insights in physiology 2012

Insights in Insights in Insights in Insights in Insights in PhysiologyPhysiologyPhysiologyPhysiologyPhysiology

Sudha Vinayak Khanorkar MBBS MD (Physiology)Associate Professor (Retd)Department of Physiology

Indira Gandhi Medical CollegeNagpur, Maharashtra, India

Insights in Insights in Insights in Insights in Insights in PhysiologyPhysiologyPhysiologyPhysiologyPhysiology

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Publisher: Jitendar P VijPublishing Director: Tarun DunejaCover Design: Seema Dogra

Insights in Physiology

First Edition: 2012

ISBN: 978-93-5025-516-2

Printed at

Dedicated to

My son Shantanu

who was killed

in an air crash in 2000,

while the writing of the book

was going on

Preface

On popular demand from students, the effort was made to consolidate my lecturenotes in the form of a book.

The book is useful for students as well as teachers. The teachers may find somelectures lengthy and some short. This is to keep information regarding one subjectcompact. The two short lectures may be combined together and lengthy lecturesmay be split into two.

Utmost effort has been made to avoid mistakes; if some have crept in inadvertentlythe author will be glad to correct them.

The author can be contacted at [email protected]

Sudha Vinayak Khanorkar

Acknowledgments

I am grateful to my students, undergraduates as well as postgraduates for theircontinuous demand, which inspired me to undertake the work of compiling mylecture notes in the form of a book.

My thanks are due to my children Dr Sonali and late Shantanu and son-in-lawDr Deepak, who gave me their invaluable support. My grandchildren Anuradhaand Ajinkya motivated me to go on.

My friends encouraged me to complete the work. I thank them immensely.Mr Janardan K Iyer and Mr Ritesh Parmar from Shree Govind Computers, Bopal,

Ahmedabad, Gujarat, India did the computer work for me. My thanks are due tothem.

Lastly, I am thankful to the publishers, M/s Jaypee Brothers Medical Publishers(P) Ltd. without their support the book would not have seen the light of the day.

Contents

SECTION I: GENERAL PHYSIOLOGY

1. Introduction to Physiology ........................................................................................................................ 1Physiological Processes 1Outline of Human Physiology 2

2. Internal Environment Homeostasis and Feedback Mechanisms ...................................................... 5Internal Environment Homeostasis 5Feedback Mechanisms 7

3. Body Fluid Compartments, Extracellular Fluid and Intracellular Fluid.......................................... 9Daily Intake of Water 9Daily Loss of Body Water 9Body Fluid Compartments 10Total Body Water 12

4. Formation of Interstitial Fluid and Lymph .......................................................................................... 14Formation of Interstitial Fluid 14Formation of Lymph 15

5. Cell Membrane and Principles of Biological TransportAcross Cell Membrane ..................... 17Cell Membrane 17Principles of Biological Transport 19

6. Bioelectricity ............................................................................................................................................... 24Membrane Potential at Rest and during Activity 24Genesis of Resting Membrane Potential (RMP) 25

7. Intercellular Communications and Genetics ....................................................................................... 30Chemical Messengers 31Mechanisms by which Chemical Messengers Act 31Second Messengers and Mechanism of Actions of Second Messengers 31Receptor Diseases 32Molecular Basis of the Genes 32Alleles 34

SECTION II: HEMATOLOGY

8. Composition and Function of Blood and Plasma Proteins ............................................................... 37Blood 37Plasma Proteins 39

9. Erythrocytes, Erythropoiesis, Fate and Functions of RBC ................................................................ 43Erythrocytes 43Functions of RBC 45Erythropoiesis 45

xii Insights in Physiology

10. Hemoglobin and Anemias ....................................................................................................................... 50Hemoglobin 50Anemias 54

11. White Blood Corpuscles or Leukocytes ................................................................................................ 58White Blood Corpuscles 58Types of Leukocytes 58Inhibitory Factors 64Granulopoiesis 64

12. Immunity ..................................................................................................................................................... 67Innate Immunity 67Acquired Immunity 68Humoral Immunity 69Cell Mediated Immunity 70Autoimmunization 75AIDS 76

13. Platelets (Thrombocytes) and Coagulation ......................................................................................... 77Platelets 77Coagulation 79Bleeding Disorders 83

14. Blood Group ................................................................................................................................................ 87Sites 87Blood Group Antibodies or Agglutinins 87Classical ABO Blood Groups 88Rhesus (Rh) Blood Groups 89M and N Blood Groups 91

SECTION III: NERVE AND MUSCLE PHYSIOLOGY

15. Structure and Classification of Nerves ................................................................................................. 93Dendrites 93Axon 93Cell Body or Soma 94Nerve Fibers 94

