote cell division is termed binary fission. The prokaryotic chromosome is a single DNA molecule that first replicates, then attaches each copy to a different part of the cell membrane. When the cell begins to pull apart, the replicate and original chromosomes are separated. Following cell splitting (cytokinesis), there are then two cells of identical genetic composition (except for the rare chance of a spontaneuous mutation). The prokaryote chromosome is much easier to manipulate than the eukaryotic one. We thus know much more about the location of genes and their control in prokaryotes. One consequence of this asexual method of reproduction is that all organisms in a colony are genetic equals. When treating a bacterial disease, a drug that kills one bacteria (of a specific type) will also kill all other members of that clone (colony) it comes in contact with.

Eukaryotic Cell Division ∑ Due to their increased numbers of chromosomes, organelles and complexity, eukaryote cell division is more complicated, although the same processes of replication, segregation and cytokinesis still occur. ∑ Cell division is the basis of life itself; it is how animals grow and reproduce. When cells divide two daughter cells are produced from one mother cell. Each new cell has exactly the same genetic material (DNA) as the cell that produced it. ∑ The period between two successive divisions is called generation time.

Functions of Cell Division Cellular division has three main functions: 1. The reproduction of an entire unicellular organism, 2. The growth and repair of tissues in multicellular animals, and 3. The formation of gametes (eggs and sperm) for sexual reproduction in multicellular animals.

118 HUMAN ANATOMY AND PHYSIOLOGY Steps of Cell Division ∑ ∑ ∑ ∑

3.27

Cellular division has two steps. First, the genome is divided up inside the nucleus by either mitosis or meiosis. Second, the cytoplasm (the rest of the content of the cell) is divided. The cell is actually split in two in a process called cytokinesis, in which the cellular membrane is pinched in the middle like a balloon squeezed in the centre.

CELL CYCLE

S

G1

Interphase period of cell growth (2n DNA content)

RNA and Cytoplasmic active protein synthesis

inesis

G

(4n DNA Content)

Mitosis

Cytok

VARIABLE DURATION (7–12 hrs)

DNA Synthesis G2 or Replication RNA and Cytoplasmic Synthesis (4n DNA content (2–5 hrs)

M

NUCLEAR DIVISION

(1 hr)

IC

ASM OPL N CYT IVISIO D

Fig. 3.28 Eukaryotic cell cycle The cell cycle involves many repetitions of cellular growth and reproduction. With few exceptions (for example, red blood cells), all the cells of living things undergo a cell cycle. The cell cycle is generally divided into two phases: interphase and mitosis. During interphase, the cell spends most of its time performing the functions that make it unique. Mitosis is the phase of the cell cycle during which the cell divides into two daughter cells.

Interphase The interphase stage of the cell cycle includes three distinctive parts: the G1 phase, S phase, and G2 phase.

/2D=IA ∑ The period prior to the synthesis of DNA. ∑ In this phase, the cell increases in mass in preparation for cell division.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 119 ∑ Note that the G in G1 represents gap and the 1 represents first, so the G1 phase is the first gap phase. The G1 phase follows mitosis and is the period in which the cell is synthesizing its structural proteins and enzymes to perform its functions. ∑ For example, a pancreas cell in the G1 phase will produce and secrete insulin, a muscle cell will undergo the contractions that permit movement, and a salivary gland cell will secrete salivary enzymes to assist digestion. ∑ During the G1 phase, each chromosome consists of a single molecule of DNA and its associated histone protein. ∑ In human cells, there are 46 chromosomes per cell (except in sex cells with 23 chromosomes and red blood cells with no nucleus and hence no chromosomes.

52D=IA ∑ The period during which DNA is synthesized. In most cells, there is a narrow window of time during which DNA is synthesized. Note that the S represents synthesis. During the S phase of the cell cycle, the DNA within the nucleus replicates. ∑ During this process, each chromosome is faithfully copied, so by the end of the S phase, two DNA molecules exist for each one formerly present in the G1 phase.

/ 2D=IA ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

The period after DNA synthesis but prior to the start of prophase is the G2 phase. The cell synthesizes RNA and proteins and continues to increase in size. In the G2 phase, the cell prepares for mitosis. Proteins organize themselves to form a series of fibers called the spindle, which is involved in chromosome movement during mitosis. The spindle is constructed from amino acids for each mitosis, and then taken apart at the conclusion of the process. Spindle fibers are composed of microtubules. To conclude we can say that interphase cell shows following characteristics. Nuclear envelope remains intact. Nucleolus is distinct. Centriole divides into two and remains with in the centrosome. Heterochromatin is distinct. Nucleus exhibit homogenous structure. Replicated centrioles Nuclear wall Nucleus Chromatin network Cytoplasm

No centrioles

Fig. 3.29 Interphase in (a) animal cell (b) plant cell

120 HUMAN ANATOMY AND PHYSIOLOGY

Telophase Interphase (Highly coiled chromosome) Centromere Anaphase (Late)

Chromatid

Prophase (Early)

Metaphase (Shortest and thickest chromosome) Chromatid Prophase

Prophase (Late)

Fig. 3.30

3.28

Prophase

Condensation of chromosomes during various stages of mitosis

MITOSIS

The term mitosis is derived from the Latin stem mito, meaning “threads.” When mitosis was first described a centrury ago, scientists had seen “threads” within cells, so they gave the name mitosis to the process of “thread movement.” During mitosis, the nuclear material becomes visible as threadlike chromosomes. The chromosomes organize in the center of the cell, and then they separate, and 46 chromosomes move into each new cell that forms. Mitosis is a continuous process but for convenience in denoting which portion of the process is taking place, scientists divide mitosis into a series of phases— prophase, metaphase, anaphase and telophase. These phases of karyokinesis (division of nucleus) are followed by cytokinesis (division of cytoplasm).

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 121 Prophase Movement of centrioles towards opposite poles

No centrioles

Nucleus Nuclear wall disappearing Shortening of chromosomes Early prophase Middle prophase (a)

Fig. 3.31 ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

Late prophase

Early prophase Middle prophase Late prophase (b)

Prophase in (a) animal cell (b) plant cell

Nuclear wall starts disappearing. Nucleolus start disappearing. Condensation of the chromosomes to form visible threads begins. Two copies of each chromosome exist; each one is a chromatid. Two chromatids are joined to one another at a region called the centromere. Chromatin network condenses into long filamentous structures called spirmes as at this stage chromosome looks like a ball of wool. As prophase unfolds, the chromatids become visible in pairs, the spindle fibers form, the nucleoli disappear, and the nuclear envelope dissolves. In animal cells during prophase, microscopic bodies called the centrioles begin to migrate to opposite sides of the cell. When the centrioles reach the poles of the cell, they produce, and are then surrounded by, a series of radiating microtubules called an aster. Aster and spindle together is called amphiaster. Centrioles and asters are not present in most plant or fungal cells. As prophase continues, the chromatids attach to spindle fibers that extend out from opposite poles of the cell. The spindle fibers attach at the region of the centromere at a structure called the kinetochore, a region of DNA that as remained undivided. Eventually, all pairs of chromatids reach the center of the cell, a region called the equatorial plate.

Metaphase Centriole

Chromosomes on equatorial plate

(a)

Fig. 3.32

(b)

Metaphase in (a) animal cell (b) plant cell

122 HUMAN ANATOMY AND PHYSIOLOGY ∑ During this stage chromosomes become shortest, thickest and most conspicuous. This is the best stage to observe chromosomes under microscope. ∑ Metaphase is the stage of mitosis in which the pairs of chromatids line up on the equatorial plate. ∑ This region is also called the metaphase plate. ∑ In a human cell, chromosomes in 46 pairs align at the equatorial plate. ∑ Each pair is connected at centromere, where the spindle fiber is attached (more specifically at the kinetochore). ∑ At this point, the DNA at the kinetochore duplicates, and the two chromatids become completely separate from one another.

Anaphase Movement of chromosomes towards opposite poles

Early anaphase

Middle anaphase

Late anaphase

(a)

Early anaphase

Middle anaphase

Late anaphase

(b)

Fig. 3.33

Anaphase in (a) animal cells (b) plant cell

∑ At the beginning of anaphase, the chromatids move apart from one another. ∑ The chromatids are chromosomes after the separation. ∑ Each chromosome is attached to a spindle fiber, and the members of each chromosome pair are drawn to opposite poles of the cell by the spindle fibers. ∑ During anaphase, the chromosomes can be seen moving. ∑ They take on a rough V shape because of their midregion attachement to the spindle fibers. ∑ The movement toward the poles is accomplished by several mechanisms, such as an elongation of the spindle fibers, which results in pushing the poles apart.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 123 ∑ The result of anaphase is an equal separation and distribution of the chromosomes. ∑ In humans cells, a total of 46 chromosomes move to each pole as the process of mitosis continues.

Chromomeres

Homologous chromosomes Nucleolus

Centiole Nucleolus Nuclear Membrane

Dyad

Leptotene

Zygotene

Crossing over between homologous chromosomes Tetrad

Chromatides Centromere

Pachytene

Diplotene

Tetrads Centromere

Equator Spindle

Centrosome

Centrosome Diakinesis

Metaphase-I Cytokinesis takes place

Chromatids moved to opposite poles Anaphase-I

Telophase-I

Fig. 3.34 Various stages of meiosis -1

124 HUMAN ANATOMY AND PHYSIOLOGY Daughter cell

Daughter cell

Prophase-II

Prophase-II

Metaphase-II

Metaphase-II

Anaphase-II

Anaphase-II

Parental Recombinant Telophase-II

Recombinant Parental Telophase-II

Four daughter cells formed at the end of meiosis two parental and two recombinants

Fig. 3.35

Various stages of meiosis-II

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 125 Telophase Duplicating centrioles Cell furrow formation Disappearing spindle

Centrosome formation Daughter cell

Nucleus appears

Daughter cell

Early telophase

Late telophase (a)

Nuclear wall appearing

Cell plate formation

Early telophase

Late telophase (b)

Fig. 3.36

Telophase in (a) animal cell (b) plant cell and cytokinesis

∑ In telophase, the chromosomes finally arrive at the opposite poles of the cell. ∑ The distinct chromosomes begin to fade from sight as masses of chromatin are formed again. ∑ The events of telophase are essentially the reverse of those in prophase. ∑ The spindle is dismantled and its amino acids are recycled, the nucleoli reappear, and the nuclear envelope is reformed.

3.29

CYTOKINESIS

Cytokinesis in Animals ∑ Cytokinesis is the process in which the cytoplasm divides and two separate cells form. ∑ In animal cells, cytokinesis begins with the formation of a furrow in the center of the cell. ∑ With the formation of the furrow, the cell membrane begins to pinch into the cytoplasm and the formation of two cells begins. ∑ This process is often referred to as cell cleavage. ∑ Microfilaments contract during cleavage and assist the division of the cell into two daughter cells.

126 HUMAN ANATOMY AND PHYSIOLOGY Cytokinesis in Plants ∑ In plant cells, cytokinesis occurs by a different process because a rigid cell wall is involved. ∑ Cleavage does not take place in plant cells. ∑ Rather, a new cell wall is assembled at the centre of the cell, beginning with vesicles formed from the golgi body.

Plasma membrane Cytoplasm Furrow Daughter nucleus 1

2 Cell wall

Daughter nucleus

Plasma membrane

Phragmoplast

Cell plate

Vesicles A

Fig. 3.37

B

C

Cytokinesis in (1, 2) animal cell, (A, B, C) plant cell

∑ As the vesicles join, they form a double membrane called the cell plate. ∑ The cell plate forms in the middle of the cytoplasm and grows outward to fuse with the cell membrane. ∑ The cell plate separates the two daughter cells. As cell wall material is laid down, the two cells move apart from one another to yield two new daughter cells.

3.30

MEIOSIS

∑ Meiosis is the process of cellular division that produces the gametes which take part in sexual reproduction. ∑ Where mitosis produces two daughter cells from one mother cell, meiosis produces four daughter cells from one mother cell. ∑ The end products of meiosis, the gametes, contain only half the genome of an organism. ∑ The two gametes fuse to produce a zygote.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 127 ∑ Because each gamete has half the genetic material of the mother cell. This fusion results in a zygote with the correct amount of genetic material. ∑ Sexual reproduction occurs only in eukaryotes. ∑ During the formation of gametes, the number of chromosomes are reduced by half, and returned to full amount when the two gametes fuse during fertilization.

Ploidy ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

Haploid and diploid are terms referring to the number of sets of chromosomes in a cell. Diploid organisms are with two sets. Human beings (except for their gametes), most animals and many plants are diploid. Diploid abbreviate as 2n. Ploidy is a term referring to the number of sets of chromosomes. Haploid organisms/cells have only one set of chromosomes, abbreviated as n. Organisms with more than two sets of chromosomes are termed polypoid. Chromosomes that carry the same genes are termed homologous chromosomes. The alleles on homologous chromosomes may differ, as in the case of heterozygous individuals. Organisms (normally) receive one set of homologous chromosomes from each parent. Meiosis is a special type of nuclear division which segregates one copy of each homologous chromosome into each new “gamete”. ∑ Mitosis maintains the cell’s original ploidy level (for example, one diploid 2n cell producing two diploid 2n cells; one haploid n cell producing two haploid n cells; etc.). ∑ Meiosis, on the other hand, reduces the number of sets of chromosomes by half, so that when gametic recombination (fertilization) occurs the ploidy of the parents will be re-established.

Steps of Meiosis Two successive nuclear divisions occur, Meiosis I (Reduction) and Meiosis II (Division). Meiosis produces 4 haploid cells. Mitosis produces 2 diploid cells. The old name for meiosis was reductional division. Meiosis I reduces the ploidy level from 2n to n (reduction) while Meiosis II divides the remaining set of chromosomes in a mitosis-like process (division). Most of the differences between the processes occur during Meiosis I. There are two stages in meiosis—meiosis I and meiosis II. Meiosis

Meiosis I (A) Prophase I (B) Metaphase I (C) Anaphase I (D) Telophase I

Leptotene Zygotene Pachytene Diplotene Diakinesis

Meiosis II (E) Prophase II (F) Metaphase II (G) Anaphase II (H) Telophase II

128 HUMAN ANATOMY AND PHYSIOLOGY

Kinetochore

LEPTOTENE

Homologous chromosomes

Synapsing or pairing of Homologous chromosomes

Bivalent ZYGOTENE Sister chromatids

Tetrad / Quadrivalent

Sister chromatids Kinetochores

PACHYTENE Nonsister chromatids

Tetrad Noncross-over chromatid Cross-over chromatids Noncross-over chromatid

Tetrad

AFTER CROSSING OVER IN DIPLOTENE Chromosomes Homologous chromosomes ANAPHASE-I

Chromosomes TELOPHASE-I

Fig. 3.38

Changes in chromosomes during various stages of meiosis

MEIOSIS I At the beginning of meiosis I, a human cell contains 46 chromosomes, or 92 chromatids (the same number as during mitosis). Meiosis I proceeds through the following phases :

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 129 A. Prophase I (i) Leptotene

Cell membrane Cytoplasm Pairing chromosomes (Bivalent) Nuclear membrane Nucleolus

Fig. 3.39

Leptotene

∑ Chromosomes thicken, shorten and detach from the nuclear envelope. ∑ Similar to mitosis, the centrioles migrate away from one another and both the nuclear envelope and nucleoli breakdown. (ii) Zygotene

Cell membrane Cytoplasm Pairing chromosomes (Bivalent) Nuclear membrane Nucleolus

Fig. 3.40

Zygotene

∑ During this phase coming together of homologous chromosomes takes place. ∑ This process of pairing is called synapsis. Synapsis may be procentric (starting from centromeres towards ends), proterminal (from ends to centromere) or intermediate between the two. ∑ Since pair of chromosomes has two threads, it is called bivalent. ∑ Syneptonemal complex is formed.

130 HUMAN ANATOMY AND PHYSIOLOGY (iii) Pachytene

Cell membrane Nuclear membrane Paired chromosomes (Tetrad) Nucleolus

Fig. 3.41 ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

Pachytene

The two homologous chromosomes which came near each other consist of two chromatids. They now split into four chromatids aligned next to one another. This combination of four chromatids is called a tetravalent or quadrivalent. After synapsis has taken place, the process of crossing over occurs. In this process, segments of DNA from one chromatid in the tetrad pass to another chromatid in the tetrad. They result in a genetically new chromatid. Crossing over is an important driving force of evolution. After crossing over has taken place, the four chromatids of the tetrad are genetically different from the original four chromatids. During crossing-over, chromatids break and may be reattached to a different homologous chromosome. To understand crossing over, let us consider a pair of homologous chromosomes with following alleles: A

B

C

D

C

D

B

E

A a

a

b

b

E

c

d

c

d

e

F

F f

e f

∑ If there is a crossing-over event between non-sister chromatids between B and C of first chromosome and b and c of second chromosome then it will produce the following chromosomes.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 131 A

B

C

D

C

D

B

E

E

A

F

F

a

b

c

d

e

f

A

B

C

D

E

F

C

D

a A

a

E

b B

F c

d

c

d

b

e

f

e f

∑ ∑ ∑ ∑

Crossing over occurs by breakage and reunion of chromatid segments. Breakage is called micking which is assisted by an enzyme endonuclease. Reunion is termed as annealing which is aided by an enzyme R-protein. Thus, instead of producing only two types of chromosome (all capital), four different chromosomes are produced. ∑ The occurrence of crossing-over is indicated by a special structure, a chiasma (plural chiasmata) since recombined inner alleles will align more with others of the same type. (iv) Diplotene Cell membrane Cytoplasm Nuclear membrane

Nucleolus (degenerating) Chromosomes showing crossing over

Fig. 3.42

Diplotene

∑ After completion of crossing over the homologous chromosomes begin to separate slightly, although they remain attached at chiasmata.

132 HUMAN ANATOMY AND PHYSIOLOGY (v) Diakinesis Cell membrane

Nuclear membrane (degenerating)

Chiasmata Centromere

Fig. 3.43 ∑ ∑ ∑ ∑ ∑

Diakinesis

Terminalisation takes place. The nucleus dissolves. Nuclear membrane is disassembled. The spindle apparatus forms. The chromosomes begin their migration to the metaphase plate.

B. Metaphase I

Pole Spindle fibers

Fig. 3.44 ∑ ∑ ∑ ∑

Metaphase I

The tetrads align on the equatorial plate. The centromeres attach to spindle fibers, which extend from the poles of the cell. One centromere attaches per spindle fiber. The centromeres of homologous chromosomes are oriented toward the opposite cell poles.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 133 C. Anaphase I Pole Spindle fibers

Chromosomes (moving to poles)

Fig. 3.45

Anaphase I

∑ In anaphase I, the homologous chromosomes separate. ∑ One homologous chromosome (consisting of two chromatids) moves to one side of the cell, while the other homologous chromosome (consisting of two chromatids) moves to the other side of the cell. The result is that n chromosomes (each consisting of two chromatids) move to one pole, and n chromosomes (each consisting of two chromatids) move to the other pole. ∑ Essentially, chromosome number of the cell is halved. ∑ For this reason the process is a reductional division.

D. Telophase I ∑ In telophase I of meiosis, the nucleus reorganizes, the chromosomes become chromatin, and a cytoplasmic division into two cells takes place. ∑ Each daughter cell (with 23 chromosomes each consisting of two chromatids) then enters interphase, during which there is no duplication of the DNA. The interphase period may be brief or very long, depending on the species of organism. ∑ Once movement is complete, each pole has a haploid number of chromosomes. ∑ In most cases, cytokinesis occurs at the same time as telophase I. ∑ At the end of telophase I and cytokinesis, two daughter cells are produced, each with one half the number of chromosomes of the original parent cell. ∑ Depending on the kind of cell, various processes occur in preparation for meiosis II. ∑ The genetic material does not replicate again. Nuclear membrane (reappears) Nucleolus (reappears) Chromosomes

Fig. 3.46

Telophase I

134 HUMAN ANATOMY AND PHYSIOLOGY MEIOSIS II Meiosis II is the second major subdivision of meiosis. It occurs in essentially the same way as mitosis. In meiosis II, a cell containing 46 chromatids undergoes division into two cells, each with 23 chromosomes. Meiosis II proceeds through the following phases:

E. Prophase II Cell membrane Nuclear membrane Chromatin material Nucleolus

Fig. 3.47

Prophase II

∑ Prophase II is similar to the prophase of mitosis. ∑ The chromatin material condenses, and each chromosome contains two chromatids attached to the centromere. ∑ The 23 chromatid pairs, a total of 46 chromatids, then move to the equatorial plate. ∑ The nuclear membrane and nuclei break up while the spindle network appears. ∑ Chromosomes do not replicate any further in this phase of meiosis. ∑ The chromosomes begin migrating to the metaphase II plate (at the cell’s equator).

F. Metaphase II

Spindle fibers Chromosomes

Fig. 3.48

Metaphase II

∑ In metaphase II of meiosis, the 23 chromatid pairs, gather at the centre of the cell prior to separation. ∑ This process is identical to metaphase in mitosis. ∑ The chromosomes line up at the metaphase II plate at the cell’s centre.

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 135 G. Anaphase II

Chromosomes (moving to poles)

Fig. 3.49

Anaphase II

∑ During anaphase II of meiosis, the centromeres divide, and the 46 chromatids become known as 46 chromosomes. ∑ Then the 46 chromosomes separate from each other. Spindle fibers move one chromosome each other from each pair to one pole of the cell and the other member of the pair to the other pole. ∑ In all, 23 chromosomes move to each pole.

H. Telophase II

Nucleolus appearing Nuclear membrane appearing Chromosomes rearranging into chromatin

Fig. 3.50 Telophase II ∑ During telophase II, the chromosomes gather at the poles of the cells and become indistinct. ∑ Again, they form a mass of chromatin. ∑ The nuclear envelope develops, the nucleoli reappear, and the cells undergo cytokinesis as in mitosis. ∑ Distinct nuclei form at the opposite poles and cytokinesis occurs. ∑ At the end of meosis II, there are four daughter cells each with one half the number of chromosomes of the original parent cell.

136 HUMAN ANATOMY AND PHYSIOLOGY 3.31

CELL DIVISION IN HUMAN BEINGS

During meiosis II, each cell containing 46 chromatids yields two cells, each with 23 chromosomes. Originally, there were two cells that underwent meiosis II; therefore, the result of meiosis II is four cells, each with 23 chromosomes. Each of the four cells is haploid; that is, each cell contains a single set of chromosomes. The 23 chromosomes in the four cells from meiosis are not identical because crossing over has taken place in prophase I. The crossing over yields variation so that each of the four resulting cells from meiosis differs from the other three. Thus, meiosis provides a mechanism for producing variations in the chromosomes. Also it accounts Meiosis in Humans. In humans, meiosis is the process by which sperm cells and egg cells are produced. In the male, meiosis takes place after puberty. Diploid cells within the testes undergo meiosis to produce haploid sperm cells with 23 chromosomes. A single diploid cell yields four haploid sperm cells through meiosis. In females, meiosis begins during the fetal stage when a series of diploid cells enter meiosis I. At the conclusion of meiosis I, the process comes to a halt, and the cells gather in the ovaries. At puberty, meiosis resumes. One cell at the end of meiosis I enters meiosis II each month. The result of meiosis II is a single egg cell per cycle (the other meiotic cells disintegrate). Each egg cell contains 23 chromosomes and is haploid. The union of the egg cell and the sperm cell leads to the formation of a fertilized egg cell with 46 chromosomes, or 23 pairs. Fertilization restores the diploid number of chromosomes. The fertilized egg cell, a diploid, is a zygote. Further divisions of the zygote by mitosis eventually yield a complete human being for the formation of four haploid cells from a single diploid cell.

3.32

SIGNIFICANCE OF CELL DIVISION

∑ Cell division is required for: (a) growth (b) repair & replacement of damaged parts (c) reproduction of the species Mitosis is Used for Growth and Repair ∑ Object of mitosis is to produce 2 identical cells (same number of chromosomes) ∑ DNA duplicates and there is a single division, giving each cell 23 pairs of chromosomes ∑ Some tissues must be repaired often : lining of gut, white blood cells, skin-cells lifespan is only a few days. Meiosis is Used for Sexual Reproduction ∑ Object of meiosis is to reduce the number of chromosomes to single copy of each (23 total) ∑ Used for making gametes : sperm and eggs (haploid) – When a sperm fertilizes an egg to form a zygote the diploid number of chromosomes are restored (23 + 23 = 46) – Used for sexual reproduction (makes sperm & eggs) – Makes 4 haploid cells (each has half the number of chromosomes)

CELL—COMPONENTS, FUNCTIONS AND CELL DIVISION 137 3.33

KARYOTYPE

6

8

7

13

14

19

20

4

3

2

1

9

15

10

16

21

22

5

X

11

12

17

18

X

X

FEMALE

Y

MALE

Fig. 3.51 Karyotype of human cell The number and structure (morphology) of chromosomes was unknown till 1956. Tjio and Levan in 1956 gave a technique by which number and structure of chromosomes can be studied. Since the metaphase stage is the best to count the number of chromosomes, photographs are taken, cut and systematically arranged in order of their size, except the sex chromosomes that are placed at the end. Such a pictorial representation of artificially arranged homologous chromosomes in order of their size with sex chromosomes at the end is known as karyogram. The study of all chromosomes in this manner is known as karyotype analysis. From karyogram, any chromosomal abnormality can be identified such as Down’s syndrome, Turner’s syndrome etc.

REVIEW QUESTIONS 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Explain the structures of prokaryotic and eukaryotic cells with the help of diagrams. Explain briefly the fluid mosaic model of plasma membrane. Also give its functions. Briefly describe the ultra structure of centriole. Comment upon the statement that the interphase is the most active stage of the cell cycle. Describe briefly various stages of the cell cycle. With the help of diagrams explain various events taking place during meiosis. With the help of illustrations, explain various stages of meiosis. Describe the process of crossing over with the help of diagrams. Also discuss its significance. Gametic reproduction involves meiosis in order to maintain constancy of specific number of chromosomes through generations. Justify the statement. Discuss the significance of mitosis and meiosis. Also tabulate differences in the two. How is cytokinesis different in animal cell as compared to plant cell. Explain with diagrams.

CHAPTER

4

ELEMENTARY TISSUES OF HUMAN BODY ph Bios ere

mmunity Co

osystem Ec

ANIMALS

PLANTS

ORGANISATION IN

Org

gan system Or

gan Or

Popula ti

on

POND RIVER FOREST DESERT MOUNTAINS PARK

Group of cells

LIVING ORGANISMS C

l el

Tis

anism

e su Types of Tissues

4.1

INTRODUCTION

The term tissue was given by French surgeon, Bichat (1771–1802). Tissue is a group of cells that have similar structure and that function together as a unit. Several tissues are found in an organ which also has its own blood and nervous supplies. An organ system performs related tasks, e.g., the 138

ELEMENTARY TISSUES OF HUMAN BODY 139 digestive system that includes the gut tube, pancreas and liver. A nonliving material, called the intercellular matrix, fills the spaces between the cells. This may be abundant in some tissues and minimal in others. The intercellular matrix may contain special substances such as salts and fibers that are unique to a specific tissue and gives those tissue distinctive characteristics. Tissues are classified according to the size, shape and functions of its’s cells. There are four main types of tissues in the body: epithelial, connetive, muscle, and nervous, each of which has it’s subdivisions. Animal Tissues

Muscular

Epithelial

Connective

Nervous

Squamous Cuboidal Columnar Ciliated Glandular Pseudo stratified (with (flattened) (cubical) (tall (with cilia) or secretory pillar-like) function)

Striated

Areolar

Dense Regular Connective Tissue

Tendon

Nonstriated

Adipose

Ligament

Hyaline

Cardiac

Fluid (Vascular Tissue)

Skeletal

Cartilage

Fibrous

Bone

Blood

Lymph

Calcified

Cells in a tissue are bound by intercellular materials. The cells of a tissue when not separated widely by intercellular materials are held together by structures called cell junctions. The study of tissues is called histology or microscopic anatomy. The term Histology was coined by Mayer in 1819. Out of the four tissues, origin of epithelial tissue may be from ectoderm, endoderm or mesoderm while that of connective and muscular tissue is from mesoderm and that of nervous system is from ectoderm.

4.2

EPITHELIAL TISSUES ∑ ∑ ∑ ∑

Epithelial tissues are widespread throughout the body. They form the covering of all body surfaces, line body cavities. This tissue is also found in glands. Animals are multicellular and heterotrophs whose cells lack cell walls. At some point during their lives, all animals perform a variety of functions which includes protection, secretion, absorption, excretion, filtration, diffusion, and sensory reception. ∑ This work is done by epithelial tissues. ∑ The cells in epithelial tissue are tightly packed together with very little intercellular matrix.

140 HUMAN ANATOMY AND PHYSIOLOGY ∑ Because the tissues form coverings and linings, the cells have one free surface that is not in contact with other cells. ∑ Opposite the free surface, the cells are attached to underlying connective tissue by a noncellular basement membrane. ∑ This membrane is a mixture of carbohydrates and proteins secreted by the epithelial and connective tissue cells. ∑ Epithelial tissue covers body surfaces and lines body cavities. ∑ Any epithelium can be simple, stratified or pseudo stratified. ∑ Simple epithelium has only a single cell layer of identical cells, mainly found on absorptive or secretory surfaces. ∑ Stratified epithelium has more than one layer of cells of various shapes. The superficial layers grow up from below. The main function is to protect underlying structures from mechanical wear and tear. These tissues may be non keratinised or keratinised. Former is subjected to wear and tear (e.g., conjunctive of eye, lining of mouth, pharynx, oesophagus and vagina, while later is helpful in protection against wear and tear (e.g., skin, hair and nails). ∑ Pseudo stratified epithelium is a single layer of cells so shaped that they appear at first glance to form two layers. Thus epithelial tissue is made of closely-packed cells arranged in flat sheets. Epithelia form the surface of the skin, line the various cavities and tubes of the body, and cover the internal organs.

Subsets of Epithelia ∑ Epithelia that form the interface between the internal and external environments.  Skin as well as the lining of the mouth and nasal cavity. These are derived from ectoderm.  Inner lining of the gastrointestinal tract, lungs, urinary bladder, exocrine glands, vagina and more. These are derived from endoderm. The apical surface of these epithelial cells is exposed to the “external environment”, the lumen of the organ or the air. ∑ Mesothelia. These are derived from mesoderm.  pleura—the outer covering of the lungs and the inner lining of the thoracic (chest) cavity.  peritoneum—the outer covering of all the abdominal organs and the inner lining of the abdominal cavity.  pericardium—the outer lining of the heart. ∑ Endothelia. The inner lining of the heart, all blood and lymphatic vessels—derived from mesoderm. The basolateral surface of all epithelia is exposed to the internal environment. The entire sheet of epithelial cells is attached to a layer of extracelluar matrix that is called the basement membrane or, better (because it is not a membrane in the biological sense), the basal lamina. Epithelia can also be classified as: (i) Simple epithelia consisting of single layer resting on a basement membrane. (ii) Compound epithelia are made of more than one layer of cells. Only the lower most layer rests on the basement membrane. Compound epithelia are further of two types:

ELEMENTARY TISSUES OF HUMAN BODY 141 – stratified: It consists of many layers. – transitional: It consists of more than one layers of cells but is much thinner and stretchable. Epithelial tissues can also be classified on the basis of their function such as: (i) Sensory epithelia which receive stimuli and conducts impulses. These are mainly found in the retina of the eye, internal ear, nasal chamber and tongue. (ii) Germinal epithelia produces gametes and is found in ovaries and testes. (iii) Absorptive epithelia helps in absorption of food in the stomach and liquid materials in the nephrons. (iv) Pigmented epithelia gives colour and found in the retina of eye. (v) Glandular epithelia is present in glands and secretes materials.

Functions of Epithelial Cells ∑ Movement of materials in, out, or around the body. ∑ Protection of the internal environment against the external environment. ∑ Secretion. ∑ Lining, protecting, and forming glands. The function of epithelia always reflects the fact that they are boundaries between masses of cells and a cavity or space. Some examples are: ∑ The epithelium of the skin protects the underlying tissues from:  Mechanical damage  Ultraviolet light  Dehydration  Invasion by bacteria. ∑ The columnar epithelium of the intestine  Secretes digestive enzymes into the intestine.  Absorbs the products of digestion from it. ∑ An epithelium also lines our air passages and the alveoli of the lungs. It secretes mucus which keeps it from drying out and traps inhaled dust particles. Most of its cells have cilia on their apical surface that propel the mucus with its load of foreign matter back up to the throat. ∑ Germinal epithelium of the ovaries and seminiferous tubules of the testes produce ova and spermatozoa respectively. ∑ Pigmented epithelium of retina darkens the cavity of eye ball. ∑ The epithelium of nephrons is specialised for urine formation.

Types of Simple Epithelium Epithelial cells may be squamous, cuboidal, or columnar in shape and may be arranged in single or multiple layers. Simple epithelium can be classified into five types: ∑ Squamous epithelium ∑ Cuboidal epithelium

142 HUMAN ANATOMY AND PHYSIOLOGY ∑ Columnar epithelium ∑ Ciliated epithelium ∑ Glandular epithelium

Squamous Epithelium Squamous epithelial cells

Basement membrane

Connective tissue

Fig. 4.1

Simple squamous epithelium

Characteristics ∑ Formed of thin flat, disc like polygonal cells fitted like tiles of the floor. Therefore, these are also called pavement epithelium. ∑ Nuclei are flattened and often lie in the centre. ∑ Cells are compactly arranged. ∑ Free surface of the cells may be smooth or have cilia or microvilli.

Location ∑ These mainly line Bowman’s capsules of nephrons, bronchioles, alveoli, blood vessels, lymph vessels, heart, coelomic cavities, tongue and skin. ∑ Simple squamous epithelium is found in peritoneum which is a secretory membrane that secretes a watery lubricant on the abdominal organs as they rub together. ∑ Stratified squamous epithelium is found in the skin and the mouth. In the mouth, it is part of a mucous membrane lubricated by a thick, more sticky mucus. ∑ Mucus is secreted into the mouth by the exocrine (ducted) salivary glands. ∑ Cornified or keratinized stratified squamous epithelium is found in the outermost layer of the skin. The cornified layer is composed of many dead, scaly cells.

Functions ∑ ∑ ∑ ∑ ∑

Protects the underlying parts from injury. Gives protection from germs and chemicals. Prevents underlying tissues from drying. Epithelia also form selectively permeable surface to allow filteration. Stratified keratinized squamous epithelium with flattened cells of superficial layer contains fibrous protein, the keratin and gives high resistant to mechanical injury.

ELEMENTARY TISSUES OF HUMAN BODY 143 Cuboidal Epithelium Cube like cells

Plasma membrane Nucleus Cytoplasm Basement membrane

Fig. 4.2

Cuboidal epithelium

Characteristics ∑ ∑ ∑ ∑ ∑ ∑

Cells are box-like with a round nucleus. They look like cubes. These are square in section. Their free surface appear to be hexagonal. Epithelia may be aliated, pigmented, germinal or brush bordered. These may form microvilli. Nucleus of each cell is rounded and centric.

Location ∑ Mostly it is found as a simple layer, i.e., thyroid follicles, bile and kidney ducts. In the sweat gland ducts are lined with two-layers and are therefore stratified. ∑ They also line small pancreatic and salivary ducts, parts of internal ear, proximal parts of the nephrons, ovaries and seminiferous tubules of testis.

Functions ∑ These mainly help in absorption, excretion and secretion. ∑ These also provide mechanical support. ∑ This tissue helps in movement of nephric filtrate, absorption of light, forming gametes and reabsorption of useful materials from nephric filtrate into blood.

Columnar Epithelium

Cytoplasm Plasma membrane Nucleus Columnar cell Basement membrane

Fig. 4.3

Columnar epithelium

144 HUMAN ANATOMY AND PHYSIOLOGY Characteristics ∑ ∑ ∑ ∑ ∑ ∑

Cells are shaped like columns and look like pillars. Cell are taller than broad. Nucleus lies towards base. Free ends may have microvilli or cells. In a surface view they appear to be polygonal. Nucleus is generally oval.

Location ∑ Simple columnar epithelium lines the digestive tract from the stomach to the rectum. In the small intestine food absorption occurs through this layer. ∑ Ciliated columnar epithelium is found in the oviducts or fallopian tubes. ∑ A more complex pseudo stratified columnar is found in the trachea, bronchioles and bronchi. ∑ In a pre cancerous stage of lung cancer, this ciliated layer is replaced with a stratified squamous layer in the bronchioles. ∑ Stratified columnar is found in the parts of the urethra that empties the bladder. ∑ It also forms lining of gall bladder. ∑ These are also found in nasal chambers, taste buds, trachea and primary branchi.

Functions ∑ It’s main functions include absorption and secretion. ∑ Certain cells of this epithelium contains and secretes mucous and care called gobletuts ∑ These cells also occur in gastric glands, intestinal glands and in pancreas where they have secretory function. ∑ Some columnar cells are neuro sensory each having sensory hair on one side and nerve fibres on the other side.

Ciliated Epithelium Cilia Basal granules

Cytoplasm Columnar cell Nucleus Plasma membrane

Basement membrane

Fig. 4.4 Ciliated as well as columnar epithelium

ELEMENTARY TISSUES OF HUMAN BODY 145 Characteristics ∑ This epithelium consists of cells bearing cilia on free surfaces. ∑ These cilia remain in rhythmic motion and create a current to transport materials. ∑ Ciliated epithelia are either cuboidal or columnar in shape.

Location ∑ Mainly found in the sperm ducts, trachea, bronchi, kidney tubules and fallopian tubes where movement of material is required. ∑ Goblet cells mainly occur at intervals in between ciliated cells so that mucus spreads over the epithelium as a thin layer.

Functions ∑ Beating cilia moves in one direction through the ducts. ∑ These help in spreading of mucus over the membrane. ∑ These also help in traping dust particles when present in trachea and nose.

Glandular Epithelium Microvilli Mucus Cytoplasm Goblet cell Nucleus Plasma membrane Absorptive cell Basement membrane

Fig. 4.5

Glandular epithelium.

Characteristics ∑ ∑ ∑ ∑ ∑ ∑

Glands can be single epithelial cells, such as the goblet cells that line the intestine. Multicellular glands include the endocrine glands. Vertebrates have keratin in their skin cells to reduce water loss. Many other animals secrete mucus or other materials from their skin. Glands thus may be unicellular or multicellular Multicellular may be simple tubular, simpled coiled tubular, alveolar, compound tubular etc.

146 HUMAN ANATOMY AND PHYSIOLOGY

Simple tubular

Simple coiled tubular

Simple alveolar

Fig. 4.6

Compound tubular

Compound alveolar

Compound tubuloalveolar

Types of glands

Location ∑ Mainlly found in mucosa of stomach and intestine. ∑ These are also found in trachea and nasal chambers.

Functions ∑ Secrete mucus ∑ These form either exocrine, endocrine or heterocrine glands.

Pseudostratified Epithelium Mucus

Goblet cell

Kinocilia

Long cell Nucleus Cytoplasm Short cell Basement membrane

Fig. 4.7

Pseudostratified epithelium—Columnar and ciliated columnar

Characteristics ∑ Epithelium is made of single layer but appears to be two layered, as cells present in the layer are of different sizes. ∑ Pseudostratified epithelium may be without cilia (parotid glands, salivary glands and urethra of the human male) or it may be ciliated as in trachea and branchi.

4.3

MUSCLE TISSUES ∑ Muscle tissue is composed of cells that have the special ability to shorten or contract in order to produce movement of the body parts. ∑ The tissue is highly cellular and is well suppled with blood vessels.

ELEMENTARY TISSUES OF HUMAN BODY 147 ∑ The cells are long and slender so they are sometimes called muscle fibers, and these are usually arranged in bundles or layers that are surrounded by connective tissue. ∑ Actin and myosin are contractile proteins in muscle tissue. ∑ Muscle tissue facilitates movement of the animal by contraction of individual muscle cells (referred to as muscle fibres). ∑ Muscle tissue can be categorized into skeletal muscle tissue, smooth muscle tissue, and cardiac muscle tissue. ∑ Muscle cell moves tissues including bones by contracting or shortening. ∑ Cells of the musclers are held together by areolar tissue. ∑ Cytoplasm of the muscles is called sarcoplasm in which less number of parallel proteinaceous threads called myofibrils. ∑ Endoplasmic reticulum of muscle cells is known as sarcoplasmic reticulum. ∑ Muscle fibre may bound by a specialised member one called sarcolemma. ∑ There are three types. – skeletal/striated/striped/voluntary muscles – visceral/smooth/unstriated/involuntary muscles – cardiac muscles.

Skeletal Muscle Tissue Sarcolemma

Sarcoplasm Nucleus Dark bands Myofibrils

Fig. 4.8

Structure of striated muscle tissue.

Characteristics ∑ In striated Skeletal Muscle stripes or striations are composed of the contractile proteins — actin and myosin. ∑ Cells are multi-nucleated with the nuclei at the edges of the rod-like cells. ∑ They contract with a great deal of force in moving bones as levers but, compared to the other types, fatigue easily. ∑ Each fibre is elongated, bound by sarcolemma. ∑ Skeletal muscle fibers are cylindrical, multinucleated, striated, and under voluntary control. ∑ Muscle fibers are multinucleated, with the nuclei located just under the plasma membrane. ∑ Most of the cells are occupied by striated, thread-like myofibrils.

148 HUMAN ANATOMY AND PHYSIOLOGY ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

Within each myofibril there are dense Z lines. A sarcomere (or muscle functional unit) extends from Z line to Z line. Each sarcomere has thick and thin filament. The thick filaments are made of myosin and occupy the center of each sarcomere. Thin filaments are made of actin and anchor to the Z line. Skeletal (striated) muscle fibers, have alternating bands perpendicular to the long axis of the cell. These cells function in conjuntion with the skeletal system for voluntary muscle movements. Dark bands are called A-bands or aniso tropic bands. Each A-band has its light zone called H-zone or Henson’s line. Light bands are called I-bands or isotropic bands which have in its centre dark line called Z-line or Z-disc line or krause’s membrane or Dobie’s line. The place of between two Z-lines is called sarcomere. Each sarcomere consists of two types of longitudanal myofilaments namely primary and Secondary. Primary myofibril is thicker and lies only in A-band. These are made of myosin and bear minute projections called cross bridges. These are free at both ends. Secondary filaments are thinner and present in I-bands. These also extend to some distance into A-band between primary filaments. Secondary myofilaments are made of protein actin, tropomyosin and trophin. These filament are attached to Z-line by one end and free on other end. This partial overlapping of primary and secondary myofilements give dark appearance to A-band. Z-membrane

A - band

H

A-band I-band

Sarcomere

H

Fig. 4.9

Z-membrane

Secondary filaments

Primary filaments

Structure of striated muscle (Detailed)

Location ∑ These are found in the body wall, limbs, tongue, pharynx and oesophagus. ∑ It constitutes about eighty per cent of the soft tissues.

ELEMENTARY TISSUES OF HUMAN BODY 149 Functions ∑ These muscles are responsible for voluntary movement of various body parts. ∑ It also helps in locomotion.

Smooth Muscle Tissue Myofibrils Nucleus Tapering end

Sarcolemma Sarcoplasm

Fig. 4.10

Smooth muscle tissue.

Characteristics ∑ Smooth muscles do not have striations and thus also called smooth, plain, nonstriated or unstriped muscles. ∑ These cells are shaped like spindle rollers, round in the center and pointed at the ends. ∑ Smooth muscle fibres lack the banding, although actin and myosin still occur. ∑ Cells are spindle shaped, have a single, centrally located nucleus, and lack striations. ∑ Smooth muscles are also called involuntary muscles. ∑ In the cytoplasm myofibrils are arranged longitudanaly. ∑ There is no sarcolemma but fibre is enclosed by plasma membrane. ∑ Smooth muscles are of two types—single unit smooth muscles and multi unit smooth muscles. ∑ In single unit one, fibres are joined together by cytoplasmic bridges and contract simultaneously as a single unit e.g., in walls of gastro intestinal. ∑ In multi unit fibres are not so closely joint and contract as independent unit e.g., dermis of skin.

Location ∑ These muscles are found in following internal organs like alimentary canal, respiratory tracts, urino genital ducts, urinary bladder, gall bladder, bile duct, blood vessels and ciliary body of eyes, skin dermis etc. ∑ Smooth muscles of dermis of skin are called arrector pilli muscles which help in erection of hair. ∑ They are found around the gut where they produce the food moving, squeezing motion of peristalsis.

Functions ∑ These cells function in involuntary movements and /or autonomic responses (such as breathing, secretion, ejaculation, birth etc. ∑ These help in peristalsis.

150 HUMAN ANATOMY AND PHYSIOLOGY Cardiac Muscle Tissue Sarcoplasm Intercalated disc Intercalated disc (tight junction) Nucleus

Branched Fibres

Muscle fiber Magnified view Z-line Nucleus Sarcolemma

Myofibrils Sarcolemma

Intercalated Gap junction disc

(a) Light microscopic appearance

Fig. 4.11

(b) Detailed structure

Cardiac muscle tissue

Characteristics ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

Cardiac muscle is found in the heart. It is striated but the rod-like cells are shorter and have round, centrally located nuclei. Weaving with each other, they join at intercalated discs. Cardiac muscle will not enter into a state of constant contraction (tetanus) as does skeletal muscle and it is resistant to fatigue. Cardiac muscle has branching fibers, one nucleus per cell, striations, and intercalated discs. Its contraction is not under voluntary control. These muscles lack sarcolemma. Cardiac muscles have characteristics of both striped and unstriped muscles. Like striped muscles these possess fibres, nucleus and sarcomeres but like unstriped these possess intercelated discs. Connective tissue fills the space between the network which is highly vascular.

Location ∑ Wall of the heart is made of cardiac muscles and is called myocardium.

Functions ∑ Cardiac muscles contract rhythmically and thus heart beats.

ELEMENTARY TISSUES OF HUMAN BODY 151 4.4

CONNECTIVE TISSUES ∑ The cells of connective tissue are embedded in a great amount of extracellular material. This matrix is secreted by the cells. It consists of protein fibers embedded in an amorphous mixture of proteinpolysaccharide (“proteoglyan”) molecules. ∑ It binds together and supports many tissues. It has three basic materials: 1. Ground substance is a secreted material outside and mainly consists of glyconsaminoglycans and structural glycoproteins. 2. Connective tissue cells. Fibroblasts, Adipose cells, plasma cells, mast cells, marophages, lymphocytes. 3. Fibers. Collagen, elastic and reticular fibres ∑ Connective tissues can be classified into three main categories: Connective tissue

Connective tissue proper

Areolar

4.5

Adipose

Vascular

Skeletal

Dense

Bone

Cartilase

Blood

Lymph

CONNECTIVE TISSUE PROPER

Connective tissue proper can be further classified into the following: ∑ Areolar connective tissue ∑ Adepose connective tissue ∑ Dense Connective tissue

Areolar Connective Tissue Characteristics ∑ Areolar tissue is a loose connective tissue which forms a protective covering around various organs. ∑ It also fills empty spaces. ∑ Matrix or ground material is present in plenty. ∑ It is highly vascular and innervated by nerves and fibres. ∑ Areolar tissues consists of three kinds of fibres namely collages, elastic and reticular. (a) Collagen fibres (white fibres) are made of collagen protein. These are in nospace elastic and unbranched. Collagen protein changes to gelatin when boiled. Collagen proteins form one third of the total proteins of human body. They occur as bundles called fascia. These are colorless and hyaline. (b) Elastic fibres (yellow fibres) are light yellow fibres made of protein elastin which is most resistant of all the body proteins to chemical changes. These fibres are elastic, branched and occur singly and are resistant to boiling.

152 HUMAN ANATOMY AND PHYSIOLOGY (c) Recticular fibres are made of protein reticulin these are small branched, in elastic and delicate fibres. They always form network. These are found in embryo, young born individuals and in newly formed interstitial fluid present in the wound. Chemically reticulum is also a type of collagen. ∑ Matrix contains six types cells in it besides above discussed fibres. These are: (i) Fibroblasts are spindle shaped cells and largest of other cells. These are delicate and their nucleus is either round or oval in shape. These cells form fibres and matrix when young and active they are called fibroblasts while the old and inactive ones are called fibrocytes. They form all the three kinds of proteins required for formation of fibres, secrete mucopoly sacchharides and proteins to form matrix. Vitamin C deficiency leads to disturbance in the activity of these cells. (ii) Adipose cells are spherical cells which store fat. These are also called adipocytes or lipocytes. These occur in areolar tissue around blood vessels. (iii) Plasma cells are small, rounded or amoeboid cells whose nucleus is placed on one side. They produce antibodies. These are also known as plasmolytes. They survive for 2 – 3 days. (iv) Mast cells are round, oval or polygonal cells with granular cytoplasm. These secrete histamine, heparin and serotonin. Histamine is vasodilator and thus helps in dilating blood capillaries in inflammatory and allergic reactions. Heparin is an anticoagulant and prevents blood clotting in the blood vessels itself. Serotonin is a vaso constrictor and thus assists bleeding by contracting blood capillaries. (v) Macrophages are large amoeboid cells which feed on microorganisms by phagacytosis and thus named. These are also called histocytes or clasmatocytes. These cells may either be fixed or wandering. Fixed ones bear thread like processes—filopodia which are similar to fibroblasts. Thus these can be called as stellate cells. Many macrophages unite to form largy giant cell to engulf large particles. Macrophages of lungs are called dust cells while those of sinusoids of liver, moroglis of brain and spinal cord are called kupffer’s cells. (vi) Lymphocytes are smallest and most numerous, small, spherical or ovoid cells. They can actively move with the help of pseudopodia. These help in synthesis and transportation of antibodies. Fibrocyte

Elastin Fibre

Lymphocytes Bundle of white fibres (Collagen Fibres)

Mast Cell Reticulin fibres

Blood Vessel

Plasma Cell

Fig. 4.12

Macrophage

Areolar connective tissue

ELEMENTARY TISSUES OF HUMAN BODY 153 Location ∑ It is found between the skin and epithelia, nerves, blood vessels, respiratory tracts, mesenteries. ∑ It is found between muscles and the skin.

Functions ∑ ∑ ∑ ∑ ∑

It binds different organs together. It helps in combating foreign materials. It helps in rapid diffusion of materials. It helps in sliding movements of epithelia. It facilitates migration of required cells at the site of infection and injury.

Adipose Connective Tissue Adipose cell

Ground tissue Collagen fibers Fat drops

Connective Tissue cells Cytoplasm

Fig. 4.13 Adipose tissue

Characteristics ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

This tissue contains large numbers of adipocytes or lipocytes. Adipose tissue has enlarged fibroblasts storing fats and reduced intracellular matrix. Yellow fat cells have a very large fat vacuole and a very small amount of cytoplasm. Brown fat is rare as a tissue. It has lots of blood vessels and the cells are filled with mitochondria. Brown fat is thought to regulate fat metabolism About 10–15 percent of body weight in humans is because of this. White fat contains only single large fat globule while brown ones are multilocular and possess brown pigment.

154 HUMAN ANATOMY AND PHYSIOLOGY Location ∑ It is found as yellow or white fat in the hollow portions (diaphyseal marrow cavity) of bones, around the heart, and in the lowest layer of the skin.

Functions ∑ ∑ ∑ ∑

It acts as a fat depot. Adipose tissue facilitates energy storage and insulation. It also acts as shock absorber. It protects delicate organs of body.

Dense Fibrous Connective Tissue Collagen fibres

Row of fibroblasta

Fig. 4.14 Dense regular connective tissue

Characteristics ∑ ∑ ∑ ∑ ∑ ∑

Fibrous connective tissue has many fibers of collagen losely packed together. FCT occurs in tendons, which connect muscle to bone. Ligaments are also composed of FCT and connect bone to bone at a joint. Due to large amount of fibres these are highly tensile. Fibres are of two types-white fibrous connective tissue and yellow fibrous connective tissue. White one is made of collagen fibres with fibroblasts passing between them. It is large though and in elastic and forms tendons. ∑ Yellow tissue is formed of yellow elastic fibres and is highly elastic and forms ligaments.

Location ∑ Walls of trachea and arteries. ∑ Found in tendons and ligaments where the collagen fibers are parallel. ∑ Ligaments join phalanges and toes.

ELEMENTARY TISSUES OF HUMAN BODY 155 ∑ True vocal cords. ∑ Capsule of spleen.

Functions ∑ It joins muscles with bones (tendons). ∑ It joins bones with bones (ligaments).

4.6

SKELETAL CONNECTIVE TISSUE

Perichondrium Chondroblasts in lacunae

Chondroblasts

Dividing cells

Matrix Lacuna

Matrix White fibres

Lacuna

(a)

(b) Chondroblasts in lacunae Yellow fibres Lacuna Nucleus of chondroblast Chondroblast amidst division Matrix (c)

Fig. 4.15

Cartilage: (a) Hyaline (b) White fibrous (c) Elastic

Cartilage Characteristics ∑ ∑ ∑ ∑ ∑

Cartilage has structural protein deposites in the matrix between cells. Cartilage is softer of the two “rigid” connective tissues. Cartilage is made up of cells namely chondrocytes and matrix called chondrin. Chondrin contains a sort of network of collagen fibres. Matrix is formed of chondromucoproteins which is like material made up of chondroitin sulphate and hyaluronic acid. ∑ Chondrocytes are present in spaces called lacunae.

156 HUMAN ANATOMY AND PHYSIOLOGY ∑ Inside the lacunae there is one chondrocyte present which may divide mitotically and add the number to about two or three. ∑ Mature cartilage is surrounded by a connective tissue called perichondrium, central (conter fibrous layer and inner layer of fibroblasts). ∑ Chondroblasts secrete chondrin and are thus called chondrocytes. ∑ There are no blood vessels and nerves in the cartilage. ∑ Because of lack of blood supply, injured cartilage takes long time to heal up. ∑ Exchange of materials between chondrocytes and blood vessels occurs in the blood vessels of perichondrium. ∑ Cartilage forms the embryonic skeleton of vertebrates and the adult skeleton of sharks and rays. ∑ It also occurs in the human body in the ears, tip of the nose, and at joints such as the knee and between bones of the spinal column.

Types Cartilage is of three types, such as: 1. Hyaline Cartilage: a clear, white cartilage composed of some what brittle protein ground substance secreted by chondrocytes into collagen fibers. Its matrix is homogenous. It is found in the nose and on the ends of long bones where they come together and make joints. It is mainly found in foetus and is later replaced by bones in the adult. Hyaline cartilage persists in the adult as artiular cartilage like thin pads between joints of long bones, rings of trachea, bronchi, hyoid, larynx etc. It with stands pressure, tension and torsion at joints. 2. Elastic Cartilage: has large number of elastic fibers. Found in the ears and the epiglottis. It has abundant branched elastic fibres. It is yellow and elastic. Perichondrium is absent. It is found in ear pinnel, epiglottis, nose tip etc. 3. Fibro Cartilage: filled with collagen fibres and a small amount of cartilage ground substance. In the vertebral disc, it makes a tire-like circle around the highly vascularized, gelatin-like central pulp. Also it is found in the pubic symphysis which joins the pelvic bones anteriorly. Perichondrium is absent, ground substance is in plenty. It is dense and firm.

Bone

Periosteum concentric lamella Haversian canal Lamellae Lacuna Canaliculi

Osteocyte in lacuna Cytoplasm

Lacuna Canaliculi

Interstitial lamellae

Nucleus Processes of osteocytes (a)

Fig. 4.16

Marrow cavity (b)

Concentric lamellae

(a) Two osteocytes and their processes (b) T.S. mammalian bone

ELEMENTARY TISSUES OF HUMAN BODY 157 Characteristics ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑



Bones are hard due to calcification. Bone has calcium salts in the matrix, giving it greater rigidity and strength. Bone also serves as a reservoir (or sink) for calcium. Protein fibers provide elasticity while minerals provide elasticity. Two types of bone occur. Dense bone has osteocytes (bone cells) located in lacunae connected by canaliculi. Lacunae are commonly referred to as Haversian canals. Spongy bone occurs at the ends of bones and has bony bars and plates separated by irregular spaces. The solid portions of spongy bone pick up stress. Outer most layer of the bones is called periosteum which is thick and tough. Periosteum consists of outer layer of dense fibrous tissue with fibroblasts and inner layer of osteoblasts. Fibrous layer consists of blood vessels and nerve fibres. Matrix of the bone is hard and made of a protein called ossein. Ratio of organic and inorganic matter is 7 : 3. With age inorganic matter increases making the bone more fragile which can get fractured easily. Matrix consists of calcium phosphate, caclcium carbonate salts (hydroxy apatite = Ca10 (P04)6 (OH)2], traces of calcium hydride and magnesium chloride. Matrix is present in layers called lamellae which are arranged in concentric rings around narrow longitudinal cavities called Haversian canals. Lamella contains numbers of bone cells called osteocytes which bear delicate branching processes forming a sort of network between cells. Each osteocyte lies in a lacunae which leads into fine channels, canaliculi. Branched canaliculi extends into the matrix in which branched process of osteocytes are present. Branched canalicule interconnects lacunae with each other. Ground substance is made of sulphide mucopolysacharide or glycosaminoglycans or glycoproteins. Haversian canals are interconncted by transverse channels called volkman’s canals. Inner layers of osteoblasts lies between matrix and osteum. This layer is well arranged with the help of which bone grows inwards. Endosteum is a fibrous layer which is like the lining of bone marrow cavity. It adds to thickness of bone from two sides. Bone marrow is cavity lying inside the endosteum in long bones like humerus, femur. It is filled with soft semisolid neuro vascular tissue called bone marrow which may be red or yellow. Redish one is active vascular reticular in nature while yellow is inactive vascular tissue containing fat cells. Former produces blood cells while later produces blood cells only during emergency. Bone may be—compact/periosteal or spongy/bone anellous compact bone has regularly arranged lamellae, haversian system without gap found is shafty long bone, cavity contains yellow bone marrow.

158 HUMAN ANATOMY AND PHYSIOLOGY ∑ Spongy bone has lamellae called trabacular that forms intereplacing network with small spaces which contain red bone marrow. There is no Haversian system: Expanded ends of long bones vertebra, ribs, skull bones are made of spongy bones.

4.7

FLUID CONNECTIVE TISSUE

Blood Various components of blood are: 1. 2. 3. 4.

Plasma Erythrocytes/RBCs/red blood corpuscles/red blood cells. Leucocytes/WBCs/white blood corpuscles/white blood cells. Thrombocytes/Platelets.

1. Plasma It is pale yellowish, slightly alkaline fluid in which the blood corpuscles float. It has the following composition: Water : 90% Proteins : 7–8% Inorganic salts : 1% (Mainly NaCl, NaHCO3) Other substances : As traces (Glucose, hormones, amino acids, waste products, etc.) Plasma also ontains plasma proteins, which are part of the blood itself, that is , they are not being carried to the tissues for their metabolism. They are made in the liver and enter the plasma. These three proteins are: albumin, globulin and fibrinogen. Albumin contributes 70-80% of the osmotic pressure of plasma proteins. It also helps in the transport of several substances like free fatty acids, bilirubin, Ca2+ and steroid hormones. Globulins are the antibodies formed in the defence of the body agianst foreign germs. Fibrinogen has importance in the coagulation of blood. If concentration of albumin and globulins falls, it can lead to filteration of water from the blood into the tissues. This produces oedema or retention of water mainly in hands and feet. Plasma from which the protien fibrinogen has been removed is called serum. Plasma = serum + fibrinogen Or Serum = plasma – fibrinogen

2. Erythrocytes These are the most numerous cells in the blood and contain a substance called haemoglobin, which gives them red colour. They are bi-concave (flat in the center, and thick at the periphery), non-nucleated discs. They are very small, having a diameter of about 7.5 micrometeres or 1/3200 inch. There are about five to six million red blood corpuscles per millilitre of normal blood. Erythrocytes are formed in the red marrow of the bones. The process of the production of erythrocytes is known as

ELEMENTARY TISSUES OF HUMAN BODY 159 erythropoiesis. Decrease number of red blood cells is known as erythrocytopenia and increase in number of RBC’s much more than normal is called polycythemia. Life span of erythrocyte is 120 days.

3. Leucocytes These are colourless cells containing cuclei and are a little larger in size than the red cells i.e., 10 micrometres or 1/2,500 inch but their number is much less than RBCs (1 WBC to 500 RBC). The total number of white blood corpuscles is 5,000 to 10,000 per millilitre. Formation of leucocytes is known as leuopoiesis. It takes place in lymphnodes, bone marrow, spleen and thymus. Life span of leucocytes is 3–4 days. An increase in this normal number is called leucocytosis and decrease in the normal number is a leucopenia. Leucocytes are of mainly two main kinds: Granular and Agranular. Leucocytes

Granulocytes Neutrophils

Agranulocytes

Eosinophils

Basophils

Lymphocytes

Monocytes

Granulocytes. These make up about 70% of white blood cells and are recognized by the granules in their cytoplasm and by their nuclei. They are mainly of three types: (a) Neutrophils. They are the most numerous, making up 60% of the total white cell count. Their cytoplasm contains very fine granules and stain with neutral dyes. The nucleus may have three to five lobes; the older the cell, the more lobes its nucleus has. Horse shoe shaped nucleus Sideview

Cytoplasm

Surface view

Platelets (non-nucleated)

Nucleus with dent lymphocyte

Erythrocyte (denucleated)

Two lobed nucleus

3–5 lobed nucleus

Monocyte Indistinctly lobed nucleus

Cytoplasm Neutrophil

Eosinophil

Fig. 4.17

Cytoplasm

Basophil

Blood cells

(b) Eosinophils. They make up 3% of total WBC count. Cytoplasmic grains stain bright red with eosin which is an acidic dye. Nucleus mainly has two lobes. (c) Basophils. They form less than 1% of the total WBCs. Their cytoplasmic granules stain with the basic dye. i.e., methylene blue. Basophils contain heparin. Nucleus is large and indistictly lobed.

160 HUMAN ANATOMY AND PHYSIOLOGY Agranulocytes. Their cytoplasm does not contain granules and there presents a single large nucleus. They are of two types: (a) Lymphocytes. They form about 30% of the total WBC count and are the smallest of all WBCs but a little larger than RBCs. They have a large spherical nucleus with a slight depression on one side. (b) Monocytes. They form about 6% of the total WBC count. They are largest of all the white blood corpuscles and have a large kidney or horseshoe shaped nucleus.

4. Thrombocytes These are minute oval nucleated structures floating in blood normally numbering from 150 to 400 ¥ 109/litre. They are formed by giant cells present in bone marrow. They are smaller than RBC’s. Formation of thrombocytes is known as thrombopoiesis. Decrease in number of thrombocytes is known as thrombocytopenia and their increase is known as thrombocytosis. Life span of blood platelets is 3–7 days.

Functions of Blood Plasma 1. Transport of materials. It helps to transport digested food, excretory products, hormones etc., to various body organs. 2. Antibodies. Antibodies are globulins which are important in the defence of the body against foreign proteins and bacteria. 3. Coagulation of blood. Fibrinogen is important in the coagulation of blood. 4. Buffering action. The plasma proteins together with inorganic salts form buffere, which keep the plasma pH constant. 5. Exertion of osmotic pressure. The molecules of albumin and globulin in the plasma exert an osmotic pressure because they are too large to pass through the walls of the capilaries and thus no protein is left in the normal tissue fluid. The molecules of the inorganic salts pass freely through the capillary walls so that their concentration in the plasma and in the tissue fluid remains the same; they, therefore, set up no osmotic pressure. 6. It helps in keeping the body temperature constant.

Erythrocytes 7. They have a respiratory pigment known as haemoglobin which has the ability to combine readily with oxygen to form oxyhaemoglobin, an unstable compound which can readily break into oxygen and haemoglobin.

Leucocytes 8. Lymphocytes, a type of leucocyte plays the main part in the cellular immune response. Their number increases in chronic infections. 9. Leucocytes show slow amoeboid movements especially neutrophil cells. This movement is known as diapedesis. They engulf the foreign particles e.g., bacteria. Neutrophils are therefore an important part of the body’s defence agaisnt acute infections.

ELEMENTARY TISSUES OF HUMAN BODY 161 10. At the time of injury WBCs migrate through the walls of the blood vessels and fight against germs. Pus consists of a tissue fluid containing harmful bacteria, very large number of dead neutrophils and tissue cells are destroyed by bacteria.

Thrombocytes Platelets are necessary for coagulation of the blood. Blood Clotting: Since humans are liable to injury and the shedding of blood, a mechanism is provided within the body whereby there is a spontaneous tendency for the loss of blood to be limited. Within a few minutes of leaving the blood vessels, normal blood sets into a clot. Soon the clot shrinks, becomes firmer and squeezes out serum. The essential change in the coagulation of blood is the conversion of the protein fibrinogen into a substane fibrin which forms fine threads which entangle the blood cells and then contract to form clot. Blood clotting involves various steps: (a) Thrombocytes and the injured tissues cells release a substance known as thromboplastin at the site of injury. (b) Thromboplastin leads to the conversion of prothrombin into thrombin which is a plasma globulin made in the liver in the presence of vitamin K. Prothrombin is converted to thrombin only in the presence of calcium ions and thromboplastin. (c) Action of thrombin on fibrinogen converts it to fibrin. (d) Fibrin traps red and white cells and platelets in its meshes, forming a clot from which serum is expressed by contraction of the fibrin threads. Damaged tissues Prothrombin

+ Ca

2+

+ Thromboplastin

Blood Platelets Plasma

Thrombin

+

Fibrinogen

Fibrin

Chemicals which prevent clotting of blood are known as anticoagulants e.g., heparin prevents clotting of blood in the blood vessels. Hirudin is another anticoagulant which is found in the salivary glands of leeches.

Lymph It is the fluid contained within the lymph vessels. It is very much like plasma, pale yellow and clear, unless it contains fatty acids and glycerol following the absorption of fats from the intestine. Like plasma, it is mostly water with dissolved proteins, inorganic salts, food materials and waste produts. It contains a varying number of WBCs mostly lymphocytes.

Lymphatic Vessels The lymphatic vessels form a second pathway for fluid returning from the tissues to the heart. In many tissues especially under epithelial surfaces, there is a network of lymphatic capillaries, which are very much like blood capillaries. These unite to form lymphatic vessels which are like very small

162 HUMAN ANATOMY AND PHYSIOLOGY veins in structure. Under the action of the muscle pump and the intra-abdominal pressure, the lymph flows along the vessels. They unite to form larger vessels which conver upon the thoracic duct. The negative intrapleural pressure associated with respiration assists the lymph flow upwards through the thorax in the thoracic duct to the root of the neck, where it and other regional lymph trunks open into the great veins. In this way all the lymph is added to the blood. Before the lymph reaches the blood, however, it always passes through at least one lymph node, where it is filtered and any foreign particles and bacteria are removed.

Lymphatic Tissues Lymphatic tissue performs two functions: (a) It produces cells, like lymphocytes, monocytes and plasma cells. (b) It acts as a filter for (i) tissue fluid (ii) lymph and, (iii) blood. The tissues of the body are permeated by a vast network of capillaries containing blood. The walls of the capillaries consist of a single layer of cells and, WBCs are able to make their way through these walls. The tissues are bathed in tissue fluid which may be regarded as an intermeditary between the blood and the tissue; all interchange of nourishment and waste products between them takes place through the midium of tissue fluid. The lymphatic system is a subsidiary circulatory system which drains the tissue fluid. From the tissue spaces, the tissue fluid passes into lymph capillaries which unite to form larger trunks which then open into a pair of veins (right and left subclavian veins) entering the right auricle. Lymph is the name given to the tissue fluid when enters the lymphatic vessels.

Lymph Nodes They are situated in the course of the lymph vessles and generally occur in groups and are oval or kidney shaped. They are rich with phagocytes and lymphocytes. They thus act as filters for the microorganisms. Lymphatic system runs parallel to the veins and lymph flow is unidirectional i.e., from tissues to the heart.

Functions of Lymph 1. Fats from the intestine are absorbed into the lacteals present in the intestinal villi and thus lymph carries it towards blood vessles. 2. Lymph drains away excessive tissue fluid and returns various metabolic substances like proteins to the blood. 3. Lymphocytes and monocytes of the lymph perform most important function to defend the body. 4. Lymph provides nutrition and oxygen to various parts of the body where blood cannot reach. 5. Tonsils are lymphatic tissues which protect from infections. 6. Lymph nodes localise the infection and prevent it from spreading to other body parts.

ELEMENTARY TISSUES OF HUMAN BODY 163 Differences between Blood and Lymph Blood 1. It is a red fluid. 2. It consists of plasma, erythrocytes, leucocytes and thrombocytes. 3. It has haemoglobin. 4. It transports materials from one organ to another. 5. It is contained in arteries and veins. 6. It’s flow is fast. 7. It contains proteins. 8. It flows from the heart into the blood vessels and again comes back to the heart.

4.8

Lymph 1. It is a colourless fluid. 2. It consists of plasma and leucocytes. 3. It lacks haemoglobin. 4. It transports materials from tissue fluid to blood. 5. It is contained in lymph vessels. 6. It’s flow is slow. 7. It contains less proteins. 8. It starts from the tissue spaces, enters the lymph vessels and finally joins blood in heart.

NERVOUS TISSUES

Characteristics ∑ The neuron is the functional unit of the nervous system. ∑ Human beings have about 100 billion neurons in their brain alone! ∑ Nervous tissue is composed of two main types of cells: neurons and glial cells. Neurons are specialized for the conduction of nerve impulses. ∑ A typical neuron consists of the following: 1. A cell body which contains the nucleus 2. A number of short fibers—dendrites—extending from the cell body 3. A single long fibre, the axon. ∑ Dendrites receive information from cell to cell and transmit the message to the cell body. ∑ The cell body contains the nucleus, mitochondria and other organelles typical of eukaryotic cells. ∑ The axon conducts messages away from the cell body. ∑ Nervous tissue is found in the brain, spinal cord, and nerves. ∑ It is responsible for coordinating and controlling many body activities. ∑ It stimulates muscle contraction, creates an awareness of the environment, and plays a major role in emotions, memory, and reasoning. ∑ To do all these things, cells in nervous tissue need to be able to communicate with each other by way of electrical nerve impulses. ∑ Nervous tissue also includes cells that do not transmit implulses, but instead support the activities of the neurons. ∑ These are the glial cells (neuroglial cells), together termed the neuroglia. ∑ Supporting, glia, cells bind neurons together and insulate the neurons. ∑ Some are phagocytic and protect against bacterial invasion, while others provide nutrients by binding blood vessels to the neurons. ∑ Glial cells surround neurons. Once thought to be simply support for neurons, they turn out to serve several important functions.

164 HUMAN ANATOMY AND PHYSIOLOGY ∑ These are of three types: 1. Schwann cells. These produce the myelin sheath that surrounds many axons in the peripharal nervous system. 2. Oligodendrocytes. These produce the myelin sheath that surrounds many axons in the central nervous system (brain and spinal cord). 3. Astrocytes. These often star-shaped cells are clustered around synapses and the nodes of ranvier where they perform a variety of functions: – Stimulating the formation of new synapses; – Modulating the activity of neurons; – Repairing damage; – Supplying neurons with materials secured from the blood. (It is primarily the metabolic activity of astrocytes that is being measured in brain imaging by positron-emission tomography (PET) and functional magnetic resonance imaging (fMRI). ∑ In addition, the central nervous system contains many microglia—mobile cells that respond to damage (e.g., from an infection) by – engulfing cell debris – secreting inflammatory cytokines like tumor necrosis factor (TNF-μ) and interleukin-1 (IL-1) ∑ Neurotransmittors help in transmiting messages from one nerve cell to another across synapse. For example, acetylecholine.

Structure of Neurons Each nerve cell consists of two parts: 1. Cell body or Cyton 2. Axon Cytons of neurons vary in size from small to large, their shape varies from round, or oval to pyramidal. In the centre there is present a nucleus which is usually centrally placed, large, spherical and has a prominent nucleolus. The cytoplasm of neurons contains Nissl’s granules. From the cyton, there may extend several processes known as dendrites which are helpful in conveying impulses towards the cell body. From the cyton there extends a long process known as axon. Which often branch. Axons are surrounded by myelin sheath which is fatty substance. The amount of myelin varies considerably; in fact some small fibres have less or no myelin. They are known as unmyelinated. Outside the neuron there is an additional covering known as neurilemma sheath which is made up of Schwann cells. These cells lay down the myelin around the fibres. This myelin, laid down by neurilemma cells, is notched at regular intervals. These notches are known as nodes of Ranvier. Neuron having two sheaths i.e., inner thick myelin (or medullated) sheath and outer thin neurilemma sheath are known as myelinated or meduallated, while those having only neurilemma are called as nonmyelinated or nonmedullated.

ELEMENTARY TISSUES OF HUMAN BODY 165

Dendron Nucleus

Nucleolus Dendrites

Cyton Nissl’s granules Axon Nucleus

Medullary sheath or myelin sheath Node of ranvier

Axon endings

Synapse

Fig. 4.18

Neuron.

Types of Neurons Neurons can be classified in various ways depending on their functions and branching. Functionally neurons can be classified as sensory, motor and mixed. Neurons convey impulses from sense organs to the central nervous system while motor neurons convey impluses from the central nervous system to the sense organs. Mixed ones can work both ways. Depending on nature of their branching, they are classified as: 1. Unipolar Neuron. This type of neuron consists of cytoplasmic process at one point only. There are no dendrites. Axon finally forms T-shaped Axon bulb. All types of sensations like pain, touch, temperature etc., are carried on by unipolar neurons.

166 HUMAN ANATOMY AND PHYSIOLOGY

Cyton Nucleus Axon

Axon bulb

Fig. 4.19 Unipolar neuron 2. Bipolar Neuron. In this type of neuron cyton branches at two points. On one side it has dendrites and on the other side it has a long process axon finally forming axon bulb. These neurons are mainly associated with sensory impulses like smell, sight etc. Dendrite Cyton Nucleus Axon

Axon bulb

Fig. 4.20

Bipolar neuron

3. Multipolar Neurons. In this type of neuron, cyton is branched at many points thus forming many poles. These are associated with many functions.

Dendrites Cyton Nissl’s granules Nucleus Dendron Nucleus

Axon Node of ranvier Myelin sheath or medullary sheath Axon bulb

Fig. 4.21

Multipolar neuron

ELEMENTARY TISSUES OF HUMAN BODY 167 Each neuron is a separate structure i.e., it does not have any cytoplasmic continuity with other neuron. Two neurons are connected only by passage of impulse across intervening junctions which is called synapse. The information passing through neurons is in the form of chemical and electrical signals called nerve impulse.

Functions Nervous tissue functions in the integration of stimulus and control of response to that stimulus.

4.9

MEMBRANES

Body membranes are thin sheets of tissue that cover the body, line body cavities, and cover organs within the cavities in hollow organs. They can be categorized into epithelial and connective tisssue membrane.

Epithelial Membranes Epithelial membranes consist of epithelial tissue and the connective tissue to which it is attached. The two main types of epithelial membranes are the mucous membranes and serous membranes.

Mucous Membranes Mucous membranes are epithelial membranes that consist of epithelial tissue that is attached to an underlying loose connective tissue. These membranes, sometimes called mucosae, line the body cavities that open outside. The entire digestive tract is lined with mucous membranes. Other examples include the respiratory, excretory, and reproductive tracts.

Serous Membranes Serous membranes line body cavities that do not open directly outside, and they cover the organs located in those cavities. Serous membranes are covered by a thin layer of serous fluid that is secreted by the epithelium. Serous fluid lubricates the membrane and reduces friction and abrasion when organs in the thoracic or abdominopelvic cavity move against each other or the cavity wall. Serous membranes have special names given according to their location. For example, the serous membrane that lines the thoracic cavity and covers the lungs is called pleura.

Connective Tissue Membranes Connective tissue membranes contain only connective tissue. Synovial membranes and meninges belong to this category.

Synovial Membranes Synovial membranes are connective tissue membranes that line the cavities of the freely movable joints such as the shoulder, elbow, and knee. Like serous membranes, they line cavities that do not open outside. Unlike serous membranes, they do not have a layer of epithelium. Synovial membranes

168 HUMAN ANATOMY AND PHYSIOLOGY secrete synovial fluid into the joint cavity, and this lubricates the cartilage on the ends of the bones so that they can move freely and without friction.

Meninges The connective tissue covering on the brain and spinal cord, within the dorsal cavity, are called meninges. They provide protection for these vital structures.