16. Effect of Injury to Peripheral NervesDegeneration and Regeneration ..................................... 97Degenerative Changes in the Nerve Cell Body 97Degenerative Changes in Nerve Fiber 98Further Degenerative Changes 98Regenerative Changes 99

17. Properties of Nerve Fiber ....................................................................................................................... 100Excitability or Irritability 100Conductivity 101Antidromic Activity and Orthodromic Conduction 102Refractory Period 102Summation 102Adaptation or Accommodation 102Infatiguability 103All or None Phenomenon 103

Contents xiii

18. Neuromuscular Transmission ............................................................................................................... 104Electron Microscope Appearance 104Characteristic Features of Neuromuscular Junction 104Synthesis and Storage of Acetylcholine 105Fatigue at Neuromuscular Junction 107

19. Classification of Muscle and Structure of Skeletal Muscle ............................................................ 110Classification of Muscle 110Structure of Skeletal Muscle 110Types of Muscle Fibers 111

20. Mechanism of Contraction ..................................................................................................................... 116Sliding Filament Mechanism 116Excitation Contraction Coupling 118

21. Characteristics of Muscle Contraction ................................................................................................ 120Motor Unit and Its Properties 120Types of Contraction 121Energy for Muscle Contraction 124Oxygen Debt 124Heat Production in Muscle 125

22. Properties of Skeletal Muscle................................................................................................................ 126Excitability and Contractility 126Conductivity 132Tonicity 132Refractory Period 132

23. Physiology of Smooth Muscle .............................................................................................................. 133Functional Anatomy 133Mechanical Properties 135Nerve Supply to Smooth Muscle 136Excitatory Junctional Potential (EJP) 137Denervation Hypersensitivity 137Cause 137

SECTION IV: DIGESTIVE SYSTEM

24. Physiological Anatomy and Innervations of Digestive System .................................................... 139General Plan and Activities of Alimentary Canal 139Mucous Coat 140Main Functions of Alimentary Canal 143Functions of Different Sections of Alimentary Canal 143

25. Movements of Digestive System .......................................................................................................... 144Mastication and Deglutition 144Movements of Stomach 146Movements of the Pylorus 146Cause of Movements 147Movements of Small Intestine 148Law of Intestine 148Movements of Large Intestine 149

xiv Insights in Physiology

26. Salivary and Gastric Secretion .............................................................................................................. 151Salivary Secretion 151Gastric Secretion 155

27. Composition of Gastric Secretion and Mechanism of Gastric Acid Secretion .......................... 158Composition of Gastric Juice 158Mechanism of Gastric Acid Secretion 158Gastric Function Tests 161

28. Functions of Liver .................................................................................................................................... 164Liver Function Tests 167

29. Secretion of Bile, Pancreatic Juice and Succus Entericus ................................................................ 170Secretion of Bile 170Pancreatic Juice 172Succus Entericus 176

30. Large Intestine and Absorption in GI Tract ....................................................................................... 178Large Intestine 178Absorption in GIT 180

31. Nutrition and Balanced Diet ................................................................................................................. 185Nutrition 185Balanced Diet 196

SECTION V: RESPIRATORY SYSTEM

32. Physiological Anatomy and Composition of Air .............................................................................. 197Respiratory Tract 197Blood Supply 199Alveolar Surface Tension 200Composition of Inspired, Expired and Alveolar Air 200

33. Mechanics of Respiration ....................................................................................................................... 202Inspiration and Expiration 202Intrapleural Pressure (Intrathoracic Pressure) 205Compliance 206Surfactant 207Airway Resistance 208

34. Pulmonary Volumes and Capacities/Pulmonary Function Tests .................................................. 209Pulmonary Volumes 209Pulmonary Capacities 210Pulmonary Function Tests for Diffusion 216

35. Oxygen Carriage ....................................................................................................................................... 217LungsDiffusion of Oxygen 217Oxygen Transport in Blood 219In the TissuesOxygen Transfer 220Factors Affecting Oxygen Transfer or Oxygen Dissociation 220

36. Carbon Dioxide Carriage........................................................................................................................ 222Transfer of Carbon Dioxide from Tissues to Blood 222Carbon Dioxide Transport 222Dissolved Carbon Dioxide 223

Contents xv

Carbon Dioxide Transport as Bicarbonates 223Carbon Dioxide Transport as Carbamino Compounds 224Carbon Dioxide Dissociation Curve 224Mechanism of Haldane Effect 226

37. Regulation of Respiration ...................................................................................................................... 227Neural Control of Breathing 227Higher Neural Influences 229Chemical Regulation of Respiration 231Peripheral Chemoreceptors 232

38. Hypoxia and Acclimatization to High Altitude ................................................................................ 234Hypoxia 234Acclimatization 238

39. Abnormal States of Respiration ........................................................................................................... 240Hyperpnea (Hyperventilation)Increased Breathing 240Dyspnea 241Orthopnea 241Apnea 241Asphyxia 243Decompression Sickness (Caissons Disease, the Bends) or Dysbarism 244Cyanosis 245Hypercapnia 246

SECTION VI: CARDIOVASCULAR SYSTEM

40. General Considerations .......................................................................................................................... 247Functions of the Heart 248Pressure Gradients in Systemic Circulation 248Resistance to the Flow (R) 249Pressure at the Input Side of the Heart (P2) 249Vis a Fronte 251Blood Vessels 251

41. Structure and Properties of Heart Muscle .......................................................................................... 253Structure of Heart Muscle 253Properties of Heart Muscle 257

42. Origin and Spread of Cardiac Impulse ............................................................................................... 259Cardiac Excitation 259Action Potential 260Conduction of Cardiac Impulse 262

43. Cardiac Cycle ............................................................................................................................................ 263Duration of Cardiac Cycle or Cardiac Cycle Time 263Phases of Cardiac Cycle 263Atrial Events 263Ventricular Events 264Fundamental Rule 266Important Feature of Ventricular Systole 266Important Feature of Ventricular Diastole 266

xvi Insights in Physiology

44. Pressure Changes in Heart and Blood Vessels During Cardiac Cycle ......................................... 267Ventricular Pressure Changes 268Intra-atrial Pressure Changes 268Intra-aortic Pressure Changes 269Jugular Pressure (Pulse) Tracing or Jugular Venous Pressure (JVP) Changes 270

45. Heart Sounds, Pulse, and Radial Pulse Tracing ................................................................................ 272Heart Sounds 272Pulse 276Radial Pulse Tracings 277

46. Cardiac InnervationHeart Rate and Its Regulation ...................................................................... 279Vagus 279Cardiac Sympathetic Nerves 280Heart Rate 281Regulation of Heart Rate 282Summary of Factors Influencing Heart Rate 286

47. Cardiac Output ......................................................................................................................................... 288Cardiac Index 288Venous Return 289Force of the Heartbeat 290Frequency of Heartbeat(Heart Rate) 291Peripheral Resistance 291

48. Methods of Measuring Cardiac Output and Summary of FactorsInfluencing Cardiac Output .................................................................................................................. 292In Animals 292In Men 293Measurement of Cardiac Output by Direct Application of Fick Principle 293Summary of Factors Influencing Cardiac Output 296

49. Physiology of Blood Vessels and Hemodynamics ........................................................................... 298Structural Features of Components of Blood Vessels (Vascular Tree) 298Vasodilatation 299Hemodynamics or Dynamics of Flow of Blood 300Law of Laplace 304

50. Peripheral Resistance .............................................................................................................................. 306Velocity of Blood Flow 306Viscosity of Blood 306Elasticity of Blood Vessel 308Lumen of Blood Vessel 308Effect of Vessel Length 308Control of Peripheral Resistance 308Local Mechanisms 308Input from the Periphery 310Input from Higher Centers 312

51. Blood Pressure .......................................................................................................................................... 313In Animals 313In Men 313Cause of the Sounds 314

Contents xvii

Normal Blood Pressure 316Functional Significance (Importance) of Blood Pressure 316Physiological Variation of Blood Pressure 316

52. Factors Determining Arterial Pressure and Regulation of Blood Pressure ................................. 318Factors Determining Arterial Pressure 318Regulation of Arterial Blood Pressure 318

53. Electrocardiogram (ECG) ........................................................................................................................ 323Recording Apparatus 323Leads 326Cardiac Vector or Cardiac Axis 328Heart Block 330

54. Coronary Circulation ............................................................................................................................... 334AnatomyRight and Left Coronary Arteries 334Cardiac Veins 335In Animals 337

55. Regional Circulation ............................................................................................................................... 342Cerebral Circulation 342Blood-brain Barrier 344Determination of Cerebral Blood Flow 344

56. Pulmonary Circulation ........................................................................................................................... 348Anatomical Considerations 348Functions of Pulmonary Circulation 350

57. Capillary Circulation ............................................................................................................................... 353Structure of Capillary 353Regulation of Vasomotion 354Transcapillary Exchange 354Diffusion 354Micropinocytosis 355Filtration and Reabsorption 355Edema 357