Pleura (or pleural membrane) – surrounds the lungs – outer layer = parietal pleura – inner layer = visceral pleura

Pericardium (or pericardial membrane) – surrounds the heart – outer layer = parietal pericardium – inner layer = visceral pericardium

Peritoneum (or peritoneal membrane) – – – –

surrounds all the organs within the abdominopelvic cavity outer layer = parietal peritoneum inner layer = visceral peritoneum Between the layers of each membrane is a lubricating fluid which is called SEROUS FLUID

CANCER The progression of normal cells to malignant cells is characterized by changes in cell structure and activity. Precancerous changes include a change in cell structure: 1. metaplasia (change of one normal tissue type to another normal type; e.g., the bronchial epithelium of smokers lungs changes from pseudostratified ciliated columnar to stratified squamous), 2. dysplasia (cells are not cancerous, but they have abnormal structure, such as very large nuclei). 3. anaplasia (cells are dividing rapidly and change in function). When the cells lose control of mitosis, abnormally high cell division rates (hyperplasia) results in a tumor. If the cells of a tumor are abnormal in structure, the mass is called a neoplasm (new tissue).

TUMORS These are masses of cells that do not serve a normal purpose, e.g., tumors of the adrenal cortex may result in an over-secretion of the steroid hormones it produces, certain other types of tumors may decrease the secretion of an endocrine gland. A tumor may be benign or malignant. A tumor becomes malignant when the hyperplastic tissue cells invade other tissues. Tumors may be confined or nodular, or they may be diffuse, spreading gradually into normal tissues. Malignant cells secrete a growth/migration factors and metaloprotease enzymes that break down the collagen of basement membranes. When the tumor is larger, these cells secrete angiogenesis factors to vascularize (make

ELEMENTARY TISSUES OF HUMAN BODY 169 blood vessels to serve) the tumor. Then the invasive cells make their way to blood vessels, lymph vessels and other stromal (under the basement membrane) tissues; thus, spreading to other locations and on to other organs in a process called metastasis. One newly developing tumor acts to supply seed cells for satellite tumors. Generally, the satellite tumors are from the original tumor, the worse the prognosis for survival. Mutations of DNA are required for each stage (metaplasia, dysplasia or anaplasia, hyperplasia and metastasis). The current theory is that the mutations of suppressor genes cause the cells to revert to an “embryonic” state in that they lose control over mitosis and secrete the enzymes and growth factors that produce metastasis.

REVIEW QUESTIONS 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Describe various kinds of epithelial tissues found in human beings. Draw related diagrams. List various characteristics of nervous tissue. Also explain the structure and types of neuron. Write an essay on connective tissue. Explain with the help of diagrams structure of various types of muscular tissue. Explain in detail structure and functions of cartilage and bone. Distinguish between striped, unstriped and cardiac muscles. Explain — chondrocytes, osteocytes, neuron, cyton, dendrites, axon, striated muscle. What is a tissue? Explain different types of tissues seen in human beings. Classify connective tissues. Discuss characteristics and functions of each type. Explain various classes of plasma proteins and leucocytes.

CHAPTER

5

THE OSSEOUS SYSTEM Cranium

Skull

Eye orbit Maxilla Mandible

Nasal bone Cervical vertebrae

Clavicle Pectoral girdle Sternum Humerus

Ribs Vertebral column

Radius

Pelvic girdle Sacrum

Ulna

Coccyx

Carpals Matacarpals Phalanges

Femur Patella

Fibula

Tibia

Tarsals

Metatarsals Phalanges

5.1

INTRODUCTION

The human skeleton consists of 206 bones. We are actually born with more bones, about 300, but many fuse together as child grows up. These bones support our body and allows us to move. These bones support the body and provide protection for organs such as the brain, heart and lungs. The bones of the skeleton act as a frame to which muscles are attached. These skeletal muscles allow the body to move; they are attached to bones by bands of tough elastic tissues, called tendons, and it is by 11

170

THE OSSEOUS SYSTEM 171 means of tendons that they exert their pull. Another important task of bones is to produce blood cells. Finally, the bones provide a store of chemicals such as calcium salts, which are released into the bloodstream as per their need. Bone is a type of connective tissue. It consists of water, organic constituents (30), bone cells and inorganic constituents mainly calcium phosphate (70%). The maintenance of constant level of calcium and phosphorous in blood stream is regulated by parathyroid and cafitoin hormones of the parathyroid and thyroid respectively.

Functions of Skeleton System Main functions of skeletal system (bones) are as follows: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

To serve as a firm framework for the entire body. To protect such delicate structures as the brain and the spinal cord. To serve as levers, which are actuated by the muscles that are attached to them. To serve as a storehouse for calcium, which may be removed and become a part of the blood if there is not enough calcium in the diet. To produce blood cells and store important minerals. Skeleton provides spaces for the attachment of skeletal muscles. Bone marrow produces red blood cells and white blood cells. Various structures in the body are suspended through skeleton. Skeleton forms lever enabling organisms to move from one place to another and lifting weight. Bone marrow also stores fat. Ear ossicles conduct sound ware to internal ear bones help in feeding. Jaw bones help in feeding. Hyoid apparatus supports the floor of buccopharynx.

Classification of Bones On the basis of their formation, bones are of three types. Bones

Replacing – Formed by ossification directly on the cartilages – Elongated – Hard – e.g., humerus, fibula

Dermal – Membranous bones – Formed by ossification in the dermis in the skin – e.g., skull bones

Sesamoid – Formal by ossification of a tendon at the joints of the bones – Small sized – Disc like – e.g., patella

On the basis of their shapes, bones are classified as 1. The long bones in the limbs, they are thin, hollow and light. They play as essential role in all types of movements.

172 HUMAN ANATOMY AND PHYSIOLOGY 2. Flat circular bones: - e.g.,:- bones that form the spine or vertebral column. 3. Long circular bones: - e.g.,:- Ribs, they are strong but elastic giving the chest the flexibility and springiness it needs for breathing. 4. Flat irregular bones: - e.g.,:- shoulder, blades, hips and skull these are strong but light and protect delicate organs, such as the brain. 5. The short bones - e.g., carpals (wrist)

5.2

HUMAN SKELETON

Cranium

Cranium Eye or bit

Clavicle

Nasal bone Mandible

Cervical vertebra Pectoral girdle

Scapula

Sternum Ribs

Ribs Humerus

Thoracic vertebra

Radius Ulna

Lumbar vertebra

Sacrum

Pelvis

Pelvis

Carpal bones

Coccyx

Sacrum

Metacarpal bones Phalanges

Coccyx

Femur

Femur

Pateua Patella Tibia Tibia

Fibula

Fibula

Tarsal bones Metatarsal Phalanges

Tarsal bones Calcaneus

(a)

Fig. 5.1

(b)

Human skeleton (a) Anterior view (b) Lateral view

Metatarsal bones Phalanges

THE OSSEOUS SYSTEM 173 The body owes its shape and support to the skeleton a frame consisting of hundreds of joined bones. Head: The bones of the skull surround and protect the brain; the lower jaw is hinged to the skull. Chest: The bony age of the ribs, connected to the spine at the back and the breastbone at the front, surround and protect the organs in the chest. Arm: The bones of the arms are joined to sockets in the shoulder blades. Spinal Column: The 7 vertebrae in the neck and the 19 in the back make the spinal column. Pelvis: The bones of the pelvis surround the lower abdominal organs, support the spine and provide attachment for the legs. Hand: Eight bones make up the wrist, five the palm, and 14 hinged bones form the fingers and thumb. Leg: Three major leg bones are suspended by ball and socket joints from the pelvis. Foot: The bones of the foot form arches, so that the weight is carried on the heel and toes. As a whole, the human skeleton is the supporting framework of the body. The skeleton is composed of the individual bones and the articulations between them. The human skeleton is generally considered in two major subdivisions: the axial skeleton and the appendicular skeleton. Out of total of 206 bones axial skeleton has 80 bones while that of appendicular skeleton consists of 126 bones

∑ ∑ ∑ ∑ ∑ ∑

Axial skeleton (80 bones) Skull – 22 Vertebral column – 26 Ribs – 24 (12 pairs) Ear ossicles – 6 (3 pairs) Hyoid – 1 Sternum – 1

∑ ∑ ∑ ∑

Appendicular skeleton (126 bones) Pectoral girdles – 4 (2 + 2) Pelvic girdles – 2 (1 + 1) Forelimbs – 60 (30 ¥ 2) Hind limbs – 60 (30 ¥ 2) 126

80

5.3

AXIAL SKELETON ∑ The axial skeleton is the central supporting framework of the body. Its major components are the vertebral column (spine), the thoracic cage, and the skull. ∑ The axial skeleton consists of 80 bones that form the body’s long axis and are grouped into three regions: skull, vertebral column, and ribcage. ∑ The skull is made up of 22 bones and contains 6 ossicles, or ear bones; the hyoid bone is found in the neck. ∑ The vertebral column consists of 26 irregular bones. The ribcage consists of 12 pairs of curved ribs linked to the sternum by flexible strips of costal cartilage. ∑ The axial skeleton serves to support the head, neck, and trunk; and protects the brain, spinal cord, lungs, and heart. ∑ Together the bones forming skull, vertebral column, ribs and sternum constitute the central bony core of the body, the axis.

VERTEBRAL COLUMN (26)

CERVICAL (7) ∑ Neck

THORACIC (12) ∑ Chest

COCCYGEAL (1) 4 fused to form coccyx ∑ Vestigenal fail

UPPER ILIUM (1)

∑ ∑

Humerus upper arms (1) Radius and Ulna lower arms (2) ∑ Carbals (wrist) (8) ∑ Matacrpals (palm) (5) ∑ Phalanges (signers) (14)

FORELIMBS (30 ¥ 2 = 60) (upper area)

APPENDICULAR SKELETON (126)

INNER PUBIS AND TISCHIUM (1)

PELVIC GIRDLE (2)

EAR OSSICLES (3¥2 = 6) ∑ Malleus (2) ∑ Incus (2) ∑ Stapes (2)

Vertebral formula of man Æ C7 T12 L3 S5 C4

SACRAL (1) 5 fused to form one ∑ Pelvis

Scapukula Shoulder bones

PECTORAL GIRDLE (4)

STERNUM HYOID (I) One ∑ Formed by fusion of many paired sterne brae ∑

CLAVICLES (2) (collar bones)

RIBS Pairs

∑ 12

LUMBAR (5) ∑ Abdomen

CRANIUM (8) FACE (14) ∑ Frontal (1) ∑ Nasals (2) ∑ Parietals (2) ∑ Maxillae (2) ∑ Occipital (1) ∑ Palatines (2) ∑ Temporals (2) ∑ Zygomatics (2) ∑ Sphenoid (1) ∑ Lacrymals (2) ∑ Ethmoid (1) ∑ Inferiorturbinals (2) ∑ Vomer (1) ∑ Mandible (1)

SKULL (22)

AXIAL SKELETON (80) [skull (22) + vertebrae (26) + Ribs(24) + Hyoid (1) + Ear ossicles (6) + Sternum (1)]

HUMAN SKELETON (206)

HINDLIMBS (30 ¥ 2 = 60) ∑ Femur (thigh) (1) ∑ Tibia and Fibula (shank) (2) ∑ Patella (1) ∑ Tarsals Ankle (7) ∑ Metatarsals (sole) (5) ∑ Phalanges (Toes) (14)

Flollowing chart given below shows the bones present in human skeleton (In brackets is mentioned number of bones).

174 HUMAN ANATOMY AND PHYSIOLOGY

THE OSSEOUS SYSTEM 175 5.4

SKULL

Parietal

Frontal bone Lacrimal

Sphenoid

Ethmoid bone Eye orbit

Nasal

Maxilla

Middle choncha

Malar (Zygomatic) Inferior choncha

Maxilla

Nasal septum

Vomer Mandible

Fig. 5.2

Bones of the face: Anterior view VAULT OF SKULL

Sphenoid

Parietal

Frontal Ethmoid FACE

BACK OF THE SKULL

Lacrimal

Temporal

Nasal

Occipital

Eye orbit Malar (Zygomatic)

External auditory meatus Maxilla Styloid process BASE OF SKULL

Fig. 5.3

Coronoid process

Mandible Condyle

Bones of the cranium and face: Lateral view

The skull is the skeleton of the head region. It is located on the top of the vertical vertebral column. It has two major functional subdivisions: the cranium and the facial (visceral) skeleton.

The Skull ∑ The human skull shaped the face, protects the fragile brain, and houses and protects special sense organs for taste, smell, hearing, vision and balance. ∑ It is constructed from 22 bones, 21 of which are locked together by immovable joints, known as sutures, to form a structure of great strength.

176 HUMAN ANATOMY AND PHYSIOLOGY ∑ Blood vessels and cranial nerves enter and leave the skull through holes called foramina and canals. ∑ Skull bones are divided into two groups: cranial bones and facial bones. The bony framework of the head is called the skull, and it is subdivided into two parts, namely: Cranial bones and facial bones. 1. Cranial Bones The cranium is a spherical container that protects the brain. At the base of the cranium is a series of openings. Blood vessels and nerves enter and leave the cranial cavity through these openings. ∑ The 8 bones of the cranium support, surround and protect the brain within the cranial cavity. These are: Frontal –1 Parietals – 2 Occipital – 1 Temporals – 2 Sphenoid – 1 Ethmoid – 1 Total

8

∑ They form the roof, sides, and back of the cranium, as well as the cranial floor on which the brain rests. ∑ The frontal bones form the roof and sides of the cranium. Two temporal bones form the inferior lateral parts of the cranium, and part of the cranial floor. ∑ An opening in the temporal bone, the external auditory meatus, directs sounds into the inner part of the ear which is encased within, and which contains three small linked bones called ossicles. ∑ The occipital bones form the posterior part of the cranium and much of the cranial floor. ∑ The occipital bone has a large opening, the foramen magnum, through which the brain connects to the spinal cord. ∑ The occipital condyles articulate with the atlas (first cervical vertebra), enabling nodding movements of the head. ∑ The ethmoid bone forms part of the cranial floor, the medial walls of the orbits, and the upper parts of the nasal septum, which divides the nasal cavity vertical into left and right sides. ∑ The sphenoid bone, which is shaped like a bat’s wings, acts as a keystone by articulating with and holding together, all the other cranial bones. ∑ Cranial bones also contain air spaces lined by mucous membrane. These spaces are called sinuses which reduce the weight of the skull and also give resonant sound to the voice. ∑ Two of these sinuses namely mastoid sinuses drain into the middle ear. Inflammation in these sinuses can lead to deafness. This disease is called mastoiditis. ∑ All bones of the cranium are firmly attached to each other with immovable joints called sutures. These bones are joined by ligaments. 2. Facial Bones The facial skeleton is also referred to as the visceral skull. It is attached to the anterior and inferior surfaces of the cranium. It is the skeleton of the entrances of the respiratory and digestive systems and the orbits containing the eyes. ∑ The 14 facial bones form the framework of the face; provide cavities for the sense organs of smell, taste, and vision; anchor the teeth; form openings for the passage of food, water,

THE OSSEOUS SYSTEM 177

∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

and air; and provide attachment points for the muscles that produce facial expressions. Nasals – 2 Lacrymals – 2 Maxillae – 2 Nasal conchae – 2 Palatines – 2 Vomer – 1 Zygomatics – 2 Mandible – 1 Total – 14 Two maxilae form the upper jaw, contain sockets for the 16 upper teeth, and link all other facial bones apart from the mandible (lower jaw). Two zygomatic bones (cheekbones), form the prominences of the cheeks and part of the lateral margins of the orbits. Two lacrimal bones form part of the medial wall of each orbit. Two nasal bones form the bridge of the nose. Two palatine bones form the posterior side walls of the nasal cavity and posterior part of the hard palate. Two inferior nasal conchae form part of the lateral wall of the nasal cavity. The vomer forms part of the nasal septum. The mandible, the only skull bone that is able to move, articulates with the temporal bone allowing the mouth to open and close, and provides anchorage for the 16 lower teeth. Large aperture namely foramen magnum is present on the posterioventral side of the skull. Brain leads into the spinal cord through this aperture. On either side of this aperture are present occipital condyles which rest in the concavities of the first vertebrae namely atlas forming movable joint (hinge joint) permitting nodding of the head. Hyoid bone mainly supports the tongue and thus is also known as tongue bone.

Sinuses Sinuses are air-filled spaces found in the frontal, sphenoid, ethmoid, and paired maxillae, clustered around the nasal cavity. These spaces reduce the overall weight of the skull.

Skull Development In the foetus, skull bones are formed by intramembranous ossification. A fibrous membrane ossifies to form skull bones linked by areas of as yet unossifued areas of membrane called fontanelles. At birth, these flexible areas allow the head to be slightly compressed, and permit brain growth during early infancy.

5.5

THE VERTEBRAL COLUMN

The vertebral column is a series of individual segments, the vertebrae, and one on top of the other.

Intervertebral Discs ∑ Intervertebral disc are found between adjacent vertebrae from the second cervical vertebra (axis) to the sacrum. ∑ Each disc has an inner soft, pulp nucleus covered by an outer fibrous covering of fibrous cartilage. ∑ Each disc forms a strong, slightly movable joint. ∑ Collectively, discs cushion vertebrae against vertical shocks, and allow various movements of the backbone.

178 HUMAN ANATOMY AND PHYSIOLOGY

Atlas Cervical vertebrae (7)

Axis 7th cervical vertebra 1st thoracic vertebra

Thoracic vertebrae (12)

12th thoracic vertebra 1st lumbar vertebra Intervertebral discs Lumbar vertebrae (5) Intervertebral formina

5th lumbar vertebra Sacrum

Sacrum

Coccyx

(a)

(b)

Fig. 5.4 Vertebral column (a) Darsal view (b) Lateral view

Vertebral Curves ∑ A normal backbone has four curves that give it S-shape. ∑ The cervical and lumbar curves and convex anteriorly, while the thoracic and sacral curves are concave anteriorly. ∑ The S-shape allows the backbone to function as a spring rather than a flexible rod, thereby absorbing shock during walking running; enhancing the strength and flexibility of the backbone; and facilitating balance when upright by placing the trunk directly over the feet.

THE OSSEOUS SYSTEM 179 Regions of the Backbone ∑ An adult backbone consists of 26 vertebrae of which two, the sacrum and coccyx, are composites consisting of vertebrae that fuses during childhood. ∑ The backbone has five sections. ∑ Seven small cervical vertebrae form the neck, the most flexible part of the backbone. ∑ The uppermost cervical vertebra, the atlas articulates with the occipital condyle of the skull to enable nodding movements of the head; articulation of the atlas with the axis, the second cervical vertebra, produces shaking movement of the head. ∑ Twelve thoracic vertebrae each articulates with a pair of ribs. Five large lumbar vertebrae form the back and bear most of the weight of the head and trunk. ∑ The triangular sacrum, made of five fused bones, forms a strong anchorage for the pelvic girdle, with which it firms the pelvis. ∑ The coccyx, or tailbone, consists of four fused vertebrae. ∑ The number of vertebrae present in different regions of the vertebral column of human beings is expressed as vertebral formula. C7 T12 L5 S(4) C(5) where, C stands for cervical vertebral, T-thoracic, L-lumbar, S-caral and C for coccyxal. Presence of parenthes is in the formula indicates their fusion. ∑ Thus human vertebral column consists of generally 33 vertebral of which for fuse in the sacral and the coccygeal region to reduce the number to 26. The upper part of the vertebral column, the neck regions, and associated muscles provide the head with its various motions. The upper two vertebrae are specifically constructed for head motions. (a) The articulation between the occipital base of the skull and the atlas (the first cervical vertebra) is specially constructed for anterior-posterior motions of the head (“nodding”). (b) Between the atlas (the first cervical vertebra) and the axis (the second cervical vertebra) is a special pivotal-type joint. This joint facilitates rotary (turning) motions of the head.

Weight Bearing (a) The vertebral bodies and the associated intervertebral discs are the primary mechanism for supporting the body weight. (b) In the lumber and lumbosacral regions, the articular processes of the vertebrae is also weight bearing. (A bony projection extends upward and another extends downward from each right and left side of the neural arch of each of these vertebrae.) These projections are the articular processes. Through them, as well as through the vertebral bodies and discs, adjacent vertebrae are articulated with each other. (c) The specially constructed sacrum, at the lower end of the vertebral column receives the body weight from above and transfers it to the pelvic bones of the lower members.

Protection of the Spinal Cord and its Membranes Whereas the cranium protects the brain, the neural arches protect the spinal cord and its membranes (meninges). The neural arches of the individual vertebrae arch over the spinal cord and its membranes. The continuous series of neural arches form a continuous spinal canal.

180 HUMAN ANATOMY AND PHYSIOLOGY Motion of the Vertebral Column Together, the vertebrae, the intervertebral discs, and the associated ligaments form a semiflexible rod. This allows a certain amount of motion to the vertebral column in addition to its supporting role. (a) Role of Processes. The spinous and transverse processes of the neural arches serve as attachments for skeletal muscles. By acting as levers, these processes enable the skeletal muscles to move the vertebrae. (b) Role of Intervertebral Discs. The intervertebral discs between adjacent vertebrae serve several functions. 1. First, they allow motion to occur between adjacent vertebrae. The relative thickness of the individual intervertebral disc determines the amount of motion possible between the adjacent vertebrae. The total movement of the vertebral column (spine) is the sum of the motions of the individual intervertebral discs. 2. Secondly, the intervertebral disc acts as a shock absorber. As such, it minimizes the shocks that are transmitted to the vertebral column by the contact of the heels with the floor during walking, jumping, etc. 3. During the course of a day standing and sitting, the individual becomes about an inch shorter than he was at the beginning of the day. This is less true of older individuals. After a good night’s rest in a horizontal position, these discs regain their original thickness. As an astronaut works at zero gravity, he retains is full height. 4. With age, individuals tend to lose height. This is because the intervertebral discs shrink somewhat over the years. Since these discs also become less flexible, there is less compression from morning until night. Thus, the height in the evening is closer to the morning height than with a younger person. (c) Role of Curvatures of Vertebral Column. As a whole, the vertebral column has four curvatures. Two of these are concave to the front; two are concave to the rear. As do the intervertebral discs, these curvatures function as shock absorbers for the body.

Basic Structure of Vertebrae ∑ Each vertebra is made of various parts namely: – Centrum or body – Transverse processes – Neural arch – Neural spine – Prezygapophysis – Postzygapophysis ∑ The centrum is a central rigid body of the vertebral. ∑ Neural arch over the dorsal side centrum encloses the spinal cord. ∑ Centrum of the human vertebral is flat on both ends i.e., anterior and posterior. That is why it is amphiplatyon. This is the features of all mammals. ∑ Two laterally compressed processes arise from both dorsolateral sides of the centrum. These processes are called transverse processes. ∑ Joining of two halves of neural arch forms the median dorsal notch which possesses a spinous process called neural spine. ∑ Two pairs of articular surfaces between two adjacent vertebral are known as pre and post zygapophyses.

THE OSSEOUS SYSTEM 181 ∑ Prezygapophysis (or superior articular process) of one vertebra articulates with the postzygapophysis (or inferior articular process) of the vertebra lying in front of it. ∑ Main features of various vertebrae are discussed as under:

Atlas Vertebra Spinal foramen Posterior arch

Posterior tubercle Superior articular facet

Place of transverse ligament

Foramen transversarium

Transverse process Odontoid fossa

Lateral mass Anterior arch

Fig. 5.5

Anterior tubercle

Atlas vertebra—Anterior view

∑ ∑ ∑ ∑ ∑

It is the first cervical vertebra. Centrum is absent in the atlas and this shape of this vertebra is almost like a ring. Neural spine is in-conspicuous. Pre and postzygapophysis are absent. Front surface of the neural arch has two concavities namely occipital facets which enables occipital condyles of the skull to fix. ∑ Posterior side has two lateral articular facets which receive two convexities of the front end of second cervical vertebra (axis). ∑ Elastic transverse ligament divides neural canal of this vertebra into dorsal large spinal foramen for spinal cord and ventral small for odontoid process of axis vertebra. ∑ Foramen transversarium for vertebral artery is also present.

Axis Vertebra Odontoid process Foramen transversarium for vertebral artery Transverse process

Superior articular facet for atlas Body Pedicle

Inferior articular facet

Lamina Spinous process

Facet for articulation with atlas Lamina

Transverse process

(a)

Spinous process

Body

Inferior articular process

(b)

Fig. 5.6 Axis Vertebra (a) Anterior view; (b) Side view ∑ Axis, the second cervical vertebra lies just behind the atlas. ∑ Centrum of axis has odontoid process which passes through the odontoid foramen of the atlas, because of which axis allows turning movement to the atlas and skull together. Thus axis is specialized to serve as a pivot to rotate the skull around.

182 HUMAN ANATOMY AND PHYSIOLOGY ∑ Transverse processes of the axis vertebrae are small and looks like a nodule. ∑ Oval articular pad lies on each side of front centrum near the base of the odontoid process. These fit into the corresponding articular facets of atlas. ∑ This joint further facilitates rotation of skull upon the vertebral column and is like ball and socket joint. ∑ Foramina traversia present in the axis vertebra forms a channel for the vertebral arterty and provides protection to the same.

Typical Cervical Vertebra Spinous process (Bifurcated)

Inferior articular process

Lamina Superior articular process

Spinal foramen

Pedicle

Foramen transversarium for vertebral

Fig. 5.7 ∑ ∑ ∑ ∑ ∑

Centrum or body

Transverse process

Typical cervical vertebra: Anterior view

The third, fourth, fifth, sixth and seventh cervical vertebrae are called typical cervical vertebrae. Their centrum is flat and thus called amphiplatyon centrum. These vertebrae have bifurcated spine. It has long transverse processes. It has a coelus centrum. Superior articular process

Spinous process

Transverse process Superior articular process Neural foramen Body Pedicle Intervertebral disc Inferior articular process

Fig. 5.8

Intervertebral foramen

Cervical vertebrae: Side view.

THE OSSEOUS SYSTEM 183 Thoracic Vertebra Spinous process Superior articular process

Lamina Transverse process Pedicle

Facets for articulation with ribs

Vertebral foramen

Body

Superior articular

Lamina Arrow passing through the vertebral formation

(a)

Fig. 5.9 ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

Transverse process

Interior articular process

Anterior aspect Facets for articulation with ribs

Body centrum

Pedicle

Spinous process

(b)

Thoracic vertebrae (a) Anterior view (b) Lateral view

These are twelve in number. Those are found in the chest area of the vertebral column. Centrum is flat. Thoracic vertebrae have club shaped transverse processes. They have well developed neural spine. Inter vertebral foramina are present on both sides. Its centrum is a coelus. Centrum of these vertebrae have capitular demifacet for the articulation of capitulum of ribs.

Lumbar Vertebra Superior articular process Spinous process Lamina Metapophysis

Transverses process

Body Pedicle Transverses process Body Spine (a)

(b)

Inferior articular process

Fig. 5.10 Lumbar vertebra (a) Anterior view (b) Lateral view ∑ These are five in number. ∑ These occur in the abdominal area of the vertebral column.

184 HUMAN ANATOMY AND PHYSIOLOGY ∑ ∑ ∑ ∑ ∑

These vertebrae are largest and strongest. Its transverse processes are thin, long and well developed. Each transverse process has a small accessary process near its roof. The centrum is flat and thus called amphiplatyon centrum. Their prezygapophysis are on extensions called metapophyses and postzygapophyses are on extensions called anapophyses.

Sacral Vertebrae or Sacrum Articulating surface for intervertebral disc (body)

Articular process for L5

Promontary S1

Sacral foramen

Surfaces for articulation with the left illium

S2 S3

Foramina for passage of nerves

S4 S5 C1 C2 C3 C4

Coccyx (a)

Fig. 5.11

(b)

(a) Sacrum – Anterior view (b) Coccyx – Lateral view

∑ Sacral vertebral are five in number which fuse to form more or less triangular structure called synsacrum. ∑ These five are free in early childhood but later they fuse to form single bone in the adult. ∑ They have extra articular surface area for articulation with item of pelvic girdle. ∑ Their transverse processes are modified into broad sloping mass projected laterally from the body. ∑ The centrum is flat and hence called amphiplatyon centrum.

Coccygeal Vertebrae or Coccyx ∑ ∑ ∑ ∑

These are four in number which are fused in adults to form a curved bone coccyx. Their transverse processes are rudimentary. Coccyx is present in the vestigeal tail region. There are present two coccygeal cornnato which articulate with sacral corona.

THE OSSEOUS SYSTEM 185 5.6

RIBS Facet for clavicle

1st Thoracic vertebra

1st Rib

Prosternum

2nd Rib Meososternum Sternum Costal cartilage 6th Rib Metasternum 7th Rib 8th Rib 9th Rib 12th Thoracic 12th Rib vertebra

10th Rib 11th Rib

Fig. 5.12

Rib cage

The Rib Cage The thoracic cage consists of the ribs, the sternum and thoracic vertebrae. The 12 pairs of ribs are attached posteriorly to the thoracic vertebrae. Anteriorly, the upper 10 pairs of ribs attach directly or indirectly (via costal cartilages) to the sternum.

Function (a) Motion. Because of the segmentation of the thoracic cage into vertebrae and ribs, motion can occur in the thoracic region of the body. (b) Costal Breathing. The special construction of the ribs and their costal cartilages allows costal breathing to take place. (c) Protection. In addition, the rib cage encloses such vital structures as lungs, heart, and liver and gives them protection.

Ribs ∑ The ribs are curved, flat bones with a slightly twisted shaft. ∑ The 12 pairs of ribs form a ribcage that protects the heart, lungs, major blood vessels, stomach, and liver. ∑ Each rib is a flattened curved bone. ∑ It is distinguished into two parts– long and bony vertebral part and a short and cartilagenous sternal part. ∑ The dorsal part is forked into tuberculum and capitulum which provide points of articulation with the moracic vertebral. ∑ 1 to 7 pairs of ribs are attached to the sternum and are called true ribs. ∑ 8th, 9th and 10th pairs are not joined to the sternum but to the 7th rib and are called false ribs.

186 HUMAN ANATOMY AND PHYSIOLOGY ∑ 11th and 12th ribs are not at all attached to sternum and are called floating ribs. ∑ At its posterior end, the head of each rib articulates with the facets on the centra of adjacent vertebrae, and with the facet on a transverse process. ∑ These vertebrocostal joints are plane joints that allow gliding movements. ∑ At their anterior ends, the upper ten pairs of ribs attach directly or indirectly to the sternum by flexible costal cartilages. ∑ Together, vertebrocostal joints and costal cartilages give the ribcage sufficient flexibility to make movements up and down during breathing. ∑ Ribs 11 and 12 are ‘floating’ ribs that articulate with the sternum indirectly via the costal cartilage of another rib or not at all. It is known as MOTIONS OF THE HEAD.

Bony Thorax ∑ The cones-shaped bony thorax surrounds the thoracic cavity, and is formed by 12 thoracic vertebrae posteriorly, 23 pairs of ribs laterally, and the sternum and costal cartilages anteriorly. ∑ Its cage-like structure protects the thoracic and upper abdominal organs, supports the pectoral girldles and upper limbs, and plays a part of breathing.

5.7

STERNUM ∑ ∑ ∑ ∑ ∑

Sternum is long, flat, narrow bone present in the mid ventral line of the thorax. It has two parts—manubrium (handle) and body (the blade). The tip of the blade has a xiphoid process. Clavicles are attached to its upper end while first seven pairs of ribs are attached to it laterally. Sternum supports the heart on the ventral side and thus participates in forming thoracic basket to provide protection to delicate organs. ∑ Being part of the thoracic cavity it also plays role in respiration. Jugular (suprasternal) notch No. of Rib

Tubercle Clavicular notch

1 Manubrium

2

Facet of tubercle that articulating with transverse process of vertebra Head articulating with vertebral bodies

Angle Neck

Sternal angle

3

Costal groove Body

4

Shaft

5 Interior border

6 7 8 9 10

Xiphoid process

(a)

(b)

Depression for costal cartilage

Fig. 5.13 (a) Sternum with its attachments (b) Typical rib from below.

THE OSSEOUS SYSTEM 187 5.8

HYOID

It is horse-shoe shaped bone, lying just above the larynx and below the mandible. It forms the part of soft tissues of the neck. It does not articulate with any other bone but is attached to the styloid process of the temporal bone by ligaments. It gives attachment to the base of tongue.

5.9

EAR OSSICLES

Malleus (Hammer-like)

Incus (Anvil-Shaped)

Stapes (Stirrup-shaped)

Tympanic membrane

Fig. 5.14

Ear ossicles

Ear ossicles is a small flexible chain of three small bones namely malleus, incus and stapes. These have been named after their resemblance to hammer, anvil and stirrup respectively. Malleus is attached to the tympanic membrane towards outside and incus on the inner side. The incus is connected with stapes on inner side and malleus on outer side. Stapes is attached on the inner side with oval membrane namely fenestra ovales of the inner ear and incus on the inner side. These bones help in transmission of sound waves.

5.10

APPENDICULAR SKELETON

∑ The 126 bones of the appendicular skeleton make up the upper and lower extremities (limbs) and the girdles that attach them the axial skeleton. ∑ Both upper and lower limbs consist of three sections. The upper limb consists of 27 hand bones, the radius and ulna (forearm bones), the humerus (arm bone). ∑ The humerus articulates with a weak but very mobile pectoral girdle, consisting of the scapula and clavicle. ∑ The lower limb consists of 26 foot bones; the tibia and fibula (leg bones); and the femur (thigh bone) and patella (kneecap). ∑ The femur articulates with a strong, almost rigid pelvic girdle made up of 2 hip bones. ∑ Appendicular skeleton mainly helps in locomotion and provides surface for the attachment of forelimbs and hind limbs.

188 HUMAN ANATOMY AND PHYSIOLOGY 5.11

PECTORAL GIRDLE Acromion process Clavicular facet Coracoid process Supra spinous fossa Spine

Deltoid

Glenoid cavity

Medial border

Lateral border

Inferior angle

Fig. 5.15 Pectoral girdle—right posterior view The girdle of each upper member is called the pectoral girdle. Unlike the pelvic girdle, each pectoral girdle is very loosely attached to the axial skeleton. The sole attachment is by the sternoclavicular joint, which in turn is constructed to increase the degrees of motion. The shoulder comprises the part of the body where the arm attaches to the torso. It is made up of three bones the clavicle (collar bone), the scapula (shoulder blade), and the humerus (upper arm bone) as well as associated muscles, ligaments and tendons. The articulations between the bones of the shoulder make up the shoulder joints. The shoulder must be flexible for the wide range of motion required in the arms and hands and also strong enough to allow for actions such as lifting, pushing and pulling. The compromise between these two functions results in a large number of shoulder problems not faces by other joints such as the hip. ∑ Thus each half consists of three bones — scapula, coracoid process and clavicle. ∑ Scapula is a large flat and triangular bone which overlaps the transverse processes of 2nd to 7th thoracic vertebrae on its sides. ∑ At its apex, a concave depression namely glenoid cavity is present. ∑ This articulates with the head of the humerous to form ball and socket joint. ∑ Its posterior or back surface has a prominent edge or spine which project as a triangular acromian process. ∑ Clavicles or collar bones are present almost at the base of the neck which are attached to sternum on ventral side and shoulder girdle on dorsal side.

THE OSSEOUS SYSTEM 189 5.12

PELVIC GIRDLE Promontory of sacrum

Brim of the pelvis Iliac crest L5

Sacroiliac joint

Ilium

Anterior superior iliac spine

S3 S5

Iliopectineal line Acetabulum

Head of femur Symphysis pubis Ischium

Obturator foramen

Pubic arch Pubis

Fig. 5.16 Bones of the pelvis and upper part of the left femur Iliac crest

Posterior superior iliac spine

Anterior superior iliac spine

Posterior inferior iliac spine

Anterior inferior iliac spine

Sciatic notch

Acetabulum with lines indicating joints

Spine of ischium Ischial tuberosity

Symphysis pubis

Obturator foramen

Fig. 5.17

Joint between ischium and pubis

Pelvic girdle: Lateral view

∑ The girdle of each lower member is called the pelvic girdle. Each pelvic girdle is attached firmly to the corresponding side of the sacrum. With their ligaments, the two pelvic girdles and sacrum together form a solid bony circle known as the bony pelvis. ∑ Two pelvic girdles are composed of two distinct halves. ∑ Each comprises of three bones namely ilium, ischium and pubis. ∑ On the outer edge of each half, ilium and ischium bones meet to form a deep socket called acetabulum. Pubis does not participate in formation of acetabulum as it is separated by obturator foramen. ∑ The head of femur (thigh bone) articulates into this. Socket forms ball and socket joint. ∑ Between the ischium and pubis there is a large space in the form of hole called obturator foramen. ∑ Ventrally a line of fusion can be seen where two halves of the pelvic girdle meet by ligament. This is called pubic symphysis. ∑ The arch is completed behind by the sacrum and coccyx forming a complete ring called pelvis.

190 HUMAN ANATOMY AND PHYSIOLOGY 5.13

FORELIMBS Greater tubercle (Tuberosity)

Head

Lesser tubercle (Tuberosity)

Head

Intertubercular groove

Lesser tubercle

Shaft Deltoid ridge

Coronoid fossa

Olecranon fossa Lateral epicondyle

Medial epicondyle Trochlea

Capitulum

(a) Fig. 5.18

Medial epicondyle Trochlea

(b)

Left humerous (a) Anterior view (b) Posterior view Ulna Trochlear notch Coronoid process Radial notch

Olecranon process Radius Head Neck Radial tuberosity

Head

Fig. 5.19 Left radius and ulna: Anterior view

THE OSSEOUS SYSTEM 191

Phalanges

Distal Phalynx

Proximal phalynx Hamate

st

1 Metacarpal Trapezium Trapezoid

Pisiform Triquetrum

Capitate Lunate Scaphoid Radius

Ulna

Fig. 5.20 Bones of the right wrist, hand and fingers — Anterior view The forelimbs consist of total of 30 bones such as: – Humerus (1) – Radius ulna (2) – Carpals (8) – Metacarpals (5) – Phalanges (14) ∑ Humerus. The bone of the upper arm is long and cylinderical. It upper end has a rounded head. Head articulates into the glenoid cavity of scapula. It has two tuberosities — a greater and a lesser tubercle near the head. – The main bone is called shaft. – Shaft has as V-shaped deltoid ridge. – Lower end or distal end is flattened with two projections called lateral and medial epicondyles. – A rounded knob like structure is present below lateral condyl called capitulum. – Between capitulum and medial condyl is a pulley like structure called trochlea which articulates with ulna of lower arm. ∑ Radius Ulna – Ulna is medial and longer than radius. – Upper end of ulna has a larger olecranon process and a smaller coronoid process with a semilunar trochlear notch in between where trochlea of humerus articulates.

192 HUMAN ANATOMY AND PHYSIOLOGY – Another notch namely radial notch is present on the lateral side which articulates with radius. – Radius is lateral and shorter than ulna. – Its upper end has a head, a neck and a tuberosity. Its head articulates with the capitulum of humerus. – The lower end of radius has two articular surfaces, one for ulna and other for wrist bones. ∑ Carpals – There are eight small ones or carpals arranged in two rows forming a wrist. – Scaploid, lunate, triquetrum and pisiform form proximal row. – Trapezium, trapizoid, capitate and hamate form the distal row. ∑ Metacarpals – These are five long bones forming the palm of hand. – These are five in number. ∑ Phalanges – There are three bones in each finger and two in the thumb (pollex).

Human Hand The human hand consists of a broad palm (metacarpus) with 5 digits, attached to the forearm by a joint called the wrist (carpus). The back of the hand is formally called the dorsum of the hand.

Digits Four fingers on the hand are located at the outermost edge of the palm. These four digits can be folded over the palm which allows the grasping of objects. Each finger, starting with the one closest to the thumb, has a colloquiral name to distinguish it from the others: ∑ Index finger, pointer finger, or forefinger ∑ Middle finger ∑ Ring finger ∑ Little finger The thumb (connected to the trapezium) is located on one of the sides, parallel to the arm. The thumb can be easily rotated 90°, on a level perpendicular to the palm, unlike the other fingers which can only be rotated approximately 45°. A reliable way of identifying true hands is from the presence of opposable thumbs. Opposable thumbs are identified by the ability to be brought opposite to the fingers, a muscle action known as opposition. The human hand has 27 bones: the carpus or wrist account for 8; the metacarpus or palm contains 5; the remaining 14 are digital bones. The eight bones of the wrist are arranged in two rows of four. These bones fit into a shallow socket formed by the bones of the forearm. The bones of proximal row are (from lateral to medial): scaphoid, lunate, triquetral and pisiform. The bones of the distal row are (from lateral to medial): trapezium, trapezoid, capitate and hamate. The palm has 5 bones (metacarpals), one to each of the 5 digits. These metacarpals have a head and a shaft. Human hands contain 14 digital bones, also called phalanx bones: 2 in the thumb (the thumb has no middle phalanx) and 3 in each of the four fingers. These are:

THE OSSEOUS SYSTEM 193 ∑ the distal phalanx, carrying the nail, ∑ the middle phalanx and ∑ the proximal phalanx. Sesamoid bones are small ossified nodes embedded in the tendons to provide extra leverage and reduce pressure on the underlying tissue. Many exist around the palm at the bases of the digits; the exact number varies between different people.

Articulations Also to note is that the articulation of the human hand is more complex and delicate than that of comparable organs in any other animals. Without this extra articulation, we would not be able to operate a wide variety of tools and devices. The hand can also form a fist, for example in combat, or as a gesture. The articulations are: ∑ ∑ ∑ ∑

Interphalangeal articulations of hand Metacarpophalangeal joints Intercarpal articulations Wrist

Variation Some people have more than the usual number of fingers or toes, a condition called polydactyly. Others may have more than the typical number of metacarpal bones, a condition often caused by genetic disorders like Catel-Manzke syndrome. The average length of an adult male hand is 189 mm, while the average length of an adult female hand is 172 mm. The average hand breadth for adult males and females is 84 and 74 mm respectively. The pelvis is the bony structure located at the base of the spine (properly known as the caudal end). It is part of the appendicular skeleton. Each consists of three bones: the illium, ischium and the pubis. The illium is the largest and upper most part, the ischium is the posterior inferior (back-lower) part, and the pubis is the anterior (front) part of the hipbone. The two hipbones are joined anteriorly at the symphysis pubis and posteriorly to the sacrum. The pelvis incorporates the socket portion of the hip joint for each leg (in bipeds) or hind leg (in guadrupeds). It forms the lower limb (or hindlimb) girdle of the skeleton.

5.14

HINDLIMBS

The hindlimbs comprises of 30 bones. – Femur (1) – Tibia fibula (2) – Patella (1) – Tarsals (7) – Metatarsals (5) – Phalanges (14)

194 HUMAN ANATOMY AND PHYSIOLOGY

Head

Greater trochanter

Intercondylar eminence

Medial condyle of tibia

Lateral condyle of tibia

Neck

Head of tibia

Lesser trochanter

Fibula

Shaft

Tibia Shaft Shaft

Lateral condyle

Medial malleolus

Medial condyle Intercondylar fossa

Fig. 5.21

Left femur: Anterior view

Lateral malleolus

Fig. 5.22

Left Tibia and fibula: Anterior view

Calcaneum Talus

Cuboid

Navicular

Talus

Navicular 3 cuneiform

3rd cuneiform

1st Cuneiform

5 metatarsals

2nd Cuneiform

1 2 3 4

Metatarsal

5

Phalanges

Calcaneus

14 phalanges

Cuboid (b)

(a)

Fig. 5.23

Bones of the foot (a) Upper aspect (b) Lateral view

THE OSSEOUS SYSTEM 195 ∑ Femur – The femur is the thigh bone. In humans, it is the longest, most voluminous, and strongest bone. – The average human femur is 48 centimeters in length and 2.34 m in diameter and can support up to 30 times the weight of an adult. It forms part of the hip (at the acetabulum) and part of the knee. – The word femur in Latin is for thigh. Theoretically in strict usage, femur bone is more proper than femur, as in classical Latin femur means “thigh” and os femoris means the bone within it. – Its upper end has a rounded head, constricted neck and two eminences called greater and lesses trochanters. – Head articulates into the acetabulum of hip girdle forming ball and socket joint. – The lower end or distal end is flattened and divided into two eminances or condyles which articulates with triangular shaped sesamoid bone called patella and form knee. – Conyles have a notch like, inter condylar fossa between them. ∑ Tibia and fibula (Bones of shank) – Tibia is long, thick one which lies medially and infront. It is more developed than fibula. – Its proximal end articulates with femur and patella and forms knee. – Upper end of tibia is concave for articulation with femur. – The lower of tibia articulates with talus bone of ankle has a strong and medial process called medial malleolus. – Fibula is short, thin and located more deeply and laterally. – Upper end or head of fibula articulates with the upper end of tibia but does not reach knee joint. – Its lower end articulates with the end of tibia as well as with talus by mean of a lateral malleolus. ∑ Tarsals – Seven bones called tarsals forming the ankle are arranged in two rows. – These are calcaneum (largest, forms heel), talus, cuboid, navicular and 1st, 2nd and 3rd cuveiforms. ∑ Metatarsals – These are five in number and form sole. ∑ Phalanges – There are two bones in big toe (hallus and three bones in other toes.

Foot The foot is a biological structure found in many animals that is used for locomotion. In many animals, the foot is a separate organ at the terminal part of the leg made up of one or more segments or bones, generally including claws or nails. The human foot is of the plantigrade form. The bottom of the foot is called the sole and area just behind the toes is called the ball. The skin at the sole of the foot is denser than any other area of skin on the human body.

196 HUMAN ANATOMY AND PHYSIOLOGY The major bones in the human foot are: ∑ Phalanges: The bones in the toes are called phalanges. ∑ Metatarsals: The bones in the middle of the foot are called metatarsal bones. ∑ Cuneiforms: There are three bones in the middle of the foot, towards the centre of the body called cuneiforms. ∑ Cuboid: The bone sitting adjacent to the cuneiforms on the side of the foot is called outer cuboid. ∑ Navicular: This bone sites behind the cuneiforms. ∑ Talus: Also called the ankle bone, the talus sits directly behind the navicular. ∑ Calcaneus: Also called the heel bone, the calcaneus sits under the talus and behind the cuboid. ∑ The foot also contains sesamoid bones in distal portion of the first metatarsal bone.

5.15

FRACTURES

Femur bone fractures, on occasion, are liable to cause permanent disability because the thigh muscles pull the fragments so they overlap, and the fragments re-unite incorrectly. To avoid this, femur fracture, patients should be put into traction to keep the fragments pulled into proper alignment. With modern medical procedure, such as the insertion of rods and srcews by way of surgery (known as Antegrade [through the hip] Retrograde [through the knee] femoral rodding), those suffering from femur fractures can now generally expect to make a full recovery, though one that generally takes 3 to 6 months due to the bone’s size. Patients should not put weight on the leg without permission from an orthopedic surgeon since this can delay the healing process. The thigh is generally not put in a cast since the surgical hardware does the job of straightening the bone and holding the fracture together while it heals. Permanent complications with this procedure include the risk of intra-articular sepsis, arthritis and knee stiffness. After the bone is heald, there is no further need for the hardware but, while it is left in some patients permanently, those who lead an active lifestyle may experience discomfort where the hardware projects into the leg muscle and, in such cases, the hardware can be removed, most commonly by means of out-patient surgery.

Hip Fracture If bone is weakened, the proximal end of the femur bone near the hip joint is prone to fragility fracture. Most at risk are post-menopausal women, and osteoporosis severely increases this risk. Out of all the bones in the skeleton, the femur takes the longest to heal. This bone is the longest and strongest bone in the human body. When the average human being jumps this bone withstands a force of half a ton, that is just a testament to its strength.

5.16

JOINTS

Where two bones meet each other, this junction is referred to as a joint or articulation. The joints of the human skeleton may be characterized, in general, in three different ways.

THE OSSEOUS SYSTEM 197 1. Material Hodling Joint Together First, they are characterized by the type of material that holds the bones together at the joint. (a) If the bones are fused together with bony tissue, the articulation is called a synosteosis. (b) Thus, in a synchondrosis, the bones are held together by cartilage tissue. (c) In a syndesmosis, the bones are held together by FCT. 2. Relative Mobility A second way of categorizing joints of the human skeleton is according to relative mobility. (a) The junctions of some bones are non-mobile, such as a synosteosis. (b) Others are semimobile, as seen with some syndesmoses. (c) Being structured to facilitate motion, synovial articulations are mobile at various degrees. 3. Degrees of Freedom The term degree of freedom refers to the number of planes in which movement is permitted. This also equals the number of axes around which motion can take place at a particular joint. (a) One Degree of Freedom. One degree of freedom means that the joint is uniaxial. Motion takes place in a single plane around one axis only. An example is a “hinge” joint. (b) Two Degrees of Freedom. Two degrees of freedom mean that the joint is biaxial. Motion takes place around two different axes. (c) Three Degrees of Freedom. With three degrees of freedom, we say that the joint is multiaxial. Motion can take place around the three axes in all three planes. An example is “ball and socket” type joints. Joints Immovable OR Synarthroidal joint OR Fibrous joint – Bones of cranium – Between sacrium and ilium of pelvic girdle

Cartilagenous OR Amphiar throidal joint OR Partially movable joint

Pivot Gliding joint joint – Joint between – Joint between vertebrae skull and axis – Joints between wrist – Joint between bones of ankles – At public synphysis – Between ribs and sternum – Between radius and ulna

Synovial OR Prearthroidal joint OR Freely movable joint

Hinge joint – Elbow – Knee joint – Finger joint

Ball and socket Joint – Shoulder joint – Hip joint

Saddle Joint – Thumb of men – Bones of metacarpals, and phalanges

Fibrous or Immovable Joint ∑ ∑ ∑ ∑ ∑

This is immovable joint. At such joints there is a deep groove only which is called suture. A thin layer of white (collagen) fibrous tissue is present between the joints. This joint is also called synathrodial joint. e.g., cranium Attachment of a tooth with socket in the mouth cavity represents the gomphoses and ethmoid bone in vomer represents the shindylases.

198 HUMAN ANATOMY AND PHYSIOLOGY

Sutures

Fig. 5.24 Fibrous joints

Gliding Joint

Sutures Radius

Fig. 5.25 Gliding joint ∑ These are flat joints which allow back and forth or side to side movement. ∑ These joints are found between vertebrae as intervertebral disc, at the pubic symphysis between the ribs and sternum and between radius and ulna. ∑ There is present an elastic pad of fibro-cartilage between the joint of bones. ∑ The bones are held together by ligaments extending across the joints. ∑ This type of joint allow limited movement of bones. ∑ Such a joint is often called symphysis.

Pivot Joint

Head of radius

Radial notch of ulna

Fig. 5.26 Pivot joint ∑ In this joint, one of the bones is fixed in its place and bears a peg like projection or the pivot. ∑ Other bone fits over the pivot by concave depression. ∑ These joints allow rotational movements. e.g., Joints between skull and axis vertebra joint. – Elbow joint is combination of pivot and hinge joint.

THE OSSEOUS SYSTEM 199 Hinge Joint Muscle

Femur

Tendon

Patella

Catilage Capsule

Synovial membrane Tibia

Synovial fluid

Fig. 5.27

Hinge joint

∑ This permits movement in one plane only. ∑ This can withstand heavy load of weight. ∑ This joint is held intact by ligaments. e.g., Elbow, knee joint, finger joints and between atlas and axis.

Ball and Socket Joint Head Humerus

Glenoid cavity

Fig. 5.28 Ball and socket joint ∑ This is the most movable joint as one bone of the joint can move freely in all directions and some in rotation. ∑ It cannot withstand heavy load. ∑ One bone forms a ball like head that fits into a socket formed in the other bone. ∑ Movements of this joint may stretch, fold and rotate limbs and also draw the limb towards or away from the body. ∑ These joints are present between humerus with shoulder girdle and femur with hip girdle.

200 HUMAN ANATOMY AND PHYSIOLOGY Saddle Joints

Metacarpal Carpal

Fig. 5.29

Saddle joints

∑ These joints allow movements in two planes. ∑ This joint resembles ball and socket joint but both the ball and socket are poorly developed. ∑ These joints are found in bones of metacarpals, metatarsals and phalanges.

A "Typical" Synovial Joint

Joint capsule

Articular cartillage

Synovial (or joint) cavity Synovial membrane Diarthroses (Synovial)

Fig. 5.30

Synovial joint

∑ A synovial joint is structured to facilitate freedom of motion in one or more of the three planes around three axes of any given joint. The “typical” synovial joint is a schematic representation rather than an actual synovial joint, but it contains structural features common to all synovial joints. ∑ The synovial articulation is formed between two bones. These bones are parts of the skeleton. They are levers of motion. To them are attached skeletal muscles, which provide the forces for motion. ∑ Covering a portion of each bone is an articular cartilage. The portions covered are the ends that would otherwise be in contact during the motions of the joint. Each articular cartilage has a relatively smooth surface and in some ability is as a shock absorber. ∑ The joint area is surrounded by a dense FCT capsule that encloses the joint area. ∑ The inner surface of this fibrous capsule is lined with a synovial membrane. The synovial membrane secretes a synovial fluid into the synovial cavity, or joint space. The synovial fluid is a very good lubricant. Thus, it minimizes the frictional forces between the moving bones.

THE OSSEOUS SYSTEM 201 ∑ The bones of the synovial joint are held together by ligaments. Ligaments are very dense FCT structures that keep the bones from being pulled apart. These ligaments may occur as either discrete, individual structures or as thickening of the fibrous capsule. ∑ The skeletal muscles cross the synovial joint from one bone to other. They are attached to the bones. The tonic (continuous) contraction of these skeletal muscles holds the opposing surfaces of the bones tightly together. When properly stimulated, these muscles contract and cause motion of the bones around the joint.

5.17

DISORDER OF BONES AND JOINTS

Disorder of bones and joints can be classified into various categories, such as : 1. 3. 5. 7. 9. 11. 1.

Sprain 2. Arthritis Dislocation 4. Slipped disc Fracture 6. Osteoporosis Osteomalacia and rickets 8. Synovitis Spondylitis 10. Paget’s Disease Osteomyelitis 12. Developmental Abnormalities of bones Sprain occurs as a result of stretching of tendon or ligament beyond certain limit. This causes severe pain, swelling and redness at that place. Severe sprains are painful and require rest during healing process. 2. Arthritis is also called aching joints. This is due to inflammation of the joints causing pain and stiffness. There are three main kinds of arthritis. Types of arthritis

Osteoarthritis Caused in old age Due to decrease in secretion of synovial fluid. Drying of synovial fluid, friction at joints at the time of movement causes pain. Joints become stiff and are also called ankylosis. Disease is not curable. Exercise may help to some extent.

Rheumatoid arthritis Caused by painful inflammation of the synovial membranes simultaneously. Inflammed membrane produces more of synovial fluid. Joints swell and become painful. Start in small joints and spreads to larger ones. May cause fever, anemia, loss of weight, crippling deformities, erosion of joints. Common in women.

Gout Common in men. Due to inherited disorder of purine metabolis. Due to excess of uric acid. Crystals of sodium urate get deposited in joints. Causes severe pain Normally affects great toe.

3. Dislocation: It is displacement of bones from the normal position. It can take place as a result of unnecessary stretch on tendons and ligaments. Sometimes the ligaments get torn and articulating bones get displaced. 4. Slipped Disc: It is a displacement of vertebrae and the intervertebral fibrocartilage disc from their normal position as a result of excessive bending or jerk or defects of ligaments holding vertebrae together. It causes pain in the back. 5. Fractures: Accidental breaking of a bone is called fracture. Fractures are of various types.

202 HUMAN ANATOMY AND PHYSIOLOGY Types of fractures Green stick It is crack in the bone

Simple Breaking of bone at one point Bones (2 pieces) are not much displaced from their position

Evulsire Small part of the bone broken away from main bone Broken part remains suspended to the ligaments

Comminuted Here bone is broken into more than two pieces.

Compound Here bone gets broken into various pieces.

6. Osteoporosis: It is the loss of minerals and fibres from its matrix reducing bone mass/tissue because deposition cannot keep pace with resorption Peak bone mass occurs around 35 years of age and then gradually decreases. There can be any cause. ∑ Individuals taking lot of analgesics (pain relieving drugs and hydro cortisone for allergies) are more prone to bone loss. ∑ In the post-menopausal period imbalance of hormones oestrogen, androgens and glucocorticoids probably causes bone weakening. Decrease in bone mass increase susceptibility to fractures. Osteoporosis causes bone pain, fractures especially in the hip area (neck of femur), wrist (colles fracture) and vertebrae. Moreover skeletal deformity as a result of loss of height with age (caused by compression of vertebrae) takes place. 7. Osteomalacia and Rickets: Osteomalacia occurs in adults and rickets in children between 6 to 18 months of age, during the period of skeletal growth. These diseases are caused by deficiency of vitamin D which promotes calcification of bone and absorption of calcium in small intestine. In rickets bones become soft due to less deposition of salts resulting in easy bending of bones under the weight of the body. Ribs may get deformed producing a condition called pigeon breast. Children of rickets get bow legs and defective teeth. In osteomalacia there is softening of bones especially in the pelvic girdles and ribs in females during pregnancy and lactation. Bones during such situation are more prone to fractures. Other causes of osteomalacia can be malabsorption dietary deficiency of vitamin D, lack of exposure to sunlight, drugs like anticonvulsant including pheynyonin that results in breakdown of vitamin D and excessive loss of vitamin D precursors during chronic renal fracture or haemodialysis. 8. Synovitis: It is an inflammation leading to swelling at the joint. 9. Spondylitis: It is an inflammation of one more vertebrae. 10. Paget’s disease: In this disease osteocytes reabsorb excess bone, softening the tissue and overactive osteoplasts deposit abnormal new bone that is thickened or enlarged making it structually weak. This disease can object part of the bone, full bones or many bones. Its cause is still unknown. It remains undetected until complications arise. Bone pain, bone deformities, fractures osteoarthritis and compression of nerves due to thickening of bones are the main complications. 11. Osteomyelitis: This is the infection of bones due to access of microbes in bones through skin in compound fractures or via blood during surgical procedure or by spreading from a local focus of infection. Most common infecting orgenism is stapylococeus airreus. Symptoms include bone

THE OSSEOUS SYSTEM 203 necrosis pus formation (suppuration), sub periosted abscess that ruptures and discharges pus to the skin. 12. Developmental Abnormalities of Bones ∑ Achon droplasia is caused by genetic abnormality when there is abnormal growth of cartilage resulting in dwarfism and underdevelopment of bones at the base of the skull. ∑ Osteogenesis is due to congenital defects of osteoblasts resulting in failure of ossification. Bone becomes brittle and fractures easily either spontaneously or following slight trauma.

REVIEW QUESTIONS 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Write an essay on disorders of joints and bones. Discuss various bones which form part of axial skeleton. Draw well labelled diagrams. Explain various bones of apendicular skeleton with the help of diagrams. Describe the structure of a typical vertebra of man and give its differences with atlas, axis, thoracic and lumbar vertebrae. Discuss various parts of forelimbs and hindlimbs. What is a perfect joint? Explain its structure with the help of diagrams and give examples. Write a detailed note on rib cage. Explain — slipped disc, fracture, sprain, arthritis and dislocation. Discuss diseases of bones caused due to deficiency of minerals. State and explain the number of vertebrae in man and also explain curves of the vertebral column.

CHAPTER

6

THE MUSCULAR SYSTEM Frontal Orbicularis ocuii

Occipital Neck muscles

Orbicularis oris Deltoid Pectoralis Major biceps

Trapezius Deltoid Triceps

Rectus abdominus

Triceps Flexors of hand Serratus anterior Carpal ligament Sartorius Quadriceps femoris

Tibialis anticus

Flexors of hand

Wide muscle of back Oblique Abdominal Extensors of hand

Gluteus maximus Biceps femoris Semitendinous

Gastrocnemius

Annular Ligament

6.1

INTRODUCTION

The muscular system is the body’s network of tissues that controls movement both of the body and within it. Walking, running, jumping: all these actions propelling the body through space are 204

THE MUSCULAR SYSTEM 205 possible only because of the contraction and relaxation of muscles. These major movements, however, are not the only ones directed by muscular activity. Muscles make it possible to stand, sit, speak, and blink. Even more, without muscles blood would not rush through blood vessels, air would not fill lungs, and food would not move through the digestive system. Therefore we can say that muscles are the machines of the body which allows it to work. Muscles are attaches to internal organs, bones or blood vessels and are responsible for movement. The muscular system is composed of specialized cells called fibres. The muscles are made up of long thin muscles fibres held together by the connective tissue. Each fibre has a number of nuclei. This system responds to a stimulus from the nervous system. Muscles make up about 35% of the human body weight and 85% of the heat produced is caused by muscles contractions. Almost all the movements are due to contractions. The contraction of a muscle cell is set on motion by the release of calcium inside the cell. The response to electrical changes occurs at the cell’s surface. There are exceptions where movements aren’t caused by contraction, e.g., in the cilium or in the flagellum on sperm cells. The skeleton and muscles function together as the musculoskeletal system. This system (often treated as two separate systems, the muscular, and skeletal) plays an important homeostatic role, allowing the animal to move to more favourable external conditions. Rapid muscular contraction is important in generating internal heat and other homeostatic function. There are about 650 skeletal muscles in the whole human body. Some authors state that there are 850 muscles in the body. Exact figure is not available as scientists differ as to which ones are separate muscles and which ones are parts of large muscles. Animals use muscles to convert the chemical energy of ATP into mechanical work.

6.2

TYPES OF MUSCLES

Three different kinds of muscles are found in vertebrate animals i.e. skeletal, smooth and cardiac unstriated or involuntary muscles.

Smooth Muscles Myofibrils

Nucleus Sarcoplasm

Fig. 6.1

Smooth muscles

Characteristics The smooth muscle is also known as the visceral or involuntary muscle. They are called involuntary muscles because a person generally cannot consciously control them. They are regulated by the

206 HUMAN ANATOMY AND PHYSIOLOGY autonomic nervous system. Unlike skeletal muscles, smooth muscles have no striations or stripes. The contraction of smooth muscle is generally not under voluntary control. ∑ Smooth muscle is made of single, spindle-shaped cells. It gets its name because no striations are visible in them. Each smooth muscle cell contains thick myosin and thin actin filaments that slide against each other to produce contraction of the cell. The thick and thin filaments are anchored near the plasma membrane with the help of intermediate filaments. ∑ The cells have faint longitudinal striations. ∑ The nervous system prevents stimuli for contractions of the smooth muscle. ∑ Striations are not seen although actin and myosin are present in a net pattern. ∑ Motor units are groups of muscle fibres served as one motor neuron and its axon terminals. ∑ There may be up to 2000 fibres in each motor neuron unit in the leg, but only 3 per unit in the muscles of the larynx. ∑ Single unit smooth muscle has a few motor neurons serving many muscle cells. ∑ In multi-unit smooth muscle, each neuron serves fewer muscle cells. ∑ Smooth muscles are arranged in sheets or layers. ∑ Generally there are two layers, one running circularly (around) and the other longitudinally (up and down). ∑ As the two layers alternately contract and relax, the shape of the vessel or organ accordingly changes. ∑ Smooth muscles contract slowly and can remain contracted for a long period of time without tiring. ∑ Smooth muscle (like cardiac muscle) does not depend on motor neurons to be stimulated. ∑ However, motor neurons (of the autonomic system) reach smooth muscle and can stimulate it or relax it — depending on the neurotransmitter they release (for example, noradrenaline or nitric oxide, NO). ∑ Smooth muscle can also be made to contract by other substances released in the vicinity (paracrine stimulation). Example: release of histamine causes contraction of the smooth muscle lining our air passages (triggering an attack of asthma) by hormones circulating in the blood e.g., oxytocin reaching the uterus stimulates it to contract to begin childbirth. ∑ The contraction of smooth muscle tends to be slower than that of striated muscle. ∑ It also is often sustained for long periods. ∑ This, too, is called tonus but the mechanism is not like that in skeletal muscle.

Location Smooth muscles are found in the stomach and intestinal walls, in artery and vein walls, and in various hollow organs.

Functions ∑ Smooth muscles cells help create the structure of the skin, internal organs and blood vessels. ∑ Smooth muscles produce weak, non fatigable contractions. ∑ These are used for vasoconstriction and the movement of food (peristalsis).

THE MUSCULAR SYSTEM 207 ∑ Since smooth muscle is found in the walls of all the hollow organs of the body (except the heart) its contraction reduces the size of these structures. It, therefore: – regulates the flow of blood in the arteries – moves food along through your gastrointestinal tract – expels urine from urinary bladder – sends babies out from the uterus – regulates the flow of air through the lungs.

Striated or Skeletal of Voluntary Muscles Sarcoplasm Sarcolemma Light band Dark band Nucleus

(a)

Fig. 6.2

Myofibril

(b)

(a) Striated muscle (b) Enlarged view

Characteristics As their name implies, skeletal muscles are attached to the skeleton and move various parts of the body. They are composed of tissue fibres that are striated or stripped. The alternating bands of light and dark result from the pattern of the filaments, threadlike proteins, within each muscle cell. Skeletal muscles are also called voluntary muscles because a person controls their use, as in flexing of an arm or the raising of a foot. Skeletal muscle cells (fibres), like other body cells, are soft and fragile. The connective tissue covering furnishes support and protection for the delicate cells and allow them to withstand the forces of contraction. The coverings also provide pathways for the passage of blood vessels and nerves. ∑ Skeletal muscle, as its name implies, is the muscle attached to the skeleton. It is also called striated muscle. The contraction of skeletal muscle is under voluntary control. ∑ It is wrapped and separated into muscle compartments by a layer of dense irregular connective tissue called deep fascia. ∑ Under that is a layer of collagenous tissue called epimysium which covers one muscle. ∑ The muscle is subdivided into fascicles by the fibrous perimysium and each muscle fibre is surrounded by the thin fibrous endomysium.

208 HUMAN ANATOMY AND PHYSIOLOGY ∑ At each end there is a cylindrical tendon or a sheet-like tendon (aponeurosis) that attaches the muscle to bone. ∑ Taken all together, these energy storing, collagenous tissues within and immediately outside the muscle are called series elastic elements. ∑ The skeletal tissue is also known as the striated tissue. ∑ It is composed of long fibres. ∑ These long fibres are surrounded by sarcolemma. ∑ The skeletal tissue has sarcoplasm. ∑ The skeletal tissue contains many nuclei and has cross striations. ∑ It is supplied with nerves from the central nervous system. ∑ Since it is under a conscious control, it is known as the voluntary muscle. ∑ The skeletal muscle is attached to some parts of the skeleton by the tendons. ∑ Contractions of the skeletal muscle serve to move various bones as well as cartilages of the skeleton. ∑ A skeletal muscle is a cylindrical or flat sheet of muscle fibres or cells.

Location These are associated with the bones.

Functions They are concerned with locomotion and change of body postures.

Cardiac Muscles

Nucleus

Intercalated discs

Dark and light bands

Fig. 6.3 Cardiac muscle

Characteristics Heart muscle is also called cardiac muscle. It makes up the wall of the heart. Throughout life, it contracts some 70 times per minute pumping about 5 litres of blood each minute.

THE MUSCULAR SYSTEM 209 ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

∑ ∑ ∑ ∑

The cardiac muscle forms most of the vertebrae heart. It requires to be supplied with oxygen. Unlike the smooth muscle, the cardiac muscle is not under the voluntary control. It is filled with the nerves from the autonomic nervous system. The autonomic impulses don’t speed up or slow down. The autonomic impulse is not in charge of the rhythmic contraction characteristic of a living cardiac muscle. The mechanism of the cardiac muscle is not understood. Heart attacks occur when there is insufficient blood is supplied to the cardiac muscle. It produces relatively strong contractions which are not fatigable. They are under involuntary (autonomic nervous system) control. Nuclei are in centre of weaving cells, intercalated discs bind cells together with desmosomes and gap junction tubules allow for ion currents to pass from one cell to another. Actin and myosin make striations. Cardiac muscle has pacemaker cells which depolarize (fire) at a set rate (autorhythmicity) which can be increased or decreased by the nervous system. Cardiac or heart muscle resembles skeletal muscle in some ways: it is striated and each cell contains sarcomeres with sliding filaments of actin and myosin. However, cardiac muscle has a number of unique features that reflect its function of pumping blood. The myofibrils of each cell (and cardiac muscle is made of single cells-each with a single nucleus) are branched. The branches interlock with those of adjacent fibres by adherent junctions. These strong junctions enable the heart to contract forcefully without ripping the fibres apart. The action potential that triggers the heartbeat is generated within the heart itself. Motor nerves (of the autonomic nervous system) do run to the heart, but their effect is simply to modulate – increase or decrease – the intrinsic rate and the strength of the heartbeat. Even if the nerves are destroyed (as they are transplanted in the heart), the heart continues to beat. The action potential that drives contraction of the heart passes from fibre to fibre through gap junctions. Significance: All the fibres contract in a synchronous wave that sweeps from the atria down through the ventricles and pumps blood out of the heart. Anything that interferes with this synchronous wave (such as damage to part of the heart muscle from a heart attack) may cause the fibres of the heart to beat at random — called fibrillation. Fibrillation is the ultimate cause of most deaths and its reversal is the function of defibrillators that are part of the equipment in ambulances, hospital emergency rooms, and — recently — even on U.S. air lines. The refractory period in heart muscle is longer than the period it takes for the muscle to contract (systole) and relax (diastole). Thus tetanus is not possible (a good thing, too!). Cardiac muscle has a much richer supply of mitochondria than skeletal muscle. This reflects its greater dependence on cellular respiration for ATP. Cardiac muscle has little glycogen and gets little benefit from glycolysis when the supply of oxygen is limited. Thus anything that interrupts the flow of oxygenated blood to the heart leads quickly to damage — even death — of the affected part. This is what happens in heart attacks.

210 HUMAN ANATOMY AND PHYSIOLOGY Location These muscles are only found in the heart.

Functions These help in cardiac contraction and relaxation. These are self stimulating and nerves do not fatigue. These receive from autonomic nervous system and thus are involuntary.

6.3

MUSCULAR FUNCTION

Muscles pull on bones and act as lever system. Muscles have a tendinous origin which is immovable, and a tendinous insertion which is movable.

Classes of Levers There are three classes of levers:

E First Class Lever E

R

F

Fig. 6.4

First class lever

It resembles a see-saw with a fulcrum in the middle of the force or load and effort. It is diagrammed as E-F-R, e.g., splenius capitis which inserts on the occipital bone of the skull, extending it (the force) and pulling the chin (the resistance), extension of arm at the elbow by the action of triceps muscles.

EE Second Class Lever R

E

F

Fig. 6.5

Second class lever

The second class lever diagrammed F-R-E. It resembles a wheel barrow, e.g., the gastrocnemius muscle pulls the heel (calcaneus) upward as if you are lifting the handles of the wheel barrow causing the metatarsal/ phalange, the wheel, joint to press against the floor. When you stand up on your toes, the resistance is the weight of the body pressing down on the ankles. Gastrocnemius muscle raises weight of the body on the toes.

EEE Third Class Lever E

F

Fig. 6.6 Third class lever

R

THE MUSCULAR SYSTEM 211 In this the fulcrum and resistance are at opposite ends, the effort in between. The third class lever is diagrammed F-E-R. Examples are the adductors of the thigh, tweezers, and lifting a shovel of dirt. The fulcrum is the hip joint, the effort is the adductors’ contractions and the resistance is the weight of the leg., biceps muscles flexing the arm. Vertebrates move by application of the principles of lever. Levers amplify or increase the force or velocity of motion. The amount of amplification depends on the length of the lever. The study of different types of muscles level systems and their movements is called Kinesiology.

Levers vs. muscles of the body ∑ The majority of the muscles of the body act on bones as the power on levers. ∑ Levers of the III Class are the most common, as action of the Biceps, and Brachialis muscles on the forearm bones. ∑ Levers of the I Class are found in movements of the head where the occipito-atlantal joint acts as the fulcrum and the muscles on the back of the neck as power. ∑ Another common example is the foot when one raises the body by contracting the Gastrocnemius and Soleus. ∑ Here the ankle-joint acts as fulcrum and the pressure of toes on the ground as weight. ∑ This is frequently, though wrongly, considered a lever of the II Class. ∑ If one were to stand on one’s head with the legs up and with a weight on the plantar surface of the toes, it is easy to see that we would have a lever of the I Class if the weight were raised by contraction of the Gastrocnemius muscle. ∑ The confusion has arisen by not considering the fact that fulcrum and power in all three classes of levers must have a common basis of action. ∑ If the fulcrum rests on the earth the power must either directly or indirectly push from the earth or be attached to earth either by gravity or otherwise if it pulls toward the earth. ∑ If the power were attached to the weight no lever action could be obtained.

6.4

TYPES OF MUSCLE FIBRES

Two different types of muscle fibres can be found in most skeletal muscles—Type I and Type II fibres. These differ in their structure and biochemistry.

Type I Fibres ∑ Also called slow twitch/ oxidative /fatigue resistant/ ST/Type I/ Red fibres. ∑ These are small, red fibres with oxygen binding molecule myoglobin and therefore use aerobic glucose metabolism. ∑ These produce slow, fatigue resistant contractions necessary for posture or walking. ∑ Red muscle cells have lots of mitochondria, blood vessels and myoglobin. ∑ Marathon runners have a larger proportion of these. ∑ These are loaded with mitochondria and depend on cellular respiration for ATP production, resistant to fatigue, rich in myoglobin and hence red in colour. ∑ These are slow- conducting, also known as “slow-twitch” fibres and are dominant in muscles that depend on tonus, thus responsible for posture.

212 HUMAN ANATOMY AND PHYSIOLOGY Type II Fibres ∑ Also called fast twitch /oxidative and glycolytic/fatigue resistant/ FT-A/Type IIA/ Intermediate Fibres. ∑ These are aerobic, good for long sprints or distance runners, have less blood flow and myoglobin than the red fibres but more than white. ∑ CP and glycogen stores are moderately high and fibres size is large. ∑ White muscle cells have few mitochondria, few blood vessels, and no oxygen-binding myoglobin. ∑ They have few mitochondria, rich in glycogen and depend on glycolysis for ATP production. ∑ These fatigue easily. ∑ These are low in myoglobin hence whitish in colour. ∑ These are activated by large-diameter, thus fast-conducting motor neurons and therefore are also know as “fast-twitch” fibres. ∑ These are dominant in muscles used for rapid movement. Most skeletal muscles contain some mixture of Type I and Type II fibres, but a single motor unit that always contains one type or the other, never both. The ratio of Type I and Type II fibres can be changed by endurance training, producing more Type I fibres. For example, sprinters and power lifters have a larger proportion of these fibres in their leg and arm muscles.

6.5

STRUCTURE OF MUSCLE CELLS

Each muscle is made of hundreds to thousands of individual muscle cells. Unlike most other cells in the body, these cells are unusually shaped: they are elongated like a cylinder or a long rod. Because of their shape, muscle cells are normally referred to as muscle fibres. Whereas most cells have a single nucleus, muscle fibres have as many as 100 or more nuclei. The nuclei are located on the surface of the fibres, just under its thin membrane. Another difference between muscle fibres and other body cells is their size. They can extend the entire length of a muscle. For example, a muscle fibres in a thigh muscle could measure 0.0004 inch (0.001cm) in diameter and 12 to 16 inches (30 to 40 cm) in length.

Unit of Muscles – Myofibril ∑ The myofibril is the main unit for all muscles. ∑ Fibre or muscle cells contain several myofibrils that arrange myofilament in two types— thick and thin. ∑ The thick myofilament contains many molecules of the protein myosin. ∑ While the thick filament contains two strands of the protein actin. ∑ Myofibrils are made thick and thin myofibrils that alternative rows. ∑ These alternative rows of filaments slide along each other during contractions. ∑ Mitochondria surround the myofibril. Mitochondrion generates energy when the muscle is contracting.

THE MUSCULAR SYSTEM 213 6.6

STRUCTURE OF SKELETAL MUSCLE

Muscle belly Epimysium (deep fascla)

Tendon Epimycium

Fasciclulus Endomysium (between fibers) Sarcolemma Sarcoplasm

Muscle fibres Endomycium Fascicule

Myofibel Perimysium Single muscle fiber Nuclel (a)

Fig. 6.7

Perymycium (b)

(a) TS of muscle (b) Part of TS of muscle showing details

∑ Skeletal muscle fibre is a single cylindrical muscle cell. ∑ An individual skeletal muscle may be made up of hundreds or even thousands of muscle fibres bundled together and wrapped in a connective tissue covering. ∑ Each muscle is surrounded by a connective tissue sheath called the epimysium. ∑ Fascia, connective tissue outside the epimysium, surrounds and separates the muscles. ∑ Portions of the epimysium project inward to divide the muscle into compartments. ∑ Each compartment contains a bundle of muscle fibres. ∑ Each bundle of muscle fibre is called a fasciculus and is surrounded by a layer of connective tissue called the perimysium. ∑ Within the fasciculus, each individual muscle cell, called a muscle fibre, is surrounded by connective tissue called the endomysium. ∑ Commonly, the epimysium, perimysium, and endomysium extend beyond the fleshy part of the muscle, the belly or gaster, to form a thick rope like tendon or a broad, flat sheet-like aponeurosis. ∑ The tendon and aponeurosis form indirect attachments from muscles to the periosteum of bones or to the connective tissue of other muscles. ∑ Typically a muscle spans a joint and is attached to bones by tendons at both ends. ∑ One of the bones remains relatively fixed or stable while the other end moves as a result of muscle contraction. ∑ Skeletal muscles have an abundant supply of blood vessels and nerves. ∑ This is directly related to the primary function of skeletal muscle contraction. ∑ Before a skeletal muscle fibre can contract, it has to receive an impulse from a nerve cell. ∑ Generally, an artery and at least one vein accompany each nerve that penetrates the epimysium of a skeletal muscle. ∑ Branches of the nerve and blood vessels follow the connective tissue components of the muscle of a nerve cell and with one or more minute blood vessels called capillaries. ∑ Skeletal muscle is made up of thousands of cylindrical muscle fibres often running all the way from origin to insertion. The fibres are bound together by connective tissue through which run the blood vessels and nerves.

214 HUMAN ANATOMY AND PHYSIOLOGY Muscle Tendon

Tendon

Fasciculus of muscle fibres

Tendon attachment

A single muscle fibre

A portion of muscle fibre Muscle fibrils

Sarcolemma

A porition of a muscle fibril ‘A’ band

Sarcomere

Nucleus

‘I’ band

Z disc

Fig. 6.8 Structure of striated muscles, their fibres and myofibrils ∑ Each muscle fibre contains: – An array of myofibrils that are stacked lengthwise and run the entire length of the fibre. – Mitochondria. – An extensive smooth endoplasmic reticulum (SER) – Many nuclei. ∑ The multiple nuclei arise from the fact that each muscle fibre develops from the fusion of many cells (called myoblasts). ∑ The number of fibres is probably fixed early in life. ∑ This is regulated by myostatin, a cytokine and is synthesized in muscle cell (and circulates as a hormone later in life). ∑ Myostatin suppresses skeletal muscle development. ∑ Cattle and mice with inactivating mutations in their myostatin genes develop much larger muscles. ∑ Some athletes and other remarkably strong people have been found to carry one mutant myostatin gene.

THE MUSCULAR SYSTEM 215 ∑ These discoveries have already led to the growth of an illicit market in drugs supposedly able to suppress myostatin. ∑ In adults, increasing strength and muscle mass comes about through an increase in the thickness of the individual fibres and increase in the amount of connective tissue. ∑ In the mouse, at least, fibres increase in size by attracting more myoblasts to fuse with them. ∑ The fibres attract more myoblasts by releasing the cytokine interleukin 4 (IL-4). ∑ Anything that lowers the level of myostatin also leads to an increase in fibre size. ∑ Because a muscle fibre is not a single cell, its parts are often given special names such as – Sarcolemma for plasma membrane. – Sarcoplasmic reticulum for endoplasmic reticulum. – Sarcosome for mitochondrion. – Sarcoplasm for cytoplasm. Although this tends to obscure the essential similarity in structure and function of these structures and those found in other cells. ∑ The nuclei and mitochondria are located just beneath the plasma membrane. ∑ The endoplasmic reticulum extends between the myofibrils. Sarcomere

Z line

Z line Thick filaments

Thin filaments

H zone I band

Fig. 6.9

A band

I band

Structure of sarcomere

Under the microscope, skeletal muscle fibres show a pattern of cross banding, which gives it a name— striated muscle. The striated appearance of the muscle fibre is created by a pattern of alternating: ∑ Dark A bands and ∑ Light I bands ∑ The A bands are bisected by the H zone ∑ The I bands are bisected by the Z line. Each myofibril is made up of parallel filaments. ∑ The thick filaments have a diameter of about 15 nm. They are composed of the protein myosin. ∑ The thin filaments have a diameter of about 5 nm. They are composed chiefly actin protein along withalong with smaller amounts of two other proteins: Troponin and Tropomyosin.

216 HUMAN ANATOMY AND PHYSIOLOGY 6.7

ANATOMY OF A SACROMERE

Muscle fibres are multinucleated, located just under the plasma membrane. Most of the cells are occupied by striated, thread-like myofibrils. Within each myofibril there are dense Z lines. A sarcomere (muscle functional unit) extends from Z line to Z line. Each sarcomere has thick and thin filaments. The thick filaments are made of myosin and occupy the centre of each sarcomere. Thin filaments are made of actin and anchor to the Z line. ∑ The thick filaments produce dark A band. ∑ The thin filaments extend in each direction from Z line. Where they do not overlap thick filament, they create light I band. ∑ The H zone is that portion of A band where thick and thin filaments do not overlap. ∑ The entire array of thick and thin filaments between Z lines is called a sarcomere. Shortening of sarcomeres in a myofibril produces the shortening of myofibril and, in turn, of the muscle fibre of which it is a part.

Structure of Contractile Proteins 1. Structure of Myosin ∑ Thick filaments are made of myosin molecules ∑ Each myosin molecule has two identical heads and two pairs of helical strands forming tail. ∑ Each globulin head has actin binding site and ATP binding site. Actin binding sites

ATP binding sites

Tail

Fig. 6.10

Structure of myosin

2. Structure of Actin ∑ It is the constituent of thin filaments. Tropomyosin axis Actin filament

Troponin site

Fig. 6.11

Structure of actin

THE MUSCULAR SYSTEM 217 ∑ ∑ ∑ ∑

It resembles tow strings of beads twisted into a double helix. Each bead is a molecule of G-actin (globular actin) with 55A° diameter. It shows high affinity for calcium ions. In the presence of salts and ATP, it is converted into fibrons actin (F-actin). Troponin-I Troponin-C Troponin-T Tropomyosin Molecules G-Actin molecules (Monomers)

Groups of troponin molecules

Actin filament

Fig. 6.12

Ultrastructure of myosin and actin filaments

3. Tropomyosin ∑ It is a two-stranded a-helical rod which is located in the groove between the two helical strands of actin. ∑ A troponin complex is attached to the tropomyosin at regular intervals of about 385 A°.

4. Troponin ∑ It is a globular protein consisting of three polypeptide chains, the calcium binding subunit (TpC), the inhibitory subunit (TpC) and the tropomyosin-binding sub-unit (TpT). ∑ Troponin is an important control protein. TpC binds with calcium and turns on contraction whereas TpI binds to actin so as to inhibit the interaction of the actin with myosin TpT binds to tropomyosin and restores calcium sensitivity.

6.8

CONTRACTION OF MUSCLES

The contraction of skeletal muscle is controlled by the nervous system. In this respect, skeletal muscle differs from smooth and cardiac muscle. Both cardiac and smooth muscles can contract without being stimulated by the nervous system. Nerves of the autonomic branch of the nervous system lead to both smooth and cardiac muscle, but their effect is one of moderating the rate and/ or strength contraction.

Role of Calcium Ions ∑ Calcium ions(Ca2+) link action potentials in a muscle fibre to contraction. ∑ In resting muscle fibres, Ca2+ is stored in the endoplasmic (sarcoplasmic) reticulum.

218 HUMAN ANATOMY AND PHYSIOLOGY ∑ Spaced along the plasma membrane (sarcolemma) of the muscle fibre are inpocketings of the membrane that form tubules of the “T system”. These tubules plunge repeatedly into the interior of the fibre. ∑ The tubules of the T system terminate near the calcium-filled sacs of the sarcoplasmic reticulum. ∑ Each action potential created at the neuromuscular junction sweeps quickly along the sarcolemma and is carried into the T system. ∑ The arrival of the action potential at the ends of the T system triggers the release of Ca2+. ∑ The Ca2+ diffuses among the thick and thin filaments, where it binds to troponin on the thin filaments. ∑ This turns on the interaction between actin and myosin and the sarcomere contracts. ∑ Because of the speed of the action potential (milliseconds), the action potential arrives simultaneously at the ends of all the tubules of the T system, ensuring that all sarcomeres contract in unison. ∑ When the process is over, the calcium is pumped back into the sarcoplasmic reticulum using a Ca2+ ATPase.

Discovering the link between nerves and muscles ∑ Swiss biologist Victor Albrecht von Haller (1708–1777) was the first scientist to discover the relationship between nerves and muscles. ∑ Prior to his research, scientists knew little about the structure and function of nerves or about their interaction with muscles ∑ A popular theory at the time even held that nerves were hollow tubes through which a spirit or fluid flowed. ∑ Haller rejected this theory, since no one had ever been able to locate or identify such a spirit or fluid. Instead, he sought to prove that a muscle contracts when a stimulus is applied to it. Haller labelled this action irritability. ∑ In his research, Haller soon found that irritability increased when a stimulus was applied to a nerve connected to a muscle. ∑ He then rightly concluded that in order of a muscle to contract, a stimulus had to come from its connecting nerve.

The Sliding Filament Theory Cross bridge

Z line

Primary myofilament (Myosin)

H zone (a)

Secondary myofilament (Actin)

Z line

THE MUSCULAR SYSTEM 219 A band Sarcomere

1band

Z line

Z line A band (b)

Fig. 6.13

Muscle contraction (a) Relaxed state (b) Contracted state Active sites of actomyosin formation Movement A

Actin filament Power stroke

Hinges

Hinge

Myosin filament Active sites upon actin filament

1 2 3 4 5 6 B

Spur

Myosin filament 1 2 3 4 5 6 Cross bridge

C

1 2 3 4 5 6 D

1 2 3 4 5 6 E

Fig. 6.14 Formation of cross bridges and sliding of actin filaments upon myosin filaments towards M-line ∑ In 1950, while working to explain exactly how muscles contract, two teams of scientists developed the same theory at the same time: the sliding filament theory. ∑ Today, medical researchers accept this theory as a good description of what happens to make a muscle contract.

220 HUMAN ANATOMY AND PHYSIOLOGY ∑ According to the sliding filament theory, thick myofilaments have branches or arms that extend out from their main body. ∑ At the end of the branches are thickened heads. ∑ Normally, when a muscle is relaxed, the thick and thin myofilaments do not interact. ∑ When the muscle is stimulated to contract. ∑ The electrical charge triggered by acetylcholine stimulates the release of calcium ions (an ion is an atom or group or atoms that has an electrical charge) stored within the muscle fibre. ∑ The ions attach to the thin myofilaments and remove their protective coverings. ∑ The arms of the thick myofilaments then reach out, and the heads on the arms attach to open sites on the thin myofilaments. ∑ The arms pivot (an action called a power stroke), pulling the thin myofilaments toward the centre of the sarcomere. ∑ This shortens the sarcomere. ∑ As this event occurs simultaneously throughout all sarcomeres in a muscle fibre, shortens or contracts. ∑ A single nerve impulse produces only one contraction, which lasts between 0.01 and 0.04 second. ∑ For a muscle fibre to remain contracted, the brain must send additional never impulses. ∑ When nave impulses cease, so do the electrical charges, the release of calcium ions, and the connection between thin myofilaments and thick myofilaments. Muscle fibril

Sarcomere

A-Band I-Band

Z disc A

A H

Actin filaments

B

½ Band

Z disc

½ Spurs

M Myosin filament line H

C

z

Spurs

z

THE MUSCULAR SYSTEM 221 Myosin filament Actin filament Hexagon Trigon

D

Fig. 6.15 Ultrastructure of relaxed muscle myofibril A-Sarcomere C-A contracted sarcomere, D-Ts through terminal part of A-band

Contraction ∑ Thus muscles contract by shortening each sarcomere. ∑ The sliding filament model of muscle contraction has thin filaments on each side of the sarcomere sliding past each other until they meet in the middle. ∑ Myosin filaments have club-shaped heads that project toward the actin filaments. ∑ Each molecule of myosin in the thick filaments contains a globular subunit called the myosin head. ∑ The myosin heads have binding sites for – the actin molecules in the thin filaments and – ATP. ∑ Activation of the muscle fibre causes the myosin heads to attach to binding sites on the actin filaments. ∑ The myosin heads swivel toward the centre of the sarcomere, detach and then reattach to the nearest active site of actin filament. ∑ An allosteric change occurs which draws thin filament short distance (~10 nm) pass the thick filament. ∑ Each cycle of attachment, swivelling and detachment shortens the sarcomere 1%. ∑ Thus the linkages break (for which ATP is needed) and reform farther along the thin filament to repeat the process. ∑ As a result, the filaments are pulled past each other in a ratchet like action. ∑ There is no shortening, thickening, or folding of the individual filaments ∑ Hundreds of such cycles occur each second during muscle contraction. ∑ Energy for this comes from ATP, the energy coin of the cell. ∑ ATP binds to the cross bridges between myosin heads and actin filaments. ∑ The release of energy powers the swivelling of the myosin head. ∑ Muscles store little ATP and so must recycle the ADP into ATP rapidly. ∑ Creatine phosphate is a muscle storage product involved in the rapid regeneration of ADP into ATP. ∑ Calcium ions are required for each cycle of myosin-actin interaction. ∑ Calcium is released into the sarcomere when a muscle is stimulated to contract. ∑ This calcium uncovers the actin binding sites. ∑ When the muscle no longer needs to contract, the calcium ions are pumped from the sarcomere back into storage.

222 HUMAN ANATOMY AND PHYSIOLOGY As a muscle contracts, ∑ The Z lines come closer together ∑ The width of the I bands decreases ∑ The width of the H zones decreases, but ∑ There is no change in the width of A band. Conversely, as a muscle is stretched, ∑ The width of the I bands and H zones increases, ∑ But there is still no change in the width of the A band. Actin filament Tropomyosin

Troponin + Ca2+

Myosin binding site

Ca2+ 1. Action potential causes depolarization and

Myosin head

release of Ca2+

ADP

2+

Ca Ca2+

Resting myosin fibril

ADP

2. Ca2+ exposes myosin binding sites, myosin heads bind to actin ADP

Myosin head

4. ATP binds to myosin, causing it to release actin

3. Power stroke; filaments slide past one another

5. ATP is hydrolyzed and myosin heads return to resting position

ADP +

6. If Ca2+ is returned to sarcoplasmic reticulum. muscle relaxes

Fig. 6.16

7. If Ca2+ remains available, the cycle repeats and muscle Contraction continues

Contraction of a muscle fibre

THE MUSCULAR SYSTEM 223 Isotonic versus Isometric Contractions ∑ If a stimulated muscle is held so that it cannot shorten, it simply exerts tension. This is called an isometric (“same length”) contraction. ∑ If the muscle is allowed to shorten, the contraction is called isotonic (“same tension”). ∑ An isotonic contraction happens if muscle fibres shorten as the myosin cross-bridges move the actins. Isometric contractions occur when muscle tension increases but muscle length does not shorten, the myosin cross-bridges are “spinning their wheels” against the actins. ∑ Aerobic-isotonic contractions are said to be better for your overall bone, muscle and joint health. That’s why swimming and “power walking” (with arm weights) are good exercises. ∑ If you want to just increase muscle size, isometric contractions are best. ∑ Even though muscle fibres store some oxygen, that oxygen is quickly used up, especially during strenuous exercise. ∑ In order to convert glucose into ATP, they can continue working. It is because muscles need more oxygen via blood. ∑ That is why respiration or breathing rate increases during physical exertion. ∑ In times where work or play activities are exhausting, muscle fibres may literally run out of oxygen. ∑ If not enough oxygen is present in muscle fibres, the fibres convert glucose into lactic acid, a chemical waste product.

Contraction of Nonmuscular Cells Actin and myosin, whose interaction causes muscle contraction, occur in many other cells. Actin is attached to the inner surface of the plasma membrane. The interaction of cytoplasmic myosin and this actin causes contraction of the cell, such that coordinated contractions of intestinal cells absorb nutrients. Some fish have modified muscles that discharge electricity. These fish have electric organs consisting of modified muscles known as electroplates. The South American electric eel has more than 6000 plates arranged into 70 columns. Maximum discharge is 100 watts.

6.9

THE NEUROMUSCULAR JUNCTION ∑ Neuromuscular junctions are the point where a motor neuron attaches to a muscle. ∑ Acetylcholine is released from the axon end of the nerve cell when a nerve impulse reaches the junction. ∑ A wave of electrical changes is produced in the muscle cell when the acetylcholine binds to receptors on its surface. ∑ Calcium is released from its storage area in the cell’s endoplasmic reticulum. ∑ An impulse from a nerve cell causes calcium release and brings about a single, short muscle contraction called a twitch. ∑ Skeletal muscles are organized into hundreds of motor units, each of which is a motor neuron and a group of muscle fibres. ∑ A graded response to a circumstance will involve controlling the number of motor units. While

224 HUMAN ANATOMY AND PHYSIOLOGY

∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

individual muscle units contract as a unit, the entire muscle can contract on a graded basis due to their organization into motor units. In order to contract or shorten, muscle fibres must be stimulated by nerve impulses sent through motor neurons or nerves. These impulses originate in the brain, and then run down the spine. From there, they branch out to all parts of the body. A single motor neuron may stimulate a few muscle fibres or hundreds. A motor neuron along with all the fibres it stimulates is called a motor unit. When a motor neuron reaches a muscle fibre, it does not touch the fibre, but fits into a hollow on the surface of the muscle fibre. This region where the end of motor neuron and membrane of the muscle fibre come close is called the neuromuscular junction. When a nerve impulse reaches the end of motor neuron at the neuromuscular junction, acetylcholine (a neurotransmitter chemical) is released. Acetylcholine then travels across the small gap between the motor neuron and the muscle fibre and attaches to receptors on the membrane of the muscle fibre. This triggers an electrical charge that quickly travels from one end of the muscle fibre to the other, causing it to contract. Motor axon Yesicles containing acetylcholine (ACh)

Axon terminal

Acetylcholinesterase

ACh receptors

Muscle fiber End - plate potential (EPP) Action potential

0 Membrane potential (mv)

– 50 – 100 Time / (msec)

Nerve impulse arrives at axon terminal

∑ Nerve impulses (action potentials) travelling down the motor neurons of the sensory-somatic branch of the nervous system cause the skeletal muscle fibres at which they terminate to contract. ∑ The junction between the terminal of a motor neuron and a muscle fibre is called the neuromuscular junction. It is simply one kind of synapse. ∑ The neuromuscular junction is also called the myoneural junction. ∑ The terminals of motor axons contain thousands of vesicles filled with acetylcholine (ACh).

THE MUSCULAR SYSTEM 225 ∑ When an action potential reaches the axon terminal, hundreds of these vesicles discharge their ACh onto a specialized area of postsynaptic membrane on the fibre. ∑ This area contains a cluster of transmembrane channels that are opened by ACh and let sodium ions (Na+) diffuse in. ∑ The interior of a resting muscle fibre has a resting potential of about - 95 mV. ∑ The influx of sodium ions reduces the charge, creating an end plate potential. ∑ If the end plate potential reaches the threshold voltage (approximately – 50 mV), sodium ions flow in with a rush and an action potential is created in the fibre. ∑ The action potential sweeps down the length of the fibre just as it does in an axon. ∑ This period, called the latent period, lasts from 3 – 10 msec. Before the latent period is over, ∑ The enzyme acetylcholinesterase – breaks down the ACh in the neuromuscular junction (at a speed of 25,000 molecules per second) – the sodium channels close, and – the field is cleared for the arrival of another nerve impulse. ∑ The resting potential of the fibre is restored by an outflow of potassium ions. The brief (1- 2 msec) period needed to restore the resting potential is called the refractory period.

Tetanus ∑ The process of contracting takes some 50 msec; relaxation of the fibre takes another 50 – 100 msec. ∑ Because the refractory period is so much shorter than the time needed for contraction and relaxation, the fibre can be maintained in the contracted state so long as it is stimulated frequently enough (e.g., 50 stimuli per second). Such sustained contraction is called tetanus.

Motor Units All motor neurons leading to skeletal muscles have branching axons, each of which terminates in a neuromuscular junction with a single muscle fibre. Nerve impulses passing down a single motor neuron will thus trigger contraction in all the muscle fibres at which the branches of that neuron terminate. This minimum unit of contraction is called the motor unit. The size of the motor unit is small in muscles over which we have precise control. Examples: ∑ A single motor neuron triggers fewer than 10 fibres in the muscles controlling eye movements ∑ The motor units of the muscles controlling the larynx are as small as 2 to 3 fibres per motor neuron ∑ In contrast, a single motor unit for a muscle like the gastrocnemius (calf) muscle may include 1000 – 2000 fibres (scattered uniformly through the muscle). Although the response of a motor unit is all-or-none, the strength of the response of the entire muscle is determined by the number of motor units activated. Even at rest, most of our skeletal muscles are in a state of partial contraction called tonus. Tonus is maintained by the activation of a few motor units at all times even in resting muscle. As one set of motor units relaxes, another set takes over.

226 HUMAN ANATOMY AND PHYSIOLOGY Biceps and Triceps Ball and socket joint

Scapula

Origins

Belly of triceps (extensor)

Belly of biceps (flexor)

Hinge joint Radius Ulna

Fig. 6.17

Insertion

Biceps and triceps antagonistic muscles

A single skeletal muscle, such as the triceps muscle, is attached at its ∑ Origin to a large area of bone; in this case, the humerus ∑ At its other end, the insertion, it tapers into a glistening white tendon which, in this case, is attached to the ulna, one of the bones of the lower arm. As the triceps contracts, the insertion are pulled toward the origin and the arm is straightened or extended at the elbow. Thus the triceps is an extensor. Because skeletal muscle exerts force only when it contracts, a second muscle — a flexor — is needed to flex or bend the joint. The biceps muscle is the flexor of the lower arm. Together, the biceps and triceps make up an antagonistic pair of muscles. Similar pairs, working antagonistically across other joints, provide for almost all the movement of the skeleton.

6.10

MUSCLE CELL DEPOLARIZATION

∑ When excitation of the muscle by nerve impulses stops, calcium ions are pumped by active transport back into the sarcoplasmic reticulum by a calcium pump located in the membrane of the sarcoplasmic reticulum. This process also requires energy which is supplied by ATP. The myosin heads fall back towards thick filaments and actomyosin complex breaks which causes relaxation of the muscle with the return of Z lines back to their original place. In the relaxed period sarcolemma becomes repolarized and this change is known as resting potential. ∑ The duration upto which a muscle contract can depend upon the supply of ATP to the muscle fibre and vary in different muscles. If a muscle contraction is repeated at short intervals where relaxation period is insufficient, the muscle becomes fatigued due to accumulation of lactic acid. This condition is brought to normal by heavy and prolonged breathing during rest. The oxygen, thus supplied is utilized for the oxidation of lactic acid to glycogen and normal activity is restored. ∑ When ACh binds to its postsynaptic membrane receptors on the muscle cell, the Na+ gates open and a wave of depolarization sweep down the outer membrane or sarcolemma of the muscle cell, down into the T or transverse tubules and into the interior of the cell where the sarcoplasmic reticulum and the contractile units, the sarcomeres, are located.

THE MUSCULAR SYSTEM 227 ∑ When the wave of Na+ depolarization reaches the vicinity of the sarcoplasmic reticulum calcium ion storage sacs, the calcium gates in the S.R. are induced to open, releasing Ca++ ions into the sarcomere. ∑ Before the actins and myosins can ratchet, the myosin cross bridges must attach to the actins. ∑ They are blocked by the protein troponin – a protein which is like a gourd on rope called tropomyosin. Ca++ ions remove the troponin block by changing the shape of the troponin, then the tropomyosin/troponin complex moves over so that the myosin cross bridges can attach to the globular g actin cogs. ∑ ATP is needed to power the ratcheting action, although only 20% goes to move the actin, the balance of 80% becomes heat.

6.11

FUELING MUSCLE CONTRACTION

Creatine ~ P

Glycogen

Glycolysis Creatine + ~P

Lactic acid + ~P

Glucose or other fuel

Respiration

~P + CO2 + H2O

ATP

Muscle contraction

Fig. 6.18 Energy sources of muscle contraction ATP is the immediate source of energy of muscle contraction. A muscle fibre contains only enough ATP to power a few twitches, its ATP “pool” is replenished as needed. There are three sources of high-energy phosphate to keep the ATP pool filled. They are: ∑ Creatine phosphate ∑ Glycogen ∑ Cellular respiration in the mitochondria of the fibres.

Creatine Phosphate The phosphate group in creatine phosphate is attached by a “high-energy” bond like that in ATP. Creatine phosphate derives its high-energy phosphate from ATP and can donate it back to ADP to form ATP. Creatine phosphate + ADP ´ creatine + ATP

228 HUMAN ANATOMY AND PHYSIOLOGY The pool of creatine phosphate in the fibre is about 10 times larger than that of ATP and thus serves as a modest reservoir of ATP.

Glycogen Skeletal muscle fibres contain about 1% glycogen. The muscle fibre can degrade this glycogen by glycogenolysis producing glucose – 1 – phosphate. This enters the glycolytic pathway to yield two molecules of ATP for each pair of lactic acid molecules produced. Not much, but enough to keep the muscle functioning if it fails to receive sufficient oxygen to meet its ATP needs by respiration. However, this source is limited and eventually the muscle must depend on cellular respiration.

Cellular Respiration Cellular respiration is not only required to meet the ATP needs of a muscle engaged in prolonged activity (thus causing more rapid and deeper breathing), but is also required afterwards to enable the body to resynthesize glycogen from the lactic acid produced earlier (deep breathing continues for a time after exercise is stopped). The body must repay its oxygen debt.

6.12

MUSCLE METABOLISM

Glucose is metabolized just outside and inside the mitochondria to make ATP. There are two ways to make ATP from the energy stored in the chemical bonds of glucose and there is a supercharger system providing for a reserve of ATP. 1. Anaerobic ∑ Just outside the mitochondrion, each glucose molecule is broken down to yield a net of 2 ATP of a possible 36. ∑ The product lactic acid is produced. This process is wasteful of energy but it is quick. ∑ There is another maximum net yield of 34 ATP ’s that could be made from each glucose – a lot of energy stored in the chemical bonds of lactic acid. ∑ Lactic acid accumulations make muscles sore and if the pH drops too far, and retards breathing (small decreases of .05pH points would cause increases of breathing rate). ∑ However, the lactic acid is taken by the blood to liver where it can be reformed into glucose. ∑ Also, it can be changed back to the crossroads molecule pyruvic acid and entered into the aerobic pathway. ∑ The more lactic acid you accumulate the greater your oxygen debt which must be repaid by increased breathing. ∑ The conversion of glucose into 2 ATP ’s and pyruvic acid is called glycolysis. The conversion of pyruvic acid and 2H to lactic acid is called muscle cell fermentation. 2. Phosphagen System ∑ Reserves of high energy phosphate bonds are made when creatine phosphate (CP) is formed. ∑ The high energy phosphate is transferred to ADP to make an ATP which is used to ratchet actins in sarcomere contraction. The creatine phosphate and glycogen reserves are good for about 40 to 45 seconds of maximal muscle activity such as in sprinting the 400 m dash in the Olympics.

THE MUSCULAR SYSTEM 229 ∑ More specifically, there are 6 sec. worth of stored ATP, 30 sec. worth of creatine phosphate, the balance coming from anaerobic fermentation that supplements energy production when breathing cannon keep up with oxygen needs for aerobic cellular respiration. ∑ You know that the latter has happened because when you go anaerobic, you have to stop and breathe hard to catch your breath – you have generated an oxygen debt that has to be repaid. 3. Aerobic ∑ Remember that anaerobic metabolism leads to aerobic. Deep inside the mitochondrion, oxygen is used to fully metabolize glucose, C6H12O6 + 6O2 + 36 ADP + 36P Æ 36 ATP’s + 6CO2 + 6H2O

6.13

MUSCLE FATIGUE

∑ Muscle fatigue occurs when muscle strength fails as first glycogen and creatine phosphate deplete, then ATP runs out, Ca++ release from the SR declines, and lactic acid builds up. ∑ Fatigue and pain is felt when the liver and muscle cells stop supplying glucose that comes from the breakdown of glycogen starch. ∑ The body then switches to fat and protein catabolism to make “new glucose” and other products that can be used in cellular metabolism to make the ATP needed to keep going. ∑ Natural pain-killing opiates (endorphins) are released in the Central Nervous System at this time, resulting in “runner’s high.”

6.14

RIGOR MORTIS

∑ When a person dies, blood stops circulating through the body. ∑ The skeletal muscle, along with all other parts of the body are deprived of oxygen and nutrients, including ATP. ∑ Calcium ions leak out of their storage area in the membranes of muscle fibres, causing thick myofilaments to attach to and pull thin myofilaments. ∑ While the muscle fibres still have a stored supply of ATP, the heads of thick myofilaments are able to detach from the thin myofilaments. ∑ When the supply of ATP runs out, however, the heads cannot detach and the muscle fibres stay in a contracted position. ∑ The rigid state of muscle contraction that results is called rigor mortis. ∑ Depending on the person’s physical condition at death, the onset of rigor mortis may vary from ten minutes to several hours after death. ∑ Facial muscles are usually affected first, followed by other parts of the body. ∑ Rigor mortis lasts until the muscle fibres begin to decompose fifteen to twenty-five hours after death.

6.15

TENDONS

∑ The layers of connective tissue that bundle the various parts of a muscle usually converge or come together at the end of the muscle to form a tough, white, cord-like tissue called tendon.

230 HUMAN ANATOMY AND PHYSIOLOGY ∑ Tendons attach muscles to bone. ∑ Because they contain fibres of the tough protein collagen, tendons are much stronger than muscle tissue. ∑ The collagen fibres are arranged in a tendon in a wavy way so that it can stretch and provide additional length at the muscle-bone junction. ∑ As muscles are used, the tendons are able to withstand the constant pulling and tugging. ∑ Muscles are always attached at both of their ends. ∑ The end that is attached to a bone that moves when the muscle contracts is called the insertion. ∑ The other end, attached to a bone that does not move when the muscle contracts, is called the origin. ∑ It is important to note that not all muscles are attached to bones at both ends. ∑ The ends of some muscles are attached to other muscles and some are attached to the skin.

6.16

MUSCLE TONE

Even when the body is at rest, certain muscle fibres in all muscles are contracting. This activity is directed by the brain and cannot be controlled consciously. This state of continuous partial muscle contractions is known as muscle tone. These contractions are not strong enough to produce movement, but do tense and firm the muscles. In doing so, they keep the muscles firm, healthy, and ready for action. Muscles with moderate muscle tone are firm and solid, whereas ones with little muscle tone are limp and soft. Muscle tone is the result of different motor units throughout a muscle being stimulated by the nervous system in an orderly way. First one group of motor units is stimulated, then another. Alternate fibres contract so the muscle as a whole does not become fatigued. Muscle tone is important because it helps human beings maintain an upright posture. Without muscle tone, an individual would not be able to sit up straight in a chair or hold his or her head up. Muscle tone is also important because it generates heat to help maintain body temperature. Normal muscle tone accounts for about 25 percent of the heat in a body at rest.

6.17

MUSCLES IN THE HUMAN BODY

Human body consists of about 650 skeletal muscles some say-that number is 850. Exact figure is not available as scientists disagree about which ones are separate muscles and which ones are parts of large muscles. Here muscles are discussed under four headings:

Muscles of the Head and Neck ∑ Humans have well-developed muscles in the face that permit a large variety of facial expressions. ∑ Because the muscles are used to show surprise, disgust, anger, fear and other emotions, they are an important means of nonverbal communication. ∑ Muscles of facial expression include frontalis, orbicularis oris, laris oculi, buccinator, and zygomaticus.

THE MUSCULAR SYSTEM 231 ∑ The muscles of the face are unique: they are attached to the skull on one end and to the skin or other muscles on the other end. ∑ Muscles that are attached to the skin of the face allow people to express emotions through actions such as smiling, frowning, pouting etc. ∑ The frontalis covers the frontal bone or forehead. ∑ The temporalis is a fan-shaped muscle overlying the temporal bone on each side of the head above the ear. ∑ The orbicularis oculi encircles each eye and helps close the eyelid. ∑ The orbicularis oris is the circular muscle around the lips. ∑ It closes and extends the lips. ∑ The masseter, located over the rear of the lower jaw on each side of the face, opens and closes the jaw, allowing chewing. ∑ The buccinator, running horizontally across each cheek, flattens the cheek and pulls back the corners of the mouth. ∑ The sternocleidomastoid, located on either side of the neck and extending from the clavicle or collarbone to the temporal bone on the side head, allows the head to rotate and the neck to flex.

Fig. 6.19

Muscles of the Head and neck

∑ There are four pairs of muscles that are responsible for chewing movements or mastication. ∑ All of these muscles connect to the mandible and they are some of the strongest muscles in the body. ∑ Two of the muscles, temporalis and masseter are shown in the figure above. ∑ There are numerous muscles associated with the throat, the hyoid bone and the vertebral column, only two of the more obvious and superficial neck muscles are sternocleidomastoid and trapezius.

Muscles of Trunk ∑ The muscles of the trunk include those that move the vertebral column, the muscles that form the thoracic and abdominal walls, and those that cover the pelvic outlet.

232 HUMAN ANATOMY AND PHYSIOLOGY

Fig. 6.20 Muscles of the trunk ∑ The erector spinae group of muscles on each side of the vertebral column is a large muscle mass that extends from the sacrum to the skull. ∑ These muscles are primarily responsible for extending the vertebral column to maintain erect posture. ∑ The deep back muscles occupy the space between the spinous and transverse processes of adjacent vertebrae. ∑ The muscles of the thoracic wall are involved primarily in the process of breathing. ∑ The intercostal muscles are located in spaces between the ribs. ∑ They contract during forced expiration. ∑ External intercostal muscles contract to elevate the ribs during the inspiration phase of breathing. ∑ The diaphragm is a dome-shaped muscle that forms a partition between the thorax and the abdomen. ∑ It has three openings in it for structures that have to pass from the thorax to the abdomen. ∑ The abdomen, unlike the thorax and pelvis, has no bony reinforcements or protection. ∑ The wall consists entirely of four muscle pairs, arranged in layers, and the fascia that envelops them. ∑ The abdominal wall muscles are shown in the diagram given above. ∑ The pelvic outlet is formed by two muscular sheets and their associated fascia. ∑ On the front part of the trunk or torso, the pectoralis major are the large, fan-shaped muscles that cover the upper part of the chest. ∑ They flex the shoulders and pull the arms into the body.

THE MUSCULAR SYSTEM 233 ∑ The rectus abdominis are the strap-like muscles of the abdomen, extending from the ribs to the pelvis. ∑ Better known as the stomach muscles, they flex the vertebral column or backbone and provide support for the abdomen and its many organs. ∑ The muscles making up the side walls of the abdomen are the external oblique. ∑ In addition to helping compress the abdomen, they rotate the trunk and allow it to bend sideways. ∑ On the rear part of the trunk, the trapezius are the kite-shaped muscles that run from the back of the neck and upper back down to the middle of the back. ∑ They raise, lower, and abduct the shoulders. ∑ The large, flat muscles that cover the lower back are the latissimus dorsi. ∑ They abduct and rotate the arms and help extend the shoulders.

Muscles of the Upper Extremity ∑ The muscles of the upper extremity include those that attach the scapula to the thorax and generally move the scapula, those that attach the humerus to the scapula and generally move the arm, and those that are located in the arm or forearm that move the forearm, wrist, and hand. The figure below shows some of the muscles of the upper extremity. ∑ The fleshy, triangular-shaped muscles that form the rounded shape of the shoulders are the deltoid. Trapezius Pectoralis major Trapezius Deltoid

Deltoid

Teres minor Teres major

Coracobrachialis Biceps

Triceps Latissimus dorsi

Brachialis

Brachioradialis Extensor carpi radialis (longus and brevis)

Brachioradialis Pronator teres Palmaris longus

Flexor carpi radialis Thenar muscles

Flexor carpi ulnaris

Flexor carpi ulnaris Extensor carpi ulnaris

Extensor digitorum

Pronator quadratus Hypothenar muscles

(a) Right

Fig. 6.21

(b) Left

Muscles of the Upper Extremity

∑ They help abduct the arm, or move it away from the middle of the body. The most familiar muscle of the upper arm is the biceps brachii. ∑ Located on the front of the upper arm, the bicep makes a prominent bulge as it flexes the elbow.

234 HUMAN ANATOMY AND PHYSIOLOGY ∑ ∑ ∑ ∑

∑ ∑ ∑ ∑

On the rear portion of the upper arms is the triceps brachii. Its action is just the opposite of the biceps: it extends or straightens the forearm. The muscles of the forearm, which move the bones of the hands, are thin and long. Of these many muscles, the flexor carpi bend the wrist and the flexor digitorum bend the fingers. The muscles that have the opposite effect, extending the wrist and fingers, are the extensor carpi and the extensor digitorum. Muscles that move the shoulder and arm include the trapezius and serratus anterior. The pectoralis major, latissimus dorsi deltoid, and rotator cuff muscles connect to the humerus and move the arm. The muscles that move the forearm are located along the humerus, which include the triceps brachii, biceps brachii, brachialis, and brachioradialis. The 20 or more muscles that cause most wrist, hand and finger movements are located along the forearm.

Muscles of the Lower Extremity Anterior superior iliac spine

Inguinal ligament Femoral artery Femoral vein Superficial inguinal ring

lliopsoas

Gluteus maximus Tensor fasciae latae

Pectineus Greater trochanter of femur

Gracilis

Gracilis Adductor magnus

Sartorius Adductor longus lliotibial tract Rectus femoris

lliotibial tract

Semitendinosus Adductor magnus Biceps femoris: Short head of biceps femoris Long head of biceps femoris

Vastus lateralis Vastus medialis

Semimembranosus

Sartorius

Patella

Plantar Sartorius

Patellar ligament Peroneus longus

Tuberosity of tibia Gastrocnemius

Extensor digitorum longus Tibialis anterior

Tibia

Peroneus brevis

Soleus

Gastrocnemius

Soleus Superior extensor retinaculum Lateral malleolus

Medial malleolus Extensor hallucis longus

Inferior extensor retinaculum

ANTERIOR

Fig. 6.22

Peroneus longus

Calcaneal (Achilles tendon)

Peroneus brevis

Medial malleolus

Lateral malleolus

Calcaneus POSTERIOR

Muscles of the lower extremity

∑ The muscles that move the thigh have their origins on some part of the pelvic girdle and their insertions on the femur. ∑ The largest muscle mass belongs to the posterior group, the gluteal muscles, which, as a group, abduct the thigh.

THE MUSCULAR SYSTEM 235 ∑ The iliopsoas, an anterior muscle, flexes the thigh. ∑ The muscles in the medial compartment abduct the thigh. The diagram shown above shows some of the muscles of the lower extremity. ∑ Muscles that move the leg are located in the thigh region. ∑ The quadriceps femoris muscle group straightens the leg at the knee. ∑ The hamstrings are antagonists to the quadriceps femoris muscle group, which are used to flex the leg at the knee. ∑ The muscles located in the leg that move the ankle and foot are divided into anterior, posterior, and lateral compartments. ∑ The tibialis anterior, which dorsiflexes the foot, is antagonistic to the gastrocnemius and soleus muscles, which plantar flex the foot. ∑ Muscles of the lower limbs cause movement at the hip, knee, and foot joints. ∑ These muscles are among the largest and strongest muscles in the body. Muscles on the thigh (upper portion of the leg) are especially massive and powerful since they hold the body upright against the force of gravity. ∑ The gluteus maximum are the large muscles that form most of the flesh of the buttocks. ∑ These powerful muscles help extend the hip in activities such as climbing stairs and jumping. ∑ The adductor muscles are a group of muscles that form a mass on the inside of the thighs. As their name indicates, they adduct or press the thighs together. ∑ On the front of the thigh is a group of four muscles know collectively as the quadriceps. ∑ Together, the quadriceps help powerfully extend or straighten the knee, such as when an individual kicks a soccer ball. ∑ On the back of the thigh, a group of three muscles performs the opposite effect. Known as hamstrings, these muscles flex or bend the knee ∑ The sartorius is long, straplike muscle that crosses the front of the thigh diagonally from the outside of the hip to the inside of the knee. ∑ Although it is not that powerful, it does lie on upper surface of the thigh and is easily seen. ∑ The sartorius helps rotate the leg so an individual can sit in a cross-legged position with the knees wide apart. ∑ On the back part of the lower leg is the calf muscle, properly known as the gastrocnemius. ∑ This diamond-shaped muscle, formed in two sections,helps extend or lower the foot, such as when an individual walks on his or her toes. ∑ The strong tendon that attaches the gastrocnemius to the heel of the foot is the well-known Achilles tendon. ∑ The main muscle on the front part of the lower leg, the tibialis anterior, opposes the action of the gastrocnemius. ∑ It flexes and inverts or elevates the foot. Muscles can also be classified on the basis of the type of movement they bring about. 1. Flexor Muscles. Their contraction bends a limb by pulling two skeletal elements towards each other. 2. Extensor Muscles. Their contraction extends a limb by pulling two skeletal elements apart from each other. 3. Adductor Muscles. These muscles pull body parts towards the central long axis of the body. 4. Abductor Muscles. By their contraction the limbs are pulled away from the central long axis of the body.

236 HUMAN ANATOMY AND PHYSIOLOGY 5. 6. 7. 8. 9. 10.

Protractor Muscle. It pulls distal part of a limb forwards. Retractor Muscle. It pulls distal part of a limb backwards. Rotator Muscles. Their contraction rotates whole or part of a limb at one of its joints. Levator Muscles. By their contraction, the bone is raised. Depressor Muscles. By their contraction the bone falls down. Supinator Muscles. By their contraction the humerus can be rotated and palm becomes towards sky. 11. Pronator Muscles. By their contraction the palm can be turned downwards.

6.18

DEVELOPMENT OF THE MUSCLES

Both the cross-striated and smooth muscle, with the exception of a few that are of ectodermal origin, arise from the mesoderm. ∑ The intrinsic muscles of the trunk are derived from the myotomes while the muscles of the head and limbs differentiate directly from the mesoderm. ∑ The Myotomic Muscles. The intrinsic muscles of the trunk which are derived directly from the myotomes are conveniently treated in two groups, the deep muscles of the back and the thoraco-abdominal muscles. The deep muscles of the back extend from the sacral to the occipital region and vary much in length and size. They act chiefly on the vertebral column. The shorter muscles, such as the Interspinales, Intertransversarii, the deeper layers of the Multifidus, the Rotatores, Levatores costarum, Obliquus capitis inferior, Obliquus capitis superior and Rectus capitis posterior minor which extend between adjoining vertebrae, retain the primitive segmentation of the myotomes. ∑ Other muscles, such as the Splenius capitis, splenius cervicis, Sacrospinalis, Semispinalis, multifidus lliocostalis, Longissimus, Spinales, Semispinales, and Rectus capitis posterior major, which extend over several vertebrae, are formed by the fusion of successive myotomes and the splitting into longitudinal columns. ∑ The fascia lumbo-dorsalis develops between the true myotomic muscles and the more superficial ones which migrate over the back such as the Trapezius, Rhomboideus, and Latissimus. ∑ The anterior vertebral muscles, the Longus colli, capitis Rectus capitis anterior and Rectus capitis lateralis are derived from the ventral part of the cervical myotomes as are probably also the Scaleni. ∑ The thoraco-abdominal muscles arise through the ventral extension of the thoracic myotomes into the body wall. This process takes place coincident with the ventral extension of the ribs. In the thoracic region the primitive myotomic segments still persist as the intercostal muscles, but over the abdomen these ventral myotomic processes fuse into a sheet which splits in various ways to form the Rectus, the Obliquus exterus and internus, and the Transversalis. Such muscles as the Pectoralis major and minor and the Serratus anterior do not belong to the above group ∑ The Ventrolateral Muscles of the Neck. The intrinsic muscles of the tongue, the Infrahyoid muscles and the diaphragm are derived from a more or less continuous premuscle mass which extends on each side from the tongue into the lateral of the upper half of the neck and into it early extend the hypoglossal and branches of the upper cervical nerves. The two halves which from the Infrahyoid muscles and the diaphragm are at first widely separated from each other by the heart. As the latter descends into the thorax the diaphragmatic portion of each

THE MUSCULAR SYSTEM 237



∑ ∑ ∑

∑ ∑ ∑



6.19

lateral mass is carried with its nerve down into the thorax and the laterally placed Infrahyoid muscles move toward the midventral line of the neck. Muscles of the Shoulder Girdle and Arm. The Trapezius and Sternocleidomastoideus arise from a common premuscle mass in the occipital region just caudal to the last branchial arch; as the mass increases in size it spreads downward to the shoulder girdle to which it later becomes attached. It also spreads backward and downward to the spinous processes, gaining attachment at a still later period. The Levator scapulae, serratus anterior and the Rhomboids arise from premuscle tissue in the lower cervical region and undergo extensive migration. The Latissimus dorsi and Teres major are associated in their origin from the premuscle sheath of the arm as are also the two Pectoral muscles when the arm bud lies in the lower cervical region. The intrinsic muscles of the arm develop in situ from the mesoderm of the arm bud and probably do not receive cells or buds from the myotomes. The nerves enter the arm bud when it still lies in the cervical region and as the arm shifts caudally over the thorax the lower cervical nerves which unite to form the brachial plexus, acquire a caudal direction. The Muscles of the Leg. The muscles of the leg like those of the arm develop in situ from the mesoderm a of the leg bud, the myotomes apparently taking no part in their formation. The Muscles of the Head. The muscles of the orbit arise from the mesoderm over the dorsal and caudal sides of the optic stalk. The muscles of mastication arise from the mesoderm of the mandibular arch. The mandibular division of the trigeminal nerve enters this premuscle mass before it splits into the Temporal, Masseter and Pterygoideus. The facial muscle (muscles of expression) arise from the mesoderm of the hyoid arch. The facial nerve enters this mass before it begins to split, and as the muscle mass spreads out over the face head and neck it splits more or less incompletely into the various muscles.

MACHINE VS MUSCLES

Robots and machines that move and pick up objects like humans may no longer be found only in science fiction novels and movies. Scientists have created various artificial muscles that contract and expand just like human muscles. Unlike human muscles, however, artificial muscles have no limit to their strength. One such, artificial muscle is made out artificial silk, which is cooked and then boiled to make a rubbery, semiliquid substance. The substance is similar to structure of human muscle, composed of smaller and smaller fibres. These fibres are naturally negatively charged with electricity. When an acid (which has a positive electrical charge) is applied to this substance, the negative and positive ions attract each other and the substance contracts. When a base material (which has a negative charge) is applied, the ions repel each other and the material expands. The National Aeronautics and Space Administration (NASA) hase plans for artificial muscles. A small NASA rover destined to explore an asteroid in 2002 will be equipped with artificial muscles. Scientists hope tests like this one will eventually lead to the creation of space robots with humanlike flexibility and movement. Beyond that, they hope artificial muscles may someday be used to replace defective muscles in humans.

238 HUMAN ANATOMY AND PHYSIOLOGY 6.20

MUSCULAR SYSTEM DISORDERS

Spasms and Cramps ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

Muscle cramps occur if K+ ions depleted. The process of repolarization of muscle fibre is affected. If cell does not repolarize completely, it stays in a somewhat depolarized state. This results in spasmodic contractions or cramps. Muscle spasms and cramps are spontaneous, often painful muscle contracts. Cramps are usually defined as spasms that last over a period of time. Any muscle in the body may be affected, but spasms and cramps are most common in the calves, feet, and hands. While painful, spasms and cramps are harmless and are not related to any disorder, in most cases. Spasms or cramps may be caused by abnormal activity at any stage in the process of muscle contraction, from brain sending an electrical signal to muscle fibre relaxing. Prolonged exercise, where sensations of pain and fatigue are often ignored, can lead to such severe energy shortage that a muscle cannot relax, causing a spasm or cramp. Dehydration – the loss of fluids and salts through sweating, vomiting, or diarrhea – can disrupt ion balances in both muscles and nerves. This can prevent them from responding and recovering normally, which can lead to spasms and cramps. Most simple spasms and cramps require no treatment other than patience and stretching. Gentle stretching and massage of the affected muscle may ease the pain and hasten recovery.

Strains ∑ Strains are tears in a muscle. ∑ Sometimes called pulled muscles, they usually occur because of overexertion ( too much tension placed on a muscle) or improper lifting techniques. ∑ Strains are common and can affect anyone. ∑ Symptoms of strains range from mild muscle stiffness to great soreness. ∑ Mild strains can be treated at home. ∑ Basic first aid consists of RICE: Rest, lce for forty-eight hours, Compression (wrapping in an elastic bandage), and Elevation. ∑ Strains can be prevented by stretching and warming up before exercising and using proper lifting techniques.

Botulism ∑ Botulism, or severe food poisoning, is caused by a toxin (poison) produced by a certain bacteria that are sometime present in food not properly canned or preserved. ∑ Once released by the bacteria in the body, the toxin prevents motor neurons from releasing acetylcholine at neuromuscular junctions. ∑ Muscle fibres are then not stimulated to contract and results in paralysis ( partial or complete loss of ability to move).

THE MUSCULAR SYSTEM 239 ∑ As botulism progresses, muscles controlling breathing fail and the affected individual suffocates. ∑ Botulism is a serious disease that requires prompt medical attention. ∑ Antibiotics are not effective in preventing or treating the disease. ∑ Medical researchers have developed an antitoxin (antibody capable of acting against a toxin) for treating botulism. ∑ However, it only works on the toxin when it is not attached to nerve endings. An antitoxin must be given to an infected individual as soon as possible. ∑ Motor neuron endings that have already been affected by the toxin cannot be saved. ∑ If an individual survives a severe case of botulism, it may take weeks, months years for the body to recover fully.

Tetanus ∑ Like botulism, tetanus is also caused by a toxin released by bacteria. ∑ This bacterium invades the body most often through deep punctured wounds exposed to contaminated soil. ∑ Many people associate tetanus with wounds from rusty nails or dirty objects, but any wound can be a source. ∑ In the body, the tetanus bacteria releases its toxin, which affects motor neurons at neuromuscular junctions. ∑ Its effect, however, is opposite that of the botulism toxin. ∑ This toxin causes the repetitive stimulation of muscle fibres, resulting in convulsive muscle spasms and rigidity. ∑ Tetanus is often called “lockjaw” because one of the most common symptoms is a stiff jaw, unable to be opened. ∑ The disease sometimes affects the body only at the site of infection. ∑ More often, it spreads to the entire body. ∑ The uncontrollable muscle spasms produced are sometimes severe enough to cause broken bones. ∑ Tetanus results in death when the muscles controlling breathing become “locked” and cannot function.

The Muscular Dystrophies (MD) ∑ Together myosin, actin, tropomyosin and troponin make up over three-quarters of the protein in muscle fibres. ∑ Some two dozen other proteins make up the rest. ∑ These serve such functions as attaching and organizing the filaments in the sarcomere and connecting the sarcomeres to the plasma membrane and the extracellular matrix. ∑ Mutations in the genes encoding these proteins may produce defective proteins and resulting defects in the muscles. ∑ The most common type of genetic (inherited) muscular disorder is muscular dystrophy. ∑ This disease causes skeletal muscles to waste away slowly and progressively. Medical researchers generally recognize nine types of muscular dystrophy. ∑ The causes behind some of these types are not well understood. ∑ In others, researchers believe that proteins used by muscle fibres to protect their membranes are defective leading to deterioration of the membranes and the muscle fibres. ∑ The most frequent most dreaded type of muscular dystrophy appears in boys aged three to seven. (Boys are usually affected because it is a sex-linked condition; girls are carriers of the disease and are usually not affected.)

240 HUMAN ANATOMY AND PHYSIOLOGY ∑ The first symptom of this disease type is clumsiness in walking and a tendency to fall due to muscle weakness in the legs and pelvis. ∑ The disease then spreads to other areas in the body. ∑ Sometimes, muscle tissue is replaced by fatty tissue, giving the false impression that the muscles have become enlarged. ∑ By the age of ten, a boy is usually confined to a wheelchair or a bed. ∑ Death usually occurs before adulthood because of a respiratory infection brought on by the weakness of respiratory or breathing muscles. ∑ Another type of muscular dystrophy appears later in life and affects both sexes equally. The first signs appear in adolescence. ∑ The muscles affected are those in the face, shoulders, and upper arms. ∑ The hips and legs may also be affected. ∑ This type of muscular dystrophy occurs in about 1 out of every 20,000 people. Individuals afflicted with this disease may survive until middle age. ∑ Currently, there is no known cure for any type of muscular dystrophy. ∑ Certain drugs have been developed that slow the progression of some types. ∑ Physical therapy involving regular, nonstrenuous exercise is often prescribed to help maintain general good health. ∑ Among the most common of the muscular dystrophies are those caused by mutations in the gene for dystrophin. ∑ The gene for dystrophin is huge, containing 79 exons spread out over 2.3 million base pairs of DNA. ∑ Thus this single gene represents about 0.1% of the entire human genome (3 ¥ 109 bp) and is almost half the size of the entire genome of E. coli! ∑ Duchenne muscular dystrophy (DMD). Deletions of nonsense mutations that cause of frameshift usually introduce premature termination codons (PTCS) in the resulting mRNA. Thus at best only a fragment of dystrophin is synthesized and DMD, a very severe form of the disease, results. The gene for dystrophin is on the X chromosome, so these two diseases strike males in a typical X-linked pattern of inheritance. ∑ Becker muscular dystrophy (BMD). If the deletion simply removes certain exons but preserves the correct reading, frame, a slightly-shortened protein results that produces BMD, a milder form of the disease.

Myasthenia Gravis ∑ Myasthenia gravis is an autoimmune disorder affecting the neuromuscular junction. ∑ Patients have smaller end plate potentials (EPPs) than normal. ∑ With repeated stimulation, the EPPs become too small to trigger further action potentials and the fibre ceases to contract. ∑ Administration of an inhibitor of acetylcholinesterase temporarily can restore contractility by allowing more ACh to remain at the site. ∑ Patients with myasthenia gravis have only 20% or so of the number of ACh receptors found in normal neuromuscular junctions. ∑ This loss appears to be caused by antibodies directed against the receptors. ∑ A disease resembling myasthenia gravis can be induced in experimental animals by immunizing them with purified ACh receptors.

THE MUSCULAR SYSTEM 241 ∑ Anti-ACh receptor antibodies are found in the serum of human patients. ∑ Experimental animals injected with serum from human patients develop the signs of myasthenia gravis. ∑ Newborns of mothers with myasthenia gravis often show mild signs of the disease for a short time after their birth. This is the result of the transfer of the mother’s antibodies across the placenta during gestation. ∑ The reason for some people develop autoimmune antibodies against the ACh receptor is unknown. ∑ Myasthenia gravis is an autoimmune disease that causes muscle weakness. ∑ An autoimmune disease is one in which antibodies (proteins normally produced by the body to fight infection) attack and damage the body’s own normal cells, causing tissue destruction. ∑ In myasthenia gravis, antibodies attack receptors on the membranes of muscle fibres that receive acetylcholine, from motor neurons. ∑ Unable to receive acetylcholine, the muscle fibres cannot be stimulated to contract and weakness develops. ∑ The disease can occur at any age, but it is most common in women between the age of twenty and forty. ∑ The muscles of the neck, throat lips, tongue, face, and eyes are primarily affected. ∑ Muscles of the arms, legs, and trunk may also be involved. ∑ Depending on the severity of the disease, a person may have difficulty moving their eyes, seeing clearly, walking, speaking clearly, chewing and swallowing and even breathing. ∑ Physical exertion, heat from the Sun, hot showers, hot drinks, and stress may all increase symptoms. ∑ There is no cure for myasthenia gravis, but drugs have been developed that effectively control the symptoms in most people. ∑ The disease only causes early death if the respiratory muscles are affected and stop functioning property.

The Cardiac Myopathies Cardiac muscle, like skeletal muscle, contains many proteins in addition to actin and myosin. Muscles in the genes for these may cause the wall of the heart to become weakened and, in due course, enlarged. Among the genes that have been implicated in these diseases are those encoding: ∑ actin ∑ two types of myosin ∑ troponin ∑ tropomyosin ∑ myosin-binding protein C (which links myosin to titin) The severity of the disease varies with the particular mutation causing it (over 100 have been identified so far). Some mutations are sufficiently dangerous that they can lead to sudden catastrophic heart failure in seemingly healthy and active young adults. Eosinophilic myalgia is a muscle weakening allergic-like autoimmune attack on muscles. It was apparently caused by a contaminant in health foodstore-bought tryptophan-an amino acid used to enhance the serotonin secretions which help induce sleep in the brain. Physicians no longer advise their patients to take this for insomnia.

242 HUMAN ANATOMY AND PHYSIOLOGY 6.21 ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

6.22

HEALTHY MUSCULAR SYSTEM As humans age, all muscle tissues decrease in size and power. Muscle fibres die and are replaced by fibres connective tissue or by fatty tissue. The connective tissue makes the muscles less flexible. Movement is limited. Even muscles with normal tone will atrophy or waste away. The effects of this eventual decline in the muscular system can be offset by regular exercise throughout an individual’s life. Exercise helps control body weight, strengthens bones, tones and builds muscles, and generally improves the quality of life for people of all ages. Some types of exercise help to strengthen the heart and lungs. These activities are called aerobic exercises. Walking, jogging, cycling, swimming, and climbing stairs are just a few examples of aerobic activity. These exercises also force the large muscles of the body to use oxygen more efficiently, as well as store greater amounts of ATP. Exercises that increase the size and strength of muscles are called anaerobic exercises. These types of exercises require quick bursts of energy. Weight lifting and sprinting are two examples anaerobic activity. As muscles grow larger, they require more energy to work, even when the body is at rest. To meet this increased need, the body is forced to use its stored nutrients more efficiently. When combined with exercise, the following help keep the muscular system operating at peak efficiency: proper nutrition, healthy amounts of good-quality drinking water, adequate rest, and stress reduction. Foods that are low in fat (especially saturated fat), low in cholesterol, and high in fibre should be eaten. Fat should make up no more than 30 percent of a person’s total daily calorie intake. Breads, cereals, pastas, fruits, and vegetables should form the bulk of a person’s diet; meat, fish, nuts, and cheese and other dairy products should make up a lesser portion. Stress taxes all body systems. Any condition that threatens the body’s homeostasis or steady state is a form of stress. Conditions that cause stress may be physical, emotional, or environmental. When stress lasts longer than a few hours, higher energy demands are placed on the body. Combining exercise with proper amounts of sleep relaxation techniques, and positive thinking will help reduce stress and keep the body in balance.

MUSCLES IN SPACE

In the zero gravity of space, astronauts face many challenges. Chief among these is the effect of weightlessness on muscles. Even after spending as little as four or five days in space, astronauts have experienced significant muscle and bone changes. The reason is that more than half the muscles in the human body are designed primarily to fight gravity. In a weightless environment, those muscles are not used. As a result, they quickly weaken and atrophy or waste away. Without the stress of pumping blood through the body against the force of gravity, the muscles of the heart also begin to weaken considerably.

THE MUSCULAR SYSTEM 243 Exercising during space flights is one way astronauts have tried to counter the effects of zero gravity. Unfortunately, they have had to exercise two to three hours a day just to maintain muscle and cardiovascular strength. The National Aeronautics and Space Administration (NASA) and research centers are currently working to develop exercising devices that recreate the forces on Earth so astronauts can spend more time exploring instead of exercising. When a muscle fibre contracts, it does so completely and always produces the same amount of pull (tension). The muscle fibre is either “on” “or” “off.” This is known as the all-or-nothing principle of muscle contraction. While this principle applies to individual muscle fibres, it does not apply to entire muscles. A muscle would be useless if it could only contract completely or not at all. The amount of tension or pull in a muscle can vary depending on how many muscle fibres in that muscle are stimulated to contract.

6.23

MUSCLE FACTS

Smallest muscle in the body is Stapedius: the muscle that activates the stirrup, the small bone that sends vibrations from the eardrum to the inner ear. It measures just 05 inch (0.13 centimeter) in length. Largest muscle in the body Latissimus dorsi: the large, flat muscle pair that covers the middle and lower back. Longest muscle in the body Sartorius: the straplike muscle that runs diagonally from the waist down across the front of the thigh to the knee. Strongest muscle in the body Gluteus maximus: the muscle pair of the hip that form most of the flesh of the buttocks. Fastest-reacting muscle in the body orbicularis oculi: the muscle that encircles the eye and closes the eyelid. It contracts in less than 0.01 second. Number of muscles used to make a smile: Seventeen. Number of muscles used to make a frown: Forty-three

REVIEW QUESTIONS 1. 2. 3. 4. 5. 6.

7. 8. 9. 10.

Discuss chemistry of muscle cantraction. Explain various disorders of muscles. Explain in detail various types of muscles and their functions. Describe the sliding mechanism in theory of muscles. Explain role of muscles in the field of locomotion. Explain – (a) Muscles in space. (b) Machines with muscles. Describe development of muscles. Write an essay on – fueling muscle cantraction. Explain neuro muscular junction in detail Draw related diagrams. Discuss role of calcium in muscular contraction and relaxation.

CHAPTER

7

HAEMOPOIETIC SYSTEM Horse shoe shaped nucleus Side view

Cytoplasm

Surface view

Platelets (Non-nucleated)

Nucleus with dent lymphocyte

Erythrocyte (Denucleated)

3–5 Lobed nucleus

Neutrophil

7.1

2 Lobed nucleus

Cytoplasm

Monocyte

Indistinctly lobed nucleus

Cytoplasm Eosinophil

Basophil

INTRODUCTION

The average human adult has more than 5 litres of blood in his or her body. Blood transports oxygen and nutrients to living cells and takes away their waste products. It also delivers immune cells to fight infections and contains platelets that can form a clot in a damaged blood vessel to prevent blood loss. The liquid component of blood is plasma, which contains water, proteins, nutrients, hormones, electrolytes and metabolic waste products. It is yellow in colour which is due to the presence of bilirrubin (a waste product of haem degradation). Plasma proteins are synthesized by the liver and play a large variety of roles: transport of small molecules, maintaining osmotic pressure and clotting. Through the circulatory system, blood adapts to the body’s needs. When you are exercising, your heart pumps harder and faster to provide more blood and hence oxygen to your muscles. During an 244

HAEMOPOIETIC SYSTEM 245 infection, the blood delivers more immune cells to the site of infection, where they accumulate to ward off harmful invaders. A sample of blood can be further separated into its individual components by spinning the sample in a centrifuge. The force of the spinning causes denser elements to sink, and further processing enables the isolation of a particular protein or the isolation of a particular type of blood cell. With the use of this method, antibodies and clotting factors can be harvested from the plasma to treat immune deficiencies and bleeding disorders, respectively. Likewise, RBCs can be harvested for blood transfusion. All of these functions make blood a precious fluid. Each year large number of units of blood components is transfused to patients who need them. Blood is considered so precious that it is also called “red gold” as the cells and proteins it contains can be sold for more than the cost of the same weight of gold.

7.2

COMPONENTS OF BLOOD

Red cells

Platelets

White cells

Fig. 7.1

Main components of blood (Microscopic view)

Various components of blood are : 1. 2. 3. 4.

Plasma Erythrocytes / RBCs / red blood corpuscles / red blood cells. Leucocytes / WBCs / white blood corpuscles / white blood cells. Thrombocytes / Platelets. Average adult has about 5 litres of blood which has 1. Plasma = water + dissolved solutes Suspended in the watery plasma are various types of cell. 2. Formed elements: ∑ Red blood cells (RBCs) (or erythrocytes) ∑ White blood cells (WBCs) (or leucocytes)

246 HUMAN ANATOMY AND PHYSIOLOGY Three types of granulocytes (leucocytes with granules in their cytoplasm) 1. Neutrophils 2. Eosinophils 3. Basophils Two types of agranulocytes (leucocytes without granules in their cytoplasm) 4. Lymphocytes 5. Monocytes ∑ Platelets (or thrombocytes)

Neutrophils

Eosinophils

Lymphocytes

Monocytes

Fig. 7.2

Basophils

Platelets

Erythrocytes

Types of blood cells

If a test tube of blood is left to stand for half an hour, the blood separates into three layers as the denser components sink to the bottom of the tube and fluid remains at the top. The straw-coloured fluid that forms the top layer is called plasma and forms about 60% of blood. The middle white layer is composed of white blood cells (WBCs) and platelets, and the bottom red layer is the red blood cells (RBCs). These bottom two layers of cells form about 40% of the blood.

Plasma Leucocytes and platelets Erythrocytes

Fig. 7.3

Separation of blood components

HAEMOPOIETIC SYSTEM 247 7.3

PLASMA

It is pale yellowish, slightly alkaline fluid in which the blood corpuscles float. It has the following composition : Water

90%

Proteins Inorganic salts

7–8% 1%

(Mainly NaCl, NaHCO3) Other substances

traces

(Glucose, hormones, amino acids, waste products etc.) Plasma also contains plasma proteins, which are part of the blood itself, that is, they are not being carried to the tissues for their metabolism. They are made in the liver and enter the plasma. These three proteins are : albumin, globulin and fibrinogen. Albumin contributes 70–80% of the osmotic pressure of plasma proteins. It also helps in the transport of several substances like free fatty acids, bilirubin, Ca2+ and steroid hormones. Globulins are the antibodies formed in the defence of the body against foreign germs. Fibrinogen has importance in the coagulation of blood. If concentration of albumen and globulins fall, it can lead to filteration of water from the blood into the tissues. This produces oedema or retention of water in hands and feet. Plasma from which the protein fibrinogen has been removed is called serum. Plasma = serum + fibrinogen Or Serum = plasma – fibrinogen ∑ Albumins – 60–80% of plasma proteins – Most important in maintenance of osmotic balance – Produced by liver. ∑ Globulins – alpha and beta ¡ Some are important for transport of materials through the blood (e.g., thyroid hormone and iron) ¡ Some are clotting factors ¡ Produced by liver. – gamma globulins are immunoglobulins (antibodies) produced by lymphocytes ∑ Fibrinogen – Important in clotting. – Produced by liver.

Functions Plasma transports materials needed by cells and materials that must be removed from cells: ∑ Various ions (Na+, Ca2+, HCO3-, etc.

248 HUMAN ANATOMY AND PHYSIOLOGY ∑ Glucose and traces of other sugars ∑ Amino acids ∑ Other organic acids ∑ Cholesterol and other lipids ∑ Hormones ∑ Urea and other wastes. Most of these materials are in transit from a place where they are added to the blood, a “source”, to places (“sinks”) where they will be removed from the blood ∑ ∑ ∑ ∑

Exchange organs like the intestine Depots of materials like the liver Every cell Exchange organs like the kidney, and skin.

Serum Proteins Proteins make up 6–8% of the blood. They are about equally divided between serum albumin and a great variety of serum globulins. After blood is withdrawn from a vein and allowed to clot, the clot slowly shrinks. As it does so, a clear fluid called serum is squeezed out. Thus:

Serum is blood plasma without fibrinogen and other clotting factors. The serum proteins can be separated by electrophoresis. ∑ A drop of serum is applied in a band to a thin sheet of supporting material, like paper, that has been soaked in a slightly-alkaline salt solution. ∑ At pH 8.6, which commonly used, all the proteins are negatively charged, but some more strongly than others. ∑ A direct current can flow through the paper because of the conductivity of the buffer with which it is moistened. ∑ As the current flows, the serum proteins move toward the positive electrode. ∑ The stronger the negative charge on a protein, the faster it migrates. ∑ After a time (typically 20 min), the current is turned off and the proteins stained to make them visible (most are otherwise colorless). ∑ The separated proteins appear as distinct bands. ∑ The most prominent of these and the one that moves closest to the positive electrode is serum albumin. ∑ Serum albumin – is made in the liver, – binds many small molecules for transport through the blood, – helps maintain the osmotic pressure of the blood. ∑ The other proteins are the various serum globulins.

HAEMOPOIETIC SYSTEM 249 ∑ They migrate in the order – Alpha globulins (e.g., the proteins that transport thyroxine and retinol (vitamin A) – Beta globulins (e.g., the iron-transporting protein transferring) – Gamma globulins. ¡ Gamma globulins are the least negatively-charged serum proteins. (They are so weakly charged, in fact, that some are swept in the flow of buffer back toward the negative electrode.) ¡ Most antibodies are gamma globulins. ¡ Therefore gamma globulins become more abundant following infections or immunizations. If a precursor of an antibody-secreting cell becomes cancerous, it divides uncontrollably to generate a clone of plasma cells secreting a single kind of antibody molecule. The electrophoretic separation shows 1. Normal human serum with its diffuse band of gamma globulins; 2. Serum from a patient with multiple myeloma producing an lgG myeloma protein; 3. Serum from a patient with Waldenstrom’s macroglobulinemia where the cancerous clone secretes an lgM antibody; 4. Serum with an lgA myeloma protein.

7.4

ERYTHROCYTES

Erythrocytes, also known as red blood cells (RBCs), function to transport oxygen in the blood. The shape of erythrocytes is ideal for this function. Seen from the top, erythrocytes appear to be circular, but a side view shows that they are actually biconcaved discs. This shape increases the surface areato-volume ratio of the cell, thus increasing the efficiency of diffusion of oxygen and carbon dioxide into and out of the cell. They also have a flexible plasma membrane. In order to make room for more hemoglobin to carry more oxygen, erythrocytes loose their nucleus and other organelles as they develop in the bone marrow. Because they lack a nucleus and other cellular machinery, erythrocytes cannot repair themselves when damaged, consequently they have a limited life span of about 120 days. These are the most numerous cells in the blood and contain a substance called haemoglobin, which gives them red colour. They are bi-concave (flate in the center, and thick at the periphery), non-nucleated discs. They are very small, having a diameter of about 7.5 micrometres or 1 / 3200 inch. There are about five to six million red blood corpuscles per millilitre of normal blood. Erythrocytes are formed in the red marrow of the bones. The process of the production of erythrocytes is known as erythropoiesis. Decrease of number of red blood cells is known as erythrocytopenia and increase in number of RBC’s much more than normal is called polycythemia. The removal of old and dying erythrocytes is carried out by the spleen. Erythrocytes, which represent the most numerous cell type in the body die at a rapid rate, 2–3 million erythrocytes die every second.

250 HUMAN ANATOMY AND PHYSIOLOGY

Top view shows RBC tp ne circular

Side view shows RBC to be a biconcaved disc

Fig. 7.4

Top and side view of RBC

Characteristics ∑ Every second, 2–3 million RBCs are produced in the bone marrow and released into the circulation. ∑ These are also known as erythrocytes. ∑ RBCs are the most common type of cell found in the blood, with each cubic millimeter of blood containing 4–6 million cells. ∑ With a diameter of only 6 µm, RBCs are small enough to squeeze through the smallest blood vessels. ∑ They circulate around the body for up to 120 days, at which point the old or damaged RBCs are removed from the circulation by specializd cells (macrophages) in the spleen and liver. ∑ In humans, as in all mammals, the mature RBC lacks a nucleus. ∑ This allows the cell more room to store haemoglobin, the oxygen-binding protein, enabling the RBC to transport more oxygen. ∑ RBCs are also biconcave in shape; this shape increases their surface area for the diffusion of oxygen across their surfaces. ∑ In non-mammalian vertebrates such as birds and fish, mature RBCs do have a nucleus. ∑ If a patient has a low level of haemoglobin, a condition called anemia, they may appear pale because haemoglobin gives RBCs, and hence blood, their red colour. ∑ They may also tire easily and feel short of breath because of the essential role of haemoglobin in transporting oxygen from the lungs to wherever it is needed around the body. ∑ Red blood cells are transport haemoglobin (each RBC has about 280 million haemoglobin molecules) ∑ Typical concentration is 4–6 million per cubic mm (or hematocrit, packed cell volume, of about 42% for females and 45% for males) contain carbonic anhydrase (critical for transport of carbon dioxide)

Erythropoiesis Erythropoiesis is the process of formation of erythrocytes. RBC precursors mature in the bone marrow closely attached to a macrophage.

HAEMOPOIETIC SYSTEM 251 ∑ They manufacture haemoglobin until it accounts for some 90% of the dry weight of the cell. ∑ The nucleus is squeezed out of the cell and is ingested by the macrophage. ∑ Non-longer-needed proteins are expelled from the cell in vesicles called exosomes. Thus RBCs are terminally differentiated; that is, they can never divide. They live about 120 days and then are ingested by phagocytic cells in the liver and spleen. Most of the iron in their haemoglobin is reused. The remainder of the heme portion of the molecule is degraded into bile pigments and excreted by the liver. Some 3 million RBCs die and are scavenged by the liver each second. Thus, ∑ The body must produce about 2.5 million new RBCs every second. ∑ In adults, erythropoiesis occurs mainly in the marrow of the sternum, ribs, vertebral processes, and skull bones. ∑ Begins with a cell called a hemocytoblast or stem cell. ∑ Rate is regulated by oxygen levels: – Hypoxia (lower than normal oxygen levels) is detected by cells in the kidneys – Kidney cells release the hormone erythropoietin into the blood. Erythropoietin stimulates erythropoiesis by the bone marrow. Erythrocyte production must equal erythrocyte death or the cell population would decline. The body must have a way to assess the concentration of erythrocytes in the blood such that erythrocytes are produced at a rate that matches the body’s needs. Erythropoiesis occurs in the following way: ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

The kidney monitors the level of oxygen in the blood. If oxygen levels are low then the kidney secretes a hormone called erythropoetin. Erythropoetin enters the blood stream and travels throughout the body. All cells are exposed to erythropoetin, but only red bone marrow cells, which have erythropoetin receptors, respond to the hormone. Erythropoetin stimulates the production of erythrocytes in the bone marrow. These erythrocytes leave the bone marrow and move into the blood stream. As the erythrocyte population increases, the oxygen carrying capacity of the blood increases. When the kidney senses that oxygen levels are adequate, it responds by slowing the secretion of erythropoetin. This negative feedback loop ensures that the size of the erythrocyte population remains relatively constant and that the oxygen carrying capacity of the blood is always sufficient to meet the needs of the body.

Fig. 7.5 Erythropoiesis

252 HUMAN ANATOMY AND PHYSIOLOGY The gene encoding erythropoetin was recently cloned by a local biotech company (Amgen). Through recombinant DNA technology erythropoetin is now produced in large quantities and is available for clinical use. Clinical uses of recombinant erythropoetin include the following: ∑ It is used to boost erythrocyte production prior to surgery as a way to decrease the volume of transfused donor blood required. ∑ It is used to boost erythrocyte production following chemotherapy for cancer. Chemotherapy targets fast growing cells. Cancer cells are fast-growing and therefore die, but erythrocytes, which are also fast growing cells, suffer decline following chemotherapy.

Haemoglobin Haemoglobin is the pigment present in erythrocytes.

Characteristics It has the following characteristics. ∑ Composed of globin (made up of 4 highly folded polypeptide chains) and 4 heme groups (with iron) ∑ Each molecule can carry 4 molecules of oxygen called oxyhaemoglobin and called reduced haemoglobin when not carrying oxygen. ∑ Can also combine with carbon dioxide and helps transport carbon dioxide from the tissues to the lungs.

Functions Red blood cells are responsible for the transport of oxygen and carbon dioxide.

Oxygen Transport In adult humans, the haemoglobin (Hb) molecule consists of four polypeptides: a ) chains of 141 amino acids and (i) Two alpha (a b ) chains of 146 amino acids. (ii) Two beta (b ∑ Each of these is attached the prosthetic group heme. ∑ There is one atom of iron at the center of each heme. ∑ One molecule of oxygen can bind to each heme. The reaction is reversible. ∑ Under the conditions of lower temperature, higher pH, and increased oxygen pressure in the capillaries of the lungs, the reaction proceeds to the right. The purple-red deoxygenated haemoglobin of the venous blood becomes the bright-red oxyhaemoglobin of the arterial blood. ∑ Under the conditions of higher temperature, lower pH, and lower oxygen pressure in the tissues, the reverse reaction is promoted and oxyhaemoglobin gives up its oxygen.

HAEMOPOIETIC SYSTEM 253 Carbon Dioxide Transport Carbon dioxide (CO2) combines with water forming carbonic acid, which dissociates into a hydrogen ion (H+) and a bicarbonate ions: CO2 + H2O Æ H2CO3 Æ H+ + HCO395% of the CO2 generated in the tissues is carried in the red blood cells: ∑ It probably enters (and leaves) the cell by diffusing through transmembrane channels in the plasma membrane. (One of the proteins that forms the channel is the D antigen that is the most important factor in the Rh system of blood groups.) ∑ Once inside, about one-half of the CO2 is directly bound to haemoglobin (at a site different from the one that binds oxygen). ∑ The rest is converted — following the equation above — by the enzyme carbonic anhydrase into – bicarbonate ions that diffuse back out into the plasma and – hydrogen ions (H+) that bind to the protein portion of the hemoglobin (thus having no effect on pH). Only about 5% of the CO2 generated in the tissues dissolves directly in the plasma. (A good thing, too: if all the CO2 we make were carried this way, the pH of the blood would drop from its normal 7.4 to an instantly-fatal 4.5!) When the red cells reach the lungs, these reactions are reversed and CO2 is released to the air of the alveoli.

Anemia Anemia is a shortage of ∑ RBCs and/or the amount of haemoglobin in them. Anemia has many causes. One of the most common is an inadequate intake of iron in the diet.

Variation in RBCs The most numerous type in the blood. ∑ Women average about 4.8 million of these cells per cubic millimeter (mm3; which is the same as a microliter [m1]) of blood. ∑ Men average about 5.4 ¥ 106 per ml. ∑ These values can vary over quite a range depending on such factors as health and altitude. (Peruvians living at 18,000 feet may have as many as 8.3 ¥ 106 RBCs per ml.)

Hematocrit It is the percentage of RBCs in relation to the total volume of blood. The hematocrit measures the fraction of the blood that is made up of RBCs. It reflects the combination of the total number of RBCs, and the volume that they occupy.

254 HUMAN ANATOMY AND PHYSIOLOGY Blood is composed of plasma (liquid), cells and platelets. If blood is placed into a tube and centrifuged, the cells and the plasma will separate. The erythrocytes, which are heavy, will pack into the bottom of the tube, the plasma will be at the top of the tube, and the leukocytes and platelets will form a thin layer (buffy coat) between the erythrocytes and the plasma. The hematocrit is defined as the percentage of whole blood made up of erythrocytes. This value is determined by dividing the height of the erythrocytes by the total height of the blood in the tube and multiplying by 100. Hematocrits vary depending on sex and environmental conditions, but there is a range of values that is considered normal. Average hematocrit values are: ∑ Males................ 40–50% ∑ Females............ 38–45% ∑ Athletes............> 50% Any activity or condition that consistently lowers oxygen levels in the blood will cause an increase in erythropoesis and a subsequent rise in the hematocrit. Factors that will raise the hematocrit include: ∑ Exercise. During aerobic exercise blood oxygen levels are lowered due to rapid consumption of oxygen by active skeletal muscle. This stimulates an increase in erythropoesis, which increases hematocrit, which increases the oxygen carrying capacity of the blood. Thus regular aerobic exercise raises the hematocrit. ∑ Living at High Altitude. The air is thinner at higher altitude, therefore fewer molecules of oxygen enter the lungs with each breath. Oxygen levels in the blood are lower when breathing such thin air. A person that moves from Santa Barbara, which is at sea level, to Denver, Colorado, which has an altitude of 5000’, will experience a rise in hematocrit as compensatory response to the thin air. ∑ Injection of Recombinant Erythropoetin. Some endurance athletes use erythropoetin (illegally) to increase their hematocrit as a way to increase stamina.

Primary Polycythemia Primary polycythemia is a condition that is characterized by an excess of circulating erythrocytes and an elevated hematocrit. This condition is caused by a tumor-like condition of the bone marrow resulting in over-stimulation of erythropoesis. The hematocrit raised as high as 70–80%. The increase in blood viscosity associated with very high hematocrits causes sluggish circulation (lowering delivery of oxygen to tissues) and high blood pressure. One of the changes seen in hematocrit is during pregnancy, which drops. This occurs because although the production of RBCs does not change greatly, the plasma volume increases, i.e., the RBCs are “diluted”. Alternatively, a low hematocrit can reflect a drop in RBC production by the bone marrow. This may be attributable to bone marrow disease (damage by toxins or cancer) or due to a decrease in erythropoietin, a hormone secreted by the kidney that stimulates RBC production. Decreased RBCs may also be the result of a reduced life span of the RBCs (e.g., chronic bleeding). A high hematocrit value may truly reflect an increase in the fraction of RBCs (e.g., increased erythropoietin attributable to a tumor of RBCs called polycythemia rubra vera), or it may reflect a drop in the plasma component of the blood (e.g., fluid loss in burn victims).

HAEMOPOIETIC SYSTEM 255 7.5

LEUCOCYTES Lymphocyte Monocyte

Eosinophil White Blood Cells Basophil

Neutrophil

Fig. 7.6 Types of WBCs

Characteristics ∑ ∑ ∑ ∑

These are much less numerous than red (the ratio between the two is around 1:700). There are two main types of WBCs — agranulocytes and granulocytes. Some contain packets of granules in their cytoplasm and so are known as granulocytes. WBCs come in many different shapes and sizes. Some cells have nuclei with multiple lobes, whereas others contain one large, round nucleus. ∑ WBCs have nuclei and do not contain haemoglobin and their typical concentration is 5,000 – 9,000 per cubic millimeter.

Types of WBCs – granular white blood cells or granulocytes include: ¡ neutrophils (50 – 70% of WBCs) ¡ eosinophils (1 – 4%) ¡ basophils (less than 1%) – agranular (or non-granular) white blood cells or agranulocytes include: ¡ lymphocytes (25 – 40%) ¡ monocytes (2 – 8%) ∑ Granular which blood cells contains numerous granules in the cytoplasm, and their nuclei are lobed. ∑ Agranular which blood cells have few or no granules in the cytoplasm and have a large spherical nucleus. ∑ Granular white blood cells are produced in the bone marrow, while agranular white blood cells are produced in lymph tissue, e.g., Lymph nodes (specialized dilations of lymphatic tissues which are supported within by a meshwork of connective tissue called reticulin fibers and are populated by dense aggregates of lymphocytes and macrophages).

256 HUMAN ANATOMY AND PHYSIOLOGY ∑ Some important characteristics of White Blood Cells (particularly neutrophils): 1. phagocytic 2. capable of diapedesis (also called extravasation) 3. capable of amoeboid movement 4. exhibit chemotaxis (attracted to certain chemicals, such as those released by damaged cells)

Circulation of WBCs ∑ Despite their differences in appearance, all of the various types of WBCs have a role in the immune response. ∑ They circulate in the blood until they receive a signal that a part of the body is damaged. ∑ Signals include interleukin 1(lL-1), a molecule secreted by macrophages that contributes to the fever of infections, and histamine, which is released by circulating basophils and tissue mast cells, and contributes to allergic reactions. ∑ In response to these signals, the WBCs leave the blood vessel by sqeezing through holes in the blood vessel wall. ∑ They migrate to the source of the signal and help begin the healing process. ∑ Individuals who have low levels of WBCs may have more and worse infections. ∑ Depending upon which WBCs are missing, the patient is at risk for different types of infection. ∑ For example, macrophages are especially good at swallowing bacteria, and a deficiency in macrophages leads to recurrent bacterial infections. ∑ In contrast, T cells are particularly skilled in fighting viral infections, and a loss of their function results in an increased susceptibility to viral infections. ∑ The total number of white blood corpuscles is 5,000 to 10,000 per milliliter. Formation of leucocytes is known as leucopoiesis. It takes place in lymphnodes, bone marrow, spleen and thymus. Life span of leucocytes is 3–4 days. An increase in this normal number is called leucocytosis and decrease in the normal number is a leucopenia. Leucocytes are of mainly two main kinds : Granular or Granulocytes and Agranular or Agranulocytes. Leucocytes

Granulocytes Neutrophils

Eosinophils

Agranulocytes Basophils

Lymphocytes

Monocytes

Neutrophils ∑ Neutrophils are also known as polymorphonuclear cells because they contain a nucleus whose shape (morph) is irregular and contains many (poly) lobes. ∑ They also belong to a group of WBCs known as granulocytes because their cytoplasm is dotted with granules that contain enzymes that helps them digest pathogens. ∑ These are most abundant of the WBCs. ∑ Neutrophils squeeze through the capillary walls and into infected tissue where they kill the invaders (e.g., bacteria) and then engulf the remnants by phagocytosis.

HAEMOPOIETIC SYSTEM 257 ∑ This is a never-ending task, even in healthy people: Our throat, nasal passages, and colon harbor vast numbers of bacteria. Most of these are commensals, and do us no harm. But that is because neutrophils keep them in check. ∑ However, – heavy doses of radiation – chemotherapy – and many other forms of stress, can reduce the numbers of neutrophils so that formerly harmless bacteria begin to proliferate. The resulting opportunistic infection can be life-threatening.

Eosinophils ∑ The number of eosinophils in the blood is normally quite low (0–450/µl). ∑ However, their numbers increase sharply in certain diseases, especially infections by parasitic worms. ∑ Eosinophils are cytotoxic, releasing the contents of their granules on the invader.

Basophils ∑ The number of basophils also increases during infection. ∑ Basophils leave the blood and accumulate at the site of infection or other inflammation. ∑ There they discharge the contents of their granules, releasing a variety of mediators such as: ¡ Histamine ¡ Serotonin ¡ Prostaglandins and leukotrienes which increase the blood flow to the area and in other ways add to the inflammatory process. ∑ The mediators released by basophils also play an important part in some allergic responses such as ∑ hay fever and ∑ an anaphylactic response to insect stings

Lymphocytes ∑ Lymphocytes are round cells that contain a single, large round nucleus. ∑ There are two main classes of cells, the B cells that mature in the bone marrow, and the T cells that mature in the thymus gland. ∑ Once activated, the B cells and T cells trigger different types of immune response. ∑ The activated B cells, also known as plasma cells, produce highly specific antibodies that bind to the agent that triggered the immune response. ∑ T cells, called helper T cells, secrete chemicals that recruit other immune cells and help coordinate their attack. ∑ Another group, called cytotoxic T cells, attacks virally infected cells ∑ There are several kinds of lymphocytes (although they all look alike under the microscope), each with different functions to perform.

258 HUMAN ANATOMY AND PHYSIOLOGY ∑ The most common types of lymphocytes are – B lymphocytes (“B cells”). These are responsible for making antibodies. – T lymphocytes (“T cells”). There are several subsets of these: n Inflammatory T cells that recruit macrophages and neutrophils to the site of infection or other tissue damage n Cytotoxic T lymphocytes (CTLs) that kill virus-infected and, perhaps tumor cells n Helper T cells that enhance the production of antibodies by B cells ∑ Although bone marrow is the ultimate source of lymphocytes, the lymphocytes that will become T cells migrate from the bone marrow to the thymus where they mature. ∑ Both B cells and T cells also take up residence in lymph nodes, the spleen and other tissues where they ∑ Encounter antigens; ∑ Continue to divide by mitosis; ∑ Mature into fully functional cells.

Monocytes ∑ Monocytes are young WBCs that circulate in the blood. ∑ They develop into macrophages after they have left the blood and migrated into tissue. ∑ There they provide an immediate defense because they can engulf (phagocytose) and digest pathogens before other types of WBCs reach the area. ∑ In the liver, tissue macrophages are called Kupffer cells, and they specialize in removing harmful agents from blood that has left the gut. ∑ Alveolar macrophages are in the lungs and remove harmful agents that may have been inhaled. ∑ Macrophages in the spleen remove old or damaged red blood cells and platelets from the circulation. ∑ Macrophages are also “antigen-presenting cells”, presenting the foreign proteins (antigens) to other immune cells, triggering an immune response ∑ Macrophages are thus large, phagocytic cells that engulf: – Foreign material (antigens) that enter the body. – Dead and dying cells of the body.

Functions of the various white blood cells are: ∑ Neutrophils: phagocytosis (bacteria and cellular debris); very important in inflammation. ∑ Eosinophils: help breakdown blood clots and kill parasites. ∑ Basophils: synthesize and store histamine (a substance released during inflammation) and heparin (an anticoagulant); functions(s) remain unclear. ∑ Monocytes: phagocytosis (typically as macrophages in tissues of the liver, spleen, lungs, and lymph nodes). ∑ Lymphocytes: immune response (including production of antibodies).

HAEMOPOIETIC SYSTEM 259 7.6

THROMBOCYTES (PLATELETS)

Cytoplasmic granules

Fig. 7.7

Platelets

Characteristics ∑ Platelets are irregularly shaped fragments of cells that circulate in the blood until they are either activated to form a blood clot or are removed by the spleen. ∑ Thrombocytopenia is a condition of low levels of platelets and carries an increased risk of bleeding. ∑ Conversely, a high level of platelets (thrombocythemia) carries an increased risk of forming inappropriate blood clots. ∑ These could deprive essential organs such as the heart and brain, of their blood supply, causing heart attacks and strokes, respectively. ∑ As with all the cells in the blood, platelets originate from stem cells in the bone marrow. ∑ The stem cells develop into platelet precursors (called megakaryocytes) that “shed” platelets into the bloodstream there, platelets circulate for about 9 days. ∑ If they encounter damaged blood vessel walls during this time, they stick to the damaged area and are activated to form a blood clot. This plugs the hole otherwise, at the end of their life span they are removed from the circulation by the spleen is overactive. For example, rheumatoid arthritis and leukemia, the spleen removes too many platelets, leading to increased bleeding. ∑ Thrombocytes are: 1. Formed in the bone marrow from cells called megakaryocytes. 2. Have no nucleus, but can secrete a variety of substances and can also contract (because they contain actin and myosin). 3. Normal concentration in the blood is about 250,000 per cubic millimeter. 4. Remain functional for about 7–10 days (after which they are removed from the blood by macrophages in the spleen and liver). 5. Play an important role in hemostasis (preventing blood loss). ∑ Blood normally contains 150,000–450,000 per microliter (µl) or cubic millimeter (mm3) of platelets. ∑ This number is normally maintained by a homeostatic (negative-feedback) mechanism. ∑ If this value should drop much below 50,000/µl, there is a danger of uncontrolled bleeding because of the essential role that platelets have in blood clotting. ∑ When blood vessels are cut or damaged, the loss of blood from the system must be stopped before shock and possible death occur.

260 HUMAN ANATOMY AND PHYSIOLOGY ∑ This is accomplished by solidification of the blood by a process called coagulation or clotting. ∑ A blood clot consists of a plug of platelets enmeshed in a network of insoluble fibrin molecules.

Functions Platelets help in blood clotting. Functions of blood can be summarized as under.

Plasma 1. Transport of Materials. It helps to transport digested food, excretory products, hormones etc., to various body organs. 2. Antibodies. Antibodies are globulins which are important in the defence of the body against foreign proteins and bacteria. 3. Coagulation of Blood. Fibrinogen is important in the coagulation of blood. 4. Buffering Action. The plasma proteins together with inorganic salts form buffers, which keep the plasma pH constant. 5. Exertion of Osmotic Pressure. The molecules of albumin and globulin in the plasma exert an osmotic pressure because they are too large to pass through the walls of the capillaries and thus no protein is left in the normal tissue fluid. The molecules of the inorganic salts pass freely through the capillary walls so that their concentration in the plasma and in the tissue fluid is the same; they, therefore, set up no osmotic pressure. 6. It helps in keeping the body temperature constant.

Erythrocytes 1. They have a respiratory pigment known as haemoglobin which has the ability to combine readily with oxygen to form oxyhaemoglobin, an unstable compound which can readily break into oxygen and haemoglobin.

Leucocytes 1. Lymphocytes, a type of leucocyte plays the main part in the cellular immune response. Their number increases in chronic infections. 2. Leucocytes show slow amoeboid movements especially neutrophil cells. This movement is known as diapedesis. They engulf the foreign particles e.g., bacteria. Neutrophils are therefore an important part of the body’s defence against acute infections. 3. At the time of injury WBCs migrate through the walls of the blood vessels and fight against germs. Pus consists of a tissue fluid containing harmful bacteria, very large number of dead neutrophils and tissue cells destroyed by bacteria.

HAEMOPOIETIC SYSTEM 261 Thrombocytes 1. Platelets are necessary for coagulation of the blood.

Do You Know ∑ Normal range of haemoglobin content in human beings is 13–18 gm / dL. ∑ There is difference in the haemoglobin levels of men and women. Their values are 13–18 gm/dL and 12-16 gm/dL respectively. ∑ Haemoglobin levels are slightly lower in older men and women and children.

7.7

HAEMOPOEISIS

All of the cells found in the blood come from bone morrow. They begin their life as stem cells, and they mature into three main types of cells—RBCs, WBCs, and platelets. In turn, there are three types of WBC—lymphocytes, monocytes, and granulocytes—and three main types of granulocytes (neutrophils, eosinophils, and basophils) Blood cells are formed in the bone marrow. All blood cells arise from the same bone marrow stem cells. Stem cells are immortal, meaning they never die (at least not until you do). Stem cells are also undifferentiated, meaning they have not yet developed into a particular cell type. Furthermore, stem cells are pluripotent, meaning they have the potential to become any type of blood cell. These immortal, undifferentiated, pluripotent stem cells give rise to erythrocytes, leucocytes and platelets. The diagram below illustrates the different types of blood cells. Leucocytes, also known as white blood cells, are a group of related cell types that involved in immune function. Leukocytes include neutrophils, eosinophils, basophils, lymphocytes and monocytes. All types of blood cells are thus: ∑ Produced in the bone marrow (some 1011 of them each day in an adult human!). ∑ Arise from a single type of cell called a hematopoietic stem cell — an “adult” multipotent stem cell. These stem cells: ∑ Are very rare (only about one is 10,000 bone marrow cells); ∑ Are attached (probably by adherens junctions) to osteoblasts lining the inner surface of bone cavities; ∑ Express a cell-surface protein designated CD34; ∑ Produce, by mitosis, two kinds of progeny: – more stem cells (A mouse that has had all its blood stem cells killed by a lethal dose of radiation can be saved by the injection of a single living stem cell!). – cells that begin to differentiate along the paths leading to the various kinds of blood cells. ∑ Path taken is regulated by the need for more of that type of blood cell which is, in turn, controlled by appropriate cytokines and/or hormones. For example, Interleukin-7 (IL-7) is the major cytokine in stimulating bone marrow stem cells to start down the “lymphoid” path leading to the various lymphocytes (mostly B cells and T cells).

262 HUMAN ANATOMY AND PHYSIOLOGY Some of the cytokines that drive the differentiation of the “myeloid” leucocytes are ∑ Erythropoietin (EPO), produced by the kidneys, enhances the production of red blood cells (RBCs). ∑ Thrombopoietin (TPO), assisted by Interleukin-11 (IL-11), stimulates the production of megakaryocytes. Their fragmentation produces platelets. ∑ Granulocyte-macrophage colony-stimulating factor (GM-CSF), as its name suggests, sends cells down the path leading to both those cell types. In due course, one parth or the other is taken. – Under the influence of granulocyte colony-stimulating factor (G-CSF), they differentiate into neutrophils. – Further stimulated by interleukin-5 (IL-5) they develop into eosinophils. – Interleukin-3 (IL-3) participates in the differentiation of mort of the white blood cells but plays a particularly prominent role in the formation of basophils (responsible for some allergies). – Stimulated by macrophage colony-stimulating factor (M-CSF) the granulocyte/macrophage progenitor cells differentiate into monocytes, macrophages, and dendritic cells (DCs). – Red Blood Cells (erythrocytes) T Lymphocyte

Lymphoid Stem cell NK Lymphocyte

B Lymphocyte Plasma cell

Pluripolent Stem cell

Erythrocyte Megakaryocyte (blood clotting) Mycloid stem cell

Macrophage Monocyte Granulocytes

Fig. 7.8

7.8

Hemopoiesis

HEMOSTASIS

Hemostasis is the prevention of blood loss from broken vessel. 1. Vascular Spasm: Is vasoconstriction of injured vessel due to contraction of smooth muscle in the wall of the vessel. This ‘spasm’ may reduce blood flow and blood loss but will not stop blood loss.

HAEMOPOIETIC SYSTEM 263 2. Formation of a Platelet Plug: Blood platelets aggregate at the point where a vessel ruptures. This occurs because platelets are exposed to collagen (a protein found in the connective tissue located just outside the blood vessel). Upon exposure to collagen, platelets release ADP (adenosine diphosphate) and thromboxane. These substances cause the surfaces of nearby platelets to become sticky and, as ‘sticky’ platelets accumulate, a ‘plug’ forms. 3. Blood Coagulation (clotting): The result of all of this is a clot – formed primarily of fibrin threads (or polymers), but also including blood cells and platelets. Blood clots in the right places prevent the loss of blood from ruptured vessels, but in the wrong place can cause problems such as a stroke.

7.9

BLOOD CLOTTING

∑ When veins rupture, blood loss is relatively slow (due to low blood pressure) and can often be controlled by raising the affected region above the level of the heart. ∑ If the hemorrhage occurs towards the surrounding tissue, blood accumulation (hematome) may itself be enough to rise the pressure of the interstitial fluid to the level of the venal pressure, thus stoping blood loss. ∑ Hemorrhages due to the rupture of medium or large arteria can not usually be controlled by the organism. ∑ However, the physiological clotting mechanism are quite effective in dealing with lesions to small vessels, which are the most common in daily life. ∑ The most immediate body response to a vascular lesion is the constriction of the affected blood vessel, leading to a decrease of blood flow through the injured area. ∑ Such constriction presses the endothelial surfaces of the vessel towards each other, thus including a contact that blocks it. ∑ However, this mechanism is only able to block permanently the rupture in the thinnest capillaries, and termination of bleeding usually depends on two further mechanisms, which require platelet intervention. Since humans are liable to injury and the shedding of blood, a mechanism is provided within the body whereby there is a spontaneous tendency for the loss of blood to be limited. Within a few minutes of leaving the blood vessels, normal blood sets into a clot. Soon the clot shrinks, becomes firmer and squeezes out serum. The essential change in the coagulation of blood is the conversion of the protein fibrinogen into a substance fibrin which forms fine threads which entangle the blood cells and then contract to form clot. Blood clotting involves various steps : (a) Thrombocytes and the injured tissues cells release a substance known as thromboplastin at the site of injury. (b) Thromboplastin leads to the conversion of prothrombin into thrombin which is a plasma globulin made in the liver in the presence of vitamin K. Prothrombin is converted to thrombin only in the presence of calcium ions and thromboplastin. (c) Action of thrombin on fibrinogen converts it to fibrin. (d) Fibrin traps red and white cells and platelets in its meshes, forming a clot from which serum is expressed by contraction of the fibrin threads.

264 HUMAN ANATOMY AND PHYSIOLOGY Damaged tissues Prothrombin

+

Ca

2+

+

Thromboplastin

Blood Platelets Plasma

+

Thrombin

Fibrinogen

Fibrin

Chemicals which prevent clotting of blood are known as anticoagulants e.g., heparin prevents clotting of blood in the blood vessels. Hirudin is another anticoagulant which is found in the salivary glands of leeches.

Formation of a Platelet Plug ∑ Blood vessel rupture exposes the underlying connective tissue. ∑ Platelets adhere to collagen present in this tissue through a plasma protein (the von Willebrand factor)secreted by endothelial cells and platelets. ∑ As platelets adhere to collagen, they are induced to release the molecules (serotonin, ADP, etc.) present in their secreting vesicles. ∑ These molecules act on the platelets themselves, and lead to changes in their metabolism, shape, and surface proteins, in a process dubbed platelet activation. ∑ Some of these changes make new platelets adhere to the initial platelet layer through fibrinogen molecules, and to the formation of a platelet plug. ∑ Platelet adhesion induces them to secrete thromboxane A2, which further stimulates platelet aggregation. ∑ The platelet plug thus formed is able to seal small ruptures on blood vessels. ∑ The platelet plug only forms around the affected area, since healthy areas of the blood vessel continually secrete prostacyclin, which inhibits platelet aggregation. ∑ The platelet plug is thus prevented from expanding towards non-ruptured areas of the blood vessel.

Clotting Upon the lesion of a blood vessel, the surrounding cells release the following: ∑ Thromboplastin (also called tissue factor, or factor III). This protein then binds a plasma protein, Factor VII, and activates it. This new thromboplastin-factor VIIa complex catalyzes the activation of factors X and IX. ∑ Factor Xa, in the presence of factor Va, catalyzes the conversion of prothrombin into Thrombin, which cleaves factor XIII and converts fibrinogen into fibrin. ∑ Factor XIIIa then catalyzes the formation of covalent bonds between the fibrin molecules, which precipitate and form a clot that blocks the vessel lesion. ∑ This clotting pathway is called extrinsic pathway, because it needs a factor (thromboplastin) which is initially absent from the plasma.

HAEMOPOIETIC SYSTEM 265 ∑ Blood clotting observed when blood is collected into a glass tube (and therefore in the absence of thromboplastin) is due to a second clotting pathway: the intrinsic pathway. Initially, factor XII is activated by contact with collagen, or a wettable surface sucg as glass. This factor activates factor XI, which activates factor IX, which in the presence of VIIIa activates factor X. From this point onwards, the mechanism is the same as that of the extrinsic pathway. Under physiological conditions, blood clotting is started by the extrinsic pathway. Plasma however contains an inhibitor of the tissue factor pathway, which inhibits the activation of factor X by the thromboplastin-factor VIIa complexo. Thrombin formation through the extrinsic pathway is therefore limited. Clotting is completed by the intrinsic pathway: the small amount of thrombin produced by the extrinsic pathway activate factors V, VIII and XI, which allow the intrinsic pathway to operate. Apart from the two first steps in the intrinsic pathway, all steps in the clotting cascade require the presence of Ca2+. Besides the inhibitor of the tissue factor pathway, there are other ways to control blood clotting. Thrombomodulin, in the presence of thrombin, activates a protein (protein C), which inactivates factors VIIIa and Va (a in subscript means the “activated form” of the plasmatic clotting factors). Thrombin may also be inactivated by the joint activity of antithrombin III and heparin. The clot must eventually be dissolved. This is accomplished by the fibrinolytic system. Like the clotting pathways this system involves the sequential activation of series of proteins, and yields the activation of plasminogen into plasmin. Plasmin degrades fibrin, thereby dissolving the blood clot.

Modern Theory of Blood Clotting Blood clotting is a complex process in which many factors take part. In order to bring uniformity in nomenclature, a numerical system has been suggested for naming the twelve factors involved in the coagulation process. Clotting factors are designated by Roman numerals. The subscript ‘a’ means that the factor is in the active form. The numerical nomenclature of the clotting factors relates to their order of discovery rather than to their position in the sequence of reactions. Protein clotting factor normally interact in pairs. As a result of such interaction, each inactive factor is converted into active form. These factors operate in a cascade pattern in which the activated form of a factor catalyzes the activation of the next factor. I. II. III. IV. V. VII.

Fibrinogen Prothrombin Thromboplastin Ca++ Proacclerin Proconvertin

VIII. IX. X. XI. XII. XIII. Fig. 7.9

Antihaemophilic globulin (AHG) Christmas factor Stuart factor Plasma thromboplastin antecedent (PTA) Hageman factor Fibrin stabilizing factor

Clotting factors

The mechanism of clot formation involves two kinds of pathways : Intrinsic and extrinsic pathways that ultimately results in the formation of a fibrin clot by passing through three stages :

Stage I : Formation of Thromboplastin This is the first stage in the clotting mechanism. The thromboplastin is formed in the blood by intrinsic and extrinsic reactions.

266 HUMAN ANATOMY AND PHYSIOLOGY (i) Intrinsic Pathway. The chemical reactions take place in the plasma in which Hageman factor XII is activated by contact with a damaged blood vessel. At the same time platelets accumulate and stick to the injured part of the vessel and a phospholipids substance appears on the surface of platelets. Activated Hageman factor in turn activates plasma thromboplastin antecedent XI. The activated factor XIa then acts on Christmas factor IX to form activated IXa. Factor IXa then combines with antihaemophilic globulin VIII, phospholipids and calcium ions to form a complex called “Intrinsic factor (X) activator complex”. XII

damaged

XII a

vessel surface XI

XI a

IX a + VIII + phospholipid + Ca++

XI

Intrinsic factor X activator complex.

Fig. 7.10 Intrinsic pathway (ii) Extrinsic Pathway. For this pathway, the factors like phospholipids and protein are derived from the injured tissues by adhesion of platelets. The phospholipids protein complex activates the formation of tissue thromboplastin or tissue factor from injured part. It interacts with proconvertin VII to form extrinsic factor (X) activator complex. Injured tissues Ø Tissue thromboplastin + Factor VII Ø Extrinsic factor X activator complex Fig. 7.11

Extrinsic pathway

Intrinsic and extrinsic factors combine with inactive Stuart factor X to produce active factor Xa. Activated factor Xa combines with proaccelerin factor V, phospholipid and calcium ions to form a thrombokinase complex or thromboplastin.

Stage II : Conversion of Prothrombin to Thrombin The prothrombin is a plasma protein which is synthesized in the liver and present in the plasma. It is converted into active thrombin in the presence of thromboplastin (Xa + V + phospholipids + Ca++).

Stage III : Formation of Fibrin from Fibrinogen The protein fibrinogen combines with thrombin which is a hydrolytic enzyme. The hydrolysis of fibrinogen by thrombin results in the formation of a soluble fibrin which is soft and fragile. The soluble fibrin changes into highly insoluble fibrin in the presence of calcium ions and an enzyme fibrinase, which is derived from fibrin stabilizing factor XIII. The insoluble fibrin forms network of fine threads which trap the blood corpuscles and gets dried to form hard clot or thrombus. After sometime the clot shrinks and a clear sticky fluid is released called serum.

HAEMOPOIETIC SYSTEM 267 Factor XIII

Fibrinogen + Thrombin

Hydrolysis

Soluble fibrin + fibrinase Ca

++

Insoluble fibrin

Clot

Fig. 7.12

Formation of clot

Factors which Prevent Clotting A number of physical factors and chemical compound hamper coagulation; the effect of cold, which markedly delays the process, should be noted above all. Coagulation is also delayed if blood is poured into a glass vessel with walls covered with paraffin or silicon to prevent them being wetted by the blood. In such a vessel blood may remain fluid for several hours. The disintegration of blood platelets is greatly hampered in these conditions as a result thrombin formation does not occur. Oxalic and citric acids prevent coagulation. Sodium citrate added to blood binds calcium ions, while ammonium oxalate causes precipitation of calcium, so that formation of thromboplastin and thrombin becomes impossible. Oxalates and citrates are used to prevent coagulation of the blood only outside the organism. Certain substances like heparin which occurs in the tissues of the liver and lungs and hirudin which is secreted by the buccal glands of leeches act as anticoagulants. Heparin interferes with the action of thrombin on fibrinogen and suppresses the activity of thromboplastin. Hirudin suppresses the fibrin formation. There are other anticoagulants that have an indirect effect on coagulation. They include coumarin or dicumarol which block the synthesis of prothrombin and factor VII is the liver. The serum proteins include yet another substance, namely fibrinolysin or plasminogen, an enzyme that occurs in an inactive form in plasma. At the beginning of the coagulation pathway, certain enzymes are released from the damaged tissues. These enzymes activate an inactive enzyme called plasminogen into an active form called plasmin. The plasmin dissolves the fibrin clot. The process of dissolving fibrin within blood vessels is called fibrinolysis. damaged Phasminogen tissue enzymes (inactive)

Plasmin (active)

Fibrin clot

Fig. 7.13

Soluble products (polypeptides)

Fibrinolysis

Several strategies towards anticoagulant therapy are available: ∑ Aspirin inhibits cyclooxygenase (the enzyme which synthesizes the precursor of thromboxane A2), thereby inhibiting platelet aggregation.

268 HUMAN ANATOMY AND PHYSIOLOGY ∑ Oral anticoagulants interfere with the activity of vitamin K, which is necessary for the synthesis of several clotting factors (prothrombin, VII, IX and X) ∑ Heparin ∑ Fibrinogen blockers interfere with platelet aggregation. ∑ Plasminogen activators.

7.10

COMPLETE BLOOD COUNT

A complete blood count (CBC) is a simple blood test that is commonly ordered as part of a routine medical assessment. As the name suggests, it is a count of the different types of cells found in the blood. The test can diagnose and monitor many different diseases, such as anemia, infection, inflammatory diseases, and malignancy. A full blood count is a test that measures the number of red cells, white cells and platelets in your blood because: ∑ Red cells carry oxygen around our bodies – haemoglobin is the part of the red cell that carries the oxygen ∑ White cells help us fight infections, they include neutrophils and lymphocytes ∑ Platelets help clot the blood, to stop us bleeding when we cut ourselves. Doctor does a full blood count to: ∑ Check general health ∑ Diagnose certain conditions, such as anemia or infections. It is also an early test for blood cancers such as leukaemia and lymphomas ∑ Check the side effects of treatment – the number of cells in blood can go down when having chemotherapy There is not an exact range of normal for blood counts. The range of figures quoted as normal varies slightly and also differs between men and women.

Red Blood Cell Count It detects anemia A CBC measures the following features of RBCs: ∑ The total amount of haemoglobin (Hb) in the blood ∑ The number of RBCs (RBCs) ∑ The average size of a RBC (MCV, mean corpuscular volume) ∑ The amount of space RBCs take up in the blood (hematocrit) The CBC also includes information about RBCs that is calculated from the other measurements, e.g., the amount (MCH, mean corpuscular haemoglobin) and concentration (MCHC, mean corpuscular concentration) of haemoglobin in RBCs. The number of RBCs and the amount of haemoglobin in the blood are lower in women that in men. This is because of the menstrual loss of blood each month. Below a certain level of haemoglobin, a patient is said to be anemic, suggesting a clinically significant drop in oxygen carrying capacity. Anemia is not a diagnosis but a symptom of an underlying disease that has to be investigated.

HAEMOPOIETIC SYSTEM 269 A clue to the cause of anemia is the average size of RBC (mean corpuscular volume, MCV). Causes of a high MCV include a deficiency of B12 or folate vitamins in the diet. B12 is found in red meat therefore, a deficiency of B12 is especially common in vegetarians and vegans. Conversely, folate is plentiful in fresh leafy green vegetables, therefore, a deficiency of folate is common in the elderly, who may have a poor diet. Low MCV anemia is common and may be a result of hereditary blood disorders, such a thalassemia, but is most often caused by a deficiency of iron. For example, women of reproductive age may lose too much iron through heavy menstrual bleeding and are prone to this form of anemia, known as iron-deficiency anemia.

WBC Count The number of WBCs increases in infection and tumors. The WBC count is a count of the number of WBCs found in one cubic millimeter of blood. An increased number of WBCs is most commonly caused by infections, such as a urinary tract infection or pneumonia. It may also be caused by WBC tumors, such as leukemia. A decreased number of WBCs is caused by the bone marrow failing to produce WBCs or by an increased removal of WBCs from the circulation by a diseased liver or an overactive spleen. Bone marrow failure may be caused by toxins or by the normal bone marrow cells being replaced by tumor cells. The WBC differential part of the CBC breaks down the WBCs into five different types: neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Finding out the count of each type of WBC gives more information about the underlying problem. For example, in the early stages of an infection, most of the increase in WBCs is attributable to the increase in neutrophils. As the infection continues, lymphocytes increase. Worm infections can trigger an increase in eosinophils, whereas allergic conditions, such as hay fever, trigger an increase in basophils.

Platelet Count The number of platelets indicates whether bleeding or clotting is likely. Normally, one cubic millimeter of blood contains between 150,000 and 400,000 platelets. If the number drops below this range, uncontrolled bleeding becomes a risk, whereas a rise above the upper limit of this range indicates a risk of uncontrolled blood clotting.

7.11

HEMOGLOBIN

Hemoglobin is the oxygen-carrying protein that is found within all RBCs. It picks up oxygen where it is abundant (the lungs) and drops off oxygen where it is needed around the body. Hemoglobin is also the pigment that gives RBCs their red colour.

Heme Groups and Globins As its name suggests, hemoglobin is composed of “heme” groups (iron-containing rings) and “globins” (proteins). In fact, hemoglobin is composed of four globin proteins—two alpha chains and

270 HUMAN ANATOMY AND PHYSIOLOGY two beta chains—each with a heme group. The heme group contains one iron atom, and this can bind one molecule of oxygen. Because each molecule of hemoglobin contains four globins, it can carry up to four molecules of oxygen.

Hemoglobin Transports Oxygen In the lungs, a hemoglobin molecule is surrounded by a high concentration of oxygen, therefore, it binds oxygen. In active tissues, the oxygen concentration is lower, so hemoglobin releases its oxygen. This behavior is much more effective because the hemoglobin—oxygen binding is “cooperative”. This means that the binding of one molecule of oxygen makes it easier for the binding of subsequent oxygen molecules. Likewise, the unbinding of oxygen makes it easier for other oxygen molecules to be released. This means that the response of hemoglobin to the oxygen needs of active tissues is much quicker. Aside from the oxygen saturation of hemoglobin, other factors that influence how readily hemoglobin binds oxygen include plasma pH, plasma bicarbonate levels, and the pressure of oxygen in the air (high altitudes in particular). The molecule 2,3-disphosphoglycerate (2,3-DPG) binds to hemoglobin and lowers its affinity for oxygen, thus promoting oxygen release. In individuals who have become acclimatized to living at high altitudes, the level of 2,3-DPG in the blood increases, allowing the delivery of more oxygen to tissues under low oxygen tension.

Fetal Hemoglobin Fetal hemoglobin differs from adult hemoglobin in that it contains two gamma chains instead of two beta chains. Fetal hemoglobin binds oxygen with a much greater affinity than adult hemoglobin; this is an advantage in the womb because it allows fetal blood to extract oxygen from maternal blood, despite its low concentration of oxygen. Normally, all fetal hemoglobin is replaced by adult hemoglobin by the time of birth.

Breakdown of Hemoglobin Old or damaged RBCs are removed from the circulation by macrophages in the spleen and liver, and the hemoglobin they contain is broken down into heme and globin. The globin protein may be recycled, or broken down further to its constituent amino acids, which may be recycled or metabolized. The heme contains precious iron that is conserved and reused in the synthesis of new hemoglobin molecules. During its metabolism, heme is converted to bilirubin, a yellow pigment that can discolor the skin and sclera of the eye if it accumulates in the blood, a condition known as jaundice. Instead, the plasma protein albumin binds to bilirubin and carries it to the liver, where it is secreted in bile and also contributes to the color of feces. Jaundice is one of the complications of an incompatible blood transfusion. This occurs when the recipient’s immune system attacks the donor RBCs as being foreign. The rate of RBC destruction and subsequent bilirubin production can exceed the capacity of the liver to metabolize the bilirubin produced.

HAEMOPOIETIC SYSTEM 271 7.12

BLOOD GROUPS

The surface of erythrocytes contains a high number of glycoproteins, grouped in families called “blood groups”. The most important groups are: ∑ the ABO and ∑ Rhesus systems. The ABO blood group system is widely credited to have been discovered by the Austrian scientist Karl Landsteiner, who found three different blood types in 1900. He has awarded the Nobel Prize in Physiology or Medicine in 1930 for his work. Due to inadequate communication at the time it was subsequently found that Czech serologist Jan Jansky had independently pioneered the classification of human blood into four groups, but Landsteiner’s independent discovery had been accepted by the scientific world while Jansky remained in relative obscurity. Jansky’s classification is however still used in Russia and states of former USSR. In America Moss published his own (very similar) work in 1910. Landsteiner described A, B, and O; Decastrello and Sturli discovered the fourth type, AB, in 1902. Ludwik Hirszfeld and E. von Dungern discovered the heritability of ABO blood groups in 1910–11, with Felix Bernstein demonstrating the correct blood group inheritance pattern of multiple alleles at one locus in 1924. Watkins and Morgan, in England, discovered that the ABO epitopes were conferred by sugars, specifically N-acetylgalactosamine for the A-type and galactose for the B-type (1959). After much published literature claiming that the ABH substances were all attached to glycosphingolipids, Laine’s group (1988) found that the band 3 protein expressed a long polylactosamine chain which contained the major portion of the ABH substances attached. Later, Hakomori’s group (Yamamoto, et al., Nature 345, 229–233 (1990)), showed the precise glycosyl transferase set that confers the A, B and O epitopes.

ABO System ∑ It includes carbohydrate H and two similar variants, known as A and B. ∑ An individual may therefore be A, AB, B or O (if it only carries antigen H). ∑ Every individual carries specific antibodies against those carbohydrates it lacks: an A person carries anti-B antibodies, an O person carries anti-A and anti-B antibodies, and an AB person carries neither (there are no anti-H antibodies, since the H antigen is the core carbohydrate of both A and B antigens, and an anti-H antibody would also react against the A and B carbohydrates). ∑ During a blood transfusion, the donor’s antibodies quickly get diluted in the receptor’s bloodstream, and (in)compatibility effects arise from the interaction between the receptor’s antibodies and the antigens present in the donor’s blood. ∑ If the receptor carries specific antibodies against the donor’s erythrocytes, they will agglutinate (cross-linked through the receptor’s antibodies) and form a thrombus.

272 HUMAN ANATOMY AND PHYSIOLOGY Rhesus System ∑ This system is dependent on the presence or absence of the D antigen. ∑ Unlike the ABO system, no anti-D antibodies exist in the bloodstream of an individual who has never been exposed to the antigen. ∑ This becomes relevant during mother-fetus interaction. In parturition, the rupture of placental blood vessels leads to contact between the mother and the baby’s blood. Should the mother be Rh- and the baby be Rh+, this leads to exposure of the mother to the D antigen, and she will start to produce anti-D antibodies. In future pregnancies, these antibodies may cross the placenta and lead to agglutination of the erythocytes of a Rh+ baby, leading to sever anemia, or even death. Nowadays, this is prevented through infusion of anti-D antibodies to the Rhmother immediately after the birth of a Rh+ baby. These antibodies bind to the D antigens of the baby’s erythrocytes that are present in the mother’s bloodstream, thereby preventing them to induce the mother to synthesize antibodies. These problems do not arise in the ABO system because anti-A and anti-B antibodies are lgM antibodies, too large to cross the placenta. ∑ The Rh blood group is one of the most complex blood groups known in humans. From its discovery 60 years ago where it was named (in error) after the Rhesus monkey, it has become second in importance only to the ABO blood group in the field of transfusion medicine. It has remained of primary importance in obstetrics, being the main cause of hemolytic disease of the newborn (HDN). ∑ The complexity of the Rh blood group antigens begins with the highly polymorphic genes that encode them. There are two genes, RHD and RHCE, that are closely linked. Numerous genetic rearrangements between them has produced hybrid Rh genes that encode a myriad of distinct Rh antigens. To date, 49 Rh antigens are known. ∑ The significance of the Rh blood group is related to the fact that the Rh antigens are highly immunogenic. In the case of the D antigen, individuals who do not produce the D antigen will produce anti-D if they encounter the D antigen on transfused RBCs (causing a hemolytic transfusion reaction, HTR) or on fetal RBCs (causing HDN). For this reason, the Rh status is routinely determined in blood donors, transfusion recipients, and in mothers-to-be. ∑ Despite the importance of the Rh antigens in blood transfusion and HDN, we can only speculate about the physiological function of the proteins, which may involve transporting ammonium across the RBC membrane and maintaining the integrity of the RBC membrane.

Blood Typing Donated blood must also be tested for certain cell-surface antigens that might cause a dangerous transfusion reaction in an improperly-matched recipient. 1. In ABO System Antigens are : ∑ Type A antigen ∑ Type B antigen Antibodies are : ∑ produced if antigen is not present

HAEMOPOIETIC SYSTEM 273 ∑ produced because common intestinal bacteria have A- and B-like antigens ∑ produced by age of about 6 months.

Blood type

Antigen

Antibody

A

A

anti-B

B

B

anti-A

AB

A and B

neither

O

neither

both anti-A and anti-B

If you mix anti-A antibodies with blood cells that have the A antigen or mix anti-B antibodies with blood cells that have the B antigen, the results will be AGGLUTINATION (or clumping of red blood cells). This reaction can be used to type blood. Simply take two drops of ‘unknown’ blood and place a drop of anti-A antibody solution on one blood drop and a drop of anti-B antibody solution on the other blood drop. Then, look closely to see if any clumping occurs. If clumping occurs in the drop of blood where you added the anti-A antibodies, then you know that the A antigen is present (and, of course, if there is no clumping, then the A antigen is not present). If clumping occurs in the drop of blood where you added the anti-B antibodies, then you know that the B antigen is present (and, of course, if there is no clumping, then the B antigen is not present). This information, can determine the blood type.

Drop of blood in which anti-A antibody was added

Drop of blood in which anti-B antibody was added

Blood type

Clumping

No clumping

A

No clumping

Clumping

B

Clumping

Clumping

AB

No clumping

No clumping

O

According to the ABO blood typing system there are four different kinds of blood types: A, B, AB or O (none).

Blood group A In the blood group A, A antigens occur on the surface of red blood cells and B antibodies in blood plasma. A

A antigen

B antibody

Fig. 7.14 Blood group “A”

274 HUMAN ANATOMY AND PHYSIOLOGY Blood group B In the blood group B, B antigens occur on the surface of red blood cells and A antibodies in blood plasma. B B antigen

A antibody

Fig. 7.15 Blood group “B”

Blood group O In the blood group O (null), neither A or B antigens on the surface of red blood cells but both A and B antibodies occur in blood plasma. O

A antibody B antibody

Fig. 7.16

Blood group “O”

Blood group AB In the blood group AB, both A and B antigens occur on the surface of red blood cells and no A or B antibodies at all in blood plasma. AB B antigen A antibody

Fig. 7.17

Blood group “AB”

2. Rh System Many people also have a so-called Rh factor on the red blood cell’s surface. This is also an antigen and those who have it are called Rh+. Those who haven’t are called Rh-. A person with Rh- blood does not have Rh antibodies naturally in the blood plasma (as one can have A or B antibodies, for instance). But a person with Rh- blood can develop Rh antibodies in the blood plasma if he or she receives blood from a person with Rh+blood, whose Rh antigens can trigger the production of Rh antibodies. A person with Rh+ blood can receive blood from a person with Rh- blood without any problems. Rh + Rh antigen

Rh –

Rh antibody

Fig. 7.18

R+ and Rh– blood groups

HAEMOPOIETIC SYSTEM 275 This is ∑ inherited independent of ABO system ∑ Rh positive = antigen present on RBCs (and no antibodies) ∑ Rh negative = no antigen and antibodies will be produced IF exposure occurs. According to above blood grouping systems, you can belong to either of following 8 blood groups: 1. A Rh+ 2. A Rh3. B Rh+ 4. B Rh5. AB Rh+ 6. AB Rh7. 0 Rh+ 8. 0 RhIf a person with A+ blood receives B+ blood. The B antibodies (yellow) in the A+ blood attack the foreign red blood cells by binding to them. The B antibodies in the A+ blood bind the antigens in the B+ blood and agglutination occurs. This is dangerous because the agglutinated red blood cells break after a while and their contents leak out and become toxic. Of course you can always give A blood to persons with blood group A, B blood to person with blood group B and so on. But in some cases you can receive blood with another type of blood group, or donate blood to a person with another kind of blood group. The transfusion will work if a person who is going to receive blood has a blood group that doesn’t have any antibodies against the donor blood’s antigens. But if a person who is going to receive blood has antibodies matching the donor blood’s antigens, the red blood cells in the donated blood will clump. O

A

B

AB

Fig. 7.19 Blood and blood groups. Who can give blood to whom? People with blood group O are called “universal donors” and people with blood group AB are called “universal receivers.”

Blood Group

Antigens

Antibodies

Can give blood to

Can receive blood from

AB

A and B

None

AB

AB, A, B, O

A

A

B

A and AB

A and O

B

B

A

B and AB

B and O

O

None

A and B

AB, A, B, O

O

Blood Groups used in Detective Work: A person’s blood group never changes. Thus, it can be important in identifying blood stains or determining parentage, although this evidence is useful only in a negative sense. For example, if a

276 HUMAN ANATOMY AND PHYSIOLOGY murder suspect had their clothing stained with group A blood, and the victim was group O, this is evidence that the suspect was not stained by the victim’s blood. Even if the stains proved to be group O, it would not be conclusive evidence, for the suspect may have had their clothing stained with the blood of any person who was a group O. The determination of paternity in disputed cases is very complicated, but the same type of reasoning is used.

O A B AB

Father’s group

O O O, A O, B A, B

Mother’s group A B O, A O, B O, A O, A, B, AB O, A, B, AB O, B A, B, AB A, B, AB

AB A, B A, B, AB A, B, AB A, B, AB

Rh status is similar to blood groups. If you are Rh positive, you may have genes for both positive and negative. If you are Rh negative, you have two genes for Rh negative.

Father’s group

Rh + Rh -

Mother’s group Rh + Rh Rh + , Rh Rh + , Rh Rh + , Rh Rh -

Antigens A and B ∑ The A antigen and the B antigen are derived from a common precursor known as the H antigen (or H substance). ∑ The H antigen is a carbohydrate sequence with carbohydrates linked mainly to protein (with a minor fraction attached to ceramide moiety). ∑ The majority of the ABO determinants are expressed on the ends of long polylactosamine chains attached mainly to Band 3 protein (1), the anion exchange protein of the red cell membrane, and a minority of the epitopes are expressed on neutral glycosphingolipids (1). ∑ In blood group O, the H antigen remains unchanged and consists of a chain of beta-D-galactose, beta-D-N-Acetylglucosamine, beta-D-galactose, and 2-linked, alpha-L-fucose, the chain being attached to the protein or ceramide. ∑ H antigens can be changed into A or B antigens by enzymes coded by the blood group A or B genes, which are sugar (glycosyl) transferases. ∑ Type A has an extra alpha-N-Acetyl-D-galactosamine bonded to the D-galactose at the end, while type B has an extra alpha-D-galactose bonded to the D-galactose at the end. ∑ Antibodies are not formed against the H antigen, except by those with the Bombay phenotype. ∑ In ABH secretors, ABH antigens are secreted by most mucus-producing cells of the body interfacing with the environment, including lung, skin, liver, pancreas, stomach, intestines, ovaries and prostate.

HAEMOPOIETIC SYSTEM 277 Thus we can conclude that ∑ Red blood cell antigens determine blood group ∑ The antigens expressed on the red blood cell determine an individual’s blood group. The main two blood groups are called ABO (with blood types A, B, AB, and O) and Rh (with Rh Dpositive or Rh D-negative blood types). ∑ The functions of many of the blood group antigens are not known, and if they are missing from the red blood cell membrane, there is no ill effect. This suggests that if the blood group antigens used to have a function, e.g., one particular blood group antigen made red blood cells more resistant to invasion from a parasite, it is no longer relevant today. ∑ But the presence or absence of red blood cell antigens becomes extremely important when blood from different people mixes, e.g., when a patient receives a blood transfusion from a blood bank. This also happens when a mother becomes pregnant because during labor, a small amount of fetal blood enters her circulation. In these circumstances, exposure to the foreign antigens on the red blood cells can trigger immune reactions. ∑ It is not possible to completely remove the danger of adverse reactions when blood from two people mix, but the danger can be minimized. Before a blood transfusion takes place, the blood to be donated must be “typed and cross matched” with the patient’s blood to ensure immune compatibility. ∑ In pregnancy, the risk of the mother’s immune system attacking the foreign antigens present on her fetus’ red blood cells is prevented by giving the mother antibodies to cover fetal red blood cell antigens and removing them from the mother’s circulation before her immune cells find them. ∑ Blood groups differ around the world. ∑ The distribution of the four ABO blood types, A, B, AB, and O, varies in populations throughout the world. It is determined by the frequency of the three alleles of the ABO gene in different populations. Blood type O is the most common worldwide, followed by group A. Group B is less common, and group AB is the least common. ∑ People with blood type O are said to be “universal donors” because their blood is compatible with all ABO blood types. It is also the most common blood type in populations around the world. ∑ Blood type AB individuals are known as “universal receivers” because they can receive blood from any ABO type. It is also the rarest of the blood groups.

The classification of blood cell antigens ∑ Traditionally, newly discovered red blood cell antigens were named alphabetically (e.g., ABO, MNS, P) or were named for the first person who produced antibody against them (e.g., Duffy, Diego). ∑ In 1980, The International Society of Blood Transfusion (ISBT) Working Party on Terminology for Red Cell Surface antigens was formed to create a standard for blood group terminology. ∑ Under this terminology, each blood group antigen has a number, and it belongs to a blood group system, a collection, or a series. The current classification system can be seen here. ∑ A blood group system contains antigens controlled by a single gene (or by multiple closely linked loci), and the system is genetically distinct. ∑ At the time of writing, there are 22 blood group systems, including the ABO, Rh, and Kell blood groups which contain antigens that can provoke the most severe transfusion reactions.

278 HUMAN ANATOMY AND PHYSIOLOGY ∑ Each blood group antigen is assigned a six-digit number by the ISBT. The first three digits represent the blood group (e.g., ABO is 001, Rh is 004), and the last three identify the antigen in the order it was discovered. ∑ For example, for ABO, the A antigen was the first to be discovered and has the number 001.001 whereas the B antigen was next and is designated 001.002.

Inheritance of Blood Groups ∑ A and B are codominant, giving the AB phenotype. ∑ Blood groups are inherited from both parents. The ABO blood type is controlled by a single gene with three alleles: i, IA, and IB. ∑ The gene encodes a glycosyltransferase—that is, an enzyme that modifies the carbohydrate content of the red blood cell antigens. ∑ The gene is located on the long arm of the ninth chromosome. ∑ IA allele gives type A, IB gives type B, and i gives type O. IA and IB are dominant over i, so ii people have type O, IAIA or IAi have A, and IBIB or IBi have type B. ∑ IAIB people have both phenotypes because A and B express a special dominance relationship: codominance, which means that type A and B parents can have an AB child. ∑ A type A and a type B couple can also have a type O child if they are both heterozygous (IBi, IAi) ∑ Therefore, an O child is not a direct proof of illegitimacy, just as a child with blond hair could be born from parents who both had brown hair. ∑ The cis-AB phenotype has a single enzyme that creates both A and B antigens. ∑ The resulting red blood cells do not usually express A or B antigen at the same level that would be expected on common group A1 or B red blood cells, which can help solve the problem of an apparently genetically impossible blood group.

7.13

IMMUNE RESPONSE AND BLOOD TRANSFUSION

Many of the adverse effects of blood transfusions are mediated by the recipient’ immune system. In general, the formation of this and other immune responses occur in three stages: ∑ the immune system detects foreign material (antigen) ∑ the immune system processes the antigen ∑ the immune system mounts a response to remove the antigen from the body. The immune response varies tremendously, depending on the individual (the health of his or her immune system and genetic factors) and the antigen (how common it is and how “provocative” it is to the immune system).

Antigen Detection ∑ The red blood cells (RBCs) from one person may enter into the circulation of another person in two different ways, either by a blood transfusion or by pregnancy. ∑ The RBCs will appear foreign if they contain antigens that are not found on the patient’s own RBCs. ∑ Blood group antigens are surface markers on the red blood cell membrane.

HAEMOPOIETIC SYSTEM 279 Antigens Stimulate an Immune Response ∑ An antigen is any substance to which the immune system can respond. ∑ For example, components of the bacterial cell wall can trigger severe and immediate attacks by neutrophils. ∑ If the immune system encounters an antigen that is not found on the body’s own cells, it will launch an attack against that antigen. ∑ Conversely, antigens that are found on the body’s own cells are known as “self-antigens”, and the immune system does not normally attack these. ∑ The membrane of each red blood cell contains millions of antigens that are ignored by the immune system. ∑ However, when patients receive blood transfusions, their immune systems will attack any donor red blood cells that contain antigens that differ from their self-antigens. ∑ Therefore, ensuring that the antigens of transfused red blood cells match those of the patient’s red blood cells is essential for a safe blood transfusion.

Red Blood Cell Antigens can be Sugars or Proteins ∑ Blood group antigens are either sugars or proteins, and they are attached to various components in the red blood cell membrane. ∑ For example, the antigens of the ABO blood group are sugars. ∑ They are produced by a series of reactions in which enzymes catalyze the transfer of sugar units. ∑ A person’s DNA determine the type of enzymes they have, and, therefore, the type of sugar antigens that end upon their red blood cells. ∑ In contrast, the antigens of the Rh blood group are proteins. A person’s DNA holds the information for producing the protein antigens. ∑ The RhD gene encodes the D antigen, which is a large protein on the red blood cell membrane. Some people have a version of the gene that does not produce D antigen, and therefore the RhD protein is absent from their red blood cells. ∑ The red blood cell membrane has some of the blood group antigens attached to it. ∑ Aside from the sugar (glycan or carbohydrate) antigens, the red blood cell membrane contains three types of protein that carry blood group antigens: single-pass proteins, multi-pass proteins, and glycosylphosphatidylinositol (GPI)-linked proteins.

Antigen Processing ∑ When the macrophage encounters an antigen, it engulfs, it, digests it, and then presents the antigenic fragments on its cell surface together with MHCII (Major Histocompatibility Complex II). ∑ A T helper cell binds to the antigen/MHCII on the macrophage, and the two cells interact. ∑ The macrophage secretes cytokines to stimulate the T cell, which in turn secretes cytokines to stimulate the growth and production of more T cells. ∑ The T helper cell, now activated, leaves to activate a third type of cell, the B cell. ∑ Existing B cells are stimulated by the T cell to grow, divide, and produce genetically identical daughter cells.

280 HUMAN ANATOMY AND PHYSIOLOGY ∑ Some of the daughter cells become plasma cells that produce antibodies that are specific for the antigen that stimulated their production. ∑ The amount and type of antibody produced results from the interaction of T helper cells (which stimulate antibody production) and T suppressor cells (which inhibit antibody production). ∑ Other daughter cells remain as B cells in the circulation for many years. ∑ They serve as “memory cells”, remembering the encounter with the antigen that stimulated their production.

First Immune Response If this is the first time the antigen has been encountered, a primary immune response is mounted. Usually there is a delay of several days, then lgM antibody is produced, followed by a switch to lgG antibody production. The initial lgM molecules bind the antigen weakly, but the subsequent lgG molecules are much better targeted. lgG continues to be produced long after the encounter with the antigen, providing long-lasting immunity.

Second Immune Response If the immune system has encountered the antigen before, it will already be armed with primed B cells (memory cells) that accelerate the production of larger amounts of lgG (rather than lgM). This is called the secondary immune response. It is faster, more specific, and the production of the specific antibody may remain high for years. B cells may also undergo changes to further improve how the antibodies they produce bind to the antigen.

7.14

HEMOLYTIC DISEASE OF THE NEWBORN (HDN)

It is hemolysis of RBCs of fetus which can cause anemia or worse may occur when an Rh negative mother and Rh positive father have an Rh positive fetus. RhoGAM is the treatment for Rh disease; contains antibodies specific for Rh positive antigen (a good example of passive immunity) injected within 72 hours after birth of Rh positive baby. ABO blood group incompatibilities between the mother and child does not usually cause hemolytic disease of the newborn (HDN) because antibodies to the ABO blood groups are usually of the lgM type, which do not cross the placenta; however, in an O-type mother, lgG ABO antibodies are produced and the baby can develop ABO hemolytic disease of the newborn. Hemolytic disease of the newborn (HDN) used to be a major cause of fetal loss and death among newborn babies. The first description of HDN is thought to be in 1609 by a French midwife who delivered twins—one baby was swollen and died soon after birth, the other baby developed jaundice and died several days later. For the next 300 years, many similar cases were described in which newborns failed to survive.

Maternal antibodies cross the placenta and attack fetal red blood cells During pregnancy, some of the mother’s antibodies are transported across the placenta and enter the fetal circulation. This is necessary because by the time of birth, newborns have only a primitive

HAEMOPOIETIC SYSTEM 281 immune system, and the continuing presence of maternal antibodies helps ensure that they survive while their immune system matures. A downside to this protection is that by targeting fetal RBCs, maternal antibodies can also cause HDN. A major cause of HDN is an incompatibility of the Rh blood group between the mother and fetus. Most commonly, hemolytic disease is triggered by the D antigen, although other Rh antigens, such as c, C, E, and e, can also cause problems. Pregnancies at risk of HND are those in which an Rh D-negative mother becomes pregnant with an RhD-positive child (the child having inherited the D antigen from the father). The mother’s immune response to the fetal D antigen is to form antibodies against it (anti-D). These antibodies are usually of the lgG type, the type that is transported across the placenta and hence delivered to the fetal circulation. HDN can also becaused by an incompatibility of the ABO blood group. It arises when a mother with blood type O becomes pregnant with a fetus with a differed blood type (type A, B or AB). The mother’s serum contains naturally occurring anti-A and anti-B, which tend to be of the lgG class and can therefore cross the placenta and hemolyse fetal RBCs. HDN due to ABO incompatibility is usually less severe than Rh incompatibility. On reason is that fetal RBCs express less of the ABO blood group antigens compared with adult levels. In addition, in contrast to the Rh antigens, the ABO blood group antigens are expressed by a variety of fetal (and adult) tissues, reducing the chances of anti-A and anti-B binding their target antigens on the fetal RBCs. Less common causes of HDN include antibodies directed against antigens of the Kell blood group (e.g., anti-K and anti-k), Kidd blood group (e.g., anti-Jka and anti-Jkb), Duffy blood group (e.g., antiFya), and MNS and s blood group antibodies. To date, antibodies directed against the P and Lewis blood groups have not been associated with HDN.

Sensitization occurs during the first pregnancy Sensitization to an antigen occurs when the immune system encounters an antigen for the first time and mounts an immune response. In the case of HDN caused by Rh incompatibility, an Rh Dnegative mother may first encounter the D antigen while being pregnant with an Rh D-positive child, or by receiving a blood transfusion of Rh D-positive blood. Once a mother has been sensitized to the D antigen, her serum will contain anti-D. The direct Coombs test confirms the presence of antiD and hence that the mother has been sensitized. Only a small amount of fetal blood need enter the mother’s circulation for sensitization to occur. Typically, this occurs during the delivery of the first-born Rh D-positive child. Fetal-maternal hemorrhage is common during labor and is increased during a prolonged or complicated labor, which in turn increases the risk of sensitization. Sensitization can also occur earlier in the pregnancy, for example, during a prenatal bleed or a miscarriage. It may also occur during medical procedures, such as a termination of pregnancy or chorionic villus sampling. The risk of sensitization to the Rh D antigen is decreased if the fetus is ABO incompatible. This is because any fetal cells that leak into the maternal circulation are rapidly destroyed by potent maternal anti-A and/or anti-B, reducing the likelihood of maternal exposure to the D antigen.

282 HUMAN ANATOMY AND PHYSIOLOGY HDN occurs in subsequent pregnancies Initially, the maternal anti-D that is formed at the time of sensitization is of the lgM type, which cannot cross the placenta. In subsequent pregnancies, a repeat encounter with the Rh D antigen stimulates the rapid production of type lgG anti-D, which can be transported across the placenta and enter the fetal circulation. Once in the fetal circulation, anti-D attaches to the Rh D antigens found on the fetal RBCs, marking them to be destroyed. The rate of hemolysis determines whether the nature of HDN is mild, moderate, or severe. In mild cases, the small increase in the rate of hemolysis is tolerated by the fetus. At birth and during the newborn period, symptoms include a mild anemia and jaundice, both of which may resolve without treatment. In cases where there is a greater increase in the rate of hemolysis, the level of bilirubin may still remain low during the pregnancy because of the ability of the placenta to remove bilirubin from the fetal circulation. However, after birth the neonate’s immature liver is unable to metabolize the increased amount of bilirubin that instead accumulates in his or her blood. Within 24 hours of birth, the level of bilirubin may rise dramatically. If levels continue to rise, bilirubin may enter the brain to cause kernicterus, a potentially fatal condition that leaves permanent neurological damage in the babies that survive. An even greater rapid and prolonged destruction of RBCs leads to severe anemia in the fetus. The liver, spleen, and other organs increase their production of RBCs to compensate for their loss. The drive to produce RBCs causes the liver and spleen to increase in size (hepatosplenomegaly), and liver dysfunction can occur. Immature RBCs (erythroblasts) spill into the circulation, giving rise to the alternative name of this disease, erythroblastosis fetalis. A complication of severe HDN is hydrops fetalis, in which the fetal tissues become swollen (edematous). This condition is usually fatal, either in utero or soon after birth.

The Coombs test detects Rh incompatibility between mother and fetus To detect HDN, the presence of maternal anti-Rh lgG must be identified. In vivo, these antibodies destroy Rh D-positive fetal RBCs, but in vitro, they do not lyse cells or even cause agglutination, making them difficult to identify. Therefore, the Coombs test is used. This test uses antibodies that bind to anti-D antibodies. The test is named for Robin Coombs, who first developed the technique of using antibodies that are targeted against other antibodies.

Direct Coombs test: diagnoses HDN The direct Coombs test detects maternal anti-D antibodies that have already bound to fetal RBCs. First, a sample of fetal RBCs is washed to remove any unbound antibody (lg). When the test antibodies (anti-lg) are added, they agglutinate any fetal RBCs to which maternal antibodies are already bound. This is called the direct Coombs test because the anti-lg binds “directly” to the maternal anti-D lg that coats fetal RBCs in HDN.

Indirect Coombs test: used in the prevention of HDN The indirect Coombs test finds anti-D antibodies in the mother’s serum. If these were to come into contact with fetal RBCs they would hemolyse them and hence cause HDN. By finding maternal anti-D

HAEMOPOIETIC SYSTEM 283 before fetal RBCs have been attacked, treatment can be given to prevent or limit the severity of HDN. For this test, the mother’s serum is incubated with Rh D-positive RBCs. If any anti-D is present in the mother’s serum, they will bind to the cells. The cells are then washed to remove all free antibodies. When anti-lg antibodies are added, they will agglutinate any RBCs to which maternal antibodies are bound. This is called the indirect Coombs test because the anti-lg finds “indirect” evidence of harmful maternal antibodies, requiring the addition of fetal RBCs to show the capacity of maternal anti-D to bind to fetal RBCs.

Preventing HDN ∑ Determine Rh status of the mother As part of routine prenatal or antenatal care, the blood type of the mother (ABO and Rh) is determined by a blood test. A test for the presence of atypical antibodies in the mother’s serum is also performed. At present, Rh D incompatibility is the only cause of HDN for which screening is routine.

∑ If the mother is not sensitized, reduce the risk of future sensitization To find out whether a pregnant Rh D-negative mother has been sensitized to the Rh D antigen, an indirect Coombs test is done. If anti-D is not found in the mother’s serum, it is likely that she has not been sensitized to the Rh D antigen. The risk of future sensitization can be greatly reduced by giving all unsensitized mothers anti-D lg, which “mops up” any fetal RBCs that may have leaked into the maternal circulation, reducing the risk of first-time exposure to the D antigen. Usually, Rh D-negative mothers receive on injection of anti-D lg at about 28 weeks gestation, which is about the time when fetal RBCs start to express the D antigen, and mothers receive another dose at about 34 weeks, a few weeks before labor begins during which the risk of fetomaternal hemorrhage is high. A final dose of anti-D lg is given after the baby has been delivered. In addition, anti-D lg is given to cover other events during the pregnancy that may lead to sensitization, e.g., antepartum bleeds and pre-eclampsia. This prophylaxis regime against Rh D sensitization is effective. However, currently, there is no routine prophylaxis for HDN caused by incompatibility of other blood group antigens.

∑ If the mother is sensitized, determine whether the fetus is at risk and monitor ∑ accordingly Once the presence of maternal anti-D has been confirmed, the next step is to determine whether the fetal RBCs are a target, i.e., confirm the Rh status of the fetus. If the father is homozygous for the D allele (D/D), the fetus will be D positive. If however the father is heterozygous (D/d), there is a 50:50 chance that the fetus is D positive, and the only way to know the blood type for sure is to test a sample of fetal cells taken from the amniotic fluid or umbilical cord. If the fetus is Rh D-positive, the pregnancy is carefully monitored for sign of HDN. Monitoring includes regular ultrasound scans of the fetus and monitoring of the amount of anti-D in the mother’s

284 HUMAN ANATOMY AND PHYSIOLOGY serum. Active hemolysis is indicated by a rise in anti-D. if a fetal blood test confirms fetal anemia, depending upon its severity, a blood transfusion can be done in utero to replace the lysed fetal RBCs.

7.15

BLOOD VOLUME AND BLOOD PRESSURE

Blood pressure is the pressure exerted by the circulating volume of blood on the walls of arteries, the veins, and the chambers of the heart. To remain healthy the body must keep the blood pressure between certain levels. The heart and the blood vessels are the main parts of the body’s cardiovascular system. Its job is to carry blood around the body so that it can feed the cells with oxygen and other nutrients needed to keep the body going. In order to simplify things we can think of the heart as a big pump, the blood vessels as a collection of pipes connected in a loop from the output of the heart back to the input, and the blood as red cordial made up of a mixture of water, sugar and a lot of other bits that give it its flavour and consistency. To understand the factors effecting blood pressure we can break the cardiovascular system into four areas: ∑ ∑ ∑ ∑ 1.

things that can be changed (variables); things that detect what is going on in the system (input sensors); the brain (control centre); and things that actually make changes happen (control signals). Variables Let’s look at all the things that can change. ∑ The volume of the blood: you can imagine that the amount of fluid in the system is going to change the pressure on all the parts. If the volume changes so will the pressure. In technical terms this is called the blood volume. ∑ The size of the pump: a bigger pump will pump out more blood than a smaller pump, but this is hard to change, and is usually proportional to the size of the person. Top athletes are an exception to this. They usually have larger hearts than normal people. For the sake of our discussion we will forget about the size of the heart. ∑ The speed of the pump: you can imagine if the pump is working faster then more blood is going to be pumped around the pipes. This is an important variable in changing the blood pressure. In technical terms this is called the heart rate (HR). ∑ The clearance of the pump: imagine a pump which is basically a hollow rubber ball with tubes coming from it (an inlet and an outlet). If you squeeze the ball slowly the air comes out gradually and without much force, but if you give it a good hard squeeze a lot of air comes out quickly. The same can be done with the heart, the body can increase the amount of blood it pumps out with each squeeze (contraction). The technical term for the amount of blood squeezed out with each contraction is stroke volume (SV). This variable is linked with the stretch of the heart prior to contraction (preload), the force of the contraction (contractility) and the pressure that must be obtained to actually get the blood out of the heart (afterload). ∑ Proload: If the muscle walls of the heart are stretched prior to a stroke then they will squeeze harder on the stroke. To get a greater stretch more blood must be in the heart. This observation is called the ‘Frank-Starling law of the heart’.

HAEMOPOIETIC SYSTEM 285 ∑ Contractility: The contractility of the heart is influenced by inotropic agents that make it pump either stronger or weaker. Positive inotropic agents such as Calcium ions and adrenaline make it pump stronger, negative inotropic agents such as potassium ions make the stroke weaker. ∑ Afterload: In order to get blood out the heart the back- pressure in the blood vessels must be overcome. The harder it is to get blood out, the less blood will actually leave the heart. You can imagine if the blood vessels are clogged or narrow that this will make things harder. The amount of blood the heart pumps each minute is the Stroke Volume (SV) ¥ Heart Rate (HR). The product is called the Cardiac Output (CO). ∑ The diameter of the pipes: will make a difference to the pressure. The tighter the pipes are the harder it will be to get the blood through. ∑ The stickiness of the cordial: when we make a strong glass of cordial we all know how sticky it gets, and you can imagine that it is easier to push a runnier, weaker, cordial through a pipe than thick, gooey cordial. The same happens with blood, it can be thick or thin, and when it is thicker it is harder to push through and thus, the pressure increases. The stickiness of a fluid is called its viscosity. ∑ The length of the pipes: if we have a short pipe to push the cordial around in you can imagine it does not take much effort on the part of the pump to move it. However, imagine if the pipes are really long, the pump is going to have to do more work to get the cordial to the other end. The same is true for the blood vessels, the length of the blood vessels influences the blood pressure. Like the size of the heart, the body cannot change this variable rapidly, it is mostly a problem for obese people. The last three variables are often grouped together and referred to as factors contributing to peripheral resistance (PR). 2. Input Sensors Since all these things can change at any time we really need something with a good deal of computing power to control them all. Control is carried out in certain parts of the brain, but the brain needs feedback on what is going on, and it gets this through the nervous system. There are two main types of sensors that provide information. ∑ Pressure sensors: that measure the stretch in the walls of blood vessels. These sensors are called baroreceptors and they send messages to a part of the brain called the Cardiovascular (CV) centre. ∑ Chemical sensors: that measure the levels of carbon dioxide, oxygen, and acidity in the blood. They are called chemoreceptors, and also send messages the CV centre. Other sensors that send messages to the CV centre are the emotional and thinking parts of the brain, temperature sensors (themoreceptors), and movement sensors (proprioceptors). These cause the brain to make adjustments that will affect the blood pressure, but are not as important as the two mentioned above. 3. The Control Centre The part of the brain dedicated to controlling the cardiovascular system is called the Cardiovascular centre. It is in a part of the brain called the medulla oblongata. It controls the variables: heart rate (HR), stroke volume (SV), and blood vessel diameter. There are a few different parts to this system and they include:

286 HUMAN ANATOMY AND PHYSIOLOGY ∑ The cardiostimulatory centre which makes the heart beat faster and stronger (increasing blood pressure); ∑ The cardioinhibitory centre which slows the heart down (decreasing blood pressure); ∑ The vasomotor centre consisting of the vasoconstrictor centre which decreases blood vessel diameter (increasing blood pressure), and the vasoconstrictor centre which increases blood vessel diameter (decreasing blood pressure). 4. Control Signals There are two ways the body sends out signals to change the variables we talked about earlier: nerves and hormones. Nerves carry electrical signals to different parts of the body, while hormones are chemical signals carried in the blood that affect particular parts of the body. Let us now look at how these are used to maintain blood pressure. The CV centre has two nerve links to the heart: a link to speed the heart up (sympathetic pathway) and a link to slow the heart down (parasympathetic pathway). When the baroreceptors detect a drop in pressure the CV centre sends signals via the sympathetic pathway and as a result the heart rate (HR) and the stroke volume (SV) increase. At the same time the diameter of the blood vessels is made smaller (vasoconstriction). When the blood pressure raises the opposite happens: the parasympathetic pathway receives signals and the heart slows and loses force, at the same time the blood vessels get wider (vasodilation), and the blood pressure decreases. When the chemocreceptors detect an excess of carbon dioxide the CV centre decreases the diameter of the blood vessels increasing the blood pressure. The same nerves that cause the heart to beat harder and stronger also cause the release of hormones called adrenaline and noradrenaline. These come from a gland called the adrenal gland, and cause the heart to beat faster (HR) and harder (SV), and causes blood vessels to get bigger (vasodilation). The body also has the ability to regulate blood pressure in a localized area. An example of this is heat and cold: heat will cause vasodilation, and cold vasoconstriction.

Factors Affecting Blood Pressure Blood pumped through blood vessels is always under pressure, much like water that is pumped through a garden hose. This pressure is highest in the arteries closest to the heart and gradually decreases as the blood travels around the body. Blood keeps moving around the body because there are differences in pressure in the blood vessels. Blood flows from higher-pressure areas to lower-pressure areas until it eventually returns to the heart. Blood pressure is controlled by three things: ∑ Heart rate. The pace of which the heart beats, or heart rate, is counted in heartbeats per minute. Generally, when heart rate increases, blood pressure rises. When heart rate decreases, blood pressure drops. A number of things affect heart rate, including the body’s nervous system; chemical messengers called hormones, body temperature, medications, and diseases. ∑ Stroke volume. The amount of blood pumped out of a ventricle with each heartbeat is called stroke volume. When you’re resting, stroke volume is about the same as the amount of blood that veins carry back to the heart. But under stressful conditions, the nervous system can increase stroke volume by making the heart pump harder.

HAEMOPOIETIC SYSTEM 287 Stroke volume can also be affected by certain hormones, drugs, and diseases, as well as increases or decreases in the amount of blood in the body, called blood volume. ∑ Peripheral resistance. The third major component that affects the blood pressure is the caliber or width of the arteries. Blood traveling in narrower vessels encounters more resistance than blood traveling through a wider vessel (its harder for water to pass through a narrow pipe than a wide pipe). Depending on what a person is doing, the amount of blood the heart pumps varies enormously. Yet the blood pressure normally remains pretty stable. That’s mainly because the body adjusts the resistance of the arteries, either widening or narrowing them as appropriate, to prevent the blood pressure from swinging wildly. This ability to regulate the width of the blood vessels is called the peripheral resistance. Most of the resistance to blood flow in the circulation occurs in the small-diameter arteries called arterioles. These arterioles are especially important in the immediate regulation of blood pressure. That’s because they contain specialized smooth muscle in their walls that can relax or contract, allowing the blood vessel to get wider or narrower. These changes are caused by: – Nervous system stimulation (for example, stress, caffeine, or tobacco) – Hormones – Proteins – Substances derived from the inner lining, or endothelium of blood vessels – Substances released during the body’s inflammatory responses, called inflammatory chemicals – Certain medications.

Various Diseases Keeping the Blood Pressure Normal Generally, a change in any factor that may cause the blood pressure to rise is balanced by a change in another factor. This is how the body keeps blood pressure in a normal range. For example, when you begin to exercise, your heart rate increases, as does the amount of blood pumped out of the heart with each beat (the stroke volume). This would normally increase the blood pressure. But the blood pressure remains normal because the blood vessels widen in order to increase the capacity for the extra blood being pumped while exercising. This helps offset the increase in blood pressure associated with the increase in heart rate and stroke volume associated with exercise. On the other hand, if blood pressure suddenly drops, a series of changes restores normal blood pressure. These include short-term increases in heart rate, the strength of the heart’s contractions, and peripheral resistance. Over a longer time period, blood volume also increases due to the actions of hormo nes on the kidneys.

Pulse Pressure There is another dynamic component of blood pressure called pulse pressure. Pulse pressure is the difference in pressure between when the ventricles of the heart contract and when they relax. It can be felt as a throbbing beat in an artery, called a pulse.

288 HUMAN ANATOMY AND PHYSIOLOGY When the ventricles contract, blood is pumped out of the left ventricle into the main artery leading away from the heart to the body, called the aorta. This creates the highest pressure that occurs in the aorta, called the systolic blood pressure. The increased pressure and increased blood volume cause the aorta to stretch. Because the blood pressure in the aorta is higher than the pressure in more distant vessels, blood moves forward toward the body’s tissues. When the ventricles relax, blood stops flowing into the aorta and the pressure drops to its lowest level. This is called the diastolic blood pressure. But blood continues to move forward in the circulation even when the ventricles are relaxed. Because the walls of the aorta and other elastic arteries bounce back, they maintain pressure on the blood moving through them.

7.16

SAFETY OF DONATED BLOOD

A Variety of infectious agents can be present in blood. ∑ ∑ ∑ ∑

viruses e.g., HIV-1, hepatitis B and C bacteria like the spirochete of syphilis protozoans like the agents of malaria and babesiosis prions e.g., the agent of variant Crueutzfeldt-Jakob disease and could be transmitted to recipients. To minimize these risks, – donors are questioned about their possible exposure to these agents; – each unit of blood is tested for a variety of infectious agents. Most of these tests are performed with enzyme immunoassays (EIA) — Link — and detect antibodies against the agents. However, it takes a period of time for the immune system to produce antibodies following infection, and during this period infectious virus is present in the blood. For this reason, blood is now also checked for the presence of the RNA of these RNA viruses: ∑ HIV-1 ∑ hepatitis C ∑ West Nile virus by the so-called nucleic acid-amplificaiton test (NAT).

7.17

DISORDERS

Anemia Anemia is a condition that is characterized by a reduction in the oxygen carrying capacity of the blood. This reduction is caused by inadequate levels of hemoglobin, inadequate numbers of erythrocytes (low hematocrit) or both. Symptoms of anemia are variable, but may include: ∑ Fatigue. One of the most common and debilitating symptoms of anemia is fatigue (lack of energy), particularly with exercise. Oxygen is required to metabolize fuel molecules (sugars, fats and proteins) to obtain energy. A person with a low hematocrit cannot carry enough oxygen in the blood to meet their energy demands.

HAEMOPOIETIC SYSTEM 289 ∑ Increased Heart Rate. The body increases heart rate to compensate for the low oxygen carrying capacity of the blood. If more blood is moved faster through the tissue then tissues get more oxygen per unit time. ∑ Shortness of Breath. An anemic person may feel short of breath and then breath faster to alleviate the feeling. This is a compensation for the poor delivery of oxygen to the tissues. ∑ Low Blood Pressure. The viscosity of the blood drops as the hematocrit decreases. A decrease in blood viscosity directly lowers total peripheral resistance (TPA) to the flow of blood, thus lowering mean arterial blood pressure (MAP). ∑ Pale Skin. Hemoglobin is bright red when oxygenated and less red when deoxygenated. Because the redness of skin is due to the redness of blood, the skin of an anemic person (who has less oxygen in the blood) will less red (paler) than the average person.

Causes of Anemia As mentioned earlier, anemia is characterized by either low hemoglobin, low hematocrit, or both. There are several situations that can lead to this state. The causes of anemia include: 1. Dietary Deficiencies ∑ Iron is required for the production and function of hemoglobin. In the absence of adequate iron, hemoglobin production slows down. Low hemoglobin can lower the hematocrit. ∑ Vitamin B12 and Folic Acid are required for DNA synthesis prior to cell division. In the absence of these nutrients production of erythrocytes is reduced. The hematocrit is low and many erythrocytes are huge, fragile cells called macrocysts. B12 deficiency can be caused by a lack of intrinsic factor, this is called pernicious anemia. Intrinsic factor, which is produced in the stomach, is required for efficient absorption of B12 out of the small intestine and into the blood. 2. Hemorrhage refers to a significant loss of blood through bleeding. Hemorrhagic anemia is due to blood loss that is greater than the rate at which erythrocytes can be replaced. Blood loss may be due to injury, donating blood, ulcers, heavy menstruation, etc. 3. Hemolysis refers to the lysis (breaking) of erythrocytes. Hemolytic anemia is due to a high rate of erythrocyte lysis in the blood steam. 4. Sickle cell anemia, which is caused by defective hemoglobin, is a genetic form of hemolytic anemia. Under conditions of low oxygen (as during exercise) the hemoglobin within erythrocytes crystallizes. This causes the RBCs to adopt a sickled shape, which makes them fragile and easily lysed. 5. Bone marrow failure leads to a reduction in the production of erythrocytes. This may be due to cancer or toxic drugs. 6. Kidney disease can lead to a reduction in the synthesis of erythropoetin, resulting in a low hematocrit. 7. Hemoglobinopathies Hemoglobinopathies form a group of inherited diseases that are caused by mutations in the globin chains of hemoglobin. Sickle cell anemia is the most common of these and is attributable to mutation that changes one of the amino acids in the hemoglobin beta chain, producing hemoglobin that is “fragile”. When the oxygen concentration is low, RBCs tend to become distorted and “sickle” shaped. These deformed cells can block small blood vessels and damage the organs they are supplying. This can be very painful, and if not treated, a sickle cell crisis can be fatal.

290 HUMAN ANATOMY AND PHYSIOLOGY 8. Thalassemia Another type of anemia which is inherited is thalassemia. A fault in the production of either alpha or beta globin chains causes a range of symptoms, depending on how many copies of the alpha and beta genes are affected. Some individuals may be carriers of the disease and have no symptoms. 9. Porphyrias The prophyrias are a group of inherited disorders in which the synthesis of heme is disrupted. Depending upon the stage at which the disruption occurs. There are a range of neurological and gastrointestinal side effects. King George III of England (“the madness of King George”) was one of the most famous individuals who suffered from porphyria. 10. Excessive bleeding: ∑ Hemophilia – genetic ‘defect’ – inability to produce certain factor(s) ∑ Thrombocytopenia – abnormally low platelet count most persons have idiopathic thrombocytopenia (= unknown cause) while in others it’s an autoimmune disease.

REVIEW QUESTIONS 1. Discuss the composition of blood in detail. 2. Explain haemopoiesis. 3. Describe the structure and functions of leucocytes. Also discuss the role of leucocytes in protection of the body. 4. Discuss various blood groups. How are these useful during blood transfusion. 5. Describe the mechanism of blood clotting. 6. Write an essay on blood related disorders. 7. Explain complete blood count. 8. Discuss in detail hemolytic disease of a new born. 9. How does immune system respond to antigens at the time of blood transfusion? 10. What is Hematocrit Value? Explain various factors which affect this value.

CHAPTER

8

LYMPH AND LYMPHATIC SYSTEM Right thoracic lymph duct Right subclavian vein

Cervical nodes Left subclavian vein

Axillary nodes Left thoracic lymph duct Intercostal nodes Cisterna chyli Lumber nodes Iliac nodes Inguinal nodes

8.1

INTRODUCTION

The lymphatic system is often considered part of the cardiovascular system. Excess fluid that leaks out of capillaries to bathe the body’s cells is collected by the vessels of the lymphatic system and 291

2st Proof (Co./D/01-08.../Human Anatomy.../Ch-8) 03/09/08/1100 (Shubham Composer)

292 HUMAN ANATOMY AND PHYSIOLOGY returned to the blood. By doing so, the lymphatic system maintains the fluid balance in the body. The lymphatic system further assists the cardiovascular system in absorbing nutrients from the small intestine. These necessary actions, however, only part of the system’s vitally are important for overall function. It is the body’s main line of defence against foreign invaders such as bacteria and viruses. The lymphatic system is responsible for body immunity, filtering harmful substances out of tissue fluid (which fills the spaces between the cells) before that fluid is returned to the blood and rest of the body. For this reason, it is sometimes referred to as the immune system. A network of vessels, tissues, organs, and cells constitute the lymphatic system. Included in this network are lymph vessels, lymph nodes, the spleen, the thymus, and lymphocytes. Running throughout this network is a watery fluid called lymph. Lymph vessels are closely associated with the circulatory system vessels. Larger lymph vessels are similar to veins. Lymph capillaries are scattered throughout the body. Contraction of skeletal muscle causes movement of the lymph fluid through valves.

8.2

LYMPH

It is the fluid which is contained within the lymph vessels. It is very much like plasma, pale yellow and clear, unless it contains fatty acids and glycerol following the absorption of fats from the intestine. Like plasma, it is mostly water with dissolved proteins, inorganic salts, food materials and waste products. It contains a varying number of WBCs mainly lymphocytes.

Lymphatic Vessels The lymphatic vessels form a second pathway for fluid returning from the tissues to the heart. In many tissues especially under epithelial surfaces, there is a network of lymphatic capillaries, which are very much like blood capillaries. These unite to form lymphatic vessels which are like very small veins. Under the action of the muscle pump and intra-abdominal pressure, the lymph flows along the vessels. They unite to form larger vessels which converge upon the thoracic duct. The negative intrapleural pressure associated with respiration assists the lymph flow upwards through the thorax in the thoracic duct to the root of the neck, where it and other regional lymph trunks open into the great veins. In this way all the lymph is added to the blood. Before the lymph reaches the blood, however, it always passes through at least one lymph node, where it is filtered and foreign particles and bacteria are removed.

Lymphatic Tissues Lymphatic tissue performs two functions : (a) It produces certain cells, namely lymphocytes, monocytes and plasma cells. (b) It acts as a filter for (i) tissue fluid, (ii) lymph, and (iii) blood. The tissues of the body are permeated by a vast network of capillaries containing blood. The walls of the capillaries consist of a single layer of cells and WBCs are able to make their way through these walls. The tissues are bathed in tissue fluid which may be regarded as an intermediary between the blood and the tissue; all interchange of nourishment and waste products between them takes place through the medium of tissue fluid. The lymphatic system is a subsidiary circulatory system which

LYMPH AND LYMPHATIC SYSTEM 293 drains the tissue fluid. From the tissue spaces, the tissue fluid passes into lymph capillaries which unite to form large trunks which then open into a pair of veins (right and left subclavian veins) entering the right auricle. Lymph is the name given to the tissue fluid when it has entered the lymphatic vessels.

Lymph Nodes There are situated in the course of the lymph vessels and generally occur in groups and are oval or kidney shaped. They are rich in phagocytes and lymphocytes. They act as filters for the microorganisms. Lymphatic system runs parallel to the veins and lymph flow is unidirectional i.e., from tissues to the heart. Differences between Blood and Lymph Blood 1. It is a red fluid. 2. It consists of plasma, erythrocytes, leucocytes and thrombocytes. 3. It has haemoglobin. 4. It transports materials from one organ to another. 5. It is contained in arteries and veins. 6. It’s flow is fast. 7. It contains proteins. 8. It flows from the heart into the blood vessels and again comes back to the heart.

8.3

Lymph 1. It is a colourless fluid. 2. It consists of plasma and leucocytes. 3. It lacks haemoglobin. 4. It transports materials from tissue fluid to blood. 5. 6. 7. 8.

It is contained in lymph vessels. It’s flow is slow. It contains less proteins. It starts from the tissue spaces, enters the lymph vessels and finally joins blood in.

FUNCTIONS OF LYMPHATIC SYSTEM

The lymphatic system does several jobs in a body. It ∑ ∑ ∑ ∑ ∑

Drains fluid back into the bloodstream from the tissues Filters lymph Filters blood Fights infections Absorption of digested fats

Draining Fluid into the Bloodstream ∑ As the blood circulates, fluid leaks out into the body tissues. ∑ This fluid is important because it carries food to the cells and waste products back to the bloodstream. ∑ The leaked fluid drains into the lymph vessels. ∑ It is carried through the lymph vessels to the base of the neck where it is emptied back into the bloodstream. ∑ This circulation of fluid through the body is going on all the time.

294 HUMAN ANATOMY AND PHYSIOLOGY Filtering Lymph ∑ The lymph nodes filter lymph as it passes through. ∑ White blood cells attack any bacteria or viruses they find in the lymph as it flows through the lymph nodes. ∑ If cancer cells break away from a tumour, they often become stuck in the nearest lymph nodes. ∑ This is why doctors check the lymph nodes first when they are working out how far a cancer has grown or spread.

Filtering the Blood ∑ ∑ ∑ ∑ ∑

This is the job of the spleen. It filters the blood to take out all the old worn out red blood cells and then destroys them. They are replaced by new red blood cells that have been made in the bone marrow. The spleen also filters out bacteria, viruses and other foreign particles found in the blood. White blood cells in the spleen attack bacteria and viruses as they pass through.

Fighting Infection The lymphatic system helps fight infection in many ways such as: ∑ Helping to make special white blood cells (lymphocytes) that produce antibodies. ∑ Having other blood cells called macrophages inside the lymph nodes which swallow up and kill foreign particles, for example germs. Lymphatic system plays major roles in our immune system in defending from infection and cancer. It consists of vessels connected to several lymph nodes located throughout drains lymph from all over the body and back into the bloodstream. The lymph nodes act as filters that contain many lymphocytes or white blood cells which destroy bacteria and viruses in the lymph. While helping to fight any infection the lymph nodes can become swollen and tender in the general area. Most of the lymphocytes are formed in the lymph glands.

Absorption of Digested Fats Epithelium Mucusproducing cell

Blood capillary

Crypt

Lacteal

Lymphatic system

Fig. 8.1

A villus

LYMPH AND LYMPHATIC SYSTEM 295 ∑ This important system also absorbs digested fats from small intestine. ∑ Small quantities of very small fatty acids are able to directly enter the intestinal capillaries of the villi of small intestine and hence enter the blood stream. ∑ However, the majority of fatty acids are long chained and are absorbed quite differently. ∑ Within the intestinal lumen, bile salts form aggregates called micelles that are water soluble. ∑ Fatty acids and monoglycerides are aggregated into the centres of the micelles. ∑ The micelles transport the fatty acids and monoglycerides to brush borders of the villi. ∑ From here, the fatty acids and monoglycerides diffuse into epithelial cells of the villi. ∑ The micelles continue their ferrying function in the intestinal lumen. ∑ Within epithelial cells, fatty acids and monoglycerides are resynthesised into triglycerides. ∑ The triglycerides combine with cholesterol, lipoprotein, and phospholipids to form globules called chylomicrons. ∑ The chylomicrons leave the epithelial cells and enter into lacteal of the villus. ∑ Lymphatic vessels then carry chylomicrons to the venous blood of left subclavian vein via thoracic duct.

8.4

COMPONENTS OF LYMPHATIC SYSTEM

The components of the lymphatic system are divided into two groups — primary organs and secondary organs. Lymphatic system

Primary organs Thymus Bone marrow

Secondary organs Lymph vessels Lymph nodes Aggregated lymphoid tissue Spleen

1. Primary Organs ∑ The thymus gland and the bone marrow are primary organs. ∑ They regulate production and differentiation of lymphocytes – the cells that make up the immune system. 2. Secondary Organs ∑ The secondary organs include lymphatic vessels, lymph nodes, aggregated lymphoid tissue, and spleen. ∑ These secondary organs are involved to some extent in all three lymphatic functions. While the primary organs are only involved in immune function of the lymphatic system. The secondary organs are collectively involved in all three functions: 1. Immunity 2. Fat absorption 3. Fluid regulation

296 HUMAN ANATOMY AND PHYSIOLOGY

Tonsils Thymus Lymph nodes Lymphatic vessels Spleen Peyer patches in small intestine Appendix Bone marrow

Fig. 8.2

8.5

Various components of lymphatic system

THYMUS

The thymus is a bilobed mass of lymphatic tissue located in close association with great vessels at the base of heart. It reaches its greatest relative weight (10–15 g) at birth and its greatest absolute

Thyroid

Thymus

Right lung

Left lung

Fig. 8.3

Location of thymus

LYMPH AND LYMPHATIC SYSTEM 297 weight (30–40 g) at the time of puberty. It begins to involute after puberty (weighing about 25 g at25 years, 13 g at 50 years, and 6 g at 75 years) and may become difficult to recognize grossly because of fatty infiltration. Gonads, suprarenal glands, and the thyroid gland influence the thymus. Gonadectomy or adrenalectomy delays thymic involution while thyroidectomy accelerates involution.

Characteristics ∑ The thymus is a soft, flattened, pinkish-gray mass of lymphoid tissue located in the upper chest under the breastbone. ∑ The thymus lies behind the sternum. It reaches its maximum size during puberty, and slowly involutes thereafter. ∑ There are two thymic lobes, partitioned by septae into lobules. Each lobule has an outer cortex and an inner medulla. Epithelial cells scattered among lymphocytes produce thymic hormones. ∑ ∑ ∑ ∑ ∑

∑ ∑ ∑ ∑ ∑ ∑ ∑

In a fetus and newborn infant, the thymus is relatively large (about the size of an infant’s fist). Up to the age of puberty, the thymus continues to grow. After this point in life, it shrinks and gradually blends in with the surrounding tissue. Very little thymus tissue is found in adults. It is situated immediately posterior to the sternum in the superior mediastinum of the thorax, occasionally reaching superiorly the thyroid gland, and inferiorly may extend as far as upper part of the pericardium (in children). Thymus with two lobes is situated slightly above the heart and ventral to (below) trachea. The two lobes are held together by connective tissue. Its size varies with age. It is relatively large at birth, but after sexual maturity, it begins to degenerate and is quite small in old animals. It stops its growth during adolescence and starts to atrophy, but it continues to function at a low rate. In old age it is replaced entirely by the fibrous and fatty tissue. In its active stage, it is a bilobar glandular organ; each lobe is pyramidal in shape.

∑ It is a ductless gland.

Structure Unlike lymph nodes, thymus is composed of lobules rather than nodules, lacks afferent lymph vessels and lymph sinuses, and has a framework of cytoreticular cells, rather than a stroma of reticular connective tissue. The section of young thymus shows following features: 1. Capsule. This is the connective tissue, which surrounds thymus. 2. Trabeculae. These are projections of connective tissue, which extend inward from the capsule and divide thymus into incomplete lobules. Blood vessels course in the trabeculae. 3. Lobules. These are the units of thymus and they are roughly rectangular in shape.

298 HUMAN ANATOMY AND PHYSIOLOGY

Capsule Reticulum of epithelial cells Cortex Blood-thymus barrier

Hassall’s corpuscle Medulla

Fig. 8.4 Structure of thymus 4. Cortex. The cortex is peripheral portion of each lobule. It contains many small lymphocytes (thymocytes) and stains dark. 5. Medulla. The medulla is central portion of each lobule. Medulla is pale, and is not called a germinal center. The medullary tissue of one lobule is continuous with that of other lobules. Cells of medulla include cytoreticular cells, lymphocytes of various sizes, and a few macrophages and plasma cells. 6. Hassall’s Corpuscles (thymic corpuscles). These are aggregates of degenerating cytoreticular cells, which are located in medulla and are unique to thymus. They are acidophilic and their centers may appear hyalinized (glassy). Most corpuscles are 20-50 µm in diameter, but some may be much large. 7. Capillaries. The capillaries, especially those in the cortex of the lobule, have thick walls. The thick wall is believed to constitute a blood-thymus barrier, which prevents antigenic macromolecules of blood from reaching thymus. Layers of the barrier are: (a) The continuous layer of endothelium, which lines capillary (b) The thick basement membrane of capillary (c) The layer of cytoreticular cells closely applied to the basement membrane of capillary.

Functions Thymus is: ∑ Important for immune-competency of the body’s immune system. Undifferentiated (immature) lymphocytes migrate from the bone marrow to the thymus gland to become immunocompetent T-lymphocytes (T=thymus dependent). ∑ Forms antibodies in newborn, and plays a major role in the early development of immune system. ∑ Also an endocrine gland, thymocytes secrete a group of hormones collectively called thymosin.

LYMPH AND LYMPHATIC SYSTEM 299 These hormones: - Control the production, the differentiation and the maturation of the lymphocytes in the thymus. - Stimulate the maturation of T lymphocytes, after they leave the thymus and migrate to other lymphatic organs.

8.6

BONE MARROW

Red blood cells

Lymphocytes Monocytes

Marrow

White blood cells

Eosinophils Basophils Neutrophils

Platelets

Fig. 8.5 Bone marrow ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑ ∑

Bone marrow is the soft material in the cavities of bones. It is a network of connective tissue fibers, fat cells, blood vessels, and blood-producing cells. Bone marrow produces both red and white blood cells, including lymphocytes. Both T-lymphocytes and B-lymphocytes are produced in the bone marrow. The young T -cells move to the thymus for final development, but B-cells remain in the bone marrow during maturation. Once the B-cells are fully developed in bone marrow, they are also released into circulation and most of them take up residence in the secondary lymphatic organs. The B-cells are white blood cells that are sensitive to antigens and produce antibodies against them. Antigens are chemicals that produce an immune response in the body, such as toxins, foreign proteins, particulate matter, or bacterial cells. When an antigen is present, the B-cell becomes active and begins to produce antibodies against that antigen.

∑ Antibodies are special proteins that bind (attach) to antigens and mark them for destruction.

300 HUMAN ANATOMY AND PHYSIOLOGY ∑ Antibodies are antigen specific, and the immune system is able to remember each antigen it fights. ∑ Once B-cell makes antibodies against certain antigen, e.g., a bacteria, it keeps a memory of that antigen. ∑ If antigen appears again, B-cell can produce a large number of antibodies very rapidly. ∑ In this way, a second infection with that bacteria is often prevented.

8.7

LYMPHATIC VESSELS ∑ The lymphatic vessels link together all the secondary organs and also connect to cardiovascular system. ∑ They provide a route for one-way flow of lymph from tissues of the body to the heart. ∑ Lymph is clear, yellowish fluid that is collected from interstitial spaces (the spaces between cells of a tissue) into lymphatic capillaries. ∑ Lymphatic capillaries are interwoven with blood capillaries. Fluid and proteins are forced out of the arterial end of blood capillary and into the interstitial space. ∑ About 90% of fluid is reabsorbed in venous end of the blood capillary, but none of the proteins are able to reenter the blood vessels because they cannot fit through the tight junctions of the cells. ∑ The lymph capillaries have extremely loose cell junctions, and they are able to absorb remaining 10% of the fluid along with plasma proteins. ∑ Once inside the lymph vessels, the fluid is then termed “lymph”. ∑ The lymphatic vessels are structured similar to veins, with thin walls and valves to prevent backflow. ∑ They are not muscular vessels, and external forces such as limb movement regulate the flow of lymph. ∑ Once in capillaries, the lymph moves into progressively large vessels, passes through the lymph nodes and/or spleen, reaches large ducts, and enters blood circulation near the junctions of jugular and subclavian veins in the upper chest. ∑ Thus, the fluid and proteins eventually return to blood, which helps maintain proper balance of fluid between blood vessels and the tissues. ∑ All the lymph from the lower body, left arm, and left thorax are drained through thoracic duct into the junction of left jugular and subclavian veins. ∑ The fluids from neck, right arm, and right thorax empty into right lymphatic duct which joins the venous system at junction of the right jugular and subclavian veins. ∑ Near the small intestine, where fats are digested and absorbed, lymphatic vessels have a special function and, therefore, a special name. ∑ They are involved in absorption of digested fat from the small intestine, and are called “lacteals.” ∑ After a meal the fluid within lacteals generally has a fat content of 1-2%, and appears cloudy. This cloudy lymph in the lacteals is called “chyle.”

LYMPH AND LYMPHATIC SYSTEM 301 8.8

LYMPH NODES

Lymph nodes are round or bean-shaped structures that are widely distributed throughout the body. Imbedded in connective tissue or fat, they are concentrated in cervical, axillary, and inguinal regions – neck, armpits, and groin, respectively. They are typically less than ½ inch in length, depending on the size of an animal. The lymph nodes filter lymph before returning to veins. They are arranged so that lymph has to pass through at least one node before returning to the veins.

Cervical Supraclavicular Axillary Mediastinal Supratrochlear Mesenteric Inguinal Femoral

Popliteal

Fig. 8.6

Lymph nodes

1. Lymph nodes are encapsulated masses of lymphatic tissue up to 25 mm in diameter. Blood vessels, nerves, and lymphatics are connected to each node. The cortical zone contains T cells, and medullary cords and are dominated by B cells. 2. Lymph arrives at a lymph node via lymphatics that penetrate capsule opposite the hilus. The lymph flows through a network of cortical sinuses. 3. The lymphocytes and macrophages of lymph nodes monitor the contents of lymph as it proceeds towards lymphatic ducts and venous system. 4. Lymph nodes are largest and most abundant where the peripheral lymphatics connect with the trunk. At these sites nodes are often called lymph glands, and their swelling usually indicates peripheral inflammation or infection.

Structure of Lymph Node These are composed of stroma and parenchyma. I. Stroma It consists of three parts; (a) Connective tissue capsule rich in collagen. (b) Trabeculae extending from the capsule inward dividing the node into compartments.

302 HUMAN ANATOMY AND PHYSIOLOGY Outer covering or ‘capsule’

Wider lymph vessels leaving lymph node

Narrow lymph vessels going into node

B cells T cells

Valves to stop lymph flowing in wrong direction

Fig. 8.7

Densely packed B and T cells, macrophages and plasma cells

Lymph node

(c) Reticular fibres that traverse sinuses and parenchyma. On the fibres present reticular cells called APCs (Antigen Presenting Cells). II. Parenchyma It is composed of following zones: (a) Cortex: formed of follicles containing APCs and lymphocytes B. It is sometimes called zone of B cells. Two types of follicles are present:(i) Primary lymphoid follicles without germinal center. (ii) Secondary lymphoid follicles, many of which have a pale spherical center called germinal center. The germinal center represents the site where lymphocytes (white blood cells that plays a major role in immune response) are produced by cell division. (b) Paracortical Zone: contains T lymphocytes and APCs (zone of T cells). (c) Medulla: formed of columns (cords) of cells mainly plasmocytes (the cells that produce immunoglobulins) and APCs. Lymph nodes are enclosed by a capsule of connective tissue and comprised of several compartments called “lymph nodules.” The nodules are masses of T-cells, B-cells, and macrophages. Macrophages are specialized cells that ingest and destroy foreign material. The nodules are separated by spaces called “lymph sinuses.” The vessels that deliver unfiltered lymph are called “afferent vessels,” and there are several per node. The lymph is then filtered for antigens and particulate matter, and an immune response is generated, if necessary. The filtered lymph leaves the node through one or two efferent vessels near an indentation called the “hilum.” Blood vessels also enter and exit node at the hilum.

LYMPH AND LYMPHATIC SYSTEM 303 Flow of Lymph through a Lymph Node Lymph is percolating or oozing through a lymph node. It takes the following course: 1. Afferent lymph vessels, 2. Subcapsular sinus, 3. Peritrabecular sinus, 4. Medullary sinus, and 5. Efferent lymph vessels. The latter have open ends and collect lymph from the medullary sinuses. All the sinuses contain macrophages (part of the macrophage or reticuloendothelial system), which remove particulate matter and degenerating cells from the lymph. The medullary sinuses are extremely broad and this slows the lymph, allowing for greater phagocytic action by macrophages, which form a net across lumen of each sinus and a lining along its periphery. Many lymphocytes are added to lymph as it passes through the lymph node. These are eventually emptied into the blood stream. Lymph nodes can be felt at certain points. ∑ Under arms, in armpits ∑ In each groin (at the top of your legs) ∑ In your neck. There are also lymph nodes that cannot be felt. These are in the: ∑ Abdomen ∑ Pelvis ∑ Chest Most lymphatic nodules are small and solitary. However, some are found in large clusters. For example large aggregates of lymph nodules occur in wall of the lower portion (ileum) of small intestine. These large masses of lymph nodules are known as Peyer’s patches. Tonsils are also aggregates of lymph nodules. They are located strategically to defend against invading bacteria. The tonsils produce lymphocytes. They are located under epithelial lining of the oral cavity and pharynx. The lingual tonsils are located at the base of tongue. The single pharyngeal tonsil is located in the posterior wall of nasal portion of the pharynx above the soft palate and is often referred to as adenoids. So to summarise lymph nodules comprise: ∑ Palatine and lingual tonsils—between mouth and oral part of the pharynx. ∑ Pharyngeal tonsil—on wall of nasal part of the pharynx. ∑ Solitary lymphatic follicles. ∑ Aggregated lymphatic follicles (Peyer’s patches)—in wall of the small intestine. ∑ Vermiform appendix—an outgrowth from the caecum (first part of the large intestine).

304 HUMAN ANATOMY AND PHYSIOLOGY Functions of Lymph Nodes Main functions of lymph nodes are:

Filtering and Phagocytosis ∑ Lymph is filtered by reticular and lymphoid tissue as it passes through lymph nodes. ∑ Particulate matter may include microbes, dead and live phagocytes containing ingested microbes, cells from malignant tumours, worn out and damaged tissue cells, and inhaled particles. ∑ Organic material is destroyed in lymph nodes by macrophages and antibodies. ∑ Some inorganic inhaled particles cannot be destroyed by phagocytosis. ∑ These remain inside the macrophage either causing no damage or destroying it. ∑ Material not filtered off and dealt with in one lymph node passes on to the next and so on. ∑ Thus by the time lymph reaches blood it has usually been cleaned of all impurities such as cell debris and foreign bodies. ∑ In some instances where phagocytation is incomplete the node may swell. ∑ Swelling of lymph nodes is often an indication of an infection. ∑ You may well have experienced swollen cervical lymph nodes. ∑ These often accompany a sore throat due to streptoccocal infection. ∑ Infections, almost in any part of the body may result in swelling and tenderness of the lymph nodes associated with that part of the body.

Proliferation of Lymphocytes ∑ ∑ ∑ ∑

Activated T- and B- lymphocytes multiply in the lymph nodes. T- and B- Lymphocytes are added to lymph as it flows through the sinuses of a lymph node. Thus the lymph leaving node is riche in lymphocytes. Antibodies produced by B- lymphocytes enter lymph and the blood drains the node.

Location of Lymph Nodes 1. The Lymph Nodes of the Head and Neck ∑ Superficial Lymph Nodes Most of the superficial structures of the head and neck are drained first into small groups of nodes located superficially on the cheek, in front of the ear on the parotid gland, behind the ear, at the back of the head, and under the chin. The lymph nodes are arranged in the following groups: 1. Occipital 2. Retroauricular (mastoid) 3. Parotid 4. Facial 5. Submandibular 6. Submental.

LYMPH AND LYMPHATIC SYSTEM 305 ∑ Superficial Cervical The occipital nodes: Lie over the occipital bone. The retroauricular nodes (mastoid nodes): On the surface of mastoid process of the temporal bone (behind the ear; post auricular). The parotid nodes (preauricular): are situated on or within the substances of parotid gland. The facial nodes (buccal): situated on cheek, opposite the angle of mouth. The submandibular nodes: rest on the superficial surface of the submandibular salivary gland. They can be palpated just below the lower border of body of the mandible. The submental: under the chin. ∑ The Deep Cervical Nodes Are numerous (20–30) and of large size: they form a chain along the carotid sheath and mainly internal jugular vein, They are usually described in two groups: 1. The upper deep cervical nodes lying under Sternocleidomastoid muscle. The most significant lymph nodes of the group are jugulo-digastric lymph node(s) and retropharyngeal lymph nodes. 2. The lower deep cervical nodes: In the supraclavicular triangle, where they are closely related to the brachial plexus and subclavian vein. The most significant lymph nodes of the group are supraclavicular and jugulo-omohyoid lymph nodes. The efferents of deep cervical nodes unite and form the jugular trunk. 2. The Lymph Nodes of the Thorax In general, Groups of lymph nodes drain lungs, bronchi, and the trachea and are present in relation to the bronchial tree (tracheobronchial nodes). Their efferent vessels ascend upon trachea and unite with efferents of the internal mammary and anterior mediastinal nodes to form right and left bronchomediastinal trunks. The right bronchomediastinal trunk may join right lymphatic duct, and left thoracic duct, but more frequently they open independently of these ducts into the junction of internal jugular and subclavian veins of their own side. The deep lymph nodes are mainly grouped in the axilla. These are located in the armpit. They are very important since they receive 75% of lymphatic drainage of the breast (important route for the metastases of the breast cancer). 3. The Axillary Nodes Are of large size, vary from twenty to thirty in number, and may be arranged in the following groups: ∑ The Anterior Axillary Lymph Nodes: They receive lymph vessels from the anterior wall of trunk above the level of umbilicus including most of the mammary glands. The anterior axillary nodes are: (a) Pectoral lymph nodes: Along the lower border of pectoralis minor. (b) Interpectoral lymph nodes: Between pectoralis major and minor. Anterior axillary nodes: drain into the central and apical axillary lymph nodes. ∑ Posterior Axillary (Subscapular) Lymph Nodes: alongside the subscapular vessels. They receive lymph vessels from lateral and posterior walls of the trunk above the gluteal region including back of the neck. They drain into the central axillary and apical lymph nodes.

306 HUMAN ANATOMY AND PHYSIOLOGY ∑ Lateral (Brachial) Lymph Nodes: alongside and medial to axillary vein. They receive all the lymphatic vessels of upper limb. They drain into central axillary and apical lymph nodes. ∑ Central Lymph Nodes: in the fat of axilla. They drain anterior, lateral, and posterior axillary lymph nodes into the apical axillary group of lymph nodes. ∑ Apical (Subclavicular) Lymph Nodes: in apex of the axilla medial to axillary vein. They drain all axillary lymph nodes. 4. The Lymph Nodes of the Lower Limbs Consist mainly of popliteal and inguinal nodes. The Popliteal Nodes: are imbedded in the fat contained in popliteal fossa (behind the knee). The efferents of popliteal nodes drain into the inguinal lymph nodes. The Inguinal Nodes: they may be divided into two groups; superficial and deep. The Superficial Inguinal Nodes ∑ Immediately below the inguinal ligament. ~ 20 in number. ∑ They are divided into two groups (T- shape distribution): horizontal (superior) and vertical (inferior). Horizontal (Superior) Lymph Nodes: They receive as afferents lymphatic vessels from the external genitalia (except the testes), perineum, anus, buttocks, and abdominal wall below the level of umbilicus. The Vertical (Inferior) Lymph Nodes: Are placed on either side of upper part of the great saphenous vein; they drain vessels that accompany the long saphenous vein. The Deep Inguinal Nodes: Vary from two to three in number, and are placed under fascia lata, on medial side of the femoral vein. Efferents drain into the external iliac. Afferents: 1. Deep lymph vessels of lower limbs. 2. Popliteal lymph nodes. 3. Superficial inguinal lymph nodes. 5. The Lymph Nodes of Abdomen and Pelvis External iliac Internal iliac gland Common iliac Sacral Lumbar: Lateral (para) aortic and preaortic The External Iliac Nodes: lie along the external iliac vessels. They receive lymph vessels from deep inguinal nodes and pelvis. The Internal Iliac Nodes: receive lymphatics corresponding to the distribution of branches of the internal iliac artery, i.e., they receive lymphatics from pelvis. The Common Iliac Nodes: They drain internal and external iliac nodes, and their efferents pass to the lateral (para aortic) nodes. The Sacral Nodes: are placed in concavity of the sacrum; they receive lymphatics from pelvis.

LYMPH AND LYMPHATIC SYSTEM 307 The Lumbar (aortic) Nodes: Consist of right and left lateral aortic (para-aortic) and preaortic groups. 6. The Para-aortic Lymph Nodes (Right and Left): The nodes on either side of abdominal aorta receive: (a) The efferents of common iliac nodes, (b) The lymphatics from testes and other gonads. (c) The lymphatics from the kidney and suprarenal gland; and Efferent vessels of lateral aortic nodes converge to form right and left lumbar trunks which join cisterna chyli. The preaortic nodes: Lie in front of aorta, and are divided into celiac, superior mesenteric, and inferior mesenteric groups, arranged around the origins of corresponding arteries. ∑ They drain the viscera supplied by three arteries with which they are associated: celiac drain foregut, superior mesenteric drain midgut, and inferior mesenteric drain hindgut. ∑ The efferents unite to form intestinal trunk, which enters cisterna chyli.

8.9

AGGREGATED LYMPHOID TISSUE

Aggregated (clumped) lymphoid tissues are collections of lymphoid tissue that are not encapsulated (in a capsule). They have varying degrees of size and organization. 1. Lymphatic tissues are connective tissues dominated by lymphocytes. A lymphatic tissue has no clearcut boundaries, the lymphocytes are not surrounded by a fibrous capsule. 2. A lymphatic nodule consists of a dense aggregation of lymphocytes in an area of loose connective tissue, usually beneath an epithelium. 3. Lymphatic nodules often have a pale central area, germinal center, where mitosis occurs. 4. The pharyngeal(adenoid), palatine, and lingual tonsils are large lymphatic nodules embedded in the walls of pharynx. 5. Peyer’s patches are lymphatic nodules beneath the epithelium of small intestine. 6. Large lymphatic nodules are also found beneath the epithelium of appendix and large intestine. The most highly organized and widely known examples are ∑ tonsils and ∑ Peyer’s patches.

1. Tonsils ∑ The tonsils are glands in the back of throat. The tonsils and adenoids (also called the ‘nasopharyngeal’ tonsils) help to protect bacterial viruses, entry to digestive system and lungs. ∑ They are circular bands (rings) of lymphoid tissue around entrance of pharynx where they are located in the mucous membrane. ∑ Physicians call this ring as Waldeyer’s ring. ∑ They are named according to their location. ∑ With age they become atrophied (during adulthood).

308 HUMAN ANATOMY AND PHYSIOLOGY ∑ The adenoids are at the back of nose. ∑ These tissues serve to prevent infection in the body at areas where bacteria in abundance. There are five tonsils: a pair on either side of inner wall of the throat (palatine tonsils), one near rear opening of the nasal cavity (Pharyngeal tonsil), and a pair near base of the tongue (lingual tonsils). This “ring” around the throat helps trap and remove bacteria or other foreign pathogens entering the throat through breathing, eating, or drinking.

Sinuses Adenoids Nose

Lips Tonsils Tongue Spine

Fig. 8.8

Tonsils and Adenoids

Palatine Tonsils ∑ Are located on both sides at posterior part of the oral cavity, in lateral wall of the oropharynx. ∑ They are the largest and are most frequently infected. ∑ Lingual tonsils located at posterior of base of the tongue. ∑ Pharyngeal tonsils (Adenoids) are located in posterior wall of the nasopharynx. Tubal Tonsils ∑ They surround openings of the Eustachian tubes in nasopharynx. ∑ They are extensions of pharyngeal tonsils around opening of the auditory (Eusta-chian) tube which is a channel through which tympanic cavity of the ear communicates with nasopharynx. Palatine Tonsil and Pharyngeal Tonsil The pharyngeal tonsil or “adenoid” underlies, an epithelium present in the upper respiratory tract. Although much of the epithelium has been infiltrated with lymphocytes yet small patches are intact. A smaller number of mixed serous-mucous glands are present. Structures and Functions ∑ Connective tissue capsule. ∑ The tonsils are not fully encapsulated. The surface exposed to pharynx is covered with epithelium which contains T lymphocytes and APCs. The covering epithelium invaginates deep into their interior forming blind-ended spaces called crypts where bacteria and other foreign substances are trapped and attacked.

LYMPH AND LYMPHATIC SYSTEM 309 ∑ The presence of germinal center in a follicle indicates that some of its activated lymphocytes are still enlarged and proliferating. ∑ The presence of plasma cells within the tonsils indicates formation of antibodies. ∑ The tonsils lack afferent lymphatic vessels, a feature that distinguishes them from lymph nodes. The efferent lymphatics of tonsils contribute many lymphocytes to the lymph. These cells are capable of leaving tonsils and destroying invading microorganisms in other parts of the body.

2. Peyer’s Patches Peyer’s patches are found in lining of small intestine. Tonsils and Peyer’s patches have specialized epithelial cells that are capable of transporting antigens, they do not filter lymph, they are generally surrounded by capillaries. The main purpose of the aggregated lymphoid tissue is defense from invasion at the mucosal surfaces. These are sites where large numbers of bacterium and other microorganisms are present and can easily enter body. These specialized lymphatic cells help preventing infections from developing at these sites. Both tonsils and Peyer’s patches are small masses of lymphatic tissue (some sources consider them specialized lymph nodes). Peyer’s patches, which resemble tonsils, are located in small intestine. The macrophages of Peyer’s patches prevent infection of intestinal wall by destroying bacteria which are always present in the moist environment of intestine.

3. The Mucous Membranes Associated Lymphatic Tissue “MALT” Mucosa associated lymph tissue (MALT) along with spleen and thymus is involved in the development of immunity. However, unlike lymph nodes, MALT has no afferent lymph vessels and therefore does not filter lymph. MALT is strategically positioned to protect respiratory and gastrointestinal tracts from microbes and other foreign material. These are either dispersed lymphocytes or aggregates of lymphocytes: Gut Associated Lymphoid Tissue (GALT). ∑ They are found in mucus membrane of the gut mainly that of the tonsils, oesophagus, peyer’s patches of ileum and small intestine, appendix, and the colon. ∑ They generate plasma cells that secrete antibodies in large amounts in response to foreign bodies in the intestine. Bronchus Associated Lymphoid Tissue (BALT) Similar clusters of tissue are found along bronchi of the respiratory system “BALT” (bronchus-associated lymphoid tissue).

8.10

SPLEEN

The spleen is a spongy organ located in upper left portion of the abdominal cavity along outside curve of the stomach. It is composed of two types of tissue — red pulp and the white pulp. 1. The red pulp is mostly used to store blood and break down old red blood cells. 2. The white pulp has the lymphatic function of filtering the blood for antigens.

310 HUMAN ANATOMY AND PHYSIOLOGY The spleen traps antigens and is another site for initiation of immune response. In a sense, it is like a large lymph node. A swollen spleen can be a sign of serious infection and is easily palpated.

Gastric surface Renal surface Hilum

Splenic artery Splenic vein (a) Capsule Trabecula

Primary follicle Marginal White pulp zone Periarterial lymphatic sheath (PALS)

Vascular sinusoid

Red pulp

Germinal center Artery

Vein (b)

Fig. 8.9

(a) Spleen (b) Section of spleen

Characteristics and Functions ∑ The spleen is a soft, dark purple, bean-shaped organ located in upper left side of the abdomen, just behind bottom of the rib cage. ∑ It is the largest mass of lymphoid tissue in the body, measuring about 5 inches (12.7 centimeters) in length. ∑ Though considered to be part of the lymphatic system, the spleen does not filter lymph (only lymph nodes do so). ∑ Instead, it filters and cleanses blood of bacteria, viruses, and other pathogens. It also destroys worn or old red blood cells. ∑ As blood flows through spleen, macrophages lining the organ’s tissues, engulf and destroy both pathogens and worn red blood cells. ∑ Any remaining part of decomposed red blood cells, such as iron, are returned to the body to be used again to form new red blood cells. ∑ Other functions of spleen include production of lymphocytes, which the organ releases into the bloodstream, and blood storage. ∑ When the body demands additional blood, such as during stress or injury, the spleen contracts, forcing its stored blood into circulation.

8.11

THE LYMPHOCYTES

1. There are three distinct populations of lymphocytes—T cells, B cells, and NK cells.

LYMPH AND LYMPHATIC SYSTEM 311 2. There are several different populations of T cell. Regulatory T cells include helper and suppressor T cells that regulate immune response. Cytotoxic (killer) T cells attack invading, infected, or abnormal cells. These T cells are responsible for cellular immunity. 3. B cells are concerned with the production of antibodies, special proteins that can either cause or facilitate destruction of specific antigens. These proteins are dissolved in body fluids, and they provide what is known as humoral immunity. 4. NK cells detect the presence of abnormal antigens on cell membranes; they are responsible for immunological surveillance and removal of cancer cells from normal tissues.

Circulation of Lymphocytes 1. Lymphocytes are found in blood, bone marrow, spleen, thymus, and peripheral lymphatic tissues. The ratio of B cells to T cells varies from one site to another. 2. Lymphocytes are continually migrating in and out of blood and through lymphatic tissues and organs. 3. Lymphocytes are relatively long-lived, and some survive for decades.

Lymphopoiesis 1. Lymphocytic stem cells are produced in bone marrow. B cells and NK cells are primarily produced in bone marrow. T cells are produced by stem cells that have migrated to thymus. 2. The thymus produces the hormone thymosin. Thymosin stimulates mitosis of stem cells in the thymus. Mature T cells leave thymus and reside in other tissues, including bone marrow.

Origin of Lymphocytes Lymphocytes originate from haematopoietic stem cells in bone marrow (pleuripotent stem cells). These are immature lymphocytes. 1. The lymphocytes that are destined to become T lymphocytes migrate from bone marrow to reach thymus via blood (the thymus has no lymph vessels). In thymus, they stimulate thymocytes to secrete thymosine that controls division, differentiation, and maturation of these lymphocytes. Only the lymphocytes that acquire ability to recognize and differentiate between self (auto) and foreign antigens, i.e., become immunocompetent, will survive. Now they are called mature T lymphocytes. 2. The lymphocytes that are destined to become B lymphocytes stay in the bone marrow where they become immunocompetent. The immunocompetent T and B lymphocytes leave thymus and bone marrow respectively and reach circulation where they will distribute through the blood and lymph to organs of the body.

8.12

LYMPH

Fluid that accumulates in the spaces between cells of loose connective tissue is called interstitial fluid, or tissue fluid. Tissue fluid originates from blood plasma. Under normal conditions, more

312 HUMAN ANATOMY AND PHYSIOLOGY liquid tend to leave the capillaries of cardiovascular system then enters them forming tissue fluid. Plasma proteins do not easily pass through walls of capillaries, however, as the liquid portion of blood moves into intercellular space, it carries a small amount of plasma proteins with it. Usually these smaller molecules do not move back with water and other dissolved substances into the venule ends of capillaries. If the tissue fluid (and plasma proteins) is allowed to accumulate, the tissues swell, producing a condition called edema (oedema). As molecules accumulate in tissue space, the volume of fluid in the interstitial space increases, as does the pressure within spaces. This increasing pressure is responsible for forcing some of the tissue fluid into the lymphatic capillaries where it becomes lymph. - Lymph, found only in the closed lymphatic vessels, is a transparent, colorless, or slightly yellow, watery fluid. Lymph coming from digestive system is milky in appearance (chyle). - 2-3 liters of lymph is present in the body.

Flow of Lymph The lymph flow is slow because there is no pump like heart. The factors which support circulation of lymph are the same which support venous return to the heart: 1. Contraction of the skeletal muscles. 2. The pulsation of nearby arteries can compress lymph vessels and move lymph within them. 3. The presence of valves permitting the lymph to move only in the direction of blood stream. 4. Pressure changes due to the contraction of respiratory muscles. In addition, rhythmic contractions of smooth muscles of the walls of lymphatic ducts and trunks aid circulation.

8.13

LYMPHATIC SYSTEM

∑ The lymphatic system is a system of thin tubes that runs throughout body. These tubes are called ‘lymph vessels’. These can also be called ‘lymphatic vessels’. ∑ The lymphatic system is like blood circulation – the tubes branch through all parts of body like arteries and veins that carry blood. Except that the lymphatic system carries a colourless liquid called ‘lymph’. ∑ Lymph is a clear fluid that circulates around the body tissues. It contains a high number of lymphocytes (white blood cells). Plasma leaks out of capillaries to surround and bathe body tissues. This then drains into the lymph vessels. ∑ The lymphatic system is a network of vessels that transports nutrients to the cells and collects their waste products. ∑ The lymph system consists of lymph capillaries and lymph vessels that are somewhat similar to blood capillaries and blood vessels.

LYMPH AND LYMPHATIC SYSTEM 313 ∑ In addition, it includes lymph ducts (tubes that carry fluids secreted by glands) and lymph nodes (reservoirs that filter out bacteria and other toxins from the lymph that passes through them). ∑ In the circulatory system, blood flows from heart, through arteries, and capillaries that surround all cells. ∑ When blood reaches capillaries, a portion of blood plasma (liquid portion of blood) seeps out of capillaries and gets into the space surrounding cells. ∑ That plasma is then known as tissue fluid. Tissue fluid consists of water plus dissolved molecules that are small enough to fit through small openings in capillaries. ∑ Tissue fluid is an important component of all living animals. Nutrients pass out of tissue fluid into cells and, conversely, waste products from cells are dumped back into tissue fluid. ∑ Some of the tissue fluid returns to blood capillaries by osmosis. (Osmosis is the process by which fluids and substances dissolved in them pass through a membrane until all substances involved reach a balance.) ∑ But some tissue fluid is also diverted into a second network of tubes: the lymphatic vessels. Tissue fluid that enters this network is known as lymph. ∑ Lymph is a clear, colorless, somewhat sticky liquid. The liquid formed in a blister is lymph. ∑ Thus the lymphatic system consists. 1. Of complex capillary networks which collect lymph in various organs and tissues; 2. Of an elaborate system of collecting vessels which conduct lymph from capillaries to large veins of the neck at junction of the internal jugular and subclavian veins, where the lymph is poured into blood stream; and 3. Lymph glands or nodes which are interspaced in pathways of the collecting vessels filtering lymph as it passes through them and contributing lymphocytes. ∑ The lymphatic capillaries and collecting vessels are lined throughout by a continuous layer of endothelial cells, forming a closed system. The lymphatic vessels of small intestine receive a special designation of lacteals or chyliferous vessels; they differ in no respect from lymphatic vessels generally excepting that during the process of digestion they contain a milk-white fluid, the chyle. ∑ The fluid, now called lymph, then flows through the lymphatic system to biggest lymph vessel – the thoracic duct. The thoracic duct then empties back into the blood circulation.

8.14

MOVEMENT OF LYMPH

Tissue fluid passes out of the space between cells and through walls of lymph capillaries. Now called lymph, it follows a pathway back to heart that is somewhat similar to venous system for blood. It passes from lymph capillaries into large tubes, the lymph vessels. Like veins in blood circulatory system, lymph vessels have valves that help push lymph slowly back towards heart. Eventually lymph enters a large collecting tube, the thoracic duct, located near heart. From the thoracic duct lymph empties into blood circulatory system itself at the left subclavian vein.

314 HUMAN ANATOMY AND PHYSIOLOGY The lymph system performs a second function also. Fats that have been absorbed in the small intestine enter lymph vessels of that organ. Those fats are then carried through the lymphatic system back into blood circulatory system. 1. Lymph flows along a network of lymphatics that originate in the terminal lymphatics of lymph capillaries. 2. The lymphatic vessels from areas below the diaphragm and from the left half of upper body are connected to the large thoracic duct that empties into venous system at the left subclavian vein near junction of the left internal jugular. 3. The lymphatics servicing right half of the body above diaphragm are connected to the small right lymphatic duct that empties into the venous system in same region on the right side. The subclavian veins, which are located just under the collar bones, receive the lymph, once again circulates throughout the body as plasma. Right subclavian vein

Fig. 8.10

8.15

Left subclavian vein

Subclavian veins receiving lymph

WORKING OF LYMPHATIC SYSTEM

The exchange of materials (oxygen, carbon dioxide, nutrients, and wastes) between blood and cells in the body occurs through the capillaries. In the body of an average person, over the course of an average day, roughly 25.4 quarts (24 liters) of plasma fluid is forced out of capillaries into interstitial fluid surrounding the cells. After bathing the cells, providing them with nutrients, and picking up their wastes, this fluid is drawn back into the capillaries. However, only 85 percent of the total fluid is drawn back into the bloodstream. The remaining 15 percent, roughly 3.8 quarts (3.6 liters), remain in the interstitial fluid. If this small amount of fluid was allowed to accumulate over even for a brief period of time, massive edema (swelling caused by excessive bodily fluid) would result. If left unchecked, body would blow up like a balloon, tissues would be destroyed and death would take place. This condition is prevented by the presence of lymph capillaries, which run alongside blood vessels in most tissue spaces. The lymph capillaries act as “drains,” collecting excess fluid and returning it to the venous blood just before blood reaches heart. Proteins and other large molecules dissolved in the interstitial fluid cannot be absorbed by blood capillaries. Because the walls of lymph capillaries are more permeable (allow material to pass through easily), these large substances enter lymph capillaries and are eventually returned to the blood. This function of lymph capillaries is particularly important in small intestine. Whereas carbohydrates and certain other nutrients are small enough to pass directly from intestine into bloodstream, and not fats. Lacteals (lymph capillaries in small intestine) are able to absorb fats and

LYMPH AND LYMPHATIC SYSTEM 315 other nutrients that are too large to enter blood capillaries. After digestion, the lymph in lacteals contains as much as 1 to 2 percent fat. Milky-white in appearance, this thick mixture of lymph and tiny fat globules is called chyle. It becomes mixed with blood after lymph drains into thoracic duct. After vessels of the lymphatic system have collected excess fluid, cellular wastes, proteins, fats, and other substances too large to enter blood capillaries directly, they return all this material to the bloodstream. Before advancing to heart and reentering the circulatory system, however, any fluid and matter that enters the lymphatic system must pass through at least one lymph node. It is very likely that foreign substances, such as viruses, bacteria, and even cancer cells, are a part of the lymph that has been collected from all parts of the body. Even the dark, gritty debris of polluted city air finds its way from the lungs of city dwellers into the lymph. Without filtering abilities of lymph nodes, these foreign substances would over run the body.

8.16

THE DEVELOPMENT OF THE LYMPHATIC VESSELS

∑ The lymphatic system begins as a series of sacs (108 at points of junction of certain embryonic veins). ∑ These lymph-sacs are developed by confluence of numerous venous capillaries, which at first lose their connections with venous system, but subsequently, on formation of sacs, regain them. ∑ The lymphatic system is therefore developmentally an offshoot of venous system, and the lining walls of its vessels are always endothelial. ∑ In the human embryo lymph sacs from which the lymphatic vessels derived are six in number; two paired, the jugular and posterior lymph-sacs; and two unpaired, the retroperitoneal and the cisterna chyli. ∑ In lower mammals an additional pair, subclavian, is present, but in human embryo these are merely extensions of the jugular sacs. ∑ The position of the sacs is as follows: 1. Jugular sac, the first to appear, at the junction of subclavian vein with primitive jugular; 2. Posterior sac, at the junction of iliac vein with the cardinal; 3. Retroperitoneal, in the root of mesentery near the suprarenal glands; 4. Cisterna chyli, opposite third and fourth lumbar vertebrae. ∑ From lymph-sacs the lymphatic vessels bud out along fixed lines corresponding more or less closely to the course of embryonic blood vessels. ∑ Both in body-wall and in the wall of intestine, the deeper plexuses are first to be developed; by continued growth of these vessels, superficial layers are gradually formed. ∑ The thoracic duct is probably formed from anastomosing outgrowths from the jugular sac and cisterna chyli. At connection with the cisterna chyli is at first double, but the two vessels soon join. ∑ All the lymph-sacs except cisterna chyli are, at a later stage, divided by slender connective tissue bridges and transformed into groups of lymph glands. The lower portion of cisterna chyli is similarly converted, but its upper portion remains as adult cisterna.

316 HUMAN ANATOMY AND PHYSIOLOGY Left innominate Internal jugular External jugular Jugular lymph sac Right innominate Superior vena cava

Duct of cuvier Left cordinal

Prerenal part of inferior vena cava

Postrenal part of inferior vena cava

Posterior lymph sac

Fig. 8.11

8.17

Cisterna chyli Left renal Retro-peritoneal lymph sac

Left common iliac External iliac Hypogastric

Relative positions of primary lymph sacs

LYMPHATIC CAPILLARIES

The complex capillary plexuses which consist of a single layer of thin flat endothelial cells, lie in the connective-tissue spaces in various regions of the body to which they are distributed and are bathed by intercellular tissue fluids. Two views are at present held as to the mode in which the lymph is formed: one being by the physical processes of filtration, diffusion, and osmosis, and the other, in addition to these physical processes the endothelial cells have an active secretory function. The colorless liquid lymph has about same composition as that of blood plasma. It contains many lymphocytes and red blood corpuscles. Granules and bacteria are also taken up by the lymph from connective-tissue spaces, partly by the action of lymphocytes which pass into the lymph between the endothelial cells and partly by the direct passage of the granules through endothelial cells. The lymphatic capillary plexuses vary greatly in form; the anastomoses are usually numerous; blind ends or cul-de-sacs are especially common in the intestinal villi, the dermal papillae and the filiform papillae of the tongue. The plexuses are often in two layers: a superficial and a deep, the superficial being of smaller caliber than the deep. The caliber, however, varies greatly in a given plexus from a few micromillimeters to one millimeter. The capillaries are without valves.

Distribution of Lymphatic Capillaries ∑ The Skin. Lymphatic capillaries are abundant in dermis where they form superficial and deep plexuses, the former sending blind ends into the dermal papillae. The plexuses are especially rich over palmar surface of the hands and fingers and over plantar surface of the feet and toes. The epidermis is without capillaries. The conjunctiva has an especially rich plexus. ∑ The subcutaneous tissue is without capillaries.

LYMPH AND LYMPHATIC SYSTEM 317 ∑ The tendons of striated muscle and muscle sheaths are richly supplied. In muscle, however, their existence is still disputed. ∑ The periosteum of bone is richly supplied and they have been described in the Haversian canals. ∑ They are absent in cartilage and probably in bone marrow. ∑ The joint capsules are richly supplied with lymphatic capillaries, they do not, however, open into the joint cavities. ∑ Beneath mesothelium lining of pleural, peritoneal and pericardial cavities are rich plexuses; they do not open into these cavities. ∑ The alimentary canal is supplied with rich plexuses beneath the epithelium, often as a superficial plexus in the mucosa and a deeper submucosal plexus. ∑ Cul-de-sacs extend into filiform papillae of tongue and villi of small intestine. ∑ Those portions of the alimentary canal covered by peritoneum, have in addition a subserous lymphatic capillary plexus beneath mesothelium. ∑ The salivary glands are supplied with lymphatic capillaries. ∑ The liver has a rich subserous plexus in the capsule and also extensive plexuses which accompany hepatic artery and portal vein. The lymphatic capillaries have not been followed into the liver lobules. The lymph from liver forms a large part of that, which flows through the thoracic duct. ∑ The gall-bladder and bile ducts have rich subepithelial plexuses and the former a subserous plexus. ∑ The nasal cavity has extensive capillary plexuses in mucosa and submucosa. ∑ The spleen has a rich subserous set and a capsular set of lymphatic capillaries. Their presence in parenchyma is uncertain. ∑ The trachea and bronchi have plexuses in mucosa and submucosa but the smaller bronchi have only a single layer. The capillaries do not extend to air-cells. The plexuses around the smaller bronchi connect with rich subserous plexus of lungs in places where veins reach the surface. ∑ Lymphatics have been described in thyroid gland and in thymus. ∑ The adrenal has a superficial plexus divided into two layers, one in loose tissue about gland and other beneath the capsule. Capillaries have also been described within parenchyma. ∑ The kidney is supplied with a coarse subserous plexus and a deeper plexus of finer capillaries in the capsule. Lymphatics have been described within the substance of kidney surrounding tubules. ∑ The urinary bladder has a rich plexus of lymphatic capillaries just beneath epithelial lining, also a subserous set which anastomoses with the former through muscle layer. The submucous plexus is continuous with submucous plexus of the urethra. ∑ The prostate has a rich lymphatic plexus surrounding gland and a wide-meshed subcapsular plexus. ∑ The testis has a rich superficial plexus beneath the tunica albuginea. The presence of deep lymphatics is disputed. ∑ The uterus is provided with a subserous plexus, the deeper lymphatics are uncertain. Subepithelial plexuses are found in vagina. ∑ The ovary has a rich superficial plexus and a deep interstitial plexus. ∑ The heart has a rich subserous plexus beneath epicardium. ∑ Lymphatic capillaries have also been described beneath endocardium and throughout the muscle.

318 HUMAN ANATOMY AND PHYSIOLOGY ∑ Lymphatic capillaries are probably absent in the central nervous system, meninges, eyeball (except the conjunctiva), orbit, internal ear, within striated muscle, liver lobule, spleen pulp and kidney parenchyma. ∑ They are entirely absent in cartilage. ∑ In many places further investigation is under study.

8.18

DRAINAGE AREAS

Lymphatic drainage is organization into two separate and very unequal drainage areas. These are right and left drainage areas and normally lymph does not drain across invisible lines that separate these areas. Structures within each area carry lymph to its destination, which is to return to circulatory system.

Right drainage area

Fig. 8.12

Left drainage area

Drainage areas

The right drainage area removes lymph from the: ∑ Right side of head and neck ∑ Right arm ∑ Upper right quadrant of the body. Lymph from this area flows into right lymphatic duct. This duct returns lymph to the circulatory system by draining into right subclavian vein. The left drainage area removes lymph from the: ∑ Left side of head and neck ∑ Left arm and left upper quadrant ∑ Lower trunk ∑ Both legs The cisterna chyli temporarily stores lymph as it moves upward from lower areas of the body. The thoracic duct carries lymph upward to left lymphatic duct. The left lymphatic duct returns lymph to circulatory system by draining into left subclavian vein.

Important of Drainage ∑ Damage Disturb the Flow. When lymphatic tissues or lymph nodes have been damaged, destroyed or removed, lymph cannot drain normally from the affected area. When this happens excess lymph accumulates and results in swelling that is characteristic of lymphedema.

LYMPH AND LYMPHATIC SYSTEM 319 ∑ Drainage Areas. The treatment of lymphedema is based on natural structures and the flow of lymph. The affected drainage area determines the pattern of manual lymph drainage (MLD) and for self-message. Although lymph does not normally cross from one area to another, MLD stimulates the flow from one area to other. It also encourages the formation of new lymph drainage pathways.

8.19

MAJOR LYMPHATIC VESSELS

The three main types of lymphatic vessels are lymph capillaries, lymphatics, and lymph ducts.

Lymph Capillaries ∑ Lymph capillaries are microscopic tubes located between cells. Lymph capillaries (resemble) blood capillaries (somewhat), but differ in important ways. Whereas a blood capillary has an arterial and a venous end, a lymph capillary has no arterial end. Instead, each lymph capillary originates as a closed tube. Lymph capillaries also have a larger and more irregular lumen (inner space) than blood capillaries and are more permeable. ∑ The wall of a lymph capillary is constructed of endothelial cells that overlap one another. ∑ When fluid outside capillary pushes against the overlapping cells, they swing slightly inward—like a swinging door that moves in only one direction. Fluid inside capillary cannot flow out through these openings. ∑ Lymph capillaries branch interconnect freely and extend into almost all tissues of the body except CNS (Central Nervous System) and avascular tissues such as epidermis and cartilage. ∑ Lymph capillaries join to form larger vessels called lymphatics or lymph veins. These resemble blood-conducting veins but have thin walls and relatively large lumen, and they have more valves. In skin, lymphatics are located in subcutaneous tissue and follow same paths as veins. In viscera, lymphatics generally follow arteries and form plexuses (networks) around them. ∑ At certain locations lymphatics enter lymph nodes. These are structures that consist of lymphatic tissue. ∑ As the lymph flows slowly through lymph sinuses within tissue of the lymph node, it is filtered. Macrophages remove bacteria and other foreign matter as well as debris. ∑ Lymphocytes are added to lymph as it flows through the sinuses of a lymph node. Thus the lymph leaving node is both clean of debris and riche in lymphocytes. Lymphatics leaving lymph nodes are called efferent lymph vessels and conduct lymph toward the shoulder region. Large lymphatics that drain groups of lymph nodes are often called lymph trunks. ∑ Lymphatics from lower portion of the body coverage, form a dilated lymph vessel, the cisterna chyli, in the lumbar region of abdominal cavity. ∑ The cisterna chyli extends for about 6 centimetres just to right of abdominal aorta. At the level of twelfth thoracic vertebra, cisterna chyli narrows and becomes thoracic duct. ∑ Lymphatic vessels from all over the body, except upper right quadrant, drain into thoracic duct. This vessel delivers lymph into the base of left subclavian vein at junction of the left subclavian and internal jugular veins. In this way lymph is continuously emptied into the blood where it mixes with the plasma. At junction of thoracic duct and venous system, a valve prevents blood from flowing backward into the duct.

320 HUMAN ANATOMY AND PHYSIOLOGY ∑ Only about 1 centimetre in length, the right lymphatic duct receives lymph from the lymphatic vessels in upper right quadrant of the body. The right lymphatic duct empties lymph into base of the right subclavian vein (at the point where it unites with the internal jugular vein to form the branchiocephalic). ∑ An example of the patter of lymph circulation is: Lymph capillaries Æ lymph node Æ cisterna chyli Æ thoracic duct

Cervical lymph nodes Entrance of right lymphatic duct Axillary lymph nodes

Entrance of thoracic duct Lymphatics of mammary gland

Thoracic duct Cisterna chyli Lymphatics of upper limb

Lumbar lymph nodes Pelvic lymph nodes Inguinal lymph nodes

Lymphatics of lower limb

Fig. 8.13 Main lymphatic vessels

Lymphatic Trunks The large collecting vessels merge (unite) to form the lymphatic trunks. The principal lymphatic trunks are:

LYMPH AND LYMPHATIC SYSTEM 321 ∑ Lumbar Trunks: left and right, drain lower limbs, pelvis and abdomen except digestive system. ∑ Intestinal Trunk: drains a part of digestive system located below the diaphragm. It receives the chyle from the digestive tract. ∑ Broncho-mediastinal Trunks: left and right, drain the thorax. ∑ Jugular Trunks: left and right, drain head and neck. ∑ Subclavian Trunks: left and right, drain upper limbs. These trunks then join one of the two collecting ducts; the thoracic duct or the right lymphatic duct.

Collecting Ducts A. The Right Lymphatic Duct ∑ It is about 1.25 cm in length, if present. ∑ It ends in the angle of confluence of right subclavian and right internal jugular veins (forming beginning of right brachiocephalic vein). ∑ There are variations in the emptying point of right lymphatic duct. Tributaries: 1. The right lymphatic duct receives lymph from right side of head and neck through the right jugular trunk. 2. From the right upper extremity through right subclavian trunk. 3. From the right side of thorax, through the right bronchomediastinal trunk. These three collecting trunks frequently open separately in the angle of union of two veins or each opens in the corresponding vein.

B. The Thoracic Duct THORACIC DUCT Right lymphatic trunk Right jugular lymph trunk

Left vertebral actery Interior cervical ganglion

Left jugular lymph trunk Left subclavian lymph trunk

Right subclavien lymph trunk Right branano mediastinal lymph trunk Hemi-azygos and accessory hemiazygos cross behind thoracic duct to reach azygos vein

Upper left intercostal and mediastinal lymph trunks Descending thoracic aorta

Left and right descending moracic lymph trunks Right crus of diaphragm Cisterna chyli Right and left lumbar and interstitial lymph trunks THORACTIC DUCT

322 HUMAN ANATOMY AND PHYSIOLOGY ∑ ∑ ∑ ∑ ∑



∑ ∑ ∑ ∑





∑ ∑ ∑

Thoracic duct is 45 cm long Several terminal branches are there Many valves are present in the systems. It drains all lymph below diaphragam, left head/neck & left thorax It ascends behind right crus, to right of aorta & oesophagus, then behind oesophagus lies superficial anterior to posterior intercostals arteries and crossing azygos systems, over dome of the pleura, over anterior to left vertebral and left subclavian arteries. It drains the following areas: 2 lower limbs, pelvis and abdomen, the left half of head and neck, left half of thorax, and left upper limb. The thoracic duct conveys the greate part of lymph and chyle into the blood. It is the common trunk of all lymphatic vessels of the body, excepting those on right side of head, neck, thorax and right upper extremity. In adults it varies in length from 38 to 45 cm and extends from the lumbar vertebra to the root of neck. It begins in abdomen by a triangular dilatation, cisterna chyli, which is situated on front of the body of second lumbar vertebra, to right side of and behind the aorta. The cisterna chyli receives two lumbar lymphatic trunks, right and left, and the intestinal lymphatic trunk. The lumbar trunks are formed by union of the efferent vessels from lateral (para) aortic lymph nodes. It enters thorax through aortic hiatus (together with the aorta and the azygous vein) of the diaphragm. Opposite to fifth thoracic vertebra, the duct inclines to left crossing obliquely the midline and continues upward on left side of oesophagus. In its course through posterior mediastinum, thoracic duct receives some smaller tributaries from posterior mediastinal lymph nodes and from intercostals lymph nodes of upper six intercostals spaces on the left side. Passing into the neck it forms an arch which rises about 3 or 4 cm above the clavicle. In the neck it is joined by its tributaries; left jugular and left subclavian trunks, and sometimes by left bronchomediastinal trunk (the left bronchomediastinal trunk usually opens independently into junction of left subclavian and internal jugular veins). It ends by opening into left subclavian vein, left internal jugular vein, or at an angle of junction of these two (left brachiocephalic). At its termination, thoracic duct possesses a bicuspid valve which faces the vein, to prevent reflux of blood into the duct. Like all other lymphatic vessels, thoracic duct has valves that give its beaded appearance externally.

The Lymph Drainage of the Upper Limbs They are divided into superficial and deep lymphatics: I. Superficial lymph vessels: they accompany cephalic or basilic veins end in superficial lymph nodes of the upper limb. The superficial lymph nodes are few and of small size.

LYMPH AND LYMPHATIC SYSTEM 323 1. Supratrochlear (cubital) nodes are placed above medial epicondyle of the humerus. They receive (drain) vessels that accompany the basilic vein. 2. Delto-pectoral nodes are found beside cephalic vein, between pectoralis major and deltoid muscles, immediately below the clavicle. They drain lymph vessels that accompany cephalic vein. Both groups of lymph nodes drain into lateral (brachial) axillary lymph nodes. II. Deep lymph vessels accompany deep veins and they drain into lateral (brachial) axillary lymph nodes.

The Lymph Drainage of the Lower Limbs I. Superficial lymph vessels: (a) Vessels that accompany the saphenous vein end in vertical group of the superficial inguinal lymph nodes. (b) Vessels that accompany short saphenous vein end in the popliteal lymph nodes. II. Deep lymph vessels accompany deep veins and they drain into popliteal and deep inguinal lymph nodes.

8.20

ROLE OF THE LYMPHATIC SYSTEM IN IMMUNITY

The lymphatic system helps defend the body against invasion by disease-causing agents such as viruses, bacteria, or fungi. Harmful foreign materials are filtered out by small masses of tissue called lymph nodes that lie along network of lymphatic vessels. These nodes house lymphocytes (white blood cells), some of which produce antibodies, special proteins that fight off infection. They also stop infections from spreading through the body by trapping disease-causing germs and destroying them. The spleen also plays an important part in a person’s immune system and helps the body fight infection. Like the lymph nodes, the spleen contains antibody-producing lymphocytes. These antibodies weaken or kill bacteria, viruses, and other organisms that cause infection. Also, if blood passing through the spleen carries damaged cells, white blood cells called macrophages in spleen will destroy them and clear them from the bloodstream. Lymph nodes are made of a mesh like network of tissues. Lymph enters lymph node and works its way through passages called sinuses. The nodes contain macrophages, phagocytic cells that engulf (phagocytize) and destroy bacteria, dead tissue, and other foreign matter, removing them from bloodstream. After these substances have been filtered out, the lymph then leaves nodes and returns to veins, where it re-enters the bloodstream. When a person has an infection, germs collect in great numbers in the lymph nodes. If the throat is infected, for example, the lymph nodes of the neck may swell. Sometimes the phagocytic cells may not be able to destroy all of the germs, and a local infection in the nodes may result. Because the lymphatic system extends to far reaches of the body, it also plays a role in spread of cancer. This is why lymph nodes near a cancerous growth are usually removed.

324 HUMAN ANATOMY AND PHYSIOLOGY There are two main types of lymphocytes: ∑ T cells ∑ B cells Lymphocytes, just like other types of blood cells, develop in bone marrow. They start life as immature cells called stem cells. In early childhood, some lymphocytes then migrate to thymus, an organ in the top of the chest, where they mature to become T cells. Others remain in bone marrow and mature there to become B cells. Both T and B cells play an important role in recognizing and destroying infecting organisms such as bacteria and viruses. In normal conditions, most of lymphocytes circulating in the body are T cells. Their role is to recognize and destroy abnormal body cells (for example, cells that have been infected by a virus). B cells recognize ‘foreign’ cells and material (for example, bacteria that have invaded the body). When these cells come into contact with a foreign protein (for example, on the surface of bacteria), they produce antibodies, which then ‘stick’ to surface of the foreign cell and cause its destruction.

8.21

ROLE OF LYMPH IN HUMAN HEALTH

The lymphatic system has a variety of roles in human health ranging from returning fluid from organs back to the circulatory system, to an important part in the human immune response, to absorbing lipids from the intestines. The defining role of the lymphatic vessels is to return any fluid that has leaked from capillaries and into interstitial space back to the circulatory system through veins. This is important because if fluid was retained in tissues, results in reduced blood volume and swelling of tissues. Another important role of lymphatic system is the ability of plasma proteins to fit through lymphatic valves and into lymphatic capillary. Since most proteins have such a high molecular weight, they are unable to be reabsorbed by venous capillaries. Without reabsorption of plasma proteins, humans can die within 24 hours. The lymphatic system also has an essential role in process of digestion. Primarily, lymphatic capillaries in the gastrointestinal tract are one of the main routes for fats to be absorbed. Fats enter lymphatics before entering the blood stream. High molecular weight proteins are not only large substances that are absorbed. Microorganisms such as bacteria can also fit between endothelial cells of terminal end of the lymphatic capillary. As this occurs and bacteria are transported to next lymph node, the meshwork of node and sinuses with in the node act as a filter, catching and trapping foreign organisms. Once trapped, microorganisms can be attacked by concentrated cells of the immune system. Macrophages may consume diseasecausing bacteria. B lymphocytes may come into contact with antigens on surface of the microorganism and stimulate antibodies, and T-lymphocytes called “killer” cells that attach themselves to foreign organism and release a substance to destroy the organism. The destructive nature of the “killer” cells is enhanced by another T-lymphocyte called “helper” cells (T-helper cells also assist B-cells). If this system fails, then microorganisms are not destroyed, resulting in the spread of infection though lymphatic system and extreme infection possibly leading to death. Cancer cells that have lost adherence and break away the primary tumor are collected by lymphatic system and filtered by latticework within lymph nodes. Within lymph node T-cells release substances called lymphokine (e.g., gamma interferor and interleukin 2) that may help destroy the

LYMPH AND LYMPHATIC SYSTEM 325 cancer cells. Doctors use lymph nodes as one factor of evaluation while determining the stage of cancer. In other words, while determining how far cancer has progressed at the time of diagnosis, lymph nodes can be dissected to determine if cancer has spread (metastasized) from the original tumor or not. If cancer cells are present in the lymph nodes, then cancer receives a high stage and a less-optimistic diagnosis. In cancers that metastasize via lymphatics, the lymph nodes where cancer cells are present are often removed. This is even more common when lymph nodes in question are adjacent to tumor, when lymph nodes are located on only lymphatic vessel present in the area of tumor, or if no other lymphatics will be damaged during removal.

8.22

LYMPHATIC SYSTEM DISORDERS

The lymphatic system is involved whenever a body is fighting against foreign pathogens. The lymph nodes (especially in neck) often swell with bacteria and lymphocytes when the body gets common illnesses such as colds and influenza. However, certain diseases and disorders target lymphatic system. Some slow down the ability of system to work; others literally shut it down. The result can be life threatening. The following are a few of the diseases that can impair lymphatic system or its parts.

Autoimmune Diseases Autoimmune diseases are those in which a body produces antibodies and T cells that attack and damage the body’s own normal cells, causing tissue destruction. The reaction can either take place in a number of tissues at the same time or in a single organ. The following are just a few of the various types of autoimmune diseases. ∑ Graves’ disease, also called hyperthyroidism occurs when an antibody binds to specific cells in thyroid gland, forcing them to secrete excess thyroid hormone. Symptoms of the condition include weight loss with increased appetite, shortness of breath, tiredness, weak muscles, anxiety, and visible enlargement of thyroid gland. Treatments include drugs to stop hormone production, radioactive iodine to destroy hormone-producing cell and shrink enlarged gland, and surgery to remove a part of thyroid. ∑ Multiple sclerosis is an immune cell attack on myelin, the insulation covering nerve fibres in central nervous system (brain and spinal cord). Once the insulation, called myelin, is destroyed, nerve messages are sent more slowly and less efficiently. As a result, brain and spinal cord no longer communicate property with rest of the body. When this occurs, vision, balance, strength, sensation, coordination, and other bodily functions all suffer. Women are twice as likely to get the disease as men. Drugs have been developed that slow the progress of disease in many patients, but no cure has yet been found. ∑ Systemic lupus erythematosus (SLE) is a disease in which antibodies attack body’s own tissues and organs as if they were foreign. The cause of SLE is unknown. It can affect both men and women of all ages, but 90 percent of those afflicted are women. Among many symptoms of the disease are fevers, weakness, muscle pain, weight loss, skin rashes, joint pain, headaches, vomiting, diarrhea, and inflammation of lining of lungs or lining around heart. Treatment for SLE depends on how severe the symptoms are. Mild symptoms like inflammation can be treated with aspirin or ibuprofen. Severe symptoms are often treated with stronger drugs, including steroids. Drugs to decrease body’s immune response may also be used for severely ill SLE patients.

326 HUMAN ANATOMY AND PHYSIOLOGY Lymphangioma is a rare benign tumor of the skin or tongue caused from abnormal lymph vessels that are of two types. One appears as clear blisters in the young and often disappears. The other is known as cystic hygroma that appears as small white grapes or swelling just below the skin and common to the neck area. Lymphedema is an excess amount of lymphatic fluid in our skin tissue that causes bloating or swelling in the arms or legs. Severity ranges from mild complications to vary painful and disabling condition. Some may be susceptible to serious skin infections due to lack of oxygen or bad circulation. When blockages occur in lymphatic system the cause may be from parasites or cancer growths. Edema has similar symptoms but pertains more to water balance in a body and circulation of blood and water through capillaries. It is a condition common among individuals following surgery for breast cancer or prostate cancer is lymphedema. It is caused by blockage of lymph vessels or lymph nodes located near surgical site and can result in swollen arms or legs. If microorganisms cause swelling, then antibiotics are used as treatment.

Lymphoma Lymphoma may be any cancer that originates in lymphatic system cells, tissue, lymph nodes and spleen. Lymphoma is a type of cancer in which cells of lymphatic system (B cells and T cells) become abnormal and begin to grow uncontrollably. Because lymphatic tissue is found throughout a body and lymphomas can occur anywhere. There are many types of lymphomas, but they are generally divided into two main groups: Hodgkin’s lymphoma and non-Hodgkin’s lymphomas. The exact cause of the cancers in either group is not known. ∑ Hodgkin’s lymphoma can occur at any age, although people in early adulthood (ages fifteen to thirty-four) and late adulthood (after age sixty) are most affected. The cancer begins in a lymph node (usually in neck), causing swelling and possibly pain. After affecting one group of nodes, it progresses on to the next. In advanced cases of cancer, spleen, liver, and bone marrow may also be affected. Symptoms include fatigue, weight loss, night sweats, and itching. As the cancer spreads throughout the body, the immune response becomes less effective. Common infections caused by bacteria and viruses begin to take over. Hodgkin’s lymphoma is one of the most curable forms of cancer. However, as with any form of cancer, early detection and treatment is highly recommended. Once detected in the body, Hodgkin’s is usually treated through chemotherapy (using a combination of drugs to kill the cancer cells and shrink any tumors) or radiation therapy (using X rays or other high-energy rays to kill the cancer cells and shrink any tumors) or a combination of both. ∑ Non-Hodgkin’s lymphomas encompass over twenty-nine types of lymphomas. Again, the exact cause of these lymphomas is unknown. In general, males suffer from these cancers more than females. People between the age of sixty and sixty-nine are at the highest risk of contracting these lymphomas. Non-Hodgkin’s lymphomas also tend to strike people suffering from AIDS. Symptoms for non-Hodgkin’s lymphomas are similar to those for Hodgkin’s lymphoma. Along with the swelling of lymph nodes, patients may experience loss of appetite, weight loss, nausea, vomiting, pain the lower back, headaches, fevers, and right sweats. The liver and spleen may enlarge, as well. Immune responses may be weakened. Treatment for non-Hodgkin’s lymphomas also include chemotherapy and radiation therapy (either by themselves or in combination). In severe cases, bone marrow transplants may take place. Since the “cure” rate for non-Hodgkin’s lymphomas is not as good as it is for Hodgkin’s lymphoma. Early detection and treatment is vital.

LYMPH AND LYMPHATIC SYSTEM 327 Lymphosarcomas There are also cancers called lymphosarcomas and cancers of the lymph nodes that can affect lymphatic system. The causes of these cancers are not known and there is not a consensus on what preventative measures can be taken to reduce the risk of developing these cancers. Symptoms of cancers affecting lymphatic system include loss of appetite, energy, and weight, as well as swelling of glands. As with many cancers, treatment includes surgical removal followed by adjuvant radiation and chemotherapy Lymphadenitis. Also called adenitis, this inflammation of the lymph node is caused by an infection of tissue in the node. The infection can cause skin overlying the lymph node to swell, redden, and feel warm and tender to the touch. This infection usually affects lymph nodes in neck, and it’s usually caused by a bacterial infection that can be easily treated with an antibiotic. Lymphadenitis is the inflammation of lymph nodes. The cause is often an infection of nodes by bacteria that has entered through a cut or wound in the skin. A virus may also be the cause. The infection may occur in a limited number of nodes in a specific area or in many nodes over a wider area. If the lymph vessels connecting the affected nodes are also inflamed, that condition is known as lymphangitis. The swollen nodes are often painful to touch. The skin over the nodes may also be red and warm to touch. If accompanying lymph vessels are involved in infection, they will appear as red streaks from lymph nodes. In children, the swollen nodes often appear in neck because they are close to ears and throat—locations of frequent bacterial infections in children. Treatment for lymphadenitis and lymphangitis usually involves medications. Antibiotics, such as penicillin, are often prescribed, and infection is brought under control in three to four days. If left untreated the infection may lead to blood poisoning, which is at times fatal.

Tonsillitis Tonsillitis is another disease of lymphatic system. Tonsillitis usually involves a bacterial or viral infection located within the tonsils. The tonsils are swollen, and patient experiences fever, sore throat, and difficulty in swallowing. Tonsillitis is caused by an infection of tonsils, lymphoid tissues in the back of mouth at the top of throat that normally help to filter out bacteria. When the tonsils are infected, they become swollen and inflamed, and can cause a sore throat, fever, and difficulty in swallowing. The infection can also spread to throat and surrounding areas, causing pain and inflammation. The condition is caused by bacteria or viruses that have entered the body through mouth or sinuses. In addition to swollen and red tonsils, symptoms include a mild or severe sore throat, fever, chills, muscle aches, earaches, and tiredness. Anyone can be afflicted with tonsillitis. The disease is most common in children between the age of five and ten. For mild cases of tonsillitis, treatment usually involves bed rest and drinking extra fluids. The body usually brings infection under control within few days. If the case is more severe, penicillin or other antibiotics may be prescribed to combat the infection. If an individual suffers repeatedly from severe tonsillitis, tonsils may be removed surgically. That procedure is called a tonsillectomy.

328 HUMAN ANATOMY AND PHYSIOLOGY Lymphadenopathy. This is a condition where the lymph nodes become swollen or enlarged, usually because of infection. Swollen lymph glands in neck, for example, can be caused by a throat infection. Once the infection is treated, the swelling usually goes away. If several lymph node groups throughout the body are swollen, that can indicate a more serious disease that needs further investigation by a doctor. Splenomegaly (enlarged spleen). If someone who is healthy, the spleen is usually small enough that it can’t be felt when you press on the abdomen. But certain diseases can cause the spleen to swell several times to its normal size. Most commonly, this is due to a viral infection, such as mononucleosis. But in come cases, more serious diseases such as cancer can cause the spleen to expand. Doctors usually tell someone with an enlarged spleen to avoid sports like football for a while, because a swollen spleen is vulnerable to rupturing (bursting). And if it ruptures, it can cause a huge amount of blood loss.

AIDS Acquired immune deficiency syndrome, a disorder caused by a virus (HIV) that infects helper T cells and weakens immune responses. AIDS (acquired immune deficiency syndrome) has been described as plague of the twentieth century. AIDS is currently a leading cause of death among all men between the age of twenty-five and forty-four. Once infected, individuals may not develop symptoms of the disease for ten years or more. HIV (human immunodeficiency virus) impairs a body’s ability to produce an immune response. Specifically, virus infects helper T cells. Once inside a helper T cell, HIV can replicate or reproduce within the cell and kill it in ways that are still not completely understood. When the newly formed viruses break out of the dying helper T cell, they continue the cycle by infecting other helper T cells. In response, the body produces more helper T cells, but this only provides the virus with more hosts, which grow and spread. Because helper T cells play a central role in directing the body’s immune response. Their destruction brings about a drop in cell-mediated immunity. The number of antibodies produced in the body declines, leaving it without defenses against a wide range of invaders. Many different types of infections and cancers can develop, taking advantage of the body’s weakened immune response. These infections, normally are harmless when body is functioning properly and are known as opportunistic infections. HIV is transmitted among humans through blood, semen, and vaginal secretions. The two main ways to contact the virus are by sharing a needle with a drug user who is HIV-positive or by having unprotected sexual relations with a person who is HIV-positive. (A person who is HIV-positive is already infected with the virus.) It is possible for a pregnant woman who is HIV-positive to transfer virus to the fetus in her womb. A few individuals have become infected with the virus after receiving a transfusion of contaminated blood. HIV cannot be transferred through insect bites or stings nor through shaking hands or hugging. No one can contact the virus by sharing telephones or eating utensils, by drinking out of public water fountains, or by swimming in public pools.

LYMPH AND LYMPHATIC SYSTEM 329 There is currently no cure for the disease and no vaccine to prevent. The best defense against AIDS is avoiding sexual contact with infected individuals. Intravenous drug use (injecting drugs into the bloodstream) of any kind should always be avoided. Several antiviral drugs have been developed that slow the progress of disease in infected individuals. Combinations of these drugs—known informally as cocktails—have proven effective in improving the quality and length of life of AIDS’ patients, especially those who have been diagnosed in early stages of the disease.

Allergy An allergy is an abnormal immune reaction to harmless substance. Normally, when a foreign microorganism enters a body, antibodies are produced to bind to antigens on the foreign particles, and a series of immune reactions take place. When harmless, everyday substances cause the same series of immune reactions, the condition is known as allergy. The offending substance is called an allergen. Common allergens. People may react to airborne particles (plant pollens, animal fur, house dust, cigarette smoke), food (nuts, eggs, fish, milk), drugs (penicillin or other antibiotics), insect bites (bees, wasps, mosquitoes, fleas), or even materials (wool and latex). Symptoms depend on the specific type of allergic reaction. In the most common type of reaction, antibodies stimulated by the allergen cause certain cells to release histamine into the surrounding interstiltial fluid. Histamine causes small blood vessels in the area to expand and become “leaky.” Excess fluid and mucus develop, and the common symptoms appear: a runny nose, a scratchy or irritated throat, and red, watery eyes. Allergens that cause a reaction on the skin produce reddened, itchy skin. Those that affect digestive tract may cause a swelling or tingling in the lips or throat, nausea, cramping, or diarrhea. Most reactions begin within seconds after contact with the allergen and last about half an hour. Some may last from one to several hours after contact. A large number of prescriptions and over-the-counter drugs can treat the symptoms of allergies. Antihistamines, decongestants, and nasal sprays can all be used to decrease or counteract the effect of histamines. Lotions and creams to reduce skin inflammation caused by allergens are also available. Avoiding allergens is the best way to limit allergic reactions. This is especially true for food allergies. Learning to recognize and avoid those items that produce an allergic reaction allow most people with allergies to lead normal lives.

8.23

CARE OF LYMPHATIC SYSTEM

It is important to keep the lymphatic system healthy as it is a vital part of body immunity and overall health. Since the system is closely allied with the cardiovascular system, approaches to keep that system healthy are recommended for lymphatic system. The following play a part in keeping the lymphatic system operating at peak efficiency: ∑ ∑ ∑ ∑ ∑

Proper nutrition, Healthy amounts of good-quality drinking water, Adequate rest, Regular exercise, and Stress reduction.

330 HUMAN ANATOMY AND PHYSIOLOGY If left unchecked, infection can quickly weaken body’s immune response, leading to serious health problems. It is best to avoid sources of disease, infection, pollution, and other unsanitary substances. Caring for the body by practicing good hygiene will reduce the threat of infection from ever-present bacteria and viruses in the environment. Injuries such as scrapes, cuts, and wounds should be properly cleansed and cared for to prevent infection or the spread of infection. Serious injuries should be treated immediately by qualified medical personnel.

8.24

INTERESTING FACTS

∑ Domestic birds do not have lymph nodes. Instead, there are nodules of lymphoid tissue in the bone marrow. ∑ If an infection is present in the body, the lymph nodes nearest the site of infection may become swollen or painful. This is caused by an accumulation of cells and fluids involved in the immune response. ∑ In 24 hours, approximately 50% of the lymphocytes in the blood pass through the spleen. ∑ In a human, the lymphatic system returns 2.83 liters of lymph to the heart every 24 hours. That is about ½ a cup per hour.

REVIEW QUESTIONS 1. 2. 3. 4. 5. 6. 7. 8. 9.

Write an essay on lymphatic system of man. What is lymph? How lymphatic system forms part of transport system in human body? Write detailed notion of various lymphoid organs. Discuss various disorders related to lymphatic system. How can those be taken care of? What are lymph nodes? Discuss their locations and functions. Explain in detail aggregated lymphoid tissue. Describe (a) GALT (b) BALT (c) MALT How does movement of lymph take place in a human body? Discuss in detail development of lymphatic vessels.

CHAPTER

9

THE CARDIOVASCULAR SYSTEM Internal jugular vein

Pulmonary artery Axillary vein

Common carotid artery Subclavian vein

Common hepatic artery Subclavian artery Cephalic vein Superior vena cava

Basilic vein

Axillary artery

Splenic artery Pulmonary vein Splenic vein Cubital vein

Brachial artery

Radial vein Inferior vena cava Renal artery

Hepatic vein

Renal vein Portal vein

Abdominal aorta

Radial artery Ulnar artery Superior mesenteric artery Median vein of porearm

Common iliac artery Internal iliac artery External iliac artery

9.1

Femoral artery Great saphenous vein

Femoral vein

INTRODUCTION

All living organisms need to transport materials from one part of the body to the other. Various materials that need to be transported includes: Food, Oxygen, Water, Carbon dioxide, Waste products, Hormones, etc. All these materials are essential for the organism to survive. 331

2st Proof (Co./D/01-08.../Human Anatomy.../Ch-9) 10/09/08/1216 (Shubham Composer)

332 HUMAN ANATOMY AND PHYSIOLOGY The circulatory system (or cardiovascular system) is an organ system that moves nutrients, gases, and wastes to and from cells. It helps fight diseases and stabilize body temperature and pH to maintain homeostasis. While humans, as well as other vertebrates have a closed circulatory system (meaning that the blood never leaves the network of arteries, veins and capillaries). Some invertebrate groups have open circulatory system. The main components of human circulatory system are heart, blood, and blood vessels. The circulatory system includes: pulmonary circulation, a “loop” through the lungs where blood is oxygenated; and systemic circulation, and a “loop” through rest of the body to provide oxygenated blood. An average adult contains five litres of blood, which consists of plasma, of red blood cells, white blood cells, and platelets. Two types of fluids move through circulatory system: blood and lymph. The blood, heart, and blood vessels form cardiovascular system. The lymph, lymph nodes, and lymph vessels form lymphatic system. The cardiovascular system and lymphatic system collectively make up the circulatory system. This system is responsible for transportation of vital nutrients, gases and hormones throughout the body. The heart functions as central pump with the blood vessels: the pipes of the body. The CVS is controlled by a number of internal and external systems, which keeps the CVS in balance with needs of the body.

9.2

TRANSPORT OF MATERIALS

The transportation of materials among living organisms employs the following principles : 1. Diffusion: The movement of molecules is in the direction of concentration gradient i.e., from a region of higher concentration to the lower. The diffusion can occur only when concentration of the diffusing substance is not uniform in the system, and the process can continue only as long as the difference between the concentrations is balanced. Several gases, liquids or solutes can diffuse simultaneously at different rates and in different directions in the same place without interfering with each other. This is why oxygen diffuses into the leaf and carbon dioxide diffuses out of the leaf simultaneously through the same stomata during the process of respiration. The rate of diffusion of gases is faster as compared to that of liquids and solutes. In unicellular organisms like Amoeba, Paramecium, Chlamydomonas, transportion of material mainly takes place by the process of diffusion. 2. Osmosis: It is a special type of diffusion of liquids where two solutions of different concentrations are separated by means of a semipermeable membrane. Diffusion of solvent (which is mainly water), from the solution of lower concentration to the solution of higher concentration through a semipermeable membrane, until a state of dynamic equilibrium is attained, is known as osmosis. The osmotic entry of water into a cell, organ or system is called endosmosis while the osmotic withdrawal of water from the same is described as exosmosis. Osmotic Pressure. It can be defined as the maximum pressure which can develop in an osmotically active solution when it is separated from its pure solvent by a semipermeable membrane.

THE CARDIOVASCULAR SYSTEM 333 WATER MOLECULES

SUGAR MOLECULES

SEMIPERMEABLE MEMBRANE

H2O MOLECULES DIFFUSING MORE RAPIDLY

Fig. 9.1

Osmosis

Osmosis can be defined in terms of water potential also. Osmosis is the flow of water molecules from the region of higher water potential to that of lower water potential through a semipermeable membrane. Pure (distilled) water has the maximum water potential because it has a higher proportion of free molecules than in a concentrated solution and these free water molecules can move into the concentrated solution. If the solute is added to concentrated solution its water potential will be lowered as it will reduce the number of water molecules flowing out into the concentrated solution. On the other hand, if more solute is added to the concentrated solution more water molecules will flow into it from the less concentrated solution. Difference between Diffusion and Osmosis Diffusion 1. It occurs without semipermeable membrane. 2. Transport is from high concentration to low concentration. 3. In diffusion there is movement of the molecules of solute or solvent. 4. Diffusion is a rapid process. 5. Diffusion can occur over long distances.

9.3

Osmosis 1. It occurs through a semipermeable membrane. 2. Transport is from a solution of low concentration to that of a high concentration. 3. In osmosis there is movement of the molecules of only solvent. 4. Osmosis is a slow process. 5. In osmosis, solvent gets transported over a short distance.

TRANSPORTATION IN HUMANS

The circulatory systems in humans is closed, meaning that the blood never leaves the system of blood vessels. In contrast, oxygen and nutrients diffuse across blood vessel layers and enter

334 HUMAN ANATOMY AND PHYSIOLOGY interstitial fluid, which carries oxygen and nutrients to the target cells, and carbon dioxide and wastes in the opposite direction. The circulatory system is a transport system, carrying oxygen nutrients, hormones and other substances to the tissues, CO2 to the lungs and other waste products to the kidneys. A fluid, the blood which carries the food materials, oxygen, waste materials, etc., is forced by a pump, the heart, through a system of tubes, the blood vessels (arteries and veins) to close vicinity of every cell and then back to the heart to be pumped round again and again. The blood remains in blood vessels during its circulation around the body and does not come in direct contact with the tissue cells. That is why, humans are said to have closed circulatory system. In lower organisms like arthropods (e.g., cockroach) and mollusks (e.g., snail), blood vessels from the heart pour blood into open tissue spaces known as sinuses. This is known as open circulatory system. The open tissue spaces are referred to as haemocoel and the blood flowing through them is known as haemolymph. Differences Between Open and Closed Circulatory System 1. 2. 3. 4. 5. 6.

Open circulatory system Blood vessels from the heart pour the blood into open spaces known as sinuses. It is the characteristic of arthropods and molluscs. Red blood cells are absent. The respiratory pigment if any, is dissolved in the plasma. Blood flows slowly under low pressure. Blood is in direct contact with tissues.

Closed circulatory system 1. The blood remains in blood vessels during transportation round the body. 2. It is the characteristic of annelids and vertebrates. 3. Red blood cells are present. 4. The respiratory pigment is present. 5. Blood flows rapidly under high pressure. 6. Blood is not in direct contact with tissues.

The main features of cardiovascular system in man: ∑ A liquid, blood to transport - nutrients - wastes - oxygen and carbon dioxide - hormones ∑ Two pumps (in a single heart) - one to pump deoxygenated blood to the lungs; - The other to pump oxygenated blood to all other organs and tissues of the body. A system of blood vessels to distribute blood throughout the body. ∑ Specialized organs for exchange of materials between the blood and external environment; for example - organs like lungs and intestine that add materials to the blood and - organs like lungs and kidneys remove materials from the blood and deposit them back in the external environment.

THE CARDIOVASCULAR SYSTEM 335 9.4

EXTERNAL STRUCTURE OF HEART

The heart is a hollow, muscular organ which lies obliquely in thorax between the lungs and immediately above the diaphragm. In adults, its average weight is 300 gms in males and 250 gms in females. It is protected by a two layered sac known as pericardium. The outer layer of the sac is called parietal pericardium and the inner one as visceral pericardium. Narrow space between them i.e., pericardial cavity is filled with pericardial fluid secreted by pericardium itself. This fluid protects the heart from shocks and mechanical injury. The heart is partitioned into right and left, each consists of two parts, an upper thin walled atrium/auricle and a lower thick walled ventricle. The auricle acts as receiving chamber and the ventricle as pumping chamber. Walls of the auricles are thinner because they have to mainly receive the blood, while walls of the ventricles are thicker because they have to pump the blood. Four chambers of the heart are: 1. 2. 3. 4.

Left auricle Left ventricle Right auricle Right ventricle. Superior vena cava

Aortic arc

Right pulmonary artery

Left pulmonary artery

Pulmonary veins

Pulmonary veins

Right auricle

Left auricle Coronary sulcus

Coronary sulcus

Left ventricle

Right ventricle

Inter-ventricular sulcus

Inferior vena cava

Fig. 9.2

External structure of heart

EXTERNALLY auricles are demarcated from ventricles by an irregular groove called the coronary sulcus. A flap from each auricle projects over the corresponding ventricle. This flap is known as auricular appendix. The two ventricles are externally demarcated by an oblique groove known as interventricular sulcus.

336 HUMAN ANATOMY AND PHYSIOLOGY 9.5

INTERNAL STRUCTURE OF HEART Superior vena cava Aortic arch Right pulmonary Artery Ascending aorta Pulmonary artery Right pulmonary veins Opening of superior vena cava Pulmonary semilunar valve Opening of inferior vena cava

Descending aorta Left pulmonary artery Opening of left Pulmonary veins Left pulmonary veins Left atrium Aortic semilunar valve Bicuspid valve (mitral valve) Chordae tendinae

Tricuspid valve

Papillary muscle Left ventricle Interventricular septum

Right ventricle Inferior vena cava

Fig. 9.3

Internal structure of human heart

The Heart is made up of a powerful muscle called Myocardium. The Myocardium is composed of cardiac muscle fibers that contract and cause a wringing type of action. The size of a heart is little larger than the size of fist. The location of heart is about left-centre of your chest. The heart consists two separate pumps that continuously send blood throughout the body carrying nutrients, oxygen, and helping remove of harmful wastes. The right side of heart receives blood low in oxygen. The left side of heart receives blood that has been oxygenated by the lungs. The blood is then pumped out into the aorta further to all parts of the body. The human heart is a four-chambered muscular organ, shaped and sized roughly like a man’s closed fist with two-third of the mass to left of midline. The heart is enclosed in a pericardial sac which is lined with parietal layers of a seruous membrane. The visceral layer of serous membrane forms epicardium.

Layers of the Heart Wall Three layers of tissue form the heart wall. The outer layer of heart wall is epicardium, middle layer is the myocardium, and inner layer is the endocardium.

Chambers of the Heart The internal cavity of heart is divided into four chambers: ∑ ∑ ∑ ∑

Right atrium Right ventricle Left atrium Left ventricle

THE CARDIOVASCULAR SYSTEM 337 The two atria are thin-walled chambers that receive blood from the veins. The two ventricles are thick-walled chambers that forcefully pump blood out of the heart. Differences in thickness of the heart chamber walls are due to variations in the amount of myocardium present, which reflects the amount of force each chamber is required to generate. The right atrium receives deoxygenated blood from systemic veins; the left atrium receives oxygenated blood from the pulmonary veins.

Valves of the Heart ∑ Atrioventricular (AV) valves - prevent backflow of blood from ventricles to atria during ventricular systole (contraction) - Tricuspid valve - located between right atrium and right ventricle - Mitral valve - located between left atrium and left ventricle ∑ Semilunar valves - prevent backflow of blood from arteries (pulmonary artery and the aorta) to ventricles during ventricular diastole (relaxation) - Aortic valve - located between left ventricle and aorta - Pulmonary valve - located between right ventricle and the pulmonary artery (trunk) All valves consist of connective tissue (not cardiac muscle tissue) and, therefore, open and close passively. Valves open and close in response to changes in pressure: ∑ AV valves - open when pressure in atria is greater than pressure in the ventricles (i.e., during ventricular diastole) and closed when pressure in ventricles is greater than pressure in the atria (i.e., during ventricular systole) ∑ Semilunar valves - open when pressure in ventricles is greater than pressure in the arteries (i.e., during ventricular systole) and closed when pressure in pulmonary trunk and aorta is greater than pressure in the ventricles (i.e., during ventricular diastole)

Blood Supply to the Myocardium The myocardium of heart wall is a working muscle that needs continuous supply of oxygen and nutrients to function with efficiency. For this reason, cardiac muscle has an extensive network of blood vessels to bring oxygen to the contracting cells and to remove waste products. The right and left coronary arteries, branches of the ascending aorta, supply blood to the walls of myocardium. After blood passes through capillaries in the myocardium, it enters a system of cardiac (coronary) veins. Most of the cardiac veins drain into coronary sinus, which opens into the right atrium.

Right Atrium The right atrium is larger than left atrium but has thinner walls. The righ atrium has two major veins that returns blood to heart from all parts of the body. Two major veins returning the blood to heart are superior vena cava and inferior vena cava. These two veins are sometimes called the “great veins”. The superior vena cava returns deoxygenated blood from upper part of the body and the inferior vena cava returns deoxygenated blood from lower part of the body. The right atrium also receives blood back from heart muscle itself. After blood is collected in the right atrium it is pumped into right ventricle through tricuspid valve (three leaf valve).

338 HUMAN ANATOMY AND PHYSIOLOGY Left Atrium The left atrium receives blood from four pulmonary veins. The blood received from lungs has been oxygenated. The oxygenated blood which is collected in left atrium is then pumped into the left ventricle through the bicuspid valve.

Right Ventricle The right ventricle receives blood from right atrium. When heart contract, the blood is forced out through pulmonary semilunar valve into the pulmonary artery. The pulmonary semilunar valve is a three flap valve that stops backflow of blood. The walls of right ventricle are a little thicker than the right atrium.

Left Ventricle The chamber of left ventricle has walls that are three times the thickness of the right ventricle. This is important because the oxygenated blood that it receives from the left atrium has to be pumped throughout the body. The bicuspid valve closes and blood is collected in the left ventricle. The closing of the bicuspid valve stops the backflow of blood. When heart muscle contracts the blood is forced through the aortic semilunar valve which has the same features as that of pulmonary valve. The blood then passes through the aortic semilunar valve into the aorta.

Aorta The aorta is the largest blood vessel in the body. The inner diameter of the aorta is about 1 inch. The aorta carries oxygenated blood to every other part of the body. The aorta receives its blood from the left ventricle.

Septum The septum is a partition that separates right and left sides of the heart. There are two separate regions of septum. They are interatrial septum that separates the atriums and interventrial septum that separates the ventricles. The interatrial septum is only present in the fetal period and is open during this period. The interatrial septum closes at the time of birth. The interventrial septum is suppose to be closed all the time but sometimes an opening is present at the time is birth. This would be considered a congenital heart diseases.

Superior Vena Cava The importance of the superior vena cava is to return blood to right atrium from upper part of the body. It is one of the largest veins in the body.

Inferior Vena Cava The inferior vena cava is important for carrying blood back to the right atrium from lower part of the body.

THE CARDIOVASCULAR SYSTEM 339 Pulmonary Arteries The pulmonary arteries carry the blood from the right ventricle to both of the lungs. There the blood is oxygenated and sent to left atrium in the heart.

Pulmonary Veins The pulmonary veins carry oxygenated blood back to left atrium in the heart. INTERNALLY partition between right and left auricle is known as interauricular septum while partition between the two ventricles is known as interventricular septum. 1. Left Auricle ∑ This chamber receives four pulmonary veins, two from each lung from where they bring oxygenated blood. They do not have any valve. ∑ The left auricle empties its blood into the left ventricle through a passage known as the left auriculoventricular aperture guarded by mitral or bicuspid valve. ∑ The mitral valve has two flaps and free edges of these valves are anchored by fine cords (known as chordae tendinae) to papillary muscles of the left ventricle. ∑ These cords prevent pushing of the flaps back into auricles at the time of pumping of blood by the ventricle. 2. Left Ventricle ∑ The inner surfaces of the ventricles are ridged, the left more so than the right. Blood leaves left ventricle by large, main artery of the body called the aorta. ∑ The opening from left ventricle into the aorta is guarded by aortic valve, which consists of three semilunar cusps. ∑ Just beyond these semilunar valves is present a pair of coronary arteries which supply blood to heart itself. ∑ This blood is brought back to heart by coronary veins which join to form coronary sinus. 3. Right Auricle ∑ The right auricle has in its walls the openings of superior vena cava, inferior vena cava and coronary sinus. ∑ Blood from veins of the head, neck and upper limbs enters the right auricle by superior vena cava and from rest of the body; and lower limbs by the inferior vena cava. ∑ The coronary sinus, which drains venous blood from heart muscle, also opens into the right auricle. ∑ From the right auricle blood passes into right ventricle through a tricuspid valve. (So called because it has three cusps). ∑ This valve is anchored by, (chordae tendinae) two or three small muscles which arise from walls of ventricle and are known as papillary muscles. 4. Right Ventricle ∑ Blood leaves right ventricle through the pulmonary valve which has three semilunar cusps and enters the pulmonary artery. ∑ This artery further divides into right and left pulmonary arteries entering the two lungs where they further branch into pulmonary capillaries.

340 HUMAN ANATOMY AND PHYSIOLOGY 9.6

WORKING OF HEART

The heart is a pump responsible for maintaining adequate circulation of oxygenated blood around the vascular network of body. It is a four-chamber pump, with right side receiving deoxygenated blood from the body at low pressure and pumping it to lungs (the pulmonary circulation) and left side receiving oxygenated blood from the lungs and pumping it at a high pressure around the body (the systemic circulation). Heart does not work throughout the day. It rests double the time it works. It rests between every beat. The resting period is called diastole, its duration is twice as long as that of systole, which is the period of muscular contraction. The series of events which occur during one complete beat of the heart is known as cardiac cycle. Cardiac cycle mainly consists of three steps: 1. Auricular systole 2. Ventricular systole 3. Joint diastole Contraction of two auricles is simultaneous and is called auricular systole, relaxation of the auricles is called auricular diastole. Similarly ventricular systole is simultaneous contraction of two ventricles and ventricular diastole is their relaxation period. Cardiac cycle occurs in the following steps: 1. In the beginning, both auricles and ventricles are in a joint diastole. 2. Blood flows into left auricle from the pulmonary veins and from superior and inferior vena cava in the right auricle. 3. Next step is of auricular systole in which both auricles contract simultaneously which drives most of their blood into their respective ventricles. At this stage ventricles are in diastole i.e., they are relaxed. 4. Ventricular systole follows immediately. Pressure of blood in the ventricles forces to close the bicuspid and tricuspid valves. Left pulmonary artery Aorta Right pulmonary artery Pulmonary vein Superior vena cava

Left auricle

Right auricle Bicuspid valve Pulmonary valve Left ventricle

Inferior vena cava

Aortic valve

Tricuspid valve Right ventricle

Fig. 9.4 Direction of blood flow through human heart

THE CARDIOVASCULAR SYSTEM 341 5. The first sound “lubb” is produced when auriculo-ventricular valves get closed at the start of ventricular systole. 6. Pressure in ventricles leads to pressing of semi lunar valves of the great arteries (i.e, aorta and pulmonary artery), and thus driving blood into them. The second sound “Dubb” is produced when semi lunar valves of aorta and pulmonary artery get closed. 7. After this ventricles get relaxed or there is ventricular diastole. The auricles are still undergoing diastole. Thus we can say, all chambers are in diastole or relaxed mode. One cardiac cycle is completed in 0.8 seconds. While it is convenient to describe flow of blood through right side of the heart and then through left side. It is important to realize that both atria and ventricles contract at the same time. The heart works as two pumps, one on right and other on the left, working simultaneously. Blood flows from right atrium to right ventricle, and then is pumped to the lungs to receive oxygen. From lungs, blood flows to left atrium, then to the left ventricle. From there it is pumped to systemic circulation. The myocardium (cardiac muscle) is a specialized form of muscle, consisting of individual cells joined by electrical connections. The contraction of each cell is produced by a rise in intracellular calcium concentration leading to spontaneous depolarization, and as each cell is electrically connected to its neighbour. Contraction of one cell leads to a wave of depolarization and contraction across the myocardium. 1. This depolarization and contraction of heart is controlled by a specialized group of cells localized in sino-atrial node in right atrium- the pacemaker cells. 2. These cells generate a rhythmical depolarization, which then spreads out over atria to the atrio-ventricular node. 3. The atria then contract, pushing blood into ventricles. 4. The electrical conduction passes via Atrio-ventricular node, the bundle of, which divides into right and left branches and then spreads out from base of ventricles across the myocardium. 5. This leads to a ‘bottom-up’ contraction of ventricles, forcing blood up and out into the pulmonary artery (right) and aorta (left). 6. The atria then re-fill as the myocardium relaxes. The ‘squeeze’ is called systole and normally lasts for about 250ms. The relaxation period, when the atria and ventricles re-fill, is called diastole; the time given for diastole depends on the heart rate. What happens in the heart during each ‘mechanical’ event? Atrial Systole ¡ no heart sounds (because no heart valves are opening or closing) ¡ a slight increase in ventricular volume as blood from atria is pumped into the ventricles. Ventricular Systole ¡ the first heart sound (lubb) - this sound is generated by the closing of the AV valves (and this occurs because increasing pressure in the ventricles causes the AV valves to close) ¡ initially there is no change in ventricular volume (called the period of isometric contraction) because ventricular pressure must build to a certain level before the semilunar valves can be forced open and blood ejected. Once that pressure is achieved, and the semilunar valves open, ventricular volume drops rapidly as blood is ejected.

342 HUMAN ANATOMY AND PHYSIOLOGY Ventricular Diastole ¡ the second heart sound (dubb) - this sound is generated by closing of the semilunar valves (and this occurs because pressure in pulmonary trunk and aorta is now greater than in the ventricles and blood in those vessels moves back toward the area of lower pressure which closes the valves) ¡ ventricular volume increases rapidly (period of rapid inflow) - this occurs because blood that accumulated in the atria during ventricular systole (when the AV valves were closed) now forces open the AV valves (because the pressure in the atria is now greater than the pressure in the ventricles) and flows quickly into the ventricles. After this ‘rapid inflow’, ventricular volume continues to increase, but at a slow rate (the period of diastasis). This increase in volume occurs as blood returning to heart via veins largely flows through the atria and into the ventricles.

Diastole 1. The heart is at rest and myocardium is relaxed. 2. The atria and ventricles passively fill. AV valves allow blood to pass. 3. The aortic and pulmonary artery semilunar valves are closed because the blood in those vessels is at a higher pressure than the ventricles. 4. Blood continues to fill atria and ventricles, stretching the compliant heart cells.

Systole 1. The atria contract and eject final amount of blood into the ventricles. At rest, the atrial contraction contributes only about 10% total ventricular volume. If heart rate is high and ventricles don’t have time to fill completely, atria systole can contribute as much as 40%. 2. Atria relaxation causes atria pressure to be lower than ventricular pressure. 3. High ventricular pressure relative to atria causes the AV valves to close, preventing backflow while the ventricles contract. 4. The ventricles continue to contract, ejecting blood through the semilunar valves out to lungs and rest of the body. Fluid flows from high pressure to lower pressure. Blood within the cardiovascular system adheres to this rule. This is evident by the direction of blood flow. The higher pressure generated by left heart produces a gradient which moves blood from the left heart, through the body and into right side of the heart. When left ventricle (LV) contracts, it generates a systolic blood pressure of 100-140 millimeters of Hg (mm Hg). 1. The aortic diastolic pressure is usually 60-90 mm Hg. The LV/aortic pressure gradient causes blood to pass through aortic valve. 2. Blood flowing from LV to aorta and raises the aortic pressure to equal the LV pressure. 3. A momentary aortic systolic pressure of 100-140 mm Hg is then dissipated across the capillary beds. 4. As capillary pressure exceeds than that of the venules, this gradient causes blood to flow into the low pressure venous system.

THE CARDIOVASCULAR SYSTEM 343 5. Low pressure venous blood is returned to right atrium, aided by skeletal muscle compression, negative intra-thoracic pressure and a multitude of one-way valves that advances the blood toward the venae cavae. The pressure of blood within right atrium is the central venous pressure (CVP). The blood pressure of the venae cavae is similar to the CVP because there are no valves or flow obstructions between the venae cavae (VC) and the RA. The VC and heart’s right side can be viewed as one chamber with a contractile portion at the distal end. The CVP averages between 2-6 millimeters of mercury (mm Hg). During right ventricular (RV) diastole, the pressure within the RV is between 0-5 mm Hg. Elasticity and compliance to the ventricular myocardium help generate low intraventricular pressure. Low intraventricular pressure, aided by atrial systole, causes blood to flow across the open atrioventricular AV valve. Right ventricular systolic pressure is usually from 20-30 mm Hg. This exceeds the right atrial pressure. The pressure gradient applies greater pressure to ventricular side of the AV valve, which causes it to close. The pulmonary artery (PA) pressure, prior to systole, is normally 8-12 mm Hg. During RV systole the PA pressure will rise to equal RV pressure, usually 20-30 mm Hg. The systolic PA pressure of 20-30 Hg is quickly dissipated by compliance of the pulmonary vascular bed to a diastolic pressure of 8-12 Hg. Blood leaves pulmonary vasculature at about 4-12 mm Hg, passively entering the pulmonary veins. The pulmonary veins empty directly into left atrium. Elasticity and compliance of ventricular myocardium help generate slightly low intraventricular filling pressure. Low intraventricular pressure, aided by atrial systole, causes blood to flow across the open atrioventricular AV valve. LV systole generates 100-140 mm Hg. Aortic diastolic pressure is usually 60-90 mm Hg. The pressure gradient of 100-140/60-90 mm Hg drives blood into the aorta and onward to rest of the body. The cycle is complete. Blood Volume of blood in the entire circulation = cardiac output = 5ml/min ∑ Distribution of blood to each organ or tissue depends on the use largest amount needs of tissues. e.g.,: kidney-brain - skeletal muscle …etc. ∑ Tissues that have low resistance receive higher proportion of blood and those with high resistance receive less. It depends on the characteristics of blood vessels that supply the tissue or organ.

Blood Flow ∑ The pumping action of heart generates blood flow. ∑ The blood flow that passes through a given blood vessel depends directly on the pressure difference between the two ends of blood vessel and indirectly on the resistance of blood movement. F Blood Flow =

Pressure Gradient Peripheral Resistance

344 HUMAN ANATOMY AND PHYSIOLOGY 9.7

HEART SOUNDS AND MURMURS

∑ The contraction of heart and its anatomy cause the distinctive sounds heard when listening to heart with a stethoscope. ∑ The “lub-dub” sound is the sound of the valves in the heart closing. ∑ When atria end their contraction and ventricles begin to contract, the blood is forced back against the valves between the atria and the ventricles, causing the valves to close. ∑ This is the “lub” sound, and signals beginning of ventricular contraction, known as systole. ∑ The “dub” is the sound of valves closing between ventricles and their arteries, and signals the beginning of ventricular relaxation, known as diastole. ∑ A physician listening carefully to the heart can detect if the valves are closing completely or not. Instead of a distinctive valve sound, the physician may hear a swishing sound if they are letting blood flow backward. ∑ When the swishing is heard tells the physician where the leaky valve is located. ∑ Heart sounds are generated from closure of the valves. There are two normal heart sounds. ∑ One is generated from closure of the mitral and tricuspid valves when heart contracts and is called S1. ∑ The second heart sound is generated from closure of aortic and pulmonic valves when heart relaxes and is called S2. ∑ Abnormal heart sounds can be generated in setting of heart failure (S3) or from a very stiff ventricle, such as in the setting of long-standing high blood pressure or heart attacks (S4). Heart murmur is caused by any irregularity in the function of heart e.g., valvular in sufficiency, friction in pericardial layers, etc. Heart murmurs can range from normal (or physiologic) in the setting of normal valvular function to abnormal (or pathologic), such as in the setting of a severe leak (regurgitation) or narrowing (stenosis) in the valves. When a valve is narrowed, blood ejected through it generates a high velocity jet and turbulence, which causes the murmur. Also, if a valve leaks, a high jet of blood flows through the leaky-valve, generating a murmur. Murmurs have various characteristics and generally can tell a physician a lot of information about the function of valves of the heart. Heart sounds and murmurs are heard with a stethoscope placed over the heart, a process called auscultation.

9.8

DOUBLE CIRCULATION

Human heart has double circulation which means that blood passes through heart two times to supply once to the whole body. It involves two circulations: 1. Systemic circulation 2. Pulmonary circulation

THE CARDIOVASCULAR SYSTEM 345 1. Systemic circulation is a major circulation in the body. The aorta divides into arteries, arterioles and finally to capillaries and therefore supplies oxygenated blood to various parts of body. From there deoxygenated blood is collected by venules which join to form veins and finally vena cavae and pour blood back into the heart. 2. Pulmonary circulation is related with lungs. It starts from entry of blood into the pulmonary artery from right ventricle. It later divides into two and enter the respective lungs. In the lungs blood is oxygenated and brought back to the heart (left auricle) through pulmonary veins. Pulmonary veins

Oxygenated Blood

Left auricle Left ventricle

Lungs

Pulmonary artery

Oxygenated Blood

PULMONARY CIRCULATION

Deoxygenated blood

Aorta

SYSTEMIC CIRCULATION

Right ventricle

Arterioles All body organs except lungs

Right auricle

Deoxygenated blood

Vena cavae

Venules Veins

Fig. 9.5 Double circulation of blood in man

Systemic Circulation ∑ Systemic circulation is a portion of the cardiovascular system which carries oxygenated blood away from heart, to the body, and returns deoxygenated blood back to the heart. ∑ Arteries always take blood away from the heart, regardless of their oxygenation, and veins always bring blood back. In general, arteries bring oxygenated blood to the tissues; veins bring deoxygenated blood back to the heart. ∑ In the case of the pulmonary vessels, however, the oxygenation is reversed: the pulmonary artery takes deoxygenated blood from heart to the lungs, and oxygenated blood is pumped back through pulmonary vein to the heart. ∑ As blood circulates through the body, oxygen and nutrients diffuse from the blood into cells surrounding the capillaries, and carbon dioxide diffuses into the blood from the capillary cells.

346 HUMAN ANATOMY AND PHYSIOLOGY ∑ The release of oxygen from red blood cells or erythrocytes is regulated in mammals. It increases with an increase of carbon dioxide in tissues, an increase in temperature, or a decrease in pH. Such characteristics are exhibited by tissues undergoing high metabolism, as they require increased levels of oxygen. ∑ Blood from the aorta passes into a branching system of arteries that lead to all parts of the body. ∑ It then flows into a system of capillaries where functions of exchange take place. ∑ Blood from the capillaries flows into venules which are drained by veins. Veins draining upper portion of the body lead to superior vena cava. ∑ Veins draining lower part of the body lead to the inferior vena cava. ∑ Both empty into the right atrium.

Pulmonary Circulation ∑ Pulmonary circulation is a portion of the cardiovascular system which carries oxygendepleted blood away from heart, to the lungs, and returns oxygenated blood to the heart. ∑ Deoxygenated blood enters right atrium of the heart and flows into right ventricle where it is pumped through pulmonary arteries to the lungs. ∑ Pulmonary veins return oxygen-rich blood to the heart, where it enters left atrium before flowing into the left ventricle. ∑ From left ventricle the oxygen-rich blood is pumped out via aorta, and on to rest of the body.

Coronary Circulation ∑ The coronary circulatory system provides a blood supply to the heart. ∑ The heart needs its own reliable blood supply in order to keep beating — the coronary circulation. ∑ There are two main coronary arteries, the left and right coronary arteries, and these branch further form several major branches. ∑ The coronary arteries lie in grooves (sulci) running over surface of the myocardium, covered over by epicardium, and have many branches which terminate in arterioles supplying vast capillary network of the myocardium. ∑ Even though these vessels have multiple anastomoses, significant obstruction to one or other of main branches will lead to ischaemia in the area supplied by that branch.

9.9

PORTAL CIRCULATION

Veins from alimentary canal do not take blood to the vena cava. Instead, it first goes to liver as a hepatic portal vein. Inside liver it breaks into fine capillaries and finally, hepatic vein coming out joins the inferior vena cava. Its main use is that, the food absorbed in alimentary canal is first brought to liver which acts as a store house to regulate the quantity of certain nutrients e.g., carbohydrates.

THE CARDIOVASCULAR SYSTEM 347 Head and neck brain

Upper limbrs Subclavian veins Subclavian arteries

Superior vena cava Lungs

Aorta

Pulmonary artery

Pulmonary veins Right atrium

Left atrium

Tricuspid valve Mitral valve Right ventricle

Left ventricle Liver Stomach Spleen Intestine

Hepatic vein Inferior vena cava

Kidneys Renal arteries

Portal vein

Trunk and lower limbs Renal vein

Capillaries

Fig. 9.6 Circulation of blood in man

Liver

Portal vein Stomach

Pancreas

Large intestine

Fig. 9.7

Hepatic portal system

348 HUMAN ANATOMY AND PHYSIOLOGY 9.10

HEART BEAT

The heart beat is the contraction of heart muscles. Each beat consists of simultaneous contraction of two auricles followed by simultaneous contraction of the two ventricles. The beat recurs regularly and rhythmically through the life to maintain circulation of the blood. The beat of heart originates by muscle fibres and cells of heart which are specialized in various parts of heart to generate electric currents and cause the normal rhythmic contraction and relaxation of cardiac muscles. Contraction of heart is initiated in the right auricle. A node present there can generate a wave of contraction. That is why, it is also known as pacemaker. The heart rate is the number of times a heart beats per minute. Its value varies from 70 to 80 in an adult at rest. The heart rate usually corresponds with pulse rate.

Arterial Pulse It is recurring distension of an artery by rise in the blood pressure produced by each contraction of the ventricle. The powerful contraction of left ventricle discharges blood under high pressure into the aorta. The blood pushes onwards the blood already in the aorta, and that in turn is transmitted all through the arterial system. This pressure wave transmitted all through the arterial system (independent of blood flow) is known as pulse wave. It can be easily felt by pressing finger over an artery that has come up superficially, such as artery of the wrist. The pulse rate is the number of beats of pulse per minute. Counting of the pulse is indirectly counting of the heart beat.

Blood Pressure By blood pressure, we actually mean systemic arterial blood pressure, which the blood flowing through arteries, exerts on their walls by blood ejected from the left ventricle. The pressure is naturally great during ventricular systole. This is known as systolic pressure. During ventricular diastole pressure falls, but is maintained to some extent. Thus, diastolic pressure is the one recorded when the wave has passed over. In other words we can say that diastolic blood pressure is the pressure which blood exerts on wall of the arteries when the ventricles are relaxed. Normal blood pressure is 120 / 80 120 mm Hg-Systolic pressure 80 mm Hg-Diastolic pressure. The blood pressure is measured by an instrument called sphygmomanometer. Constriction of arterioles can lead to high blood pressure or hypertension. This increases resistance to blood flow. This can even rupture any artery causing internal bleeding. An instrument namely electrocardiograph machine can record the electrical changes during the heart beat. These electric currents are generated at certain parts of the heart which help in normal rhythmic heart beats. ECG or electrocardiogram is a record of tracings obtained during different periods of cardiac cycle.

THE CARDIOVASCULAR SYSTEM 349

STETHOSCOPE

BRACHIAL ARTERY MERCURY

A

Fig. 9.8

B

C

A. Instrument Sphygmomanometer, B. Brachial artery, C. Use of Sphygmomanometer

Pacemaker is another instrument inserted in the heart of the patient whose heart does not work normally.

9.11

BLOOD PRESSURE

Blood moves through the arteries, arterioles, and capillaries because of the force created by the contraction of the ventricles.

Blood Pressure in the Arteries ∑ The surge of blood that occurs at each contraction is transmitted through elastic walls of the entire arterial system where it can be detected as the pulse. Even during brief interval when the heart is relaxed — called diastole - there is still pressure in the arteries. When the heart contracts — called systole — the pressure increases. ∑ Blood pressure is expressed as two numbers, i.e., 120/80. ∑ The first is the pressure during systole. The unit of measure is the torr, in this example, the pressure equivalent to that produced by a column of mercury 120 mm high. The second number is the pressure at diastole. ∑ Although blood pressure can vary greatly in an individual, continual high pressure — especially diastolic pressure — may be the symptom or cause of a variety of ailments. The medical term for high blood pressure is hypertension.

Blood Pressure in the Capillaries ∑ The pressure of arterial blood is largely dissipated when blood enters the capillaries. ∑ Capillaries are tiny vessels with a diameter just about that of a red blood cell (7.5 µm). ∑ Although diameter of a single capillary is quite small, the number of capillaries supplied by a single arteriole is so great that the total cross-sectional area available for the flow of blood is increased. ∑ Therefore, the pressure of the blood as it enters the capillaries decreases.

350 HUMAN ANATOMY AND PHYSIOLOGY Blood Pressure in the Veins ∑ When blood leaves the capillaries and enters the venules and veins, little pressure remains to force it along. ∑ Blood in the veins below the heart is helped back up to the heart by the muscle pump. ∑ This is simply the squeezing effect of contracting muscles on the veins running through them. ∑ One-way flow to the heart is achieved by valves within the veins.

Exchanges between Blood and Cells ∑ With rare exceptions, our blood does not come into direct contact with the cells it nourishes. As blood enters the capillaries surrounding a tissue space, a large fraction of it is filtered into the tissue space. It is this interstitial or extracellular fluid (ECF) that brings to cells all of their requirements and takes away their products. The number and distribution of capillaries is such that probably no cell is ever farther away than 50 µm from a capillary. ∑ When blood enters the arteriole end of a capillary, it is still under pressure (about 35 torr) produced by the contraction of the ventricle. As a result of this pressure, a substantial amount of water and some plasma proteins filter through the walls of the capillaries into the tissue space. ∑ Thus fluid, called interstitial fluid, is simply blood plasma minus most of the proteins. (It has the same composition and is formed in the same way as the nephric filtrate in kidneys.) ∑ Interstitial fluid bathes the cells in the tissue space and substances in it can enter the cells by diffusion or active transport. Substances, like carbon dioxide, can diffuse out of cells and into the interstitial fluid. Blood Pressure is the force produced on the walls of blood vessels as a result of blood flow. (mmHg) ∑ Pressure results when flow is opposed by resistance. ∑ Blood pressure always refers to systemic arterial blood pressure in the large arteries. ∑ The pressure gradient (difference in pressure) is what keeps blood flowing, always from high to low pressure. Peripheral Resistance: the total resistance to flow of blood in the systemic circuit, a measure of the amount of friction blood encounters as it passes in the blood vessels. It depends on: 1. Blood viscosity: internal resistance to flow related to thickness of blood. Increased blood viscosity Æ Increased peripheral resistance Æ Decrease blood flow. Plasma proteins and blood cells (RBC’s) make blood viscous. It is normally constant. 2. Blood vessel length: longer the vessel more the resistance (normally constant). Blood vessels can’t become longer but can become shorter by forming anastomoses (communication between blood vessels mostly between artery and vein). This leads to decrease in the length of travel of blood in a vessel Æ Decrease in resistance Æ Increase in blood flow Æ Increased venous pressure.

THE CARDIOVASCULAR SYSTEM 351 3. Blood vessel diameter: Most important in determining peripheral resistance. The higher the diameter of the blood vessel lumen Æ the less friction blood encounters Æ less resistance Æ more blood flow The smaller the diameter Æ more friction because more fluid is in contact with the blood vessel wall Æ more resistance Æ less blood flow Because arterioles can dilate and constrict the most and the fact that they have the smallest diameter of all blood vessels in the systemic circulation, they are the major determinants of peripheral resistance. Blood pressure is highest in the aorta, it decreases steadily until the steepest decrease happens at the level of arterioles. (Arterioles - small diameter Æ highest resistance Æ Ø Blood Flow) Pulse Pressure: difference between systolic and diastolic blood pressure. Systolic = 120 mmHg Diastolic = 70 to 80 mmHg Pulse pressure is felt as the pulse: throbbing pulsation in an artery in systole Mean Arterial Pressure (MAP): average of blood pressure. Diastolic is more important because diastole is longer than systole in a single cardiac cycle. MAP = Diastolic Pressure + 1/3 (Pulse pressure) Arterial blood pressure can be measured by using a sphygmomanometer. It consists of a pressure measuring device and an inflatable cuff. ∑ It involves auscultation Æ Listening to the sounds made by the various body structures as a diagnostic method. ∑ Listening to Korotkoff sounds Æ sound’s heard over an artery when pressure over it is reduced below systolic arterial pressure. ∑ A stethoscope is placed over the brachial artery in the antecubital fossa. ∑ When pressure of cuff is higher than systolic, no blood flows Æ no sound heard, silence ∑ When pressure of cuff is slightly below systolic, blood will briefly be forced past the cuff at the beginning of each systole. Æ Blood flow is turbulent and is heard as sharp tapping sounds. ∑ As pressure in cuff falls below systolic, blood is forced through for longer periods with each systole Æ louder longer sounds. ∑ When cuff pressure is close to diastolic pressure, the thumping sounds become quieter. ∑ When the cuff pressure is below diastolic, the artery is no longer compressed and blood flows normally Æ no sounds. ∑ Systolic Pressure Æ first heard tapping sounds ∑ Diastolic Pressure Æ when the sound disappears.

352 HUMAN ANATOMY AND PHYSIOLOGY Regulation of Blood Pressure by Hormones The Kidney One of the functions of kidney is to monitor blood pressure and take corrective action if it should drop. The kidney does this by secreting the proteolytic enzyme renin. ∑ Renin acts on angiotensinogen, a plasma peptide, splitting off a fragment containing 10 amino acids called angiotensin I. ∑ angiotensin I is cleaved by a peptidase secreted by blood vessels called angiotensin converting enzyme (ACE) - producing ∑ angiotensin II, which contains 8 amino acids. ∑ Angiotensin II - constricts the walls of arterioles closing down capillary beds; - stimulates the proximal tubules in the kidney to reabsorb sodium ions; - stimulates the adrenal cortex to release aldosterone. Aldosterone causes the kidneys to reclaim still more sodium and thus water. - increases the strength of heart beat; - stimulates the pituitary to release antidiuretic hormone (ADH, also known as arginine vasopressin). All of these actions, which are mediated by its binding to G-protein-coupled receptors on the target cells, lead to an increase in blood pressure.

The Heart A rise in blood pressure stretches atria of the heart. This triggers the release of atrial natriuretic peptide (ANP). ANP is a peptide of 28 amino acids. ANP lowers blood pressure by: ∑ relaxing arterioles ∑ inhibiting secretion of renin and aldosterone ∑ inhibiting reabsorption of sodium ions in collecting ducts of the kidneys. The effect on kidney reduces reabsorption of water by them thus increasing the flow of urine and the amount of sodium excreted in it (These actions give ANP its name: natrium = sodium; uresis = urinate). The net effect of these actions is to reduce blood pressure by reducing the volume of blood volume in the system.

9.12

REGULATION OF HEART BEAT

The rate of heart beat is controlled by central nervous system, autonomic nervous system and hormones. (i) Central Nervous System. The cardiovascular centre lies in medulla oblongata of the brain. The sensory fibres extend from the stretch receptors present in the walls of aortic arch and vena cavae. These sensory fibres are attached with cardiovascular centre. The impulses

THE CARDIOVASCULAR SYSTEM 353 received from aortic arch decrease the heart rate, whereas impulses from vena cava increase the heart rate. (ii) Autonomic Nervous System. The sinu-auricular node receives from the brain two sets of nerve fibres like sympathetic nerves which stimulates the heart beat by secreting adrenaline (epinephrine) and parasympathetic nerves which decrease the heart beat by secreting acetylcholine. (iii) Hormones. Hormones released by medulla of adrenal glands are epinephrine (adrenaline) and non-epinephrine (non-adrenaline). Epinephrine accelerate heart beat at the time of emergency while non-epinephrine brings the heart beat to normal. Thus, both these hormones work opposite to each other i.e., antagonistically. Other factors which increase or decrease heart beat are: (a) (b) (c) (d) (e) (f)

High level of potassium and sodium ions decrease heart rate. Mental conditions such as depression and grief decrease heart rate. An excess of calcium ions increase heart rate. Increased body temperature during fever increases heart rate. Strong emotions such as fear, anger and anxiety increase heart rate. The heart beat in females is slightly higher than in males.

Heart Muscles and their Excitation ∑ Striated ∑ Cells contain numerous mitochondria (up to 40% of cell volume) ∑ Adjacent cells join end-to-end at structures called intercalated discs Intercalated discs contain two types of specialized junctions: ∑ Desmosomes (which act like rivets and hold the cells tightly together) and ∑ Gap junctions (which permit action potentials to easily spread from one cardiac muscle cell to adjacent cells). Cardiac muscle tissue forms two functional syncytia or units: ∑ The atria being one and ∑ The ventricles the other. Because of the presence of gap junctions, if any cell is stimulated within a syncytium, then the impulse will spread to all cells. In other words, the 2 atria always function as a unit and the 2 ventricles always function as a unit. However, there are no gap junctions between atrial and ventricular contractile cells. In addition, the atria and ventricles are separated by electrically nonconductive tissue that surrounds the valves. So, as will be discussed later, a special conducting system is needed to permit transmission of impulses from the atria to the ventricles. In cardiac muscle, there are two types of cells: ∑ Contractile cells and ∑ Autorhythmic (or automatic) cells.

354 HUMAN ANATOMY AND PHYSIOLOGY Contractile cells, of course, contract when stimulated. Autorhythmic cells, on the other hand, are self-stimulating and contract without any external stimulation. The action potentials that occur in these two types of cells are a bit different: On the left is the action potential of an autorhythmic cell; on the right, the action potential of a contractile cell. Autorhythmic cells exhibit PACEMAKER POTENTIALS. Depolarization is due to the inward diffusion of calcium (not sodium as in nerve cell membranes). Depolarization begins when: ∑ The slow calcium channels open, ∑ Then concludes (quickly) when the fast calcium channels open. ∑ Repolarization is due to the outward diffusion of potassium. In Contractile Cells ∑ Depolarization is very rapid and is due to the inward diffusion of sodium. ∑ Repolarization begins with a slow outward diffusion of potassium, but that is largely offset by the slow inward diffusion of calcium. So, repolarization begins with a plateau phase. Then, potassium diffuses out much more rapidly as the calcium channels close, and the membrane potential quickly reaches the ‘resting’ potential. Most of the muscle cells in the heart are contractile cells. The autorhythmic cells are located in these areas: - Sinoatrial (SA), or sinus node - Atrioventricular (AV) node - Atrioventricular (AV) bundle (also sometimes called the bundle of His) - Right and left bundle branches - Purkinje fibers Atrioventricular node Sinu-auricular node Right atrium

Interatrial septum Left atrium Annular pad

Atrioventricular valve Semilunar valve

Purkinje network Right ventricle

Fig. 9.9

Bundle of His

Interventricular septum Left ventricle

Nodal tissues of human heart

THE CARDIOVASCULAR SYSTEM 355 The AVN is located in right auricle, in the interauricular septum near the fibrous ring that separates right auricle from the ventricle. It gives rise to bundle of His, a muscular bridge that conducts stimulation from auricles to the ventricles. On entering ventricle along the interventricular septum, the bundle of His divides into two branches, one of which passes into the right ventricle and the other into the left. The terminal branches of conducting system are represented by a network of Purkinje fibres which penetrate into the myocardium. It has been demonstrated in various ways that stimulation arises initially in the sinuauricular node. Therefore SAN is the pacemaker of heart. The wave of excitation from the node passes first to muscle fibres of the right auricle and then to those of the left. This excitation results into contraction of both auricles simultaneously. The auricular contraction stimulates AVN that conveys stimuli to myocardium of the ventricles through bundle of His and Purkinje fibres. The ventricular contraction begins at the apex of heart and passes towards the origin of the great arteries (pulmonary aorta and systemic aorta). In a normal resting man, the rate of heart beat is 72/minute. Therefore, one heart beat (cardiac cycle) lasts 60/72 = 0.8 second.

Pace Maker Whenever sinuauricular node stops working for any reason, then the heart beats become slow or irregular. Thus, the heart is not able to pump that much amount of blood which is actually required by the body. For the treatment, an artificial pace maker is fitted in the heart by surgery and the heart starts functioning properly and is able to pump adequate amount of blood. Various automatic cells have different ‘rhythms’: SA node - 60 – 100 per minute (usually 70 – 80 per minute) AV node and AV bunde - 40 – 60 per minute Bundle branches and Purkinje fibers - 20 – 40 per minute SA node = has the highest or fastest rhythm and, therefore, sets the pace or rate of contraction for the entire heart. As a result, the SA node is commonly referred to as the PACE MAKER.

Spread of Cardiac Excitation ∑ Begins at the SA node and quickly spreads through both atria. ∑ Also travels through the heart’s ‘conducting system’ (AV node > AV bundle > bundle branches > Purkinje fibers) through the ventricles. ∑ For efficient pumping: - The atria should contract (and finish contracting) before the ventricles contract. This occurs because of AV nodal delay (that is, the impulse travels rather slowly through the AV node and this permits the atria to complete contraction before the ventricles begin contraction). - The atria should contract as a unit, and the ventricles should contract as a unit. This occurs because impulse spreads so rapidly that all myocardial cells in atria and ventricles, respectively, contract at about the same time. The impulse spreads rapidly through ventricles because of the conducting system.

356 HUMAN ANATOMY AND PHYSIOLOGY Thus a network of nerve fibers coordinates the contraction and relaxation of the cardiac muscle tissue to obtain an efficient, wave-like pumping action of the heart. ∑ The Sinoatrial Node (often called the SA node or sinus node) serves as natural pace maker for the heart. Nestled in upper area of the right atrium, it sends the electrical impulse that triggers each heart beat. The impulse spreads through the atria, prompting cardiac muscle tissue to contract in a coordinated wave-like manner. ∑ The impulse that originates from sinoatrial node strikes the Atrioventricular node (or AV node) which is situated in lower portion of the right atrium. The atrioventricular node in turn sends an impulse through nerve network to the ventricles, initiating same wave-like contraction of the ventricles. ∑ The electrical network serving ventricles leaves the atrioventricular node through Right and Left Bundle Branches. These nerve fibers send impulses that cause cardiac muscle tissue to contract. ∑ The electrical signal begins in sinoatrial (SA) node, located at the top of right atrium. The SA node is sometimes called heart’s “natural pace maker.” An electrical impulse from this natural pace maker travels through muscle fibers of the atria and ventricles, causing them to contract. ∑ Although SA node sends electrical impulses at a certain rate, your heart rate may still change depending on physical demands, stress, or hormonal factors. ∑ The heart has two areas that initiate impulses, the SA or sinoatrial node, and AV or atrioventricular node. ∑ The heart also has special muscle fibers called Purkinje fibers that conduct impulses five times more rapidly than surrounding cells. The Purkinje fibers form a pathway for conduction of impulse that ensures that the heart muscle cells contract in the most efficient pattern. ∑ The SA node is located in wall of the right atrium, near junction of the atrium and the superior vena cava. This special region of cardiac muscle contracts on its own about 72 times per minute. ∑ In contrast, muscle in rest of the atrium contracts on its own only 40 or so times per minute. The muscle in the ventricles contracts on its own only 20 or so times per minute. Since the cells in SA node contract the most times per minute, and because cardiac muscle cells are connected to each other by intercalated discs, SA node is pace maker of the heart. ∑ When the SA node initiates a contraction, Purkinje fibers rapidly conduct the impulse to another site near the bottom of right atrium and near center of the heart. This region is the AV node, and slows the impulse briefly. ∑ The impulse then travels to a large bundle of Purkinje fibers called the Bundle of His, where they move quickly to septum that divides the two ventricles. ∑ Here, the Purkinje fibres run in two pathways toward posterior apex of the heart. ∑ At the apex, the paths turn in opposite directions, one running to the right ventricle, and other running to the left. ∑ The result is that while atria are contracting, the impulse is carried quickly to the ventricles. ∑ With AV node holding up the impulse just enough to let the atria finish their contraction before the ventricles begin to contract and blood can fill the ventricles. ∑ And, since the Purkinje fibers have carried impulse to apex of the ventricles first, the contraction proceeds from bottom of the ventricles to the top where blood leaves the ventricles through pulmonary arteries and aorta.

THE CARDIOVASCULAR SYSTEM 357 Refractory Period of Contractile Cells ∑ Lasts about 250 msec (almost as long as contraction period) The long refractory period means that cardiac muscle cannot be restimulated until contraction is almost over and this makes summation (and tetanus) of cardiac muscle impossible. This is a valuable protective mechanism because pumping requires alternate periods of contraction and relaxation; prolonged tetanus would prove fatal. Electrocardiogram (ECG) = record of spread of electrical activity through the heart P wave = caused by atrial depolarization QRS complex = caused by ventricular depolarization T wave = caused by ventricular repolarization ECG = useful in diagnosing abnormal heart rates, arrhythmias, and damage of heart muscle The heart beat results from a wave of electrical potential called the cardiac impulse. The cardiac impulse originates from nodal tissues like sinu-auricular node (SAN), auriculo-ventricular node (AVN), bundle of His and Purkinje fibres. The SAN is located in right auricle at orifices of the vena cavae and described by Keith and Flack. The node is part of conducting system of the heart and is made up of poorly-differentiated muscle fibres which are scattered in the area of both auricles. A great number of nerve cells, nerve fibres and their endings, which form a ganglionic network, also occur around the node. (a) The P wave indicates the activation of SA node. The PQ line represents time when the auricles are contracting (0.1 sec.). (b) The QR wave preceeds ventricular contraction. This wave shows spread of the impulse of contraction from AV node through bundle of His and Purkinje fibres to the ventricular muscles. (c) The RS wave represents ventricular contraction (0.3 sec.). (d) The ST wave is recorded when the ventricular muscle is relaxing (0.4 sec.). (e) Thus, each cardiac cycle takes about 0.8 sec. to occur. (f) A complete heart examination requires 12 different electrode positions. Abnormality in the working of the heart changes the wave pattern of ECG. It is valuable in diagnosing abnormal cardiac rhythms and conducting pattern and abnormalities in heart for heart block, heart attact and coronary thrombosis. The P wave is of artial origin, hence called the atrial complex, while QRST being of ventricular origin, are collectively known as the ventricular complex. Any abnormality of atrial activity, will be reflected by corresponding changes in the P wave. Some of the abnormalities are: S-A block

Fig. 9.10

Sinoatrial nodal block

358 HUMAN ANATOMY AND PHYSIOLOGY (i) Sinoatrial Block. In rare instances, the impulse from the sinus node is blocked before it enters the atrial muscles, and the lack of atrial excitation and contraction eliminates the atrial P wave. It is seen in case of atrial fibrillation. (ii) Partial AV Node Block. In this case atria depolarize regularly but the ventricles are not stimulated every time. This abnormality is known as first degree block. It can be defined as a delay of conduction from atria to the ventricles but not actual blockage of conduction.

9.13

CARDIAC OUTPUT

Cardiac output is: ∑ Volume of blood pumped by each ventricle ∑ Equals heart rate (beats per minute) times stroke volume (milliliters of blood pumped per beat) ∑ Typically about 5,500 milliliters (or 5.5 liters) per minute (which is about equal to total blood volume; so, each ventricle pumps the equivalent of total blood volume each minute under resting conditions) BUT maximum may be as high as 25 – 35 liters per minute. The amount of blood ejected from left ventricle into aorta per minute is called heart or cardiac output. Heart beats 72/minute and pumps out about 70 ml of blood during each beat. Thus, Cardiac output = Stroke volume x Ventricular systole/minute = 70 ml ¥ 72/minute = 5040 ml/minute = about 5 litres/minute Of the blood pumped out (cardiac output) each minute by heart, the distribution to different parts are : 10% to heart muscles 15% to brain 25% to digestive system 20% to kidneys 30% to other body parts Total amount of blood present in the body is 5 – 6 litre. During mild exercise cardiac output is 11 litre, during vigorous exercise it is 25 litre and in athletes, the cardiac output is 40 litres/minute.

Cardiac reserve is: ∑ The difference between cardiac output at rest and the maximum volume of blood the heart is capable of pumping per minute. ∑ Permits cardiac output to increase dramatically during periods of physical activity.

Factors Affecting Cardiac Output ∑ Changes in heart rate: - Parasympathetic stimulation - reduces heart rate - Sympathetic stimulation - increases heart rate

THE CARDIOVASCULAR SYSTEM 359 Effect of Parasympathetic Stimulation on the Heart Increased parasympathetic stimulation > release of acetylcholine at the SA node > increased permeability of SA node cell membranes to potassium > ‘hyperpolarized’ membrane > fewer action potentials (and, therefore, fewer contractions) per minute a = sympathetic stimulation, b = normal heart rate, and c = parasympathetic stimulation

Effect of Sympathetic Stimulation on the Heart Increased sympathetic stimulation > release of norepinephrine at SA node > decreased permeability of SA node cell membranes to potassium > membrane potential becomes less negative (closer to threshold) > more action potentials (and more contractions) per minute.

Regulation of Stroke Volume ∑ Intrinsic control fi related to amount of venous return (amount of blood returning to the heart through the veins) ∑ Extrinsic control fi related to amount of sympathetic stimulation.

Intrinsic Control ∑ Increased end-diastolic volume = increased strength of cardiac contraction = increased stroke volume. ∑ This increase in strength of contraction due to an increase in end-diastolic volume (the volume of blood in the heart just before the ventricles begin to contract) is called the Frank-Starling law of the heart: - Increased end-diastolic volume = increased stretching of cardiac muscle = increased strength of contraction = increased stroke volume.

Extrinsic Control ∑ Increased sympathetic stimulation - increased strength of contraction of cardiac muscle. ∑ Mechanism = sympathetic stimulation - release of norepinephrine - increased permeability of muscle cell membranes to calcium - calcium diffuses in - more cross-bridges are activated stronger contraction.

Flow Rate through Blood Vessels ∑ Directly proportional to the pressure gradient ∑ Inversely proportional to vascular resistance Flow = Difference in pressure/resistance.

Pressure Gradient It is the difference in pressure between beginning and end of vessel (pressure = force exerted by blood against vessel wall and measure in millimeters of mercury).

360 HUMAN ANATOMY AND PHYSIOLOGY Resistance ∑ Hindrance to blood flow through a vessel caused by friction between blood and vessel walls ∑ Major determinant = vessel diameter (or radius) ∑ Resistance is inversely proportional to radius to the fourth power (so, for example, doubling the radius of a vessel decreases the resistance 16 times which, in turn, increases flow through the vessel 16 times).

9.14

ELECTROCARDIOGRAPHY (ECG)

The Electrocardiograph (ECG) is clinically very useful, as it shows the electrical activity within the heart, simply by placing electrodes at various points on the body surface. This enables clinicians to determine the state of the conducting system and of the myocardium itself, as damage to the myocardium alters the way the impulses travel through it. ∑ When looking at an ECG, it is often helpful to remember that an upward deflection on the ECG represents depolarization moving towards the viewing electrode, and a downward deflection represents depolarization moving away from the viewing electrode. Below is a normal lead II ECG. ∑ The P wave represents atrial depolarization- there is little muscle in the atrium so the deflection is small. ∑ The Q wave represents depolarization at the bundle of His; again, this is small as there is little muscle there. ∑ The R wave represents the main spread of depolarization, from inside out, through base of the ventricles. This involves large amounts of muscle so the deflection is large. ∑ The S wave shows subsequent depolarization of rest of the ventricles upwards from base of the ventricles. ∑ The T wave represents repolarisation of the myocardium after systole is complete. This is a relatively slow process- hence the smooth curved deflection.

Atrial systole

Ventricular systole

Atrial/ Ventricular diastole

O Millivolts

R

T

P

Q

S Milliseconds

Fig. 9.11

Normal ECG

THE CARDIOVASCULAR SYSTEM 361 9.15

BLOOD VESSELS

Blood vessels are closed transport system of blood that begins and ends at the heart. The three main types are: arteries, veins and capillaries. When the heart contracts blood moves into large arteries Æ smaller arteries Æ arterioles Æ metarterioles Æ capillary beds Æ venules Æ small veins Æ large veins Æ back to the heart. to heart

From heart

Capillaries artery

Vein

Fig. 9.12 Main blood vessels There are three main types of blood vessels: 1. Arteries 2. Veins 3. Capillaries

Artery An artery is a blood vessel which carries blood (generally oxygenated) from the heart to all parts of the body. Aorta is the main artery about 2-5 cm in diameter and arising from the left ventricle. The first 5 cm ascends upwards and is known as ascending aorta. The arch of aorta then bends to left and backwards and known as descending aorta which passes downward through thorax in the middle and close to vertebral column. Arteries further divide into arterioles and capillaries. Arteries have thick muscular walls, a narrow lumen and blood in it flows with jerks.

Characteristics ∑ Serve as passageways for blood from heart to tissues ∑ Act as pressure reservoirs because the elastic walls collapse inward during ventricular diastole (when there is less blood in the arteries). ∑ Blood pressure averages 120 mm Hg during systole (systolic pressure) and 80 mm Hg during diastole (diastolic pressure) (and the difference between systolic and diastolic pressures is called the pulse pressure) ∑ An artery is relatively thick-walled, muscular, pulsating blood vessel that carries blood in a direction away from the heart. ∑ With the exception of pulmonary and umbilical arteries, arteries convey oxygenated blood.

362 HUMAN ANATOMY AND PHYSIOLOGY Structure and Function of Different Types of Arteries In general, all blood vessel walls are made of three layers: ∑ Tunica intima (interna) — endothelium (simple squamous epithelium) ∑ Tunica media — circumferentially arranged smooth muscle and elastic fibers. This is a layer that undergoes vasodilation (increase diameter of lumen) or vasoconstriction (decrease diameter of lumen). Therefore, it is important in regulating blood flow and blood pressure. ∑ Tunica externa (adventitia) — loose collagen fibers that protect and strengthen blood vessel. Arteries are divided into three types: ∑ Elastic Conducting Arteries ¡ Largest arteries: aorta and its branches ¡ Large diameter: 2.5 to 1 cm ¡ Low resistance pathways (because of large diameter) ¡ Most elastic fibers than any other type - enables them to withstand high pressure. ¡ Flow is pulsatile - goes up and down (rhythmic) ¡ They expand in systole and recoil in diastole - this moves blood onward ¡ They have smooth muscle but it is not active in vasoconstriction. ∑ Muscular Distributing Arteries ¡ Diameter 1 cm to 0.3 cm ¡ Delivers blood to specific organs ¡ Thick tunica media - a lot of smooth muscle ¡ Active in vasoconstriction and vasodilation ∑ Arterioles ¡ Diameter 0.3 cm to 10 micrometer ¡ Large arterioles have more smooth muscle ¡ Smaller arterioles have a small amount of muscle ¡ Their diameter is most important in determining blood flow into capillaries ¡ The most important site of resistance in the whole systemic circulation ¡ They constrict and dilate in response to neural and chemical stimuli ¡ If all arterioles are in vasodilation Æ Ø BP reduction in amount of blood going back to the heart Æ Ø Venous return Æ shock / fainting falling flat (easier to get blood to brain).

Arterioles ∑ Distribute cardiac output amount systemic organs (whose needs vary over time). ∑ Resistance (and, therefore, blood flow) varies as a result of VASODILATION and VASOCONSTRICTION. ∑ Factors that influence radius of arterioles are: - Intrinsic (or local) control - Extrinsic control.

THE CARDIOVASCULAR SYSTEM 363 Intrinsic (local) control: ∑ Changes within a tissue that alter the radius of blood vessels and adjust blood flow ∑ Especially important in skeletal muscles, heart, and brain ∑ Increased blood flow in an active tissue results from active hyperemia: Increased tissue (metabolic) activity > increases levels of carbon dioxide and acid in the tissue and decreases levels of oxygen > these changes in the concentrations of acid, CO2, and O2 cause smooth muscle in walls of the arterioles to relax and this, in turn, causes vasodilation of the arterioles > vasodilation reduces resistance with the vessel and, as a result, blood flow through the vessel increases. So, blood flow increases when a tissue (e.g., skeletal muscle) becomes more active and increased blood flow delivers the needed oxygen and nutrients.

Extrinsic control occurs via: ∑ Sympathetic division of Autonomic Nervous System ∑ Parasympathetic division of the Autonomic Nervous System. The sympathetic division innervates blood vessels throughout the body while the parasympathetic division innervates blood vessels of the external genitals. Varying degrees of stimulation of these two divisions, therefore, can influence arterioles (and blood flow) throughout the body.

Capillaries These are very fine blood vessels. Arteries branch into small and smaller arteries and finally into capillaries. Capillaries are the thinnest blood vessels. Inside the organ O2 is given out and CO2 is taken in and capillaries join to form venules, veins and finally vena cavae. All functions of the blood are carried out through capillaries like digested food is picked up from the small intestine, O2 from the alveoli, CO2 and other wastes from every cell and so on. Difference between Arteries and Veins 1. 2. 3. 4. 5. 6. 7. 8. 9.

Arteries They carry blood from the heart to all body organs. Carries oxygenated blood with the exception of pulmonary artery. Deeply placed. Thick muscular walls. Narrow lumen. Progressively branched and thus decreasing in size. Blood flows with jerks. Walls elastic. They do not collapse when empty.

1. 2. 3. 4. 5. 6.

Veins They bring blood from various organs to the heart. Carries deoxygenated blood with the exception of pulmonary vein. Superficially placed. Thin and less muscular walls. Wider lumen. Progressively unite thus increasing in size.

7. Blood flows uniformly. 8. Walls non-elastic. 9. They collapse when empty.

364 HUMAN ANATOMY AND PHYSIOLOGY ∑ Site of exchange of materials between blood and tissues ∑ Exchange may occur by simple diffusion ∑ Diffusion enhanced by: - Thin capillary walls (just one cell thick) - Narrow capillaries (so the red blood cells and plasma are close to the walls) - Large numbers (the human body has 10 – 40 billion capillaries!) which translate into a tremendous amount of surface area through which exchange can occur - Relatively slow flow of blood (providing more time for exchange to occur) ∑ Exchange also occurs through pores (located between the cells forming the capillary walls), by vesicular transport (e.g., pinocytosis), and by bulk flow.

Bulk Flow ∑ protein-free plasma filters out of capillaries, mixes with surrounding interstitial fluid, and is then reabsorbed. Plasma filters out at the arteriole end of capillaries because hydrostatic (blood) pressure (an outward force) exceeds osmotic pressure (an inward force). At the venous end of capillaries, the filtrate tends to move back in because osmotic pressure now exceeds hydrostatic pressure. ∑ because the outward force at the arteriole end exceeds the inward force at the venous end, more plasma filters out than moves back in to the capillaries. So, fluid tends to accumulate in the tissues. The lymph vessels pick up this fluid and transport it back to the blood. ∑ Bulk flow is: 1. not very important in exchange (much more exchange occurs by way of diffusion). 2. important in regulating the ‘distribution’ of fluids between the plasma and interstitial fluid (which is important in maintaining normal blood pressure).

Veins These blood vessels bring blood from various parts of the body towards the heart and mainly contain deoxygenated blood with the exception of pulmonary vein. It has thin muscular walls and wider lumen and the blood flows uniformly. The veins are large and hold more blood than the arteries. Veins have semilunar valves which prevent the backward flow of blood. ∑ It serve as low-resistance passage, ways to return blood from tissues to the heart ∑ It serve as a BLOOD RESERVOIR (under resting conditions nearly two-thirds of all your blood is located in the veins) and, therefore, veins are important in permitting changes in stroke volume.

9.16

ARTERIAL SYSTEM

The distribution of the arteries is like a highly ramified tree, the common trunk of which, formed by the aorta, commences at the left ventricle, while the smallest ramifications extend to the peripheral parts of the body and contained organs. Arteries are found in all parts of the body, except in hairs, nails, epidermis, cartilages, and cornea; the larger trunks usually occupy the most protected situations, running in the limbs, along the flexor surface, where they are less exposed to injury.

THE CARDIOVASCULAR SYSTEM 365 There is considerable variation in the mode of division of the arteries: occasionally a short trunk subdivides into several branches at the same point, as may be observed in the celiac artery and the thyrocervical trunk: the vessel may give off several branches in succession, and still continues as the main trunk, as is seen in arteries of the limbs; or the division may be dichotomous, as, for instance, when aorta divides into two common iliacs. A branch of an artery is smaller than the trunk from which it arises; but if an artery divides into two branches, the combined sectional area of two vessels is, in nearly every instance, somewhat greater than that of the trunk; and combined sectional area of all the arterial branches greatly exceeds that of the aorta; so that the arteries collectively may be regarded as a cone, the apex of which corresponds to the aorta, and the base to capillary system. Superficial temporal artery Posterior auricular artery Common carotid artery Subdavian artery Brachiocephalic trunk

External carctid artery Internal carctid artery Vertebral artery Acrta and arch

Axillary artery

Pulmonary artery Cardiac artery

Deep brachial artery

Thoracic aorta

Brachial artery Acrta

Celiac trunk

Radal artery

Superior mesenteric artery

Interosseous artery

Renal artery Gonadal artery

Ulnar artery

Inferior mesenteric artery

Deep palmar arch Superficial palmar arch

Common iliac artery External iliac artery Internal iliac artery Deep femoral artery Femoral artery

Descending genicular artery

Popliteal artery

Anterior tibial artery Peroneal artery Posterior tibial artery

Fig. 9.13 Arterial system The arteries, in their distribution, communicate with one another, forming what are called anastomoses, and these communications are very free between the large as well as small branches. The anastomosis between trunks of equal size is found where great activity of the circulation is requisite, as in the brain; here the two vertebral arteries unite to form basilar, and two anterior

366 HUMAN ANATOMY AND PHYSIOLOGY cerebral arteries which are connected by a short communicating trunk; it is also found in the abdomen, where the intestinal arteries have very ample anastomoses between their large branches. In limbs the anastomoses are numerous and of largest size around the joints, and the branches of an artery above uniting with branches from the vessels below. These anastomoses are of considerable interest to a surgeon, as it is by their enlargement that a collateral circulation is established after an application of a ligature to an artery. The smaller branches of arteries anastomose more frequently than the large ones and between the smallest twigs these anastomoses become so numerous as to constitute a close network that pervades nearly every tissue of the body. The pulmonary artery conveys venous blood from right ventricle of the heart to the lungs. It is a short, wide vessel, about 5 cm in length and 3 cm in diameter, arising from conus arteriosus of the right ventricle. It extends obliquely upward and backward, passing at arch, where it divides, about the level of fibrocartialge between fifth and sixth thoracic vertebrae, into right and left branches of nearly equal size. The aorta is the main trunk of a series of vessels which convey oxygenated blood to tissues of the body for their nutrition. It commences at upper part of the left ventricle, where it is about 3 cm in diameter, and after ascending for a short distance, arches backward and to left side, over root of the left lung; it then descends within the thorax on left side of the vertebral column, and passes into the abdominal cavity through aortic hiatus in the diaphragm, and ends, considerably diminished in size (about 1.75 cm in diameter), opposite lower border of the fourth lumbar vertebra, by dividing into right and left common iliac arteries. Hence it is classified as ascending aorta, the arch of the aorta, and descending aorta, which lastly is again divided into thoracic and abdominal aortae. The ascending aorta is about 5 cm in length. It commences at upper part of the base of left ventricle, on a level with lower border of third costal cartilage behind left half of the sternum; it passes obliquely upward, forward, and to right, in direction of the heart’s axis, as high as upper border of the second right costal cartilage, describing a slight curve in its course, and being situated, about 6 cm behind posterior surface of the sternum. As its origin it presents, opposite the segments of aortic valve, three small dilatations called aortic sinuses. All union of the ascending aorta with aortic arch the caliber of vessel is increased, owing to a bulging of its right wall. This dilatation is termed as bulb of the aorta, and on transverse section presents a somewhat oval figure. The ascending aorta is contained within the pericardium, and is enclosed in a tube of the serous pericardium, common to it and the pulmonary artery. The arch of aorta begins at level of upper border of the second sternocostal articulation of the right side, and runs at first, upward, backward, and to left in front of the trachea; it is then directed backward on left side of the trachea and finally passes downward on left side of the body of fourth thoracic vertebra, at lower border of which it becomes continuous with the descending aorta. It thus forms two curvatures: one with its convexity upward, the other with its convexity forward and to left. Its upper border is usually about 2.5 cm below superior border to the manubrium sterni.

THE CARDIOVASCULAR SYSTEM 367 The descending aorta is divided into two portions, thoracic and abdominal, in correspondence with the two great cavities of the trunk in which it is situated. Main arteries are:

The Coronary Arteries ∑ Arteries are vessels that carry blood away from the heart. The coronary arteries are the first blood vessels that branch off from the ascending aorta.

Branches: ∑ Right Coronary Artery - Supplies oxygenated blood to walls of ventricles and right atrium. ∑ Left Main Coronary Artery - Directs oxygenated blood to left anterior descending artery and left circumflex. ∑ Left Anterior Descending Artery - Supplies oxygenated blood to walls of the ventricles and left atrium (front region of the heart). ∑ Left Circumflex Artery - Supplies oxygenated blood to walls of the ventricles and left atrium (back region of the heart).

Brachiocephalic Artery ∑ Arteries are vessels that carry blood away from heart. The brachiocephalic (Brachi, -cephal) artery extends from aortic arch to the head. It branches off into right common carotid artery and right subclavian artery.

Carotid Arteries ∑ Arteries are vessels that carry blood away from heart. The common carotid arteries are two of several arteries that supply blood to head. The right common carotid artery branches from brachiocephalic artery and extends up the right side of neck. The left common carotid artery branches from aorta and extends up the left side of neck. Each carotid artery branches into internal and external vessels near top of the thyroid.

Branches: ∑ Internal Carotid Artery - Supplies oxygenated blood to the brain and eyes. ∑ External Carotid Artery - Branches off to supply oxygenated blood to the throat, neck glands, tongue, face, mouth, ear, scalp and dura mater of the meninges.

Subclavian Arteries ∑ Arteries are vessels that carry blood away from the heart. The right subclavian artery extends from brachiocephalic artery to right side of the body. The left subcalvian artery extends from aortic arch to left side of the body.

368 HUMAN ANATOMY AND PHYSIOLOGY Chest Region ∑ Visceral Branches - Supply blood to lungs, pericardium, lymph nodes, and esophagus. ∑ Parietal Branches - Supply blood to chest muscles, diaphragm, and spinal cord.

Abdominal Region Celiac Artery ∑ Left Gastric Artery - Supplies blood to oesophagus and portions of the stomach. ∑ Hepatic Artery - Supplies blood to liver. ∑ Splenic Artery - Supplies blood to stomach, spleen, and pancreas. (i) Superior mesenteric artery - Supplies blood to intestines. (ii) Inferior mesenteric artery - Supplies blood to colon. ∑ Renal Arteries - Supplies blood to kidneys. ∑ Ovarian Arteries - Supplies blood to female reproductive organs. ∑ Testicular Arteries - Supplies blood to male reproductive organs.

Common Iliac Artery ∑ Arteries are vessels that carry blood away from heart. The common iliac artery extends from descending aorta and branches into internal and external iliac arteries.

9.17

VENOUS SYSTEM

Veins carry blood from capillaries of different parts of the body to heart. They consist of two distinct sets of vessels, pulmonary and systemic. The Pulmonary Veins, unlike other veins, contain arterial blood, which they return from lungs to left atrium of the heart. The Systemic Veins return venous blood from the body generally to right atrium of the heart. The Portal Vein, an appendage to the systemic venous system, is confined to abdominal cavity, and returns venous blood from spleen and viscera of digestion to the liver. This vessel ramifies in substance of the liver and there breaks up into a minute network of capillary-like vessels, from which blood is conveyed by hepatic veins to the inferior vena cava.

THE CARDIOVASCULAR SYSTEM 369 Superficial temporal vein Fecial vein External jugular vein

Internal jugular vein

Subdavian vein Brachiocephalic vein Superior vena cava

Axillary vein Brachial vein Cepalic vein Basilic vein

Hepatic vein Renal vein Gonacial vein Inferior vena cava Common iliac vein

Median cubital vein Medial antebrachial veins

Internal iliac vein External iliac vein Superficial venous palmer arch

Deep femoral vein Femoral vein Great saphenous vein Poplitcal vein

Small saphenous vein Anterior tibial vein Posterior tibial vein

Doral venous arch

Fig. 9.14

Venous system

Main veins are:

The Pulmonary Veins The pulmonary veins return arterialized blood from lungs to left atrium of the heart. They are four in number, two from each lung.

The Systemic Veins The systemic veins may be arranged into three groups: 1. The veins of heart. 2. The veins of upper extremities, head, neck, and thorax, which end in superior vena cava. 3. The veins of lower extremities, abdomen, and pelvis, which end in inferior vena cava.

370 HUMAN ANATOMY AND PHYSIOLOGY Some parts of this section are: ∑ The Veins of Heart Coronary Sinus (sinus coronarius). Most of the veins of heart open into coronary sinus. This is a wide venous channel about 2.25 cm in length situated in posterior part of the coronary sulcus, and covered by muscular fibers from left atrium. It ends in right atrium between the opening of inferior vena cava and atrioventricular aperture, its orifice being guarded by a semilunar valve, the valve of the coronary sinus (valve of Thebesius). ∑ The Veins of Head and Neck may be subdivided into three groups: 1. The veins of exterior of head and face. 2. The veins of neck. 3. The diploic veins, veins of the brain, and venous sinuses of the dura mater. The superior vena cava drains blood from upper half of the body. It measures about 7 cm in length, and is formed by junction of two innominate veins. It begins immediately below cartilage of the right first rib close to sternum, and descending vertically behind the first and second intercostals spaces, ends in upper part of right atrium opposite upper border of third right costal cartilage: the lower half of vessel is within pericardium. In its course it describes a slight curve, the convexity of which is to right side. ∑ The Veins of Abdomen and Pelvis - External Iliac Vein. The upward continuation of femoral vein, begins behind the inguinal ligament, and, passing upward along brim of the lesser pelvis, ends opposite sacroiliac articulation, by uniting with hypogastric vein to form the common iliac vein. On right side, it lies at first medial to artery: but, as it passes upward, gradually inclines behind it. On left side, it lies altogether on medial side of the artery. It frequently contains one, sometimes two valves. - Common Iliac Veins. These are formed by the union of external iliac and hypogastric veins, in front of sacroiliac articulation; passing obliquely upward toward right side. They end upon fifth lumbar vertebra, by uniting with each other at an acute angle to form inferior vena cava. The right common iliac is shorter than left, nearly vertical in its direction, and ascends behind and then lateral to its corresponding artery. The left common iliac, longer than the right and more oblique in its course, is at first situated on medial side of the corresponding artery, and then behind right common iliac. Each common iliac receives iliolumbar, and sometimes lateral sacral veins. The left receives, in addition, middle sacral vein. No valves are found in these veins. - Renal Veins. These are of large size, and placed in front of the renal arteries. The left is longer than the right, and passes in front of aorta, just below the origin of superior mesenteric artery. It receives left spermatic and left inferior phrenic veins, and, generally, the left suprarenal vein. It opens into inferior vena cava at a slightly higher level than the right. - Suprarenal Veins. These are two in number: right ends in the inferior vena cava; left, in the left renal or left inferior phrenic vein. - Inferior Phrenic Veins. These follow the course of inferior phrenic arteries; the right ends in inferior vena cava; the left is often represented by two branches, one of which ends in left renal or suprarenal vein, while the other passes in front of esophageal hiatus in diaphragm and opens into inferior vena cava.

THE CARDIOVASCULAR SYSTEM 371 - Hepatic Veins. These commence in the substance of liver. In the terminations of portal vein and hepatic artery, are arranged in two groups, upper and lower. The upper group usually consists of three large veins, which converge toward the posterior surface of liver, and open into inferior vena cava, while that vessel is situated in the groove on back part of the liver. The veins of lower group vary in number, and are of small size; they come from right and caudate lobes. The hepatic veins run singly, and are in direct contact with hepatic tissue. They are destitute of valves.

The Portal System of Veins The portal system includes all the veins which drain blood from abdominal part of the digestive tube (with the exception of the lower part of the rectum) and from spleen, pancreas, and gall-bladder. From these viscera blood is conveyed to liver by the portal vein. In the liver this vein ramifies like as artery and ends in capillary-like vessels termed sinusoids, from which blood is conveyed to inferior vena cava by the hepatic veins. From this it will be seen that blood of portal system passes through two sets of minute vessels, viz., (a) the capillaries of digestive tube, spleen, pancreas, and gall-bladder; and (b) the sinusoids of liver. In an adult portal vein and its tributaries are destitute of valves; in fetus and for a short time after birth valves can be demonstrated in tributaries of the portal vein; as a rule they soon atrophy and disappear, but in some subjects they persist in a degenerate form. The portal vein (vena portae) is about 8 cm in length and is formed at the level of the second lumbar vertebra by junction of the superior mesenteric and lineal veins, the union of these veins taking place in front of inferior vena cava and behind the pancreas. It passes upward behind superior part of the duodenum and then ascends in right border of lesser omentum to the right extremity of the porta hepatic, where it divides into a right and a left branch, which accompany the corresponding branches of hepatic artery into the substance of liver. In lesser omentum it is placed behind and between common bile duct and hepatic artery, the former lying to the right of the latter. It is surrounded by hepatic plexus of nerves, and is accompanied by numerous lymphatic vessels and some lymph glands. The right branch of portal vein enters right lobe of the liver, but before doing so generally receives cystic vein. The left branch, longer but of smaller caliber than the right, crosses left sagittal fossa, gives branches to caudate lobe, and then enters left lobe of the liver. As it crosses left sagittal fossa it is joined in front by a fibrous cord, the ligamentum teres (obliterated umbilical vein), and is united to inferior vena cava by a second fibrous cord, the ligamentum venosum (obliterated ductus venosus).

9.18

COMMON HEART DISORDERS

Poor or abnormal function of the cardiovascular system may be result of: ∑ Insufficient blood supply due to dehydration, bleeding or swelling. ∑ A poor blood supply to the heart, where there is not enough oxygen and other nutrients for its work.

372 HUMAN ANATOMY AND PHYSIOLOGY ∑ Poor lung function or obstruction to blood flow in the lungs, which places a strain on the heart muscle; ∑ Too many or too few electrolytes (e.g., potassium, magnesium) that cause irregular heart beats or dangerous rhythms in the heart. ∑ Weakness of blood vessel walls. ∑ Heart muscle weakness.

Arteriosclerosis The coronary arteries arise at point of maximum blood pressure in the circulatory system. Over the course of time, arterial walls are apt to lose elasticity, which limits the amount of blood that can surge through them and hence limits the supply of oxygen to heart. This condition is known as arteriosclerosis.

Atherosclerosis Fatty deposits, called plaque, may accumulate on the interior surface of the coronary arteries. This is particularly common in people who have high levels of cholesterol in their blood. Plaque deposits reduce the bore of coronary arteries and the amount of blood they can carry. Atherosclerosis (usually along with arteriosclerosis) may ∑ so limit the blood supply to heart that during times of stress heart muscle is so deprived of oxygen that pain of angina is created. ∑ trigger formation of a clot causing a coronary thrombosis. This stops the flow of blood through the vessel and capillary network it supplies, causing a heart attack. The portion of the heart muscle deprived of oxygen dies quickly of starvation of oxygen. If the area is not too large, the undamaged part of heart can, in time, compensate for the damage. Coronary bypass surgery uses segments of leg veins to bypass the clogged portions of coronary arteries.

Cardiomyopathy There are a wide variety of reasons that cardiomyopathies may develop. The cardiomyopathies can be classified into number of different broad categories. There are also specific cardiomyopathies that exist. ∑ Dilated Cardiomyopathy Dilatation and marked enlargement of the heart that leads to impaired pumping of left or both ventricles. Often referred to as idiopathic due difficulty of identifying a direct cause. There are four factors associated with DCM: viral, autoimmune, alcoholic/toxic and pregnancy. ∑ Hypertrophic Cardiomyopathy Marked left and occasionally right ventricular enlargement, often asymmetrical, which usually involves interventricular septum. Mutations in certain proteins cause the disease in many patients. It is common for there to be a family history. ∑ Restrictive Cardiomyopathy In this disorder heart muscle becomes stiff (but usually not thickened). This restricts filling of one or both ventricles during the relaxation (diastolic) phase of the cardiac cycle. The heart’s

THE CARDIOVASCULAR SYSTEM 373 contraction (systolic function) is maintained at normal or near-normal. This may be associated with other diseases, (e.g., amyloidosis, endomyocardial disease). ∑ Arrhythmogenic Right Ventricular Cardiomyopathy Progressive replacement of the right, and to some degree left, ventricular muscle with fibrous and fatty tissue. Familial disease is common. ∑ Ischaemic Cardiomyopathy This is caused by multiple heart attacks. When a person has had a heart attack or acute myocardial infarction a part of the heart muscle dies and scar tissue is formed. This scar tissue does not contribute to pumping action of the heart. ∑ Unclassified Cardiomyopathy Diseases that do not fit readily into any category. Examples include systolic dysfunction with minimal dilatation, mitochondrial disease, and fibroelastosis. Familial Haemolytic Anaemia. In this case, R.B.C. formation is abnormal, making it fragile and can be easily broken down. Mediterranean Anaemia. It is also called Thalassemia or Cooley’s anaemia. This is due to very small fragile R.B.Cs, containing haemoglobin F. Pernicious Anaemia. This is the most common type of megaloblastic or macrocytic or nutritional or Addison’s anaemia, in which lack of intrinsic factor in the stomach makes it impossible for vitamin B12 to be absorbed. In this abnormality, maturation of erythrocytes is delayed and immature red blood cells come in the circulation and may rupture there. Anaemia. It is the condition where the number of red blood cells is reduced below the normal limit. Aplastic Anaemia. This is due to the defective formation of red blood cells in bone marrow. It may be due to deposition of fatty tissue, fibrous tissue or tumour cells in bone marrow. Heart Block. Defective production of sinoatrial impulse or its conduction in the heart is called heart block. There may be four main types according to the site of damage. 1. Sino-atrial Heart Block. The S.A. node may fail to generate the impulse occasionally, so that the whole heart misses one beat. 2. Atrioventricular Heart Block. The impulse may be normally generated but its transmission into the ventricles is faulty. The defect lies in the A.V. node or in bundle of His or in both. 3. Bundle of His Block. One branch of the bundle may be defective producing either right or left bundle branch block. The ventricle on normal side will contract a little earlier than the other one producing reduplication of the first round. 4. Arborisation Block. The defect lies in the Purkinje fibres. This is found in chronic myocardial damage and can only be detected with electrocardiogram. Angina. It is also called ‘angina pectoris’. It is caused due to deficiency of oxygen supply to heart muscle. The angina pain normally starts in the centre of the chest and spreads down the left arm. Hypertension. It is referred to as high blood pressure. Blood pressure is a measure of how hard a heart is working to pump blood through the body. As systolic or diastolic pressure rises, the heart has to work harder and the blood vessels, as well as heart, become damaged. High blood pressure can harm three vital organs. It compels the heart to work excessively, due to which the congestive heart disease may set in at an early age. In brain, it can cause haemorrhage, or infarctions, leading to various disabilities. It can affect kidneys, leading to renal failure.

374 HUMAN ANATOMY AND PHYSIOLOGY Tachycardia. It means an increased heart rate. The normal heart rate ranges from 60 to 100 beats per minute. A heart rate that continues to beat above 100 beats per minute is called tachycardia. It can be caused by a variety of factors, for example, anxiety, anger, laughter or while exercising. Bradycardia. It means reduced heart rate. Long-term training, such as that carried out by athletes, results in an increase in stroke volume because the heart gets stronger. Therefore, in order to maintain a constant cardiac output at all times, their resting heart rate is reduced. Murmur. Inborn defects in the development of heart or damaging effects of rheumatic fever affects the cardiac valves. The defect is easily detected by changes in nature of the heart sound (murmur) produced during the closure of the defective valves. Thrombosis. It involves the formation of a blood clot called thrombus inside the blood vessels. It blocks the blood flow and proves fatal, if formed inside the coronary vessel or carotid vessel. When a thrombus is transported by the blood flow, then it is called embolus which when deposited in a specific part of the vessel and cuts off circulation, then it is called embolism.

9.19

COMMON METHODS OF TREATMENT

Coronary Care When a person is admitted with a diagnosis of cardiomyopathy the main aims of therapy are to rest the person, to reduce workload of the heart and to improve pumping ability of the heart. This treatment is generally drug therapy, which aids in improving the pumping action of the heart muscle and treatment to ensure proper volume of blood in the body. Patients may be admitted to either an Intensive Care Unit or a Coronary Care Unit depending on the situation. Signs and Symptoms ∑ ∑ ∑ ∑ ∑ ∑

Shortness of breath (especially when laying down) due to collection of fluid in the lungs. Palpitations — the sensation of feeling the heart beat. Dizziness. Cough. Loss of appetite. Increased fatigue and decreased exercise tolerance due to the heart’s inability to increase its workload with increased demand. ∑ Increased weight and swelling of hands, legs or feet due to fluid retention. Low blood pressure due to failure of cardiovascular system to compensate for the failing heart.

Treatments of Heart Diseases (i) Non-surgical — In coronary heart disease (CAD), the coronary arteries are blocked thereby either completely stopping the blood to reach the heart or the blood supply is reduced. Angioplasty and Stent procedures are to clear the arteries. In this case, a catheter with a deflated balloon on its tip is introduced into the patients body through the leg to reach the site of blocked. On reaching the site the balloon is inflated and pushed in and out to clear the blocked artery. Thus, the flow of blood is created. In certain cases a stent (wire mesh tube) is inserted at the site of clearance of blocked and there the stent keeps the artery open. In such cases, recurrence of CAD is minimized.

THE CARDIOVASCULAR SYSTEM 375 (ii) Surgical — In certain acute cases, where two or three coronary arteries are completely blocked and the cardiologist feels that these can not be opened by angioplasty, bypass surgery is performed where veins from other parts of the body are taken out and planted in the coronary position and thus the flow of blood to heart is maintained.

REVIEW QUESTIONS 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.

Explain structure of heart (external and internal) with the help of diagrams. Write an essay on disorders of circulatory system. Describe the arteries of human body and draw a neat and labeled diagram of the same. Explain - (a) Pace maker (b) Cardiac output (c) Heart valves and sounds (d) Systolic and diastolic pressures. What is portal system? Write an essay on portal system present in man. Describe the transport of oxygen and carbon dioxide in man. Explain human venous system. Explain cardiac cycle and correlate it with heart rate. What is pace maker? Why is it called a life saving instruments? What is ECG? What does it show? Discuss various abnormalities. What are nodal tissues? Explain their role in heart beat. Discuss hepatic portal system in man. Also discuss its significance. Discuss pulmonary and systemic circulations in men. Write an essay on various kinds of blood vessels. Discuss common methods of treatment of heart disorders.

CHAPTER

10

THE DIGESTIVE SYSTEM

Parotid Salivary gland Mouth Pharynx Submaxillary and sublingual salivary glands

Oesophagus Pylorus

Liver Stomach Gall bladder

Pancreas

Duodenum

Splenic flexure

Hepatic flexure

Transverse colon

Ascending colon Tenia coli

Descending colon

Caecum

Sigmoid colon

Vermiform appendix

10.1

Jejunum

Anal canal

Rectum

INTRODUCTION

Food is our fuel, and its nutrients give our bodies’ cells the energy and substances they need to operate. But before food can do that, it must be digested into small pieces the body can absorb and use. The food we eat cannot be used by the body as it is, as animals ingest their food as large, complex molecules that must be broken down into small molecules (monomers) that can then be distributed throughout the body of every cell. This vital function is accomplished by a series of specialized organs that comprise the digestive system. The nutrition for the cells of the body is required to keep them growing and working. They must be in a simple form: amino acids, simple sugars, and fatty acids. It is the job of digestive system to take the complex organic molecules of the foods we 376

THE DIGESTIVE SYSTEM 377 ingest-proteins, carbohydrates, and fats-and break them into their simple building blocks. This process is called digestion. Once digestion has occurred, the simple molecules (nutrients) are absorbed from the digestion system by cardiovascular and lymphatic systems and transported to cells throughout the body.

10.2

STEPS OF NUTRITION

Ingestion Digestion Absorption Assimilation Egestion

i.e., taking complex organic food through mouth. i.e., change of complex food into simple, soluble and diffusible components. i.e., passing simple, soluble nutrients into the blood or lymph. i.e., utilization of absorbed food; and i.e., expelling the undigested food.

Example: Mammals, Amoeba, Hydra.

10.3

PARTS OF THE DIGESTIVE SYSTEM

Digestive system of man comprises of the following two parts : 1. Alimentary Canal 2. Digestive Glands

Alimentary Canal Alimentary canal consists of following parts: 1. Mouth.............................. Buccal Cavity Tongue Teeth 2. Pharynx 3. Oesophagus 4. Stomach 5. Small intestine.............. Duodenum Jejunum Ileum 6. Large intestine.............. Ascending colon Transverse colon Descending colon 7. Rectum 8. Anus

Digestive Glands The digestive glands are of the following types: 1. Salivary Glands 2. Gastric Glands 3. Pancreas 4. Liver 5. Intestinal Glands

378 HUMAN ANATOMY AND PHYSIOLOGY Part of the alimentary Canal

Alimentary canal

Function

Buccal cavity

: ingestion, mastication

Pharynx

: swallowing

Oesophagus

: links pharynx to stomach

Stomach

: food storage and digestion of proteins

Duodenum

: digestion and absorption

Ileum

: completion of digestion and absorption

Colon

: absorption of water

Rectum

: formation and storage of faeces

Anus

: egestion

Salivary glands : lubrication and partial digestion of starch Digestive glands

: emulsification of fats by bile salts

Pancreas

: digestion of starch, proteins, fats and nucleic acids

ALIMENTARY CANAL

SALIVARY GLANDS

10.4

Liver

PAROTID SUBMANDIBUL SUBLINGUAL

Tongue

Oesophagus

Stomach Liver Hepatic duct Gall bladder

Common bile duct Pancreas

Duodenum Pancreatic duct

Transverse colon Large intestine

Jejunum Ascending colon Ileum

Small intestine Descending colon

Caecum Appendix Rectum Anus

Fig. 10.1

Alimentary canal of man along with digestive glands

THE DIGESTIVE SYSTEM 379 Mouth ∑ Food enters the body through mouth, or oral cavity. ∑ The lips form and protect the opening of mouth, the cheeks form its sides, the tongue forms its floor, and the hard and soft palates form its roof. ∑ The hard palate is at the front; the soft palate is in the rear. Attached to the soft palate is a fleshy, fingerlike projection called uvula. ∑ Two U-shaped rows of teeth line the mouth-one above and one below. Three pair of salivary glands open at various points into the mouth. ∑ The muscular tongue is attached to the base of mouth by a fold of mucous membrane. ∑ On the upper surface of the tongue are small projections called papillae, many of which contain taste buds. ∑ Most of the tongue lies within the mouth, but its base extends into the pharynx.

Teeth Soft palate Uvula Palatopharyngeal arch Palatine tonsil Palatoglossal arch Posterior wall of pharynx Tongue Lower lip

Fig. 10.2

Buccal cavity

∑ Located at the base of tongue are the lingual tonsils, small masses of lymphatic tissue that serve to prevent infection. It is a longitudinal slit like aperture bounded by labrum anteriorly, labium posteriorly, mandibles (jaws) on the sides. It is meant for ingestion. (a) Buccal Cavity. Oral cavity is known as buccal cavity. The floor of buccal cavity has a tongue bearing taste buds on it. Anterior part of roof of the buccal cavity is hard and is known as hard palate while posterior part of it is soft and called soft palate. (b) Tongue. Tongue is a voluntary glandular and muscular structure found on the floor of mouth. It helps in swallowing, and essential for creating a distinct speech, mastication and mucus secretion.

380 HUMAN ANATOMY AND PHYSIOLOGY Taste buds. Sensations of sweetness, saltness, sourness and bitterness are found on the human tongue. Surface and lingual papillae. Lingual papillae: Three types of lingual papillae containing taste buds give rough surface to our tongue. These are circumvallate, fungiform and filiform papillae.

Circumvallate papillae

Bitter

Fungiform papillae

Filiform papillae

lt

Sa

lt

Sa

Sweet

Fig. 10.3

Diagram of tongue showing areas of different tastes and papillae

(c) Teeth. Teeth in man are present in both the jaws and are embedded in sockets of the jaw bones (thecodont). They develop in two sets (diphyodont). (i) Milk or deciduous teeth (ii) Permanent or successional teeth Milk Teeth are smaller, weaker and temporary. They are replaced by permanent teeth between 6-12 years of age. They are 20 in number, 10 in each jaw. There are four types of teeth (heterodont). (i) Incisors (ii) Canines (iii) Premolars (iv) Molars Incisors. The incisors are the sharp cutting, or biting teeth situated in front. The incisor teeth have a crown consisting of a sharp cutting edge and a single pointed root. Canines. They lie immediately behind the incisors and are used for grasping. The canines have a crown which terminates in a point, and a single root. Canine teeth are absent in rodents and rabbits and leave a toothless interval, the diastema. Premolars. Behind the canines are premolars. These along with molars form the grinding teeth. The upper premolars have two roots while the lower premolars have a single root. Crown consists of two elevations or cusps (which explains why they are sometimes called bicuspids). Molars. These lie behind the premolars and work as grinding teeth. The molars have a squareshaped crown with four cusps. The upper molars possess three roots, the lower two roots. Last molars in human beings are called wisdom teeth.

THE DIGESTIVE SYSTEM 381 1 Canine 2 Incisors

2 Premolars

3 Molars

Roots

Upper

Neck Crown

Lower

Fig. 10.4

Shapes of human teeth

The formula showing the number and arrangement of teeth in one half of each jaw is called dental formula. Dental Formula of Milk Teeth: i

2 1 0 2 , c , pm , m , 2 1 0 2

Dental Formula of Permanent Teeth:

i

2 1 2 3 , c , pm , m , 2 1 2 3 Incisors 1

A B Incisors Canine

Bicuspids or premolars

D

Fig. 10.5

5

Six year molar E

(a)

Canine

3 4

C

Milk molars

Position of six year molar

2

Twelve year molar Wisdom tooth

6 7 8

(b)

Arrangement of the teeth. (a) Temporary teeth (b) Permanent teeth

Although the shape of different teeth varies, all the teeth have similar basic structure. Each teeth has the following three parts:

382 HUMAN ANATOMY AND PHYSIOLOGY

Enamel

CROWN ®

Dentine

Layer of odontoblasts

NECK ®

Gum Pulp (arteries, veins, nerves) Bone A Cellular cement

ROOT ®

Peridontal membrane

Cellular cement

Fig. 10.6

V.S. of a typical human tooth

(i) Crown (ii) Neck (iii) Root Crown is the outer part of teeth formed of hardest substance known as enamel. Neck is usually covered by fleshy part called the gum. Root is embedded in the socket of the jaw bone and is fixed by a bone like cementum and a thick fibrous periodontal membrane. Pulp Cavity present in the centre of the teeth is formed of connective tissue cells, blood vessels and nerves. Outer most layer of tooth is enamel, inner to it is dentive and pulp cavity (rich in blood vessels and nerves. Dental carries occur as a result of action of bacteria on sugars producing acids thus softening and demoneralising enamel. Bacterial cells and food stick to teeth forming dental plaque. Brushing teeth removes this plaque otherwise it leads to erosion of enamel and dentine. If cavity reaches till the pulp area which has lot of nerve endings, pain becomes unbearable, causing inflammation and infection.

Pharynx ∑ The pharynx, or throat, is a short, muscular tube extending about 5 inches (12.7 centimeters) from mouth and nasal cavities to the oesophagus and trachea (windpipe). ∑ It serves two separate systems: the digestive system (by allowing the passage of solid food and liquids) and the respiratory system (by allowing the passage of air).

THE DIGESTIVE SYSTEM 383 The pharynx is short, conical region beyond the soft palate. The food and air passages cross here. The pharynx may be divided into two parts: (i) Nasopharynx (ii) Oropharynx (i) The nasopharynx lies immediately behind the nasal cavities and extends to the level of soft palate. It has internal nares in the roof, openings of cut achieve canals on sides and two masses of lymphoid tissues called pharyngeal tonsils (adenoides). In child upto 7 years of age. (ii) The oropharynx is situated behind the mouth, extending from the soft palate above to the bone below. The buccal cavity opens into it. The opening to larynx is called glottis. It lies on the floor of oropharynx behind the tongue. It bears a leaflike, bilobed cartilaginous flap, the epiglottis, at its anterior border. During swallowing it fits over the glottis to prevent the entry of food into it. Laryngopharynx is the lowest part of the pharynx which has two apertures — anterior slit like gloltis and posterior gullet. The wall of pharynx has well developed constrictor muscles which force the bolus of food into the oesophagus during swallowing or deglutination.

Oesophagus ∑ The oesophagus to as the gullet, is muscular tube connecting pharynx and stomach. ∑ It is approximately 10 inches (25 centimeters) in length and 1 inch (2.5 centimeters) in diameter. In thorax oesophagus lies behind the trachea. ∑ At the base of oesophagus, where it connects with the stomach, is a strong ring of muscle called lower oesophageal sphincter. ∑ Normally, this circular muscle is contracted, preventing contents in the stomach from moving back into the oesophagus. Serosa

Muscle layer Muscularis mucosa Submucosa Mucosa Stratified squamous epithelium

Longitudinal muscle layer Circular muscle layer Longitudinal muscle layer Blood capillary Connective tissue

Fig. 10.7 Histology of oesophagus of man

Stomach The stomach is the dilated portion of alimentary canal, situated between oesophagus and beginning of small intestine. Stomach leads into small intestine through pyloric aperture guided by a valve

384 HUMAN ANATOMY AND PHYSIOLOGY called pyloric sphincter or pylorus. Pyloric sphincter does not open till the food in stomach is fully mixed and churned. ∑ The stomach is located on left side of the abdominal cavity just under the diaphragm. ∑ When empty, stomach is shaped like the letter J and its inner walls are drawn up into long, soft folds called rugae. ∑ When stomach expands, the rugae flatten out and disappear. ∑ This allows the average adult stomach to hold as much as 1.5 litres of material. ∑ The dome-shaped portion of the stomach to left of the lower esophageal sphincter is fundus. The large central portion of stomach is the body. ∑ The part of stomach connected to small intestine (the curve of the J) is the pylorus. ∑ The pyloric sphincter is a muscular ring that regulates the flow of material from stomach into the small intestine by variously opening and contracting. ∑ That material, a soupylike mixture of partially digested food and stomach secretions, is called chyme. ∑ The four tunics of stomach are named and described below, beginning with the outermost layer and continuing inward to the mucous membrane. 1. Serosa. The outer layer consists of loose connective tissue covered on its superficial aspect by a mesothelium. Small blood vessels, lymphatics, and nerves lie in the connective tissue. 2. Muscularis. The muscularis externa contains three smooth muscle layers; an outer longitudinal, a middle circular, and an inner oblique. The oblique layer is best developed in cardia and corpus. ∑ The circular layer is thickest in pylorus where it forms the pyloric sphincter, which helps control evacuation of food. ∑ The longitudinal layer is continuous with longitudinal muscle layer of oesophagus and duodenum. ∑ The myenteric plexus lies in the connective tissue lamina, which separates the circular from longitudinal muscle fibres. Cardiac sphincter

Fundus

Oesophagus

Cardia

Pyloric sphincter

Body

Duodenum

Pyloric canal

Fig. 10.8

Pyloric antrum

Stomach of man

THE DIGESTIVE SYSTEM 385 Peritoneal layer

Longitudinal muscle layer Circular muscle layer

Muscle layer

Oblique muscle Sub-mucosa Musculari mucosae Peptic cells Columnar epithelial cells Mucous cells Oxyntic cells

Fig. 10.9

Histology of Stomach of man

3. Sub-mucosa. This layer separates muscularis from mucous membrane. It consists of coarse collagenous fibers and many elastic fibers, plus blood vessels, lymph vessels, nerves, and plexus of Meissner. Glands are absent. 4. Mucosa. As in other parts of alimentary tract, the mucous membrane has an epithelium, which rests on a basement membrane, a lamina propria, and a muscularis mucosae. It measures from 0.3-1.5 mm in thickness, being thinnest in cardia and thickest in corpus and fundus. The lamina propria contains glands, which differ in each histological region of the stomach.

Small Intestine The small intestine is a convoluted tube, extending from pylorus of stomach to the ileo-caecal valve, where it joins the large intestine. It is approximately 5 m (16ft) long and consists of three parts. (i) Duodenum (ii) Jejunum (iii) Ileum Duodenum. It is the first part of the small intestine. It is approximately 25-30 cm (10-12 inches) long and lies in a C-shape around the head of pancreas. Jejunum. The jejunum forms two-fifths of small intestine, while ileum forms the remaining threefifths. Ileum is about 3.5 metres long and opens into large intestine. Its wall is thinner and less vascular than that of jejunum. Inner surface of small intestine is thrown into a series of permanent circular folds called plicae circulates or valvulae connirentes. The plicae are called villi. ∑ The small intestine extends about 20 feet (6 meters) from the stomach to the large intestine. ∑ The small intestine is divided into three regions or sections. The first section, the duodenum, is the initial 10 inches (25 centimeters) closest to the stomach. ∑ Chyme from the stomach and secretions from pancreas and liver empty into this section.

386 HUMAN ANATOMY AND PHYSIOLOGY ∑ The middle section, the jejunum, measures about 8.2 feet (2.5 meters) in length. Digestion and absorption of nutrients occur mainly in the jejunum. ∑ The final section, ileum, is also the longest, measuring about 11 feet (3.4 meters) in length. ∑ The ileum ends at ileocecal valve, a sphincter that controls the flow of chyme from ileum to large intestine. ∑ The inner lining of small intestine is covered with tiny, fingerlike projections called villi (giving it an appearance much like the nap of a plush, soft towel). ∑ The villi greatly increase intestinal surface area available for absorbing digested material. ∑ The intestinal lining has a complex structure. Peritoneal layer Longitudinal muscle layer Circular muscle layer Brunner’s glands Sub-mucosa Crypt of Lieberkuhn Mucous cells Goblet cell

Fig. 10.10

Histology of duodenum Serosa Circular muscle Longitudinal muscle Sub-mucosa Mucosa Meissner’s nerve plexus Epithelial lining Muscularis mucosae Myenteric nerve plexus Mucosal gland Sub-mucosal gland Mesentary

Fig. 10.11

TS of gut

∑ Multiple layers: - Serosa: layer closest to blood; continuous with mesentery - 3 Muscle layers (smooth muscle, except in oesophagus, which has some striated) ¡ Longitudinal muscles ¡ Circular muscles ¡ Mucosal muscles

THE DIGESTIVE SYSTEM 387 - 2 Nerve networks: ¡ Myenteric (Auerbach) plexus ¡ Sub-mucosal (Meissner) plexus - Sub-mucosa - Mucosa— lamina propria, lined with epithelium ¡ Organized into projections called villi ∑ Entire digestive system has this structure, with minor exceptions - Oesophagus and distal rectum have no serosa.

Large Intestine Small intestine leads into the large intestine or colon. There is present a blind dilated sac situated right at the place where small intestine opens into large intestine. This sac is known as caecum. Caecum terminates into a fine finger like projection known as vermiform appendix. Large intestine consists of three parts : (i) Ascending Colon (ii) Transverse Colon (iii) Descending Colon Ascending Colon. The ascending colon passes upwards on right side of the abdominal cavity until it reaches the right lobe of liver where it sharply bends to become transverse colon. Transverse Colon. The transverse colon stretches across the abdominal cavity from the ascending colon on right to the spleen on the left side, where it bends sharply downwards to form the descending colon. Descending Colon. The descending colon passes downwards in the left lumbar region and finally opens into rectum. Main function of colon is conservation of water, sodium or other minerals and formation of faeces. About 90% of the fluid is absorbed here. The bend between ascending and transverse colon is called right colic flexure or hepatic flexure and that between transverse and descending colon is termed left colic flexure or splenic flexure. Hepatic flexure

Splenic flexure

Transverse colon

Descending colon

Ascending colon

Ileum Haustra Caecum

Sigmoid colon Anal canal

Appendix Rectum

Fig. 10.12

External Internal

Anal sphincters

Large intestine of man

388 HUMAN ANATOMY AND PHYSIOLOGY ∑ Material in the large intestine is mostly indigestible residue and liquid. ∑ Movements are due to involuntary contractions that shuffle contents back and forth and propulsive contractions that move material through the large intestine. ∑ The large intestine performs three basic functions in vertebrates: 1. recovery of water and electrolytes from digested food; 2. formation and storage of feces; and 3. microbial fermentation: The large intestine supports an amazing flora of microbes. Those microbes produce enzymes that can digest many of molecules indigestible by vertebrates. ∑ Secretions in large intestine are an alkaline mucus that protects epithelial tissues and neutralizes acids produced by bacterial metabolism. Water, salts, and vitamins are absorbed, the remaining contents in the lumen form feces (mostly cellulose, bacteria, bilirubin). Bacteria in large intestine, such as E. coli, produce vitamins (including vitamin K) that are absorbed. ∑ The cecum is a pouch at the beginning of large intestine that joins small intestine to the large intestine. ∑ The colon extends from the cecum up the right side of the abdomen, across upper abdomen, and then down the left side of abdomen, finally connecting to rectum. The colon has three parts: ascending colon; transverse colon, which absorb fluids and salts; and the descending colon, which holds the resulting waste. Bacteria in the colon help to digest the remaining food products.

Rectum It is slightly dilated part about 13 cm long and concerned with temporary storage of undigested food. The rectum is where faeces are stored until they leave the digestive system through the anus as a bowel movement.

Anus Rectum leads into anus, which helps in elimination of undigested waste.

10.5

DIGESTIVE GLANDS

Various glands associated with alimentary canal are: 1. Salivary glands 2. Gastric glands 3. Pancreas 4. Liver 5. Intestinal glands

THE DIGESTIVE SYSTEM 389 1. Salivary Glands The salivary glands secrete first of the digestive juices the saliva. There are three pairs of salivary glands : (i) The parotid glands (ii) The sub-maxillary gland (iii) The sub-lingual gland.

Buccal cavity

Parotid gland Duct of parotid gland

Tongue

Sublingual gland

Duct of sublingual gland

Submaxillary gland

Duct of submaxillary gland

Fig. 10.13

Salivary glands of man

(i) The parotid gland is the largest and lies below the external auditory canal. Saliva is carried by parotid or stensen’s ducts. (ii) The sub-maxillary gland is an avoid mass which lies beneath the jaw angles. These pour saliva through Wnarton’s ducts. (iii) The sublingual gland. These are the smallest sized and lie beneath the tongue. These pour saliva through Bartholin’s ducts or ducts of Rivinus. Saliva serves many roles, some of which are important to all species, and others to only a few: ∑ Lubrication and binding: the mucus in saliva is extremely effective in binding masticated food into a slippery bolus that (usually) slides easily through the oesophagus without inflicting damage to the mucosa. Saliva also coats the oral cavity and oesophagus, and food basically never directly touches the epithelial cells of those tissues. ∑ Solubilizes dry food: in order to be tasted, the molecules in food must be solubilized. ∑ Oral hygiene: The oral cavity is almost constantly flushed with saliva, which floats away food debris and keeps the mouth relatively clean. Flow of saliva diminishes considerably during sleep, allow populations of bacteria to build up in the mouth - the result is dragon breath in the morning. Saliva also contains lysozyme, an enzyme that lyses many bacteria and prevents overgrowth of oral microbial populations. ∑ Initiates starch digestion: in most species, the serous acinar cells secrete an alpha-amylase which can begin to digest dietary starch into maltose. Amylase is not present, or present only in very small quantities, in the saliva of carnivores or cattle. ∑ Provides alkaline buffering and fluid: this is of great importance in ruminants, which have non-secretory forestomachs.

390 HUMAN ANATOMY AND PHYSIOLOGY ∑ Evaporative cooling: clearly of importance in dogs, which have very poorly developed sweat glands - look at a dog panting after a long run and this function will be clear.

2. Gastric Glands Numerous, simple or branched tubular glands lie in the mucus membrane of stomach. These are called gastric glands. They secrete gastric juice which is a clear, watery, strongly acidic, contains HCl, enzymes and mucus. The total quantity of 1.5 to 2 litres is secreted each day. Each gastric gland consists of various types of cells. (a) Oxyntic cells also known as parietal cells secrete HCl. (b) Goblet cells secrete mucus. (c) Peptic cells also known as zymogen or chief cells secrete two proenzymes pepsinogen and prorennin and one enzyme gastric lipase. (d) Argentaffic cells lie in pyloric glands and secrete gastric hormone secretion of gastric juices is under nervous and hormonal control. Normal gastric juices also contain blood forming factor of castle’s intrinsic factor from oxyntic cells which help in absorption of vitamin B12 i.e., cyanocobalamin. Opening of gastric gland Goblet cell Columnar epithelium

Oxyntic or parietal cell Duct of oxyntic cell

Peptic cells

Fig. 10.14

L.S. gastric gland

3. Pancreas The pancreas, the second largest gland of the human body is a heterocrine gland (i.e., has both endocrine and exocrine functions), located in C-shaped curve of the duodenum. It secretes pancreatic juice which contains enzymes to help in digestion of carbohydrates, proteins and fats. Pancreatic juice is poured into the duodenum with the help of pancreatic duct. Pancreas comprises head, body and tail. The head lies in the curve of duodenum, body behind the stomach and tail reaches the

THE DIGESTIVE SYSTEM 391 spleen lying in front of left kidney. Main pancreatic duct (duct of Wirsung) is formed from smaller ducts within pancreas. An accessory pancreatic duct namely duct of santoring is also present in the pancreas and opens directly into the duodenum. Pancreas has two parts - exocrine and endocrine. Exocrine parts consist of rounded lobules i.e., acint. Endocrine part consists of islet of Langerhans. Human have about one million islets.

Cystic duct

Hepatic duct

Gall bladder Common bile duct

Pancreas Duodenum

Pancreatic duct

Fig. 10.15

Diagram of biliary tract and pancreas

4. Liver

Intralobular duct Pancreatic duct

Interlobular septum Islets of Langerhans Blood capillary Blood vessel Acinus

Fig. 10.16

Histology of pancreas

The liver lies in the abdominal cavity, in contact with diaphragm. Its mass is divided into several lobes, the number and size of which vary among species. In most mammals, a greenish sac — the gall bladder — is seen attached to the liver and careful examination will reveal the common bile duct, which delivers bile from liver and gallbladder into the duodenum. Two main lobes of liver are —

392 HUMAN ANATOMY AND PHYSIOLOGY Large right and small left, while small lobes are — quadrate and caudate lobe. Each liver lobe is formed of hexagonal lobules, surrounded by a connective tissue sheath called Glissons capsule. ∑ The liver produces and sends bile to small intestine via hepatic duct, ∑ Bile contains bile salts, which emulsify fats, making them susceptible to enzymatic breakdown. ∑ In addition to digestive functions, the liver plays several other roles: 1. Detoxification of blood; 2. Synthesis of blood proteins; 3. Destruction of old erythrocytes and conversion of hemoglobin into a component of bile; 4. Production of bile; 5. Storage of glucose as glycogen, and its release when blood sugar level drops and 6. Production of urea from amino groups and ammonia. ∑ The gall bladder stores excess bile for release at later time. ∑ We can live without our gall bladders, in fact many people got removed. ∑ The drawback, however, is a need to be aware of the amount of fats in the food they eat since the stored bile of gall bladder is no longer available. ∑ Liver diseases: Gall bladder. This is a pear-shaped sac, with a capacity of approximately 60 ml attached to the under surface of right lobe of the liver. Liver secretes bile, which is temporarily stored in gall bladder. Bile is a yellowish-green juice formed of water, sodium bicarbonates, bile pigments and bile salts. Bile has no enzymes thus shows no chemical action on food. Green colour of bile is due to two bile pigments namely biliverdin and bilirubin. Bile from left and right lobes of the liver is drained out through left and right hepatic ducts which join with cystic duct from the gall bladder to form a common bile-duct. The common bile-duct joins the pancreatic duct and pours bile into the duodenum. Hepato-pancreatic duct swells and forms ampulla of vater before opening into duodenum guarded by a sphincter of Oddi.

Functions of the Liver The functions of the liver are numerous. It is the principal organ of metabolism and has a part to play in many different bodily processes. 1. Metabolism. The liver plays an important role in the metabolism of carbohydrates, fats and proteins. 2. Storage. The liver stores glycogen, fat, iron and vitamins A, D and B (especially B12). 3. Bile Secretion. Liver secretes bile which helps in emulsification of fats. 4. Synthesis. The liver synthesizes plasma proteins, fibrinogen, albumin, globulin and prothrombin. 5. Detoxication. The liver enables the body to get rid of unwanted and possibly harmful substances such as certain drugs, in two ways : the substance may be combined with another to form a compound which is excreted in the urine, or it may be destroyed in the liver.

THE DIGESTIVE SYSTEM 393 Left lobe of liver Cystic duct

Oesophagus

Gall bladder Stomach

Left hepatic duct

Right lobe of liver

Common hepatic duct Bile duct

Pancreas

Hepatopancreatic duct Duodenum

Fig. 10.17

Liver and biliary tract

6. Excretion. The liver eliminates some substances from the body, e.g., bile pigments and cholesterol. Bile pigments are formed by breakdown of worn-out RBCs. Two bile pigments are bilirubin and biliverdin. 7. Heart production. Because of biochemical activity of the liver cells, considerable heat is produced in the liver. 8. Blood formation. In foetus, two to four months old, the liver is one of the main sites for formation of red blood corpuscles. In post-natal life liver does not manufacture red cells under normal circumstances.

5. Intestinal Glands Intestinal glands occur throughout the small intestine between villi. Intestinal glands are of two types. (a) Crypts of Lieberkuhn secrete enzymes and mucus. These are simple tubular glands which occur throughout the small intestine between the villi. These crypts have at and the base paneth and argentaffin cells. ∑ Paneth cells are particularly in duodenum. These are in the bottom of crypts. They are rich in zinc and containing acidophilic granules. Function of these cells is not certain but there is evidence that they secrete some enzyme. ∑ Argentaffin cells synthesize secretion hormone. (b) Brunner’s Glands secrete alkaline watery fluid, a little enzyme and mucus. These are branched tubular glands and are found only in the duodenum. These glands open in the crypts of Lieberkuhn. Secretions of both glands is collectively known as intestinal juice or succus entericus which contains enzymes to digest carbohydrates, proteins and fats.

394 HUMAN ANATOMY AND PHYSIOLOGY

Goblet cell Absorptive cells

Villus

Crypt of lieberkuhn

Intestinal epithelium Intestinal wall

Duct of brunner’s gland Brunner’s glands

Fig. 10.18

10.6

Intestinal glands of man

PHYSIOLOGY

1. Ingestion. Taking in of food is called ingestion. When a mouthful of food gets masticated and well mixed with saliva the movements of tongue and cheeks convert it into a soft rounded mass called bolus. This bolus is swallowed and carried down the oesophagus by contraction of its muscular walls. The special method of muscular contraction by which the bolus of food is carried down the oesophagus is called peristalsis. The circular muscle of the tube immediately behind the bolus contracts, while that directly in front relaxes. This results in bolus being forced into the relaxed portion. In this way the bolus is passed steadly forward. Wave of contraction

Wave of relaxation

Bolus

Bolus

Bolus

Fig. 10.19

Diagram illustrating peristalsis

THE DIGESTIVE SYSTEM 395 Swallowing is both a voluntary and involuntary action. Once food has been properly chewed and mixed with saliva to create a bolus, tongue forces the bolus toward back of the mouth and into the pharynx. This a voluntary action; the individual has total control over moving the bolus while it is in the mouth. When the bolus presses against the soft palate, the soft palate and the uvula rise to close off the nasal passages to prevent the bolus from entering there. Once bolus enters the pharynx, swallowing becomes an automatic reflex action and cannot be stopped. The larynx, upper part of the trachea that contains vocal cords, rises. As it does so, a flaplike piece of tissue at the top of the larynx, the epiglottis, folds down to cover its opening. This prevents the bolus from passing into the trachea. 2. Digestion. The process of digestion involves breaking down of complex food molecules into simpler ones. (i) Carbohydrates. Polysaccharides (i.e., starch) have to be broken down into di-saccharides (i.e., maltose) and finally into mono-saccharides (i.e., glucose). (ii) Proteins are broken down to proteoses, peptones, peptides and finally to amino-acids. (iii) Fats are converted to fatty acids and glycerol. Enzymes. All digestive enzymes can be classified into three main groups : ∑ Amylolytic enzymes—break carbohydrates, ∑ Proteolytic enzymes—break proteins, ∑ Lipolytic enzymes—break fats. Activity: To study action of salivary amylase on starch. Saliva added

Does not show blue black colour with iodine solution A

Fig. 10.20

Shows blue black with iodine solution

1 mI Starch solution B

Experiment to show actions of salivary amylase on starch solution

Apparatus Test tubes, test tube stands, starch, H2O, iodine solution. Procedure 1. Take two test tubes A and B and put 1ml of starch solution (1%) in both tubes. 2. Add about 1ml of saliva in A-test tube. 3. Keep both test tubes undisturbed for about 20 minutes. 4. Then add few drops of iodine solution in both the test tubes. 5. Colour of starch solution in test tube B, in which no saliva was added, turns blue black but in test tube A result comes out to be negative. Conclusion Since starch gives blue black colour with iodine, this experiment proves that, in test tube-A starch was not there. It was converted to something else due to the action of saliva.

396 HUMAN ANATOMY AND PHYSIOLOGY Table 10.1. Showing Digestion of Food in Man Site of Action Mouth

Digestive Juice Saliva

Stomach

Enzyme Salivary amylase or ptyalin

Substrate

Product

Starch, dextrins

Limit dextrins, maltose, and isomaltose

Gastric juice (i) Pepsin Rennin (in young)

Proteins Casein in milk

Proteoses, peptides, paracasein

Liver

Bile juice

Bile salts

Fats

Fat droplets

Duodenum

Pancreatic juice

(i) Amylase

Starch, dextrins glycogen Proteins Chymotrypsinogen (inactive) Procarboxypeptidase proelastase (inactive) Fibrinogen (blood) Casein in milk Peptides DNA RNA Emulsified fats Triglycerides

Maltose, isomaltose, limit dextrins Peptides Chymotrypsin (active) Carboxypeptidase (active) Elastase (active) Fibrin (clot) Paracasein (Curd) Smaller peptides, amino acids Deoxyribonucleosides Ribonucleosides Tri, di and mono glycerides, fatty acids and glycerol

Amylase

Limit dextrins

Maltose

Maltase Sucrase Lactase Isomaltase

Maltose Sucrose Lactose Limit dextrins and Isomaltose Trypsinogen

Glucose + Glucose Glucose + Fructose Glucose + Galactose Glucose

Peptides

Small peptides and amino acids Amino acids Nucleosides and phosphate Purine, pyrimidines and sugars Fatty acids and glycerol

(ii) Trypsin

(iii) Chymotrypsin (iv) Carboxypeptidase (v) DNAse (vi) RNAse (vii) Lipase

Small intestine (Jejunum and Ileum)

Intestinal juice (succus entericum)

Erepsin

Enteropeptidase (non digestive enzyme) Aminopeptidases Dipeptidases Nucleotidases Nucleosidase

Dipeptides Nucleotides Nucleosides

Lipase

Triglycerides

Digestion hydrolyses macromolecules into their building blocks ∑ Digestion is the revere of biosynthesis. ∑ Requires ATP energy.

Trypsin

THE DIGESTIVE SYSTEM 397 ∑ It involves addition of water. This process is called hydrolysis as breaking of macromolecules occur in presence of water.: - Proteins + H2O Æ Amino Acids (20 types) - Polysaccharides + H2O Æ Simple Sugars - Triglycerides + H2O Æ Glycerol + Fatty Acids - Nucleic Acids + H2O Æ N-bases + Pentose Sugars + Phosphate ∑ Food macromolecules are broken down into their building blocks. ∑ Hydrolysis is necessary because: - Our bodies cannot directly use food proteins, polysaccharides and other macromolecules as - Body needs to fulfil, it's own requirements of nutrients. - It is difficult to transport macromolecules across cell membranes. Digestion is spontaneous process and it does not require ATP energy. (in contrast to biosynthesis.) ∑ Macromolecules spontaneously take up water and breakdown into their building blocks. The digestive system has several ways of speeding up hydrolysis. ∑ Although macromolecules spontaneously breakdown, the process is often very slow. ∑ All organisms speed up digestion in several ways, such as - Mechanical breakdown— chewing, churning. - Solubilization— emulsification of fats. ¡ Bile salts made by liver and stored in gall bladder which act as detergents. - Enzymes— catalyze hydrolysis reactions of all the major macromolecules: Digestion of food are performed by various body organs in the following way: (a) The Mouth and Pharynx ∑ Mechanical breakdown of food and chemical breakdown of carbohydrates begin in the mouth. ∑ In the mouth food gets mixed up with saliva, secreted by salivary glands. Saliva contains enzyme ptyalin, an amylolytic enzyme which breaks polysaccharide starch and glycogen first to dextrins (oligosaccharide) and then into disaccharides like maltose, isomaltose and small dextrins called limit dextrins. ∑ Saliva consists of H2O (99%), electrobytes (Na+, K+, Cl¯, HCO3¯), mucus, ptyalin / amylase and lysozyme (bacteriolytic enzyme). ∑ 30% of starch present in food is hydrolysed in the mouth. ∑ The tongue manipulates food during chewing and swallowing; mammals have tastebuds clustered on their tongues. ∑ Mucus moistens food and lubricates the oesophagus. Bicarbonate ions in saliva neutralize the acids in foods. ∑ This mixture of food and saliva is then pushed into the pharynx and oesophagus. ∑ Swallowing moves food from mouth through pharynx into the oesophagus and then to stomach.

398 HUMAN ANATOMY AND PHYSIOLOGY (b) Oesophagus ∑ The oesophagus is a muscular tube their contractions (peristalsis) propel food to the stomach. ∑ Muscles in the oesophagus propel bolus by waves of involuntary muscular contractions (peristalsis) of smooth muscle lining the oesophagus. ∑ The bolus passes through gastroesophogeal sphincter, into the stomach. ∑ Heartbum results from irritation of the oesophagus by gastric juices that leak through this sphincter. (c) Stomach In the stomach food is churned by action of muscles of the stomach. Moreover the food gets mixed with gastric juice which contains dil. HCl and two pro enzymes. A weak gastric lipase enzyme is also secreted by peptic cells. Functions of HCl (i) Softens food. (ii) Kills the bacteria present in the food. (iii) Stops the action of saliva. (iv) Provides acidic medium for enzymes present in the gastric juice to act. Churning of food and action of enzymes in the stomach leads to formation of a milky white sludge called chyme, which is poured through pyloric sphincter into the duodenum. ∑ Gastric juice thus contains hydrochloric acid, pepsinogen, and mucus; ingredients important in digestion. ∑ Secretions are controlled by nervous (smells, thoughts, and caffeine) and endocrine signals. ∑ The stomach also mechanically churns the food. ∑ Alcohol and aspirin are absorbed through stomach lining into the blood. ∑ Epithelial cells secrete mucus that forms a protective barrier between cells and the stomach acids. ∑ Pepsin is inactivated when it comes into contact with mucus. ∑ Bicarbonate ions reduce acidity near cells lining the stomach. ∑ Tight junctions link epithelial stomach-lining cells together. ∑ Food is mixed in lower part of the stomach by peristaltic waves that also propel the acid-chyme mixture against the pyloric sphincter. ∑ Increased contractions of stomach push food through the sphincter and into small intestine as the stomach empties over a 1 to 2 hour period. ∑ High fat diets significantly increase time period. ∑ Further reducing or preventing stomach acids from passing. Mucosa of pyloric stomach secretes hormone namely gastric which is released after entry of food in the stomach. It stimulates: ∑ Secretion of gastric juice. ∑ Constricts cardiac sphincter muscles.

THE DIGESTIVE SYSTEM 399 Peptic cells of stomach secrete two inactive enzymes (proenzymes): - Pepsinogen - Prorennin. Pepsinogen is activated to pepsin which further activates other pepsinogen molecules. This is called auto catalysis. Pepsin

Æ peptones + proteoses Proteins ææææ Prorennin is also activated by HCl into rennin and it is found only in the gastric juice of infants. Casein (soluble milk protein)

Rennim

Paracasein

Pepsin Paracaseinate

Calcium

Calcium paracaseinate (insoluble)

Coagulated curd

Peptones + proteoses + polypeptides

Rennin hydrolyses case in to para case in, which in vein changes to calcium paracaseinate in the presence of calcium. This forms coagulated curd. Paracaseinate is acted on by pepsin and broken to peptones, proteoses and polypeptides. Peptic Ulcers Imbalance in the rate of secretion of gastric juice leads to peptic ulcer which are depressed lesions in mucous membrane of the stomach. More secretion of HCl causes irritation in wall of the stomach because of which there is less formation of mucus which forms a protective lining. Finally, mucus layer is totally eroded leading to lesions or ulcers. ∑ Peptic ulcers result when these protective mechanisms fail. ∑ Bleeding ulcers result when tissue damage is so severe that bleeding occurs into the stomach. ∑ Perforated ulcers are life-threatening situations where a hole has formed in the stomach wall. ∑ At least 90% of all peptic ulcers are caused by Helicobacter pylori. ∑ Other factors, including stress and aspirin, can also produce ulcers. (d) Duodenum. Duodenum receives juices from: (i) liver i.e., bile (ii) pancreas (pancreatic juice) Bile. Bile does not contain any enzyme. It is an alkaline juice, yellowish-green in colour. It contain no enzymes but H2O, mucin, lecithin, cholesterol, bile salts (sodium carbonate, sodium glycocholate and sodium taurocholate) and bile pigments (bilirubin and biliuerdin). Bile salts emulsifies fats and oils. Bile pigments are excretory products formed by breakdown of haemoglobin of worn out red blood cells. Haematin is oxidized to bilirubin (yellow pigment) which further gets oxidized to green pigment namely biliverdin. Bicarbonate ions make the medium alkaline. It has three main functions:

400 HUMAN ANATOMY AND PHYSIOLOGY (i) It emulsifies fats, i.e. breaks large fat droplets to smaller ones. (ii) It helps in fat absorption. (iii) It makes the medium alkaline by first neutralizing the acid from the stomach so as to enable the enzymes present in the pancreatic juice to show their action on food. Pancreatic juice. It consists of pro enzymes namely trypsinogen, chymotrypsinogen and procarboxy-peptidases and enzyme namely amylase and lipolytic enzyme namely lipase. Trypsin breaks proteins, proteoses, peptones and peptides into amino acids. Trypsin

Æ Amino acids Proteins, Proteoses, Peptones ææææ Amylase breaks starch to maltose. Amylase

Starch ææææÆ Maltose Lipase breaks fats to fatty acids and glycerol. Lipase

Fats æææÆ Fatty acids + Glycerol Pancreatic juice-secretions

Proenzymes

Others

Trypsinogen Chymotrypsinogen Procarboxypeptidases

Amylase DNA ase RNA ase Bicarbonates Water by acinar Cell

Pancreatic juice is stimulated by hormone namely secretin which is produced by epithelial layer of the duodenum. Secritin is secreted as a result of entry of acidic chyme from the stomach into the duodenum. - Inactive trypsinogen is acted upon by nondigestive enzyme namely enterokinase present in the intestinal juice. - This gets converted to active trypsinogen. Enterokinase of

Trypsinogen ææææææ Æ Trypsin intestinal juice - Trypsin, activates additional trypsinogen, chymotrypsinogen and procarboxypeptidases by the process of auto catalysis. - Duodenal mucosa secretes hormone namely entero gastrone, when chyme enters duodenum. It slows down gastric contractions and also stops secretion of gastric juice. - The pancreas secretes digestive enzymes and stomach acid neutralizing bicarbonate. - Bile emulsifies fats, facilitating their breakdown into progressively smaller fat globules until they can be acted upon by lipases. Bile contains cholesterol, phospholipids, bilirubin, and a mix of salts. (e) Ileum. From the duodenum food slowly moves toward ileum where it gets mixed with intestinal juice called succus entericus secreted by intestinal glands. Intestinal juice consists of amylolytic, proteolytic and lipolytic enzymes. In the small intestine food becomes an alkaline emulsion which is called chyle.

THE DIGESTIVE SYSTEM 401 Enzymes present in the intestinal juice breaks carbohydrates, proteins and fats as shown under. Peptidases

Æ Amino acids Peptides æææææ Lipase

Fats æææÆ Fatty acids + Glycerol Maltase

Æ Glucose + Glucose Maltose ææææ Sucrase

Æ Glucose + Fructose Sucrose ææææ Lactase

Æ Glucose + Galactose Lactose ææææ Isomaltase

Æ Glucose Isomaltose and æææææ Limit dextrins Intestinal glands are stimulated by two hormones namely duocrinin and enter oerinin produced by intestinal epithelium itself. Intestinal glands

Goblet cells ∑ Secrete mucus

Enterocytes cells

Brunner’s glands

Crypts of Lieberkuhn

∑ Present in intestinal ∑ Stimulated by Duocrinin ∑ Stimulated by enterocrinin crypts ∑ Secretes enzymes and ∑ Release mucus and mucus alkaline watery fluid ∑ Secrete water and electrolytes

Mixture of intestinal juice is named as succus entericus. Intestinal mucosa secretes hormone villikinin on the entry food into small intestine. It increases movement of villi. 3. Absorption Epithelial cells Central lacteal Villus

Fatty acids and glycerol

Capillaries

Lymph vessel

Fig. 10.21

Absorption of fats in the villus

402 HUMAN ANATOMY AND PHYSIOLOGY Absorption of digested food occurs through epithelial surface of the villi of small intestine. ∑ Monosaccharides and amino acids are absorbed into blood capillaries of the villi by process of passive transport which occurs along concentration gradient or active transport which requires expenditure of energy by the epithelial cells. Later, allow absorption to take place even when there are very small concentrations of these substances in the intestine. ∑ Fatty acids are first absorbed in the lymph vessels namely lacteals and then poured into the blood stream. ∑ In addition small intestine absorbs iron, vitamins and calcium (later in the presence of vitamin D). Any fluid that is ingested is also absorbed as follows. Carbohydrates ∑ Most absorption occurs in the duodenum and jejenum (second third of the small intestine). ∑ The inner surface of intestine has circular folds more than triple the surface area for absorption. ∑ Villi covered with epithelial cells increase the surface area by another factor of 10. ∑ The epithelial cells are lined with microvilli that further increase the surface area; a 6 meter long tube has a surface area of 300 square meters. ∑ Each villus has a surface that is adjacent to inside of small intestinal opening covered in microvilli that form on top of an epithelial cell known as a brush border. ∑ Each villus has a capillary network supplied by a small arteriole. ∑ Absorbed substances pass through brush border into the capillary, usually by passive transport ∑ Maltose, sucrose, and lactose are the main carbohydrates present in small intestine; they are absorbed by the microvilli. ∑ Starch is broken down into two-glucose units (maltose) elsewhere. ∑ Enzymes in cells convert these disaccharides into monosaccharides that then leave the cell and enter capillary. ∑ Lacose intolerance results from genetic lack of the enzyme lactase produced by the intestinal cells. Proteins ∑ Peptide fragments and amino acids cross the epithelial cell membranes by active transport. ∑ Inside the cell they are broken into amino acids that then enter capillary. ∑ Gluten enteropathy is the inability to absorb gluten, a protein found in wheat. Fat. End products of fat digestion are fatty acids, monoglycerides, diglycerides and glycerol. Out of these, glycerol is water soluble and thus is absorbed by the intestinal cells. Fatty acids and glycerides are insoluble in water and therefore cannot be directly absorbed. These combine with bile salts (sodium carbonate, sodium glycocholate and sodium taurocholate) and phospholipids to form water-soluble micelles. Many micelles joint to form one emulsion

THE DIGESTIVE SYSTEM 403 droplet. These are actively absorbed into the intestinal cells. Inside these cells bile salts are freed while fatty acids, monoglycerides, diglycerides and glycerol resynthesize to form fat molecules (triglycerides). These fat molecules get surrounded by b-lip proteins and form fine globules called chylomicrons. Chylomicrons are absorbed into central lacteals and get mixed with the lymph giving it a milky appearance. From the lacteals, fats are directly poured into the blood stream without going to the liver. Bile salts are carried to liver by the help of hepatic portal vein for reuse in bile formation. Bile Salts Fatty acids and glycerol ææææÆ micelles Æ Intestinal cells Æ Chylomicrons Æ Lacteals Æ Lymphatic duct Æ Left subclavian vein Æ Heart Æ Blood Stream Æ Cells ∑ Digested fats are not very soluble. ∑ Bile salts surround fats to form micelles, that can pass into epithelial cells. ∑ The bile salts return to lumen to repeat the process. ∑ Fat digestion is usually completed by the time food reaches ileum (lower third) of the small intestine. ∑ Bile salts are in turn absorbed in the ileum and are recycled by liver and gall bladder. ∑ Fats pass from the epithelial cells to small lymph vessel that also runs through the villus. Sodium is absorbed into the cell by several mechanisms, but chief among them is by contransport with glucose and amino acids — this means that efficient sodium absorption is dependent on absorption of these organic solutes. Absorbed sodium is rapidly exported from cell via sodium pumps — when a lot of sodium is entering the cell, a lot of sodium is pumped out of the cell, which establishes a high osmolarity in small intercellular spaces between adjacent enterocytes. Water diffuses in response to osmotic gradient established by sodium — in this case into the intercellular space. It seems that bulk of the water absorption is transcellular, but some also diffuses through the tight junctions. Water, as well as sodium, then diffuses into capillary blood within the villus. Absorption takes place by two mechanisms : (i) Passive Absorption. It occurs down the concentration gradient where special physical force is not required. The main factors believed to be involved are, simple diffusion, osmosis and facilitated diffusion. (a) In simple diffusion the concentration of end products of digestion is higher in the intestine than in blood. This difference initiates diffusion currents from lumen of intestine into the blood stream. The small nutrient molecules dissolved in water such as amino acids and monosaccharides are absorbed through simple diffusion. (b) Water is absorbed by osmosis partly in the small intestine and mostly in the large intestine where the solute concentration is higher in blood than in intestinal contents. (c) In facilitated diffusion a carrier (protein) molecule is required for transport across the membrane. The nutrient (fructose) binds to the earlier protein at the outer surface of the membrane to form a carrier metabolite complex. This diffuses along the concentra-

404 HUMAN ANATOMY AND PHYSIOLOGY tion gradient and nutrient is set free at inner surface of the membrane. This process is, however, more rapid than simple diffusion. (ii) Active Transport. This process occurs both down and against the concentration present. It can move the nutrient molecules not only down the concentration but also against concentration gradient. It is brought about by the carrier protein molecules of cell membrane. Process requires energy which is derived from hydrolysis of ATP by the enzyme ATPase. Active absorption can occur even when the concentration of a substance is much lower in pestinal lumen than in blood. Important nutrients like amino acid, glucose, fructose, se, Na+ ions, etc. are absorbed through contransportation channels. This type of active transport is called contransport or symport system. From capillaries of portal vein, the nutrients are carried to liver and finally enter circulation. Thus, the simple forms of food pass to different cells and tissues of the body. 4. Assimilation: It is a process by which absorbed nutrients are utilized to resynthesize complex molecules like carbohydrates, proteins and fats inside the cells. (a) Carbohydrates. Glucose is used to release energy. Excess of glucose is brought to the liver and converted to glycogen (glycogenesis) and stored there. As need arises the glucose is reformed from glycogen (glycogenolysis) and released into the blood stream. (b) Proteins. Most of the amino acids are used in the protein synthesis which help in growth and repair of body tissues. Proteins may act as structural proteins or act as enzymes and thus control various metabolic activities of the body. Amino-acids which are not used as such, are deaminated in the liver i.e. the amino-group (-NH2) is removed. The amino group forms ammonia (NH3) which is highly toxic and must be removed. This is done by liver cells which convert it to harmless urea, which is then excreted by the kidneys. Urea is formed only in the liver. (c) Fats. Fats release energy. Excess of fats are stored in liver and in the form of adipose tissue. Some fats enter into the composition of cell organelles. 5. Egestion. Removal of waste products from the body is known as egestion or defaecation.

10.7

GLYCOGEN

∑ Glycogen is a polysaccharide made of chains of glucose molecules. ∑ In plants starch is the storage form of glucose, while animals use glycogen for the same purpose. ∑ Low glucose levels in the blood cause release of hormones, such as glucagons, that travel to liver and stimulate breakdown of glycogen into glucose, which is then released into the blood(raising blood glucose levels). ∑ When no glucose or glycogen is available, amino acids are converted into glucose in the liver. ∑ The process of deamination removes the amino groups from amino acids. ∑ Urea is formed and passed through the blood to the kidney for export from the body. ∑ Conversely, the hormone insulin promotes the take-up of glucose into liver cells and its formation into glycogen.

THE DIGESTIVE SYSTEM 405 10.8

HORMONAL CONTROL Table 10.2.

Hormone 1. Gastrin

2. Enterogastrone 3. Secretin

4. Cholecystokinin

Source Mucosa of pyloric stomach

Hormonal Control of Digestive Secretions

Stimulus For Secretion Distesion of stomach of food entry

Action 1. Stimulates secretion of gastric juice 2. Constricts cardic sphincter muscles.

Duodenal

Chyme entry into

mucosa

duodenum

Duodenal mucosa

Chyme entry into duodenum

Duodenal mucosa

Target Organ Stomach

Presence of fats in duodenum

(CCK-PZ)

Stomach

1. Slows gastric contraction. 2. Stops secretion of gastric juice.

Pancreas

1. Release of sodium bicarbonate in pancreatic juice.

Liver

2. Steps up secretion of bile.

Stomach

3. Inhibits secretion of gastrin.

Pancreas Gall

1. Release of enzymes in pancreatic juice.

Bladder

2. Release of bile from gall bladder.

5. Duocrinin

Duodenal mucosa

Acidic chyme in intestine

Intestine

1. Release of mucus from Brunner’s glands.

6. Enterocrinin

Duodenal mucosa

Acidic chyme in intestine

Intestine

1. Release of enzymes from crypts of Lieberkuhn’s.

7. Villikinin

Intestinal mucosa

Food in small intestine

Intestine

1. Increases movement of villi.

∑ The hypothalamus in the brain has two centres controlling hunger. One is the appetite center, the other the satiety center. ∑ Gastrin, secretin, and cholecystokinin are hormones that regulate various stages of digestion. ∑ The presence of protein in the stomach stimulates secretion of gastrin, which in turn will cause increased stomach acid secretion and mobility of the digestive tract to move food. ∑ Food passing into the duodenum causes the production of secretion, which in turn promotes release of alkaline secretions from the pancreas, stops further passage of food into the intestine until the acid is neutralized. ∑ Cholecystokinin (CCK) is released from intestinal epithelium in response to fats, and causes the release of bile from gall bladder and lipase (a fat digesting enzyme) from pancreas. As you might expect, secretion from exocrine pancreas is regulated by both neural and endocrine controls. During interdigestive periods, very little secretion takes place, but as food enters the stomach and, a little later, chyme flows into the small intestine, pancreatic secretion is strongly stimulated. Like stomach, pancreas is innervated by the vagus nerve, which applies a low level stimulus to secretion in response to anticipation of a meal. However, the most important stimuli for pancreatic secretion comes from three hormones secreted by the enteric endocrine system:

406 HUMAN ANATOMY AND PHYSIOLOGY ∑ Cholecystokinin: This hormone is synthesized and secreted by enteric endocrine cells located in the duodenum. Its secretion is strongly stimulated by the presence of partially digested proteins and fats in the small intestine. As chyme foods into the small intestine, cholecystokinin is released into blood and binds to receptors on pancreatic acinar cells, ordering them to secrete large quantities of digestive enzymes. ∑ Secretin: This hormone is also a product of endocrinocytes located in epithelium of the proximal small intestine. Secretion is secreted (!) in response to acid in the duodenum, which of course when acid-laden chyme from stomach flows through the pylorus. The predominant effect of secretion on the pancreas is to stimulate duct cells to secrete water and bicarbonate. As soon as this occurs, the enzymes secreted by the acinar cells are flushed out of the pancreas, through pancreatic duct into the duodenum. ∑ Gastrin: This hormone, which is very similar to cholecystokinin, is secreted in large amounts by the stomach in response to gastric distention and irritation. In addition to stimulating acid secretion by parietal cell, gastrin stimulates pancreatic acinar cells to secrete digestive enzymes. Enterogastrone: It is secreted by duodenal epithelium. It inhibits secretion gastric juice and slows gastric contraction. Duocrinin: It is secreted by duodenal epithelium and stimulates Brunner’s glands to release mucus and enzymes into the intestinal juice. Entrerocrinin: It is secreted by duodenal epithelium and stimulates crypts of lieberkuhn to release enzymes into intestinal juice. Villikinin: It is secreted by the epithelium of entire small intestine and accelerates movement of intestinal villi. ∑ Pancreatic secretions contain enzymes which are needed to digest proteins, startch and triglyceride. When these substances enter stomach, and especially the small intestine, they stimulate release of gastrin and cholecystokinin, which in turn stimulate secretion of enzymes of destruction. ∑ Pancreatic secretions are also the major mechanism for neutralizing gastric acid in small intestine. When acid enters small gut, it stimulates secretion to be released, and the effect of this hormone is to stimulate secretion of lots of bicarbonate. As proteins and fats are digested and absorbed, and acid is neutralized, the stimuli for cholecystokinin and secretion disappear and pancreatic secretion falls off.

10.9

THE GASTROINTESTINAL IMMUNE SYSTEM

∑ Beside all of its other functions, the gastrointestinal tract is a lymphoid organ, and lymphoid tissue within it is collectively referred to as the gut-associated lymphoid tissue or GALT. ∑ The number of lymhocytes in the GALT is roughly equivalent to those in spleen, and, based on location, these cells are distributed in three basic populations: ∑ Peyer’s Patches: These are lymphoid follicles similar in many ways to lymph nodes, located in mucosa and extending into submucosa of the small intestine, especially the ileum. In adults, B lymphocytes predominate in Peyer’s patches. Smaller lymphoid nodules can be found throughout the intestinal tract. ∑ Lamina propria lymphocytes: These are lymphocytes scattered in lamina propria of the mucosa. A majority of these cells are lgA-secreting B cells.

THE DIGESTIVE SYSTEM 407 ∑ Intraepithelial lymphocytes: These are lymphcytes that are positioned in the basolateral spaces between lumenal epithelial cells, beneath tight junctions (they are “inside” the epithelium, but not inside epithelial cells as the name may incorrectly suggest). ∑ Another important component of the GI immune system is the M or microfold cell. M cells are a specific cell type in the intestinal epithelium over lymphoid follicles that endocytose a variety of protein and peptide antigens. Instead of digesting these proteins, M cells transport them into the underlying tissue, where they are taken up by local dendritic cells and macrophages. ∑ Dendritic cells and macrophages that receive antigens from M cells present them to T cells in the GALT, leading ultimately to appearance of immunoglobulin A-secreting plasma cells in the mucosa. Dendritic cells below the epithelium can also sample lumenal antigens by pushing pseudopods between epithelial cells. The secretory lgA is transported through epithelial cells into the lumen, where, it interferes with adhesion and invasion of bacteria. ∑ T cells exposed to antigen in Peyer’s patches also migrate into lamina propria and epithelium, where they mature to cytotoxic T cells, providing another mechanism for containing microbial assaults. ∑ In addition to the GALT discussed above, lymph nodes that receive lymph draining from the gut (mesenteric nodes) Kupffer cells (phagocytic cells in the liver) play important roles in protecting the body against invasion.

10.10

DIGESTIVE SYSTEM DISORDERS

Vomiting It involves relaxation of cardiac sphincter and a violent contraction of the diaphragm and abdominal muscles which result in the ejection of food contents through the mouth. These events are controlled by impulses brought by both vagal and sympathetic afferents to vomiting centre of the medulla. A feeling of nausea preceeds vomiting because certain portions of vomiting centre are associated with the sensation of nausea.

Diarrhoea It is a familiar phenomenon with unusually frequent liquid bowel movements, excessive watery evacuations of faecal material. The opposite of constipation. Disease-causing bacteria often irritate the intestinal wall, and results in increased reverse peristalsis. In interferes seriously with the digestive process and reduces the amount of food absorption.

Constipation It means slow movement of faeces through the large intestine, it is often associated with large quantities of dry, hard faeces in the descending colon that accumulate because of long time available for absorption of fluid. The symptoms include headache, sluggishness, a feeling of depression and discomfort in the abdomen.

Indigestion Certain foods are not properly digested and cause greater expulsion of gases, which lead to distention of stomach and intestine leading to a feeling of fullness. The main causes of indigestion

408 HUMAN ANATOMY AND PHYSIOLOGY may be overeating and eating of spicy food, food poisoning, excess acid secretion and insufficient enzyme secretion. Anorexia nervosa: Eating disorder usually occurring in young women that is characterized by an abnormal fear of becoming obese, a persistent aversion to food, and severe weight loss. Appendicitis, an inflammation of the appendix, most often affects kids and teens between 11 and 20 years old, and requires surgery to correct. The classic symptoms of appendicitis and abdominal pain, fever, loss of appetite, and vomiting. Cirrhosis: Chronic disease of the liver in which normal liver cells are damaged and then replaced by scar tissue. Crohn’s disease: Disorder that causes inflammation and ulceration of all layers of the intestinal wall, particularly in small intestine. Diverticulosis: Condition in which the inner lining of the large intestine bulges out through its muscular wall; if the bulges become acted, the condition is called diverticulitis. Gallstones: Solid crystal deposits that form in the gall bladder. Gastrointestinal infections can be caused by viruses, by bacteria (such as Salmonella, Shigella, Campylobacter, or E. coli), or by intestinal parasites (such as amebiasis and giardiasis). Abdominal pain or cramps, diarrhoea, and sometimes vomiting are the common symptoms of gastrointestinal infections. Hepatitis: Inflammation of liver, caused mainly by a virus. Lactose intolerance: Inability of body to digest significant amounts of lactose, the predominant sugar in milk. Ulcer: Any sore that develops in the lining of the lower oesophagus, stomach, or duodenum.

REVIEW QUESTIONS 1. 2. 3. 4. 5. 6. 7.

8. 9. 10.

Explain hormonal regulation of digestive secretion. With the help of suitable diagrams, describe alimentary canal of man. Discuss physiology of human digestive system. What are enzymes? Discuss role of enzymes in human digestive system. Write an essay on absorption and assimilation of food in men. Trace main steps in the digestion of carbohydrates in man. Discuss its hormonal control as well. Describe (a) Coagulation of milk in the alimentary canal. (b) Role of bile in digestion and absorption of fats. Discuss various disorders related to digestive system. Discuss the histology of alimentary canal. Draw a labelled diagram of a portion of human alimentary canal showing the location of liver, pancreas and gall bladder. Also show their associated ducts. Explain the role of liver and pancreas in digestion.

CHAPTER

11

THE RESPIRATORY SYSTEM Nose

Nose

Air taken in

Air thrown out Trachea

Trachea Thorax Ribs moving Upwards & outwards

Ribs moving downwards & inwards Thorax Lungs Diaphragm moving upwards

Lungs Diaphragm moving downwards

Air rushing in Inhalation

11.1

Air rushing out Exhalation

INTRODUCTION

All living cells need a constant supply of oxygen to enable them to carry out essential biochemical reactions of their metabolism. This oxygen supply is provided by blood which also removes CO2 and other waste products. The oxygen comes from the outside air, into which also the CO2 is discharged. The respiratory system provides means of doing this. Anabolism. It is synthetic or constructive metabolism. In this case small molecules unite to form large molecules. i.e., photosynthesis. Catabolism. It is destructive metabolism which involves breaking down of large organic molecules. This is often accompanied with the liberation of energy i.e., respiration. Metabolism. The sum total of the constructive (anabolism) and the destructive (catabolism) chemical changes occurring in living beings. Respiration has two meanings in biology. Such as: 1. At the cellular level, it refers to O2 requiring chemical reactions that take place in the mitochondria and are the chief source of energy in eukaryotic cells. 11

409

410 HUMAN ANATOMY AND PHYSIOLOGY 2. At the level of whole organism, it designates the process of taking in O2 from the environment and returning CO2. ∑ In respiration O2 consumption is directly related to energy expenditure. ∑ Energy requirements are usually calculated by measuring O2 intake or CO2 release. ∑ Energy expenditure at rest is known as basal metabolism.

11.2

TRANSPORTATION OF GASES—DIFFUSION

In every organism from amoeba to man, gas exchanges i.e., the exchange of O2 and CO2 between cells and the surrounding environment takes place by diffusion. Diffusion is the net movement of particles from a region of high concentration to a region of low concentration as a result of their random movement. In describing gases, scientists speak of pressure of a gas rather than its concentration. At sea level, air exerts a pressure of one atm. This pressure is enough to support a column of mercury 760 mm high. Dalton’s Law of Partial Pressure - Status “the total pressure of a mixture of gases is sum of pressures of separate gases in the mixture”. Thus we can say that: ∑ The pressure of each gas is proportional to its concentration i.e., p μ c. ∑ O2 makes up 21% of composition of dry air therefore 21% of the total air pressure or 160 mm of Hg results from the pressure of O2–partial pressure of O2–designated as pO2–if H2O is present then pO2 = 160 mm Hg. ∑ Atmospheric pO2 = 21% ¥ 760 mm Hg = 160 mm Hg. Partial pressure of oxygen is more in the arterial blood. ∑ Similarly percentage of carbon dioxide in the atmosphere is 0.04, therefore, pCO2 - 0.04% ¥ 760 mm Hg = 0.3 mm Hg. Partial pressure of carbon dioxide is more in the venous blood.

11.3

RESPIRATION AND BREATHING

Breathing. The process involving inspiration (intake of air or oxygen) and expiration (removal of air or carbon-dioxide) is called breathing. No enzymes are involved in the process. Respiration. It is a catabolic process involving burning up of food substnces such as carbohydrates, fats and proteins within the tissues to produce energy. The released energy is temporarily stored as ATPs i.e., Adenosine triphosphate molecules. Respiration may be direct or indirect. Direct respiration is the direct exchange of gases without involvement of blood e.g. diffusion in amoeba. Indirect respiration those do not involve any direct contact between the body cells and the surrounding air or water. There is intermediate fluid i.e., blood or lymph to transport gases.

THE RESPIRATORY SYSTEM 411 Differences between Breathing and Respiration Breathing 1. It is simply an intake of oxygen and removal of CO2. 2. It is an extracellular process. 3. No energy is released

Respiration 1. It is an oxidation of food to form CO2, H2O and energy. 2. It is an intracellular process. 3. Energy is released in the form of ATP molecules. 4. Enzymes are involved.

4. No enzymes are involved.

Activity: To demonstrate that carbon dioxide is given out during the process of breathing. Air pump or pichkari Process of exhalation Glass tube

Rubber/glass tube

Test tube containing limewater, turning milky

Lime water A

B

Fig. 11.1. Apparatus to demonstrate release of CO2 during breathing. Apparatus Two test tubes, lime water, air pump or pichkari, glass tube, rubber tube.

Procedure 1. Take two test tubes and label them as A and B. 2. Put same amount of lime water in both of these. 3. Blow air with the help of glass or rubber tube in one test tube. 4. Note down time required to turn limewater milky in this test tube. 5. Then use syringe or pichkari to pass air through lime water in other test tube. 6. Note down time for turning lime water milky in this test tube. 7. Compare time taken to convert limewater milky in both the test tubes, A and B.

Conclusion Time taken to turn lime water milky in test tube A is more than the one in test tube B. This tells that exhaled air has more CO2 than atmospheric air.

412 HUMAN ANATOMY AND PHYSIOLOGY

Functions of Respiration 1. Interchange of gases. To carry oxygen from the lungs to the tissues for internal respiration and to bring back carbon dioxide to the lungs for excretion through expiration. 2. Maintenance of pH. This function is carried out by balancing excretion of CO2. 3. Maintenance of circulation. It affects the heart rate and cardiac output. Blood pressure also changes during respiration. 4. Excretion. Volatile substances like ammonia, ketone bodies, water vapour etc. are excreted through expiration. 5. Metabolic function. It helps in maintaining metabolism in the tissue. 6. Temperature regulation. Heat is lost through the expired air. 7. Water regulation. Water vapours are excreted during expiration from the lungs.

Types of Respiration 1. Aerobic Respiration. It is a type of respiration which occurs in the presence of oxygen. In animals there is normally aerobic respiration using oxygen. This involves three steps: (a) Uptake of oxygen by tissue cells, (b) Oxidation of food inside the cells by enzymes, and (c) Elimination of CO2 from tissues. The organisms showing aerobic respiration are called aerobes. C6 H12 O6 + 6O 2 ææ Æ 6CO 2 + 6H2 O + 2830 kJ ( 686 Kcal)

Break down of glucose occurs in various steps which can be summarized as:

C6 H12 O 6 Glucose ( 6 - carbon molecule )

In Cytoplasm

In mitochondria

ææææææ Æ Pyruvate + Energy ææææææ Æ CO 2 + H 2 O + Energy. Absence of O Presence of O Glycolysis

2

(3 - carbon molecule)

Kreb ¢s cycle

2

Total number of ATP molecules formed in these steps is 38. 2. Anaerobic Respiration. When food is oxidized without using molecular oxygen is called anaerobic respiration. Anaerobic respiration is exceptional in some cases as in tape worms living inside the human intestines. Anaerobic respiration is also called fermentation. It is found in lower organisms like anaerobic bacteria and yeasts, and may involves any one of the following reactions: Bacteria

Æ 2CH3 CHOHCOOH + Energy (i) C6 H12 O6 ææææ Lactic Acid

Bacteria (ii) C6 H12 O6 ææææ Æ 2C2 H5 OH + 2CO 2 + 118 kJ ( 50 Kcal) Ethanol

Bacteria

(iii) C6 H12 O6 ææææ Æ C3 H7 COOH + CO2 + Energy Butanoic acid

Anaerobic respiration or fermentation consists of two steps: ∑ Glycolysis where glucose breaks into pyruvate. ∑ Anaerobic breakdown of pyruvate.

THE RESPIRATORY SYSTEM 413 As a result of this, two ATP molecules are released from one molecule of glucose. ATP is the energy molecule. Its full form is Adenosine triphosphate. ATP molecules are formed by using energy released during various steps of respiration by using ADP molecule (Adenosine diphosphate) and inorganic phosphate (iP) Energy

Æ ADP ∼ P ææ Æ ATP ADP + iP ææææ About 30.5 KJ/mol of energy releases as a result of breaking of terminal phosphate linkage in ATP in the presence of H2O. Temporary anaerobic respiration may occur even in our own body (in the fast working skeletal muscles,) fast running, walking, swimming etc. The fatigue experience is due to lactic acid accumulated in the muscles due to shortage of oxygen, a condition which may be called oxygen debt. When one rests after the exercise the lactic acid gets slowly oxidized by oxygen later available and then the “debt” is cleared. Glycolysis

Æ Lactic acid C6 H12 O6 ææææÆ Pyruvic acid ææ All this discussion shows that aerobic energy releases more energy and organisms need to take in sufficient energy to survive. Activity: To demonstrate the products formed during fermentation. Delivery tube

Lime water

Sugar solution + Yeast

Fig. 11.2

Stand

Apparatus to demonstrate the products formed during fermentation.

Apparatus Conical flask, fruit juice, sugar solution, yeast, beaker or test tube with one-holed cork, twice bent glass tube, lime water.

Procedure 1. Take a conical flask and put the sugar solution or fruit juice in it. 2. Now add some yeast to it. 3. Fix flask with single holed cork with a twice bent glass tube in it.

414 HUMAN ANATOMY AND PHYSIOLOGY 11.4

PHASES OF AEROBIC RESPIRATION

An important source of energy for cells is glucose C6 H12 O6 + 6O2 Æ 6CO2 + 6H2 O + Energy (686K cal or 38 ATPs) Cells gradually break down glucose in a series of reactions & use small amount of energy released in these reactions to produce ATP (Adenosine Triphosphate) from ADP (Adenosine Diphosphate). ATP can be broken down as under : A—— P ++ P ++ P A ——P +++P + P + 7700 calories NH2 N HC

N

N CH N O CH2–O

P O

HO

OH

Fig. 11.3

OH

OH O

P

OH O

O

P

OH

O

3 phosphate bonds

Structure of ATP.

Respiration takes place in cytoplasm and mitochondria. Mitochondria have: ∑ an outer membrane that encloses the entire structure ∑ an inner membrane that encloses a fluid-filled matrix ∑ between the two is the intermembrane space. ∑ the inner membrane is elaborately folded with shelflike caristae projecting into the matrix. ∑ a small number (some 5-10) circular molecules of DNA The Outer Membrane The outer membrane contains many complexes of integral membrane proteins that form channels through which a variety of molecules and ions move in and out of the mitochondrion. The Inner Membrane The inner membrane contains 5 complexes of integral membrane proteins: ∑ ∑ ∑ ∑ ∑

NADH dehydrogenase (complex I) succinate dehydrogenase (complex II) cytochrome c reductase (complex III; also known as the cytochrome b-c1 complex) cytochrome c oxidase (Complex IV) ATP synthase (Complex V)

The Matrix The matrix contains a complex mixture of soluble enzymes that catalyze the respiration of pyruvic acid and other small organic molecules.

THE RESPIRATORY SYSTEM 415 Cellular respiration has three main stages: 1. Glycolysis / EMP pathway / Embden Meyerhof and Parnas Pathway 2. The citric acid cycle / Kreb’s cycle/TCA or Tricarboxylic acid cycle 3. Terminal Oxidation Electron transport / ETC Oxidative Phosphorylation

1. Glycolysis or EMP Pathway ∑ Three scientists namely Embden, Meyerhof and Parnas worked out glycolysis and thus named EMP Pathway. ∑ This phase consists of series of chemical reactions taking place in cytoplasm of the cell with the help of various enzymes. ∑ To carry out these reaction, no oxygen is required ∑ That is why it is called as anaerobic phase ∑ In this process, glucose which is a six-carbon compound undergoes series of chemical reactions and finally degraded to two molecules of 3-carbon compound pyruvic acid. ∑ In these reactions various enzymes are used. ∑ Whole process of glycolysis of one molecule of glucose finally leads to the formation of 8 ATP molecules. Degradation of glucose upto pyruvic acid formation is same in both types of respiration i.e., aerobic and anaerobic. In the presence of oxygen, 2 pyruvic acid molecules formed after glycolysis enter the Kreb’s cycle. Overall, glycolysis can be summarized as: Glucose ——> 2 Pyruvic Acid (or pyruvate) + 2 ATP + 4 hydrogens (2 NADH2) Glycolysis produces 2 direct ATP (ATP produced directly from the reactions that occur during glycolysis) and 6 indirect ATP (the 4 hydrogens produced in glycolysis will subsequently go through oxidative phosphorylation and produce 3 ATP per pair, i.e., 4 hydrogens equals 2 pair and 2 pair times 3 ATP equals 6 ATP). Thus, glycolysis produces a total of 8 ATP. Glucose Glycolysis Pyruvate CO2 Acetyl coenzyme A (2C)

6C 4C Citric Acid Cycle CO2 CO2

Coenzyme A (reduced)

O2

Fig. 11.4

5C

Coenzyme A (oxidised) ATP H 2O

Steps of respiration

416 HUMAN ANATOMY AND PHYSIOLOGY Summary of chemical reaction, steps, name of the process and enzymes is given here as under. Reaction Glucose (6C) ATP

Name of the process

Enzymes

2

Hexokinase, Mg +

(1) PHOSPHORYLATION

ADP Glucose-6-phosphate (6C) Phosphohexose isomerase

(2) ISOMERISATION

Fructose-6-phosphate (6C) (3) PHOSPHORYLATION ATP Fructo ADP Phospho kinase, Mg2+ Fructose1, 6-phosphate (6C) (4) SPLITTING

Aldolase Phospho Trose phosphate Triose phosphate (Dihydroxyacetone (3-phosphate glyceraldehyde) phosphate) (3C) (3C) Triose + isomerase NAD

(5) DEHYDROGENATION AND PHOSPHORYLATION

NADH + H+ Triose phosphate dehydrogenase 2 ´ 3 Triose phosphate (1, 3-bisphosphoglyceric acid) (3C)

(6) DEPHOSPHORYLATION

ADP Phosphoglycerate kinase ATP

(7) ISOMERISATION

2 ´ Triose phosphate (3-phosphoglyceric acid) (3C) Phosphoglyceromutase H 2O 2 ´ 2-phosphoglycerate Enolase, Mg2+

(8) DEHYDRATION H 2O

2 ´ PEP (Phosphoenol pyruvate) ADP Pyruvate kinase, Mg2+, K+

(9) DEPHOSPHORYLATION ATP

2 ´ Pyruvic acid (3C)

Fig. 11.5 Schematic representation of glycolysis. In the whole process 4 ATPs are created, but 2 are used. 2 ATPs after deduction. 2 NADHs are also created. Net equations is C6 H12 O6 + 2NAD+ + 2ADP + 2H3 PO4 Æ 2 Pyruvates + 2NADH+ 2H+ + 2ATP

THE RESPIRATORY SYSTEM 417 Two molecules of NADH + H+ on oxidation produce 6 molecules of ATP therefore there is net gain of 8 ATPs during glycolysis. Next comes an intermediate step called oxidative decarboxylation: The 2 Pyruvic Acid are converted into 2 Acetyl CoA and this reaction produces 4 hydrogens (2 NADH2). Those hydrogens (i.e., 2 pair of hydrogens) go through oxidative phosphorylation and produce 6 more ATP. Finally, comes the Kerb’s Cycle or The Citric Aid Cycle:

2. Kreb’s Cycle or The Citric Acid Cycle ∑ It takes place inside mitochondria present in the cells in the presence of oxygen. ∑ Two molecules of pyruvic acid undergo series of chemical reactions by the action of enzymes and finally release 30 ATP molecules. ∑ Kerb’s cycle is also known as citric acid cycle or TCA cycle (Tricarboxylic acid cycle). ∑ It mainly involves oxidation of pyruvic acid by means of a cycle involving different organic acids. Thus complete oxidation of one molecule of glucose forms 38 ATP molecules. Glycolysis : 8 ATPs formed Kerb’s cycle : 30 ATPs formed Total 38 ATPs ∑ Temporary anaerobic respiration. Due to less or non availability of oxygen pyruvic acid molecules formed after glycolysis instead of entering Kreb’s cycle reduces to lactic acid. Lactic acid formation leads to muscle fatigue. This mainly occurs during the course of exercise. Glycolysis

∑ ∑ ∑ ∑ ∑ ∑ ∑

Temporary anaerobic respiration

Æ Lactic acid Glucose ææææÆ Pyruvic acid ææææææææ After relaxation when sufficient amount of oxygen is available, pyruvic acid molecules enter Kreb’s cycle. In each kreb’s cycle acetyl CoA combines with oxaloacetate to form citric acid 2 carbons (acetylCoA) + 4 carbons (oxaloacetic) = 6 carbons (citric) In each cycle the 2 acetyl carbons from acetyl CoA are oxidized to CO2 In different parts of the cycle NADH, FADH2 and ATP are generated In the conversion of succinyl CoA to succinate the compound formed is actually GTP (guanosine triphosphate) instead of ATP, but the GTP is rapidly converted to ATP This is a substrate level phosphorylation (like those in glycolysis)- the electron transport chain is not involved For two cycles yield of high energy compounds occurs and following molecules are produced: ¡ 2ATPs ¡ 6 NADHs ¡ 2 FADH2s ¡ The NADHs and FADH2s are shunted to the electron transport chain for generation of ATP

Series of chemical reactions taking place in the kreb’s cycle are shown as under:∑ The Citric Acid Cycle or Krebs Cycle begins after the two molecules of the three carbon sugar produced in glycolysis are converted to a slightly different compound (acetyl CoA).

418 HUMAN ANATOMY AND PHYSIOLOGY ∑ Through a series of intermediate steps, several compounds capable of storing “high energy” electrons are produced along with two ATP molecules. ∑ These compounds, known as nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD), are reduced in the process. ∑ These reduced forms carry “high energy” electrons to the next stage. ∑ The Citric Acid Cycle occurs only when oxygen is present but it dosen’t use oxygen directly. Pyruvic Acid (3-C) NAD+ Pyruvic dehydrogenase complex (Mg2+ TPP, Lipoic acid, transacetylase)

NADH2

CO2

CoA 1

Acetyl CoA (2-c)

CONDENSATION

oxalacetate (4-C)

10

CoA

H2 O

Syn

Citr

the

ate

ata

se

Citrate (6-C) H2O 2 DEHYDRATION

Aconitase

NADH2

2+

DEHYDROGENATION

Fe

Malate dehydrogenase

Cis aconitate H 2O

Aconitase

NAD+

2+

Fe

Malate (4-C)

9

Mn

4 NAD+ DEHYDRATION NADH2

2+

Oxalo-succinate (6-C) 5 DECARBOXYLATION

H 2O

8

Isocitrate (6-C)

Isocitric dehydrogenase

Fumarase

HYDRATION

3 HYDRATION

Decarboxylase

CO2

Fumarate (4-C)

DEHYDROGENATION

FAD 7

Succinate (4-C)

SPLITTING AND FORMATION OF ATP ATP

Succinyl thickinase

6

DEHYDROGENATION AND DECARBOXYLATION

NAD+

NADH2 Succinyl CoA (4-C)

ADP + Pi CoA

Fig. 11.6

de a (M ca -ke g rb t tra 2, oxy ogl ns TP la uta -s P, se ra u c Li c o t e ci po m ny ic p la ac lex se id )

a-Ketoglutarate (5-C) Succinate dehydrogenase

FADH2

CO2 COA

Schematic representations of Krebs cycle TCA cycle.

THE RESPIRATORY SYSTEM 419 Summary equation of krebs cycle is [Pyurvic acid + 4 NAD+ + FAD + 2H2O + 2H2O + ADP + Pi Æ 3 CO2 + 4 NADH + 4H+ + FADH2 + ATP] Overall, therefore, the Kreb’s cycle produces 24 ATP (2 direct & 22 indirect). OVERALL ATP PRODUCTION from glucose = 8 (from glycolysis) + 6 (from the hydrogens produced when the 2 pyruvic acid are converted into 2 acetyl CoA) + 24 (from the kreb’s cycle) for a GRAND TOTAL OF 38: Direct Indirect TOTAL (O.P) 2 6 8 1. Glucose ——> 2 Pyruvic Acid 2 6 8 2. 2 Pyruvic Acid ——> 2 Acetyl CoA 0 6 6 3. 2 Acetyl CoA ———> CO2 + H2O 2 22 24 Total = 38 ATPs

3. Terminal Oxidation This is the last step of aerobic respiration which involves passage of both electrons and protons of reduced coenzymes to oxygen

NADH2 / FADH2



NAD / FAD + 2H+ + 2e–

1 O2 + 2H+ + 2e– Æ H2O 2 Terminal oxidation consists of two processes namely: (i) Electron Transport (ii) Oxidative Phosphorylation.

(i) Electron Transport Energy-rich molecules, such as glucose or fatty acids, are metabolized by series of oxidation reactions ultimately yielding CO2 and water. The metabolic intermediates of these reactions donate electrons to specialized coenzymes, nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD), to the energy-rich reduced coenzymes, NADH and FADH2. These reduced coenzymes can, in turn, donate a pair of electrons to a specialized set of electron carriers, collectively called the electron transport chain (ETC). ∑ Electron Transport requires oxygen directly. ∑ The electron transport “chain” is a series of electrons carriers in the membrane of the mitochondria. ∑ Through a series of reactions, the “high energy” electrons are passed to oxygen. ∑ In the process, a gradient is formed, and ultimately ATP is produced. ∑ NADH and FADH2 from glycolysis and the Krebs cycle are sent to the electron transport chain (ETC) ¡ The ETC strips electrons and hydrogens from NADH and FADH2 and uses the energy to set up a hydrogen gradient across the inner mitochondrial membrane. ¡ The H ions flow through enzyme ATP synthase, using energy to generate ATP in the matrix.

420 HUMAN ANATOMY AND PHYSIOLOGY ETC consists of six proteins associated with inner mitochondrial membrane: 1. NAD dehydrogenase (complex I) 2. Succinate coenzyme Q reductase (complex II) 3. Coenzyme Q (CoQ) (also called ubiquinone) 4. Cytochrome bc 1 complex (complex III) 5. Cytochrome c (Cyt c) 6. Cytochrome oxidase (complex IV) NADH

2 e–

Complex I

FADH2

– 2 e

Complex II

Electrons are transferred from NADH to flavin mononucleotide (FMN) and through iron-sulfur carriers (Fe–S), to coenzyme Q (CoQ).

Fe – S Electrons from FADH2 enter the electron transport chain at a lower energy level where they are transferred to CoQ.

The electrons are transferred to cytochrome c(cyt c) and carried to complex IV.

FMN ATP Fe–S

CoQ

CoQ is a mobile carrier that transfers its electrons to cytochrome b (cyt b) in complex III.

Cyt b Fe–S

Complex III

ATP

Cyt c1 Cyt c Complex IV

The electrons are finally used to reduce O2 to H2O.

Cyt a ATP Cyt a3

2H+ + ½ O2 H 2O

Fig. 11.7 The electron transport chain.

THE RESPIRATORY SYSTEM 421

Various Steps of ETC ∑ In the 1st phase, NADH gives its H electrons to a FAD. The FAD becomes FADH2. The NADH becomes NAD+, and an ATP is built. To this phase come all of the NADH’s that have been created in earlier phases of the process. ∑ In the 2nd phase, the FADH2 gives H electrons to coenzyme Q. 2 H+s are released. To this phase come the 2 FADH2s that were created in the krebs cycle. Because 1 ATP has already been produced, the FADH2 eventually produces only 2 ATPs, & not 3 like NADH. ∑ The coenzyme Q with the Hs gives H electrons to cytochrome B. An ATP is built. ∑ The cytochrome B with the Hs gives H electrons to cytochrome C. 2 H+s are released. ∑ The cytochrome C with the Hs gives H electrons to cytochrome A. An ATP is released.. ∑ The cytochrome A with Hs gives H electrons to an oxygen, becomes water. ∑ This is the 1st time we see oxygen in the process, but without it, all the process except the glycolysis will get stuck. ∑ 10 NADH’s start transport from the beginning, therefore creating 30 ATPs. 2 FADH2 start transport from the 2nd phase, therefore creating 4 ATPs. Inner mitochondrial membrane Matrix of mitochondrion

2H+ Outer membrane of mitochondrion

2H+

NAD+ Inner membrane of mitochondrion

2e FeS

FeS

OH2

2e Q

2e Cy b

2H+

NADH+H+

2H 2H FMN

QH2

2H+

2e FeS

2e Q(?)

2H+

2e Cy C Cy C

2e Cy a-a3

½ O2 2H+ H 2O

Fig. 11.8 Mitochondrial Respiratory chain.

(ii) Oxidative Phosphorylation Oxidative phosphorylation is the production of ATP using energy derived from the transfer of electrons in an electron transport system and occurs by chemiosmosis.

422 HUMAN ANATOMY AND PHYSIOLOGY

Out side ATP

Stalk

Head

2H+

2H+ F1

Fo

Inner mitochondrial membrane

Inner membrane particle

ADP

P1

Matrix

Fig.

Fig. 11.9

ATP synthesis by F0 – F1 particles, inner membrane particles of mitochondria.

As the hydrogen ions accumulate on one side of a membrane, the concentration of hydrogen ions creates an electrochemical gradient of potential difference (voltage) across the membrane. (The fluid on the side of membrane where the protons accumulate acquires a positive charge; fluid on the opposite side of the membrane is left with a negative charge.) The energized state of membrane as a result of this charge separation is called proton motive force or PMF. ∑ Oxidative phosphorylation is the synthesis of energy rich ATP molecules with the help of energy liberated by oxidation of reduced coenzymes (NADH2, FADH2) produced during respiration. ∑ The enzyme required for their synthesis is called ATP synthatase. ∑ It is present in F1 or head piece of F0 - F1 or elementary particle. ∑ The particles are located in the inner mitochondrial membrane. ∑ The enzyme ATP synthatase becomes active in ATP formation only when there is proton gradient, having higher concentration of protons on the F0 side (outer side) as compared to F1 side (inner side). ∑ Because of the higher proton concentration outside the inner membrane, proton return to the matrix down the proton gradient. ∑ Just as a flow of water from a higher to a lower level can be utilised to turn a water wheel or a hydroelectric turbine, the energy released by the flow of protons down the gradient is utilised in synthesising ATP. ∑ The enzyme ATP synthatase synthesises ATP from ADP and inorganic phosphate using energy from the proton gradient. ∑ Transport of two electrons from NADH + H+ by the electron transport chain simultaneously transfers three pairs of protons to the outer compartment. ∑ One high energy ATP bond is produced per pair of protons returning to matrix through the inner membrane particles. ∑ Therefore, oxidation of one molecule of NADH2 produces 3 ATP molecules, while that of FADH2 forms only 2 ATP molecules, as the latter donates its electron further down the chain.

THE RESPIRATORY SYSTEM 423

ATP Yield Energy Produced from 1 Glucose Molecule Energy is reserved through ATP molecules, “the energy coin of the cell” there will be a calculation of the amount of ATP molecules produced in the process, and a general explanation on ATP. In the calculations of energy that is produced in the process we’ll not only count the amount of ATP that is produced, but also count NADH, FADH2 & GTP molecules that are produced. That is because GTP is very similar to ATP, & because NADH & FADH are used in the electron chain to produce ATP. (Every NADH produces 3 ATP molecules, & every FADH produces 2 ATP molecules.)

Glycolysis In the Glycolysis stage 4 ATP molecules are produced but 2 ATPs are used in the process so the total balance is 2 ATPs. In this stage 2 NADs become NADHs.

Krebs Cycle BEFORE the cycle 2 NADHs are created in creation of Azetile Coenzime A. IN the cycle 2 GTPs are created. 6 NADHs are created, & 2 FADH2s too.

Electron Chain Every NADH produces 3 ATPs. We have 10 NADHs therefore 30 ATPs are created. Every FADH2 produces 2 ATPs. We have 2 FADH2s therefore 4 ATPs are created.

Total Balance 2 ATP +2GTP +34 ATP : 38 ATP Glycolysis Krebs Cycle Electron Chain Total Prokaryotic cells can yield a maximum of 38 ATP molecules while eukaryotic cells can yield a maximum of 36. In eukaryotic cells, the NADH molecules produced in glycolysis pass through the mitochondrial membrane, which “costs” two ATP molecules. Table 11.1. Summary of ATP Production Direct ATPs

NADHs

FADH2s

ATPs From ETC

Total ATPs

Glycolysis

2

2

0

4

6

Decarboxylation of Pyruvate

0

2

0

6

6

Krebs Cycle

2

6

2

22

24

Total

4

10

2

32

36

424 HUMAN ANATOMY AND PHYSIOLOGY 11.5

ANAEROBIC RESPIRATION

The anaerobic respiration occurs mainly in microscopic organisms bacteria. The 1st phase of process is identical to the one in aerobic respiration the Glycolysis. After the Glycolysis, next phases in these respirations are different in different organisms. We are going to discuss two ways: the lactic & the cohelic anaerobic respirations. In lactic pathway the lactic way, after glycolysis, the Pyruvate is converted to Lactate (milk acid), & attached to this process is the conversion of NADHs to NAD+s. The main purpose of this phase is NOT producing energy. There are no ATPs produced. The purpose is to recycle the NADHs that are necessary to the Glycolysis phase. If those NADHs won’t be recycled, eventually the cell will run out of them, because they will all be “occupied”. The process of the recycling of the NADHs back to NAD+s is needed for normal function of the cell. The materials that are produced are not necessary to the cell. On contrary, they are harmful to it, therefore, they are taken out of the cell. While running oxygen supply to cell is insufficient to produce the needed amount of energy for action. To produce this energy, in anaerobic environment, the cell starts to use the lactic anaerobic respiration. The result is that there’s energy for the action of the muscle. But, the Lactate is a harmful substance for the cell, and when it is in the cell, we feel pain we call “a cram”. After the effort is over, oxygen flow again to the cell and the Lectate is moved out of it. As a result the pain goes away after a few days.

Cohelic Way In the cohelic way, pyruvate is converted to Acetaldehyde, with the release of a CO2 molecule, this substance is converted to Ethanol (Alcohol), and with it an NADH becomes an NAD+. The purpose of recycling of NADHs is that some kind of bacteria which breathe by this way are used in the process of making wine. Glucose Glycolysis (10 successive reactions)

NADH

NADH

Anaerobic conditions

NADH

2 Pyruvate Aerobic conditions

2 Ethanol + 2CO2

2CO2 Fermentation to alcohol NADH in yeast. 2 Acetyl-CoA

Citric acid cycle

Anaerobic conditions

2 Lactate Fermentation to lactate in vigorously contracting muscle, erythrocytes, some other cells, and in some microorganisms

NADH 4CO2 + 4H2O Animal, plant , and many microbial cells under aerobic conditions

Fig. 11.10

Aerobic and anaerobic respiration.

THE RESPIRATORY SYSTEM 425 11.6

RESPIRATORY ORGANS

Respiratory organs in human beings consist of: 1. Nostrils and nasal cavity 2. Nasopharynx 3. Larynx 4. Trachea 5. Bronchi 6. Bronchioles 7. Lungs 8. Alveoli 9. Pleura 10. Diaphragm 11. Intercostal muscles 12. 12 Ribs

Nostrils Pharynx Epiglottis

Larynx Trachea Bronchus

Glottis C-Shaped cartilagenous rings

Pulmonary artery Blood supply to lungs

Alveolus

Pulmonary vein

Bronchioles

Left lung Ribs

Right lung

Heart Diaphragm

Fig. 11.11

Respiratory system in man.

∑ Upper respiratory tract refers to: Nasal cavity, pharynx, and associated structures. ∑ Lower respiratory tract refers to: Larynx, trachea, bronchi, and lungs.

Nostrils and Nasal Cavity Nostrils are two nasal openings which serve like gateway of the respiratory system. The nasal cavity has one central septum that divides the whole cavity into two parts. The nasal cavity secretes mucus which helps to remove the dust particles from the air and also normalizes the air to body temperature.

426 HUMAN ANATOMY AND PHYSIOLOGY

Sinuses

Internal nares nasal cavity Hard palate Soft palate Pharynx epiglottis glottis Vocal cords larynx Trachea

Fig. 11.12

Oesophagus

Upper part of the respiratory tract.

∑ Usually air enters the respiratory system through nostrils. ∑ The nostrils then lead to open spaces in nose called the nasal passages. ∑ The nasal passages serve as a moistener, a filter, and to warm up the air before it reaches the lungs. ∑ The hairs existing within the nostrils prevent various foreign particles from entering. ∑ Different air passageways and the nasal passages are covered with a mucous membrane. ∑ Many of the cells which produce cells that make up the membrane contain cilia. ∑ Other secrete a type a sticky fluid called mucus. ∑ The mucus and cilia collect dust, bacteria, and other particles in the air. The mucus also helps in moistening the air. ∑ Under the mucous membrane there are a large number of capillaries. ∑ The blood within these capillaries helps to warm the air as it passes through the nose. The nose serves three purposes—Warms, filters and moistens the air before it reaches the lungs. Air also enters through the oral cavity, especially in people who have a mouth — breathing habit or whose nasal passages may be temporarily obstructed, as by cold. ∑ They obviously lose special advantages, if breathe through mouth. The framework of the nose consists of bone and cartilage. Two small nasal bones and extensions of maxillae form the bridge of nose, which is a bony portion. The remainder of the framework is cartilage and is a flexible portion. Connective tissue and skin cover the framework. The Sinuses are hollow spaces in bones of the head. Small openings connect them to the nasal cavity. The functions they serve are not clearly understood, but include helping to regulate the temperature and humidity of air breathed in, as well as to lighten the bone structure of the head and give resonance to the voice.

THE RESPIRATORY SYSTEM 427 The Adenoids are overgrown lymph tissue at the top of throat. When they interfere with breathing, they are generally removed. The lymph system, consisting of nodes and connecting vessels, carries fluid throughout the body. This system helps resist body infection by filtering out foreign matter, including germs, and producing cells (lymphocytes) to fight them.

Nasopharynx It is a junction between nasal cavity and larynx. It is guarded by epiglottis which closes the passage of air while swallowing food. ∑ The pharynx is common portion of the respiratory and digestive tracts. ∑ It receives air from the nasal cavity and food, drink, and air from the oral cavity. ∑ It’s continuous with the resp. tract at the larynx and with digest. tract at the esophagus. ∑ The pharynx is divided into three sections: nasopharynx, oropharynx, and laryngopharynx. ∑ The nasopharynx extends from posterior nasal apertures to the end of soft palate and is lined by respiratory epithelium. ∑ The soft palate is partition between the nasopharynx and the oral cavity. It’s primarily composed of skeletal muscle. ∑ The posterior-most portion that hangs down is the uvula. ∑ The soft palate and uvula flip up during swallowing and help prevent food/drink from entering the nasopharynx. ∑ The nasopharynx contains openings to the auditory tubes (a.k.a. the Eustachian tubes). ∑ Each auditory tube connects the pharynx to a middle ear cavity. ∑ They function to ensure that air pressure within the middle ear cavities is equal to atmospheric pressure. ∑ The nasopharynx also contains the pharyngeal tonsil. The epiglottis is flap of tissue that guards entrance to trachea, closing when anything is swallowed that should go into the esophagus and stomach. The Tonsils are lymph nodes in the wall of pharynx that often become infected. They are an unimportant part of germ-fighting system of the body. When infected, they are generally removed.

Larynx (also known as Adam’s apple) It is the voice box which is interposed to prevent entry of food material in the trachea. While swallowing this part rises and falls. Larynx contains two ligamentous folds called vocal cords. Air expelled between the vocal cords vibrates them producing sound. ∑ The larynx food and air down their correct passages. ∑ It cantains the vocal cords, which function in voice production. The larynx is a tube made up of 9 cartillages connected by membranes, ligaments. The cartilages include thyroid, cricold, epigtottis and three small, paired cartillages —(the arytenoids, cuneiforms, and corniculates. ∑ The vocal chords are two pairs of membrane that are stretched across inside of the larynx. ∑ As the air is expired, the vocal chords vibrate. ∑ Humans can control the vibrations of the vocal chords, which enables us to make sounds. ∑ Food and liquids are blocked from entering the opening of larynx by the epiglottis to prevent people from choking during swallowing. ∑ The larynx extends from fourth to sixth vertebral levels. ∑ The larynx is often divided into three sections: sublarynx, larynx, and supralarynx. It is formed by nine cartilages that are connected to each other by muscles and ligaments.

428 HUMAN ANATOMY AND PHYSIOLOGY ∑ The larynx plays an essential role in human speech. ∑ During sound production, the vocal cords close together and vibrate as air expelled from the lungs passes through them.

Trachea Trachea is about four inches long and extends from larynx to the level of fifth thoracic vertebra. It is composed of 16-20 incomplete cartilagenous rings. These cartiligenous rings ensure that trachea does not collapse even when there is very less air in it. The oesophagus is situated on the back of trachea. ∑ It divides into right and left bronchi at the level of fifth thoracic vertebra, channelling air toright or left lung. ∑ The hyaline cartilage in the tracheal wall provides support and keeps trachea from collapsing. ∑ The posterior soft tissue allows expansion of oesophagus, which is immediately posterior to the trachea. ∑ The mucous membrane that lines trachea is ciliated pseudostratified columnar epithelium similar to that in nasal cavity and nasopharynx. ∑ Goblet cells produce mucus that traps airborne particles and microorganisms, and the cilia propel mucus upward, where it is either swallowed or expelled. ∑ The trachea is a tube approximately 12 centimeters in length and 2.5 centimeters wide. ∑ Similar to the nasal passages, trachea is covered with a ciliated mucous membrane. ∑ Usually cilia move mucus and trapped foreign matter to the pharynx. ∑ After that, they leave the air passages and are normally swallowed. The respiratory system cannot deal with tobacco smoke very kindly. ∑ Smoking stops cilia from moving. Just one cigarette slows their motion for about 20 minutes. ∑ The tabacco smoke increases amount of mucus in the air passages. ∑ When smokers cough, their body is attempting to dispose of extra mucus.

Bronchi The bronchi are formed by the bilateral bifurcation of trachea. Bronchi further divide into bronchioles which end into alveoli inside the lungs. Alveoli are lined by a layer of epithelial cells and surrounded by a network of blood capillaries. Alveoli covers about area of 80 meter square when spread out. This large surface area helps in efficient exchange of gases. ∑ This part of respiratory system is also lined with ciliated cells. ∑ The bronchi enter the lungs and spread into a treelike fashion into smaller tubes called bronchial tubes. ∑ At the level of fifth thoracic vertebra, the trachea divides into right and left primary bronchi. ∑ The bronchi branch into small and small passageways until they terminate in tiny air sacs called alveoli. ∑ The cartilage and mucous membrane of the primary bronchi are similar to that in the trachea. ∑ As branching continues through the bronchial tree, the amount of hyaline cartilage in the walls decreases until it is absent in the smallest bronchioles. ∑ As the cartilage decreases, the amount of smooth muscle increases.

THE RESPIRATORY SYSTEM 429 ∑ The mucous membrane also undergoes a transition from ciliated pseudostratified columnar epithelium to simple cuboidal epithelium to simple squamous epithelium.

Bronchioles ∑ The bronchial tubes divide and subdivide. ∑ By doing this their walls become thin and have less and less cartilage. ∑ Eventually, they become a tiny group of tubes called bronchioles.

Lungs These are two spongy elastic organs formed of alveoli, bronchioles, blood-vessels etc. The right lung has three lobes and the left lung has two lobes. ∑ The two lungs, which contain all the components of bronchial tree beyond primary bronchi, occupy most of the space in thoracic cavity. ∑ The lungs are soft and spongy because there are mostly air spaces surrounded by the alveolar cells and elastic connective tissue. ∑ They are separated from each other by mediastinum, which contains the heart. ∑ The only point of attachment for each lung is at the hilum, or root, on the medial side. ∑ This is where the bronchi, blood vessels, lymphatics, and nerves enter the lungs. ∑ The lungs, together with heart lie in the thoracic cavity or chest. This is an air tight cavity that: ¡ provides a large surface area for gas exchange ¡ has moist gas exchange surface areas ¡ is associated with circulatory system to transport oxygen to the cells and pick up carbon dioxide produced by them. ∑ The right lung is divided into three lobes, or sections while the left lung is divided into two lobes. ∑ Lobes are separated by deep prominent fissures on surface of the lung. ¡ Each lobe is divided into lobules that are separated from each other by connective tissue but the separations are not visible as surface fissures. ¡ Because major blood vessels and bronchi do not cross connective tissues. Individual diseased lobules can be surgically removed. ¡ Nine lobules in the left lung and ten lobules in the right lung. ∑ The lungs occupy the entire thoracic cavity except mediastinum. The thoracic cavity is enclosed and bounded: ¡ Above by the upper ribs and tissues of neck. ¡ At the sides by ribs and intercostals muscles. ¡ At the back by ribs and vertebral column. ¡ In front by ribs, costal cartilages, and sternum. ¡ Below by the diaphragm (a strong dome-shaped sheet of skeletal muscle with a central tendon).

430 HUMAN ANATOMY AND PHYSIOLOGY

Alveoli Trachea C-Shaped cartilagenous rings Bronchus

Bronchioles

Capillary network around alveolus

Alveoli

Fig. 11.13 Diagram showing organs involved in exchange of gases i.e., alveoli and network of capillaries. ∑ The alveoli are very small air sacs that are the destination of air breathed in. ∑ The capillaries are blood vessels that are imbedded in the walls of alveoli. ∑ Blood passes through capillaries, brought to them by the pulmonary artery and taken away by the pulmonary vein. ∑ While in capillaries blood discharges carbon dioxide into the alveoli and takes up oxygen from air in the alveoli. ∑ The walls of the alveoli are made of simple squamous epithelial cells known as type I alveolar cells. ∑ Capillaries are lined by endothelium. ∑ When O2 and CO2 are exchanged they must pass through: 1. The simple squamous alveolar membrane. 2. The simple squamous capillary membrane. 3. The fused basal laminae between the two. ∑ There three structures, across which gas exchange occurs and are collectively known as the respiratory membrane. The respiratory membrane is extremely thin, which facilitates diffusion of O2 and CO2. ∑ When the cigarette smoke is inhaled, about one-third of the particles will remain within alveoli. ∑ There are too many particles in smoking or from other sources of air pollution which can damage the walls in alveoli.

THE RESPIRATORY SYSTEM 431 ∑ This causes certain tissues which reduce the working area of the respiratory surface and leads to a disease called emphysema ∑ The alveoli are designed for rapid gas exchange ∑ After branching repeatedly the bronchioles enlarge into millions of alveolar sacs ∑ This arrangement produces an enormous surface for gas exchange ∑ Each alveolus is surrounded by a net of capillaries ∑ Alveolar cells are thin squamous epithelium; endothelial cells lining capillaries are also thin ∑ The diffusion distance from gas in the alveoli to blood cells in the capillaries is very short ∑ Blood takes about 1 second to pass through the lung capillaries ∑ In this time the blood becomes nearly 100% saturated with oxygen and loses its excess CO2 ∑ Surfactants prevent alveoli from collapsing ∑ At air/water interfaces there is a high surface tension ∑ The high surface tension would cause alveoli to collapse, but this is prevented by surfactants ∑ Surfactants are detergent-like phospholipids which accumulate at the air/water interface and lower surface tension ∑ Reduced surfactant causes respiratory distress syndrome (seen in premature infants and some older persons)

Pleura Lung is covered by a double membrane known as ‘pleura’. The visceral layer of pleura is closely attached to the lungs. The free layer on thoracic wall is known as parietal layer. Between two pleural layers, there is a fluid which lubricates the surface and prevents friction between lungs and chest wall during respiration. The intrapleural pressure is important for bringing out respiratory movements. ∑ The parietal pleura covers thoracic wall, superior surface of the diaphragm, and mediastinum. ∑ It continues around the heart and between the lungs. ∑ At the hilum, the parietal pleura is continuous with visceral pleura, which covers the external surface of lungs themselves. ∑ The pleural produces pleural fluid which fills a slit-like pleural cavity between them. ∑ Pleural fluid reduces friction and helps parietal and visceral pleurae adhere to one another.

Functions of Pleura ∑ The pleura secretes a small amount of fluid that lubricates the surfaces so that they slide past one another as the lungs expand and contract. ∑ Pleurisy is an inflammation of these membranes that causes them to secrete fluid that collects in the thoracic cavity.

Diaphragm It is a large dome-shaped sheath of muscle which separates the thoracic cavity from the abdominal cavity. The contraction of diaphragm brings about it’s downward movement which decreases the intrathoracic pressure and increases the intra-abdominal pressure.

432 HUMAN ANATOMY AND PHYSIOLOGY

Intercostal Muscles There are two series of muscles situated in between the ribs (costae), one on inner side and the other on outer. The two series external intercostals and internal intercostals muscle fibres run in opposite direction. The intercostals muscles are responsible for an increase or decrease of the thoracic cavity.

Ribs The ribs are bones supporting and protecting the chest cavity. They move to a limited degree, helping the lungs to expand and contract.

11.7

PHYSIOLOGY

Respiration is typically divided into four processes: 1. Pulmonary ventilation or breathing is the movement of air into/out of the lungs. Ventilation is mechanics of breathing in and out. When you inhale, muscles in the chest wall contract, lifting the ribs and pulling them, outward. The diaphragm at this time moves downward enlarge the chest cavity. Reduced air pressure in the lungs causes air to enter the lungs. Exhaling reverses these steps. 2. External respiration is the movement of O2 from lungs to blood and CO2 from blood to lungs. 3. Internal respiration is the movement of O2 from blood to the cell interior and CO2 from the cell interior to the blood. 4. Cellular respiration is breakdown of glucose, fatty acids and amino acids that occurs in mitochondria and results in production of ATP. It requires O2 and produces CO2. This type of cellular respiration, which requires O2, is called “aerobic metabolism,” whereas breakdown of glucose that produces ATP but does not require O2 is considered “anaerobic metabolism”. These above mentioned processes are discussed here as follows:

Breathing/Pulmonary Ventilation (a) Inspiration: It is also known as inhalation. It is as a result of combined action of ribs and:diaphragm. ∑ Ribs move upward and outward by a set of muscles known as intercostal muscles thus enlarging the thoracic cavity. ∑ Diaphragm, which normally remains arched upward like a dome, towards the base of the lungs, flattens to an almost horizontal plane and thus enlarging thoracic cavity length wise. As a result there are two actions of ribs and diaphragm and thoracic cavity increases in size. It leads to decrease in pressure in the lungs as compared to atmospheric pressure. Therefore, the atmospheric air which is at a greater pressure rushes into the lungs.

THE RESPIRATORY SYSTEM 433 Trachea Muscles Ribs Bronchus

Lungs

Space for heart

Diaphragm Diaphragm depressed during inspiration

Fig. 11.14

Diagram showing role of diaphragm during breathing.

Air movement occurs when a pressure gradient exists between the air within the lung alveoli and the air in the surrounding atmosphere. There are three pressures vital for lung function. Such as: 1. Atmospheric pressure — pressure exerted by the air surrounding the body. 2. Intrapulmonary pressure — pressure exerted by the air within the alveoli. 3. Intrapleural pressure — pressure within the pleural cavity. The following is the sequence of normal inspiratory process: 1. Respiratory centers in ventral medulla oblongata become active. 2. Signals are sent down the phrenic nerve to diaphragm and down the intercostal nerves to the external intercostal muscles. 3. Diaphragm and external intercostals contract. 4. Contraction of the diaphragm lengthens the thoracic cavity top to bottom. Contraction of the external intercostals lifts the ribs and sternum increasing side-to-side and front-to-back dimensions of the thoracic cavity. 5. Volume of the thoracic cavity increases. 6. Lung volume increases. 7. Alveolar pressure decreases. Alveolar pressure is now lower than the atmospheric pressure. 8. Air flows from the atmosphere into the alveoli until alveolar P = atmospheric P. During forced inspiration other muscles are involved so as to further increase thoracic volume (and further decrease alveolar pressure). Such muscles include scalenes and sternocleidomastoids of the neck, and pectoralis minors of the chest. (b) Expiration: It is also known as exhalation. It is reverse to inspiration. It again involves the action of ribs and diaphragm. ∑ Ribs move downward and inward by the action of other set of intercostal muscles. ∑ Diaphragm moves upwards to form a dome shape thus putting pressure on lungs. As a result, there is increase in pressure in the thoracic cavity as compared to the atmospheric pressure. Lungs are therefore compressed forcing the air out into the atmosphere.

434 HUMAN ANATOMY AND PHYSIOLOGY Activity: To demonstrate the action of the diaphragm during breathing.

Inflated baloon

Deflated baloon

Rubber sheet pushed upwards

Expiration

Fig. 11.15

Rubber sheet pulled downwards

Inspiration

Apparatus to demonstrate the action of the diaphragm during breathing.

Apparatus Bell jar, rubber sheet, 2 rubber balloons. Procedure 1. Set the apparatus as shown in figure. 2. Sheet of rubber tied around the base of the bell jar represents diaphragm. 3. When this rubber sheet is pulled downward the rubber balloons are expanded because of the air rushing in through the tube at the top. 4. When rubber sheet is pushed upwards the balloons collapse again due to the air rushing out. 5. Rubber sheet explains the role of diaphragm and balloons represent the two lungs. Conclusion When diaphragm moves down, lungs get filled with air and as it moves up air is released into the atmosphere. This experiment explains the process of inspiration and expiration. Normal expiration is slightly different that. It is to passive rather than an active process, i.e., no skeletal muscles are contracting. 1. Phrenic and intercostal nerves cease firing. 2. Diaphragm and external intercostals relax. 3. The thoracic volume decreases. 4. Lung volume decreases. 5. Alveolar pressure increases. Alveolar pressure is now > atmospheric pressure. 6. Air flows from the alveoli into the atmosphere until alveolar P = atmospheric P.

External Respiration Exchange of gases in the lungs mainly take place by the process of diffusion. The concentration of oxygen is higher in the inhaled air than in the venous blood present in alveolar capillaries. Therefore, oxygen diffuses from the alveoli into the blood through the capillaries.

THE RESPIRATORY SYSTEM 435 Similarly, concentration of CO2 is more in the capillaries surrounding alveoli. As a result CO2 from capillaries diffuse from the blood vessels into the alveoli. This is how exchange of gases take place in human beings.

Internal Respiration Glycolysis or EMP Pathway: ∑ Three scientists namely Embden, Meyerhof and Parnas worked out glycolysis and thus named EMP Pathway. ∑ This phase consists of series of chemical reactions taking place in cytoplasm of the cell with the help of various enzymes. ∑ To carry out these reaction, no oxygen is required. ∑ That is why it is called as anaerobic phase. ∑ In this process, glucose which is a six-carbon compound undergoes series of chemical reactions and finally degraded to two molecules of 3-carbon compound pyruvic acid. ∑ In these reactions various enzymes are used. ∑ Whole process of glycolysis of one molecule of glucose finally leads to formation of 8 ATP molecules. Degradation of glucose upto pyruvic acid formation is same in both types of respiration i.e., aerobic and anaerobic. In the presence of oxygen, 2 pyruvic acid molecules formed after glycolysis enter the Kreb’s cycle. The body tissues need oxygen and have to get rid of carbon dioxide, so the blood carried throughout the body exchanges oxygen and carbon dioxide with the tissues of the body. Internal respiration is basically the exchange of gasses between the blood in the capillaries and the body cells. Without energy, human beings can not survive. All living things, including humans, need a constant supply of energy to stay alive. To get this energy, we must have food and a constant supply of oxygen.

Cellular Respiration In this, there is uptake of oxygen by the cells from blood where oxidation of food takes place and CO2 is released. This CO2 is released into the blood by cells. This is also a part of internal respiration. Human cellular respiration can be divided into two main phases: (i) Glycolysis (Anaerobic Phase) (ii) Kreb’s cycle (Aerobic Phase) Cellular respiration is summarized by this equation: Glucose + oxygen ææ Æ energy (ATP) + CO2 + H2O

11.8

FACTORS AFFECTING RESPIRATION

Like other physiological processes, respiration is influenced by a number of external and internal factors. The important ones are described below.

External Factors ∑ Oxygen. Oxygen is the most important factor, affecting the rate of aerobic respiration. In absence of O2 plants continue to respire anaerobically. Absence of O2 does not affect anaerobic organisms. However, aerobes fail to survive longer under anaerobic conditions, due to accumulation of toxic alcohol and carbon dioxide.

436 HUMAN ANATOMY AND PHYSIOLOGY ∑ Carbon Dioxide. The concentration of carbon dioxide in the atmosphere is almost constant. Therefore, it does not affect much, the rate of respiration. Under controlled conditions high concentration of carbon dioxide decreases the rate of respiration. ∑ Water. The rate of respiration is decreased, when the amount of available water is low, because the respiratory enzymes become inactive in absence of this medium. ∑ Inorganic Salts. The rate of respiration increases when tissue is transferred from water to a salt solution. The amount by which respiration is increased over normal is called ‘salt respiration’. ∑ Organic Substances. Certain organic substances such as cyanides, azides, carbon monoxide, etc, inhibit respiration, because they act as enzyme inhibitors. Small quantities of anesthetics such as chloroform, ether etc. increase the rate of respiration but in higher dozes they function as inhibitors of respiration. ∑ Injuries. Injuries enhances the rate of respiration to supply more energy for healing the injury.

Internal Factors ∑ Protoplasmic Factors. The rate of respiration is influenced by the amount and state of protoplasm. Young growing cells show higher rate of respiration than the mature cells. Dormant tissues have very low rate of respiration. ∑ Respiratory Substrate. Within limit, the rate of respiration shows a linear relation with the concentration of available respiratory subtrates, particularly sugars.

11.9

LUNG VOLUMES AND CAPACITIES

Respiratory Volumes. These can be studied by an instrument called spirometer. Following table mentions various respiratory volumes: Table 11.2 Terms

Definition

Normal values

Tidal volume

The volume of air taken in or given out during normal quiet breathing

500 ml

Inspiratory reserve volume

The volume of air that can be taken in by forced inspiration, over and above the tidal volume.

2000 ml to 3300 ml

Expiratory reserve volume

The volume of air that can be breathed out by forced expiration over and above after normal expiration.

1000 ml

Vital capacity

The volume of air that can be breathed out by forced expiration after taking forced inspiration.

4330 ml in males 3100 ml in females

Maximum breathing capacity

The volume of air that one can breathe with maximum efforts in one minute time.

80-160 litres in males 60-120 liters in females

Residual volume

The volume of air which remains in the lungs after maximum Expiration.

1200 ml

Total lung capacity

The volume of air in the lungs after maximum inspiration.

5000 ml to 6000 ml.

THE RESPIRATORY SYSTEM 437

6,000

Lung volume (milliliters)

5,000

Forced Inhalation volume

Vital capacity

4,000 3,000 2,000 1,000

Total lung capacity

Tidal volume

Forced exhalation volume Residual volume

0 time

Fig. 11.16

Various lung volumes.

Lung Volumes ∑ Tidal Volume (TV) - Volume of air moved in or out of the lungs during quiet breathing — about 500 mL. ∑ Inspiratory Reserve Volume (IRV) - Volume that can be inhaled during forced breathing in addition to tidal volume - 3000 mL. ∑ Expiratory Reserve Volume (ERV) - Volume that can be exhaled during forced breathing, in addition to tidal volume - 1100 mL. ∑ Residual Volume (RV) - Volume that remains in the lungs at all times - 1200 mL. ∑ Respiratory Minute Volume (RMV) - RMV can be obtained by multiplying tidal volume by respiratory rate per minute and is approximately equal to 500 ml ¥ 12 = 6 litres/minute. The value of course may vary widely and is increased considerably during exercise when both the tidal volume as well as respiratory rate are increased.

Dead Space ∑ Only the air in the alveoli can exchange O2 and CO2 with the blood ∑ When you breath in the first 150 mL fills tubes which are outside the alveoli (trachea, bronchi, bronchioles, etc.) ∑ This part of the tidal volume is called anatomical dead space- it does not participate in gas exchange ∑ There is also a functional dead space- not all of the alveoli are perfused with blood; air in these alveoli doesn’t exchange with the blood and is part of dead space ∑ The amount of air reaching the alveoli with each breath is the tidal volume minus dead space. Suppose you have a TV of 500 mL and a dead space of 150 mL: Air to alveoli = tidal volume – dead space Air to alveoli = 500 ml – 150 ml = 350 ml ∑ To get the alveolar ventilation multiply this number by the breathing frequency.

438 HUMAN ANATOMY AND PHYSIOLOGY Suppose you are breathing at a rate of 15 breaths/min Alveolar ventilation = Frequency ¥ (TV - dead space) Alveolar ventilation = 15 breaths/min ¥ 350 ml/breath = 5250 ml/min

Lung Capacities ∑ Inspiratory Capacity (IC). Maximum volume of air that can be inspired from the end expiratory position, i.e., TV + IRV. It is about 2.5 to 3.0 litres. ∑ Functional Residual Capacity (FRC). Volume of air remaining in the lungs after a quiet expiration RV + ERV. It is about 2.5 litres. ∑ Total Lung Capacity (TLC). Volume of air that the lung can hold after a maximum possible inspiration, i.e., IC + FRC. It is about 5.0-6.0 litres. ∑ Vital Capacity (VC). It is the volume of air that can be breathed out by maximal expiratory effort after a maximum inspiration. By definition it amounts to IC + ERV. It is about 3.5 + 1 litres = 4.5 litres. The exact amount of vital capacity depends upon age, sex and size of the individual. It also shows a racial variation. Best correlation is obtained between height in cms and vital capacity. Thus predicted vital capacity in adult male = height in cms ¥ 20 ml and in females height in cms ¥ 16 ml.

11.10

RESPIRATORY QUOTIENT

The ratio of volume of carbon dioxide produced to the volume of oxygen consumed in respiration over a period of time is called Respiratory quotient (RQ).

RQ =

Volume of CO2 evolved Volume of O 2 absorbed

RQ is determined with the help of apparatus called respirometer. The value of RQ varies with different substrates utilised in respiration. Its value can be 1, 0, more than 1 or less than 1. The value of RQ is equal to 1 or unity, if carbohydrates are respiratory substrate and the respiration is aerobic.

Æ 6CO2 + 6H2 O RQ = 6CO2/6O2 = 1 C6 H12 O6 + 6O2 ææ The value of RQ is less than one when the respiratory substrate is either fat or protein and the respiration is aerobic. RQ is about 0.7 for fats during germination of fatty seeds. Æ 102CO2 + 98H2 O RQ = 102CO2/145O2 = 0.7 2C51 H98 O6 + 145O2 ææ Tripalmitin

RQ is about 0.85 for proteins.

11.11

TRANSPORT OF OXYGEN

Oxygen carried in blood is: ∑ bound to haemoglobin (98.5% of all oxygen in the blood) ∑ dissolved in the plasma (1.5%).

THE RESPIRATORY SYSTEM 439 Oxygen is relatively insoluble in blood plasma; only about 0.3 mL of O2 will dissolve in 100 mL of plasma, at normal atmospheric pressure. ∑ Haemoglobin is the respiratory pigment of humans. ∑ Haemoglobin is made up of four subunits each of which comprises a heme unit and a polypeptide chain. ∑ The heme unit consists of a porphyrin ring with one atom of iron (Fe) at its center.

- The Fe in each heme unit can unite with one molecule of O2, thus each hemoglobin molecule can carry four molecules of O2. - The O2 molecules are added one at a time: ∑ Hb4 + O2 Hb4O2 ∑ Hb4O2 + O2 Hb4O4 ∑ Hb4O4 + O2 Hb4O6

∑ ∑ ∑



∑ Hb4O6 + O2 Hb4O8 - The combination of the first subunit of Hb with O2 increases the affinity of the second and oxygenation of the second increases the affinity of the third, etc. The amount of oxygen that can bind with haemoglobin is determined by oxygen tension or partial pressure of oxygen (PO2). The saturation level of haemoglobin in relation to PO2 of blood is expressed in the form of oxygen dissociation curve. This curve is sigmoid in shape. As blood passes through the lungs, oxygen concentration increases and more oxyhaemoglobin is formed which shifts the oxygen dissociation curve to the left. When blood reaches the tissue capillaries, carbon dioxide concentration increases which favours dissociation of oxyhaemoglobin to deoxyhaemoglobin and molecular oxygen.  Hb4 + 4O2 Hb4 O8 

Percentage of saturation of haemoglobin

Oxygen diffuses into tissue and carbon dioxide enters the blood from the tissue, which shifts the curve to right side. This indicates that the presence of carbon dioxide in blood, lowers the 95% saturated

100 90 80 70

70% saturated

60 50 40 30

95 mm. of Hg

20 10

0 10 20 30 40 50 60 70 80 90 100

Oxygen pressure in m.m. of mercury

Fig. 11.17

Oxygen haemoglobin dissociation curve.

440 HUMAN ANATOMY AND PHYSIOLOGY affinity of haemoglobin for oxygen resulting in its less percentage saturation. This is called Bohr's effect. Certain other factors like increased temperature and decrease in pH affect the oxygen binding with haemoglobin and oxygen dissociation curve shifts to the right.

Percentage saturation with oxygen

g

fH

100

.o

90

O2

20

m m.

PC

80

O2

70

40

PC

. .m

m

O2

70

of

Hg g

fH

.o

m m.

PC

60 50 40 30 20 10 0

10 20 30 40 50 60 70 80 90 100

PO2 in m.m. of Hg

Fig. 11.18

11.12

Oxygen dissociation curve showing Bohr’s effect.

TRANSPORT OF CARBON DIOXIDE

CO2 transports blood in three major ways. It is transported from the body cells back to the lungs as: 1. Bicarbonate (HCO3) — 60% It is formed when CO2 (released by cells making ATP) combines with H2O (due to enzyme in red blood cells called carbonic anhydrase). ∑ CO2 is regularly produced by cells and is diffused in the blood. If entire CO2 remains in blood as carbonic acid then survival is difficult. ∑ Therefore only 10% of the total CO2 produced, remains as carbonic acid and rest of the carbon dioxide forms bicarbonates in blood plasma and blood cells. ∑ The erythrocytes or Red Blood Corpuscles (RBC) contain haemoglobin, protein and potassium chloride. The following reaction takes place. K + HB - H + (HCO 3 ) ææ Æ KHCO 3 + HHb Potassium salt

Carbonic acid

Potassium bicarbonate

Haemoglobinic acid

∑ This reaction takes place in presence of carbonic anhydrase enzyme found in blood. ∑ The carbonic acid performs following reaction with sodium protein of blood plasma -

Na+ +

Sodium

Pr +

Plasma protein

+ H+ ÈÎHCO-3 ˘˚ = HPr + Carbonic acid

NaHCO3 Sodium bicarbonate

∑ The carbonic acid is then buffered by intracellular potassium haemoglobinate (K.Hb) resulting in the formation of potassium bicarbonate (KHCO3) and haemoglobinic acid H.Hb).

(

)

∑ Under normal conditions the walls of red cells are permeable to anions CI– , HCO –3 but im+

+

permeable to cations (Na , K ) and to the large haemoglobin molecule.

THE RESPIRATORY SYSTEM 441 ∑ Under these circumstances chloride ions diffuse into the blood cells from the plasma and react with intracellular potassium bicarbonate (KHCO3) forming potassium chloride (KCI) and releasing bicarbonate ions HCO -3 . ∑ The bicarbonate ions thus released, now diffuse out of the red blood cells into the plasma and combine with sodium ions to form sodium bicarbonate (NaHCO3). ∑ Thus, carbon dioxide is carried from tissues to lungs in the form of KHCO3 (through erythrocytes) and NaHCO3 (through plasma).

(

)

Erythrocytes Plasma 67% CO2

CO2 + H2O = H2CO3 KHb + H2O3 = KHCO3 + HHb

NaCl

Carbonic Anhydrase Cl– + KHCO3 = KCl + HCO–3

Chloride Na

+

Cl



HCO

Shift – 3

Na+ + HCO–3 = NaHCO3

Fig. 11.19

Formation of bicarbonates and chloride shift.

(

)

∑ The movement of bicarbonate ions HCO –3 from erythrocytes to plasma initiates diffusion of –

2. ∑

∑ ∑ ∑

chloride ions (CI ) from plasma into the erythrocytes to maintain ionic balance. Thus, electrochemical neutrality is maintained. This is called chloride shift. Carbaminohaemoglobin — 30% formed when CO2 combines with haemoglobin (haemoglobin molecules that have given up their oxygen) Blood proteins that bind to CO2 are called carbamino compounds. The most abundant protein bound to CO2 is haemoglobin and when CO2 is bound to haemoglobin, the combination is called carbaminohaemoglobin. The CO2 binds to globin and each globin molecule can combine with a single CO2 molecule. Haemoglobin that has released its O2 binds more readily to CO2 than haemoglobin that has O2 bound to it. This is called Haldane effect.

o In tissues, after haemoglobin has released O2, the haemoglobin has an increased ability to pick up CO2. o In the lungs, as haemoglobin binds to O2, the haemoglobin more readily releases CO2. 3. Dissolved in the plasma — 10% ∑ CO2 combines with water of plasma, forming carbonic acid.  H2 CO3 CO2 + H2 O 

Carbonic acid

442 HUMAN ANATOMY AND PHYSIOLOGY 11.13

CONTROL OF RESPIRATION IS NERVOUS AND CHEMICAL

Nervous Control ∑ The respiratory centre is gray matter in the pons and upper Medulla, which is responsible for rhythmic respiration. ∑ This centre can be divided into an inspiratory centre and an expiratory centre in the Medulla, an apneustic center in lower and midpons and a pneumotaxic center in the rostral-most part of the pons. ∑ This respiratory centre is very sensitive to pCO2 in arteries and to the pH level of blood. ∑ The CO2 can be brought back to the lungs in three different ways; dissolved in plasma, as carboxyhaemoglobin, or as carbonic acid. ∑ That particular form of acid is almost broken down immediately by carbonic hydrase into bicarbonate and hydrogen ions. ∑ This process is then reversed in the lungs so that water and carbon dioxide are exhaled. ∑ The Medulla Oblongata reacts to both CO2 and pH levels which triggers the breathing process so that more oxygen can enter the body to replace oxygen that has been utilized. ∑ The Medulla Oblongata sends neural impulses down through the spinal cord into the diaphragm. ∑ The impulse contracts down to the floor of chest cavity, and at the same time there is a message sent to the chest muscles to expand, causing a partial vacuum to be formed in the lungs. ∑ The partial vacuum will draw air into the lungs.

Chemical Control Certain chemical agents like CO2, O2 and acidity etc., stimulate the respiratory centre located in medulla oblongata (brain). Stimuli that control respiration can broadly be classified as either chemical or behavioral. Scientifically, the mechanisms of chemical control are more completely understood than their behavioral counterparts. Chemical control has evolved to meet the following general needs: 1. to remove carbon dioxide from the body 2. to insure supply of oxygen for tissue metabolism 3. to help maintain acid-base balance of the body (a) Effect of CO2. The inspiratory centre is sensitive to carbon dioxide concentration within the blood. Excess of CO2 in blood stimulates respiratory centres directly and increases the rate and depth of respiration. During exercises or