58. Cutaneous Circulation ............................................................................................................................ 358Physiological Anatomy 358Regulation of Blood Flow in the Skin 359Effect of Cold on Skin Circulation 359Conditions Affecting Skin Blood Flow 360Vascular Responses of Skin 360Causes 360

59. Syncope, Cardiogenic Shock, Causes and Effects of Shock on the Body .................................... 362Syncope 362Cardiogenic Shock 363Causes and Effects of Shock on Body 363

60. Cardiovascular Adaptations to Various Grades of Exercise ........................................................... 365Varieties of Exercise 365Grading of Exercise 366Cardiovascular Adjustments 366Renal and Splanchnic Blood Flow 368Pulmonary Blood Flow 368

xviii Insights in Physiology

Cerebral Blood Flow 368Effect of Training on Cardiovascular Function 368

SECTION VII: EXCRETORY SYSTEM

61. Physiological Anatomy ........................................................................................................................... 371Kidney 372Ureters 376Bladder 377

62. Glomerular Filtration, Tubular Reabsorption and Secretion ........................................................ 378Glomerular Filtration 378Tubular Reabsorption and Secretion 380

63. The Proximal Tubule .............................................................................................................................. 383Sodium Reabsorption 383Glucose Transport (Reabsorption) 385Amino Acid Transport 385Reabsorption of Bicarbonates 385Phosphate Reabsorption 386Chloride Reabsorption 386Potassium Reabsorption 387Water Reabsorption 387Loop of Henle 388Distal Tubule 388

64. Concentrating and Diluting Mechanism of the Kidney (Countercurrent Mechanism) ........... 391Cause of Medullary Osmotic Gradient 392Maintenance of Medullary Osmolarity Gradient 392Countercurrent Multiplier of Loop of Henle 393Mechanism of Excreting Dilute Urine 394

65. Role of Kidney in Acid-base Balance .................................................................................................. 396H+ Secretion 396Fate of H+ in the Urine 397

66. Micturition ................................................................................................................................................ 401Physiological Anatomy of Bladder and Its Nervous Connections 401Nerve Supply of Bladder and Urethra 402Functions of Afferent and Efferent Fibers 403Transport of Urine through Ureters 403Mechanism of Filling of Bladder 403

67. Renal Function Tests ............................................................................................................................... 407Tests for Renal Structural Integrity 407Test for Glomerular Functional Integrity 407Tests for Tubular Functional Integrity 410

SECTION VIII: TEMPERATURE REGULATION

68. Body Temperature and Heat Balance of the Body ............................................................................ 411Body Temperature 411Heat Balance of the Body 412

Contents xix

Reduction of Heat Loss 414Heat Loss 414

69. Thermoregulation, Fever and Hypothermia ...................................................................................... 417Thermoregulation 417Fever or Pyrexia 419Hypothermia 419

SECTION IX: ENDOCRINE SYSTEM

70. General Considerations .......................................................................................................................... 421Methods of Study 422Hormone Assays 422Regulation of Secretion of Hormone 423Modes of Action of Hormone 424

71. Endocrine Functions of Hypothalamus .............................................................................................. 427Endocrine Secretion of Hypothalamus 427Blood Supply 428

72. Pituitary Gland (Hypophysis) and Adenohypophysis (Anterior Pituitary) ............................... 431Pituitary Gland 431Adenohypophysis (Anterior Pituitary) 432

73. Posterior Pituitary (Neurohypophysis) ............................................................................................... 440Storage of Antidiuretic Hormone 440Functions of Antidiuretic Hormone (Vasopressin) 441Regulation of ADHProduction 441Diabetes Insipidus 442Oxytocin 442

74. Thyroid Gland .......................................................................................................................................... 445Physiological Anatomy of the Thyroid Gland 446Formation of Thyroid Hormones 446Metabolism of Thyroid Hormones 449Regulation of Thyroid Secretion 449Hypothalamic Control of TSH 449

75. Functions of Thyroid Hormones and Diseases of Thyroid Gland................................................ 451Functions of Thyroid Hormones 451Diseases of Thyroid Glands 454

76. Parathyroid Glands and Calcitonin ..................................................................................................... 459Parathyroid Glands 459Calcitonin 464

77. Adrenal GlandsAdrenal Cortex ........................................................................................................ 466Adrenal Cortex 466Synthesis 467Regulation of Cortisol Secretion 467Transport in the Bloodstream 467Actions of Adrenocortical Hormones 468

78. Mineralocorticoids and Disorders of Adrenocortical Function ..................................................... 472Mineralocorticoids or Salt Retaining Hormones 472Disorders of Adrenocortical Function 474

xx Insights in Physiology

79. Adrenal Medulla ...................................................................................................................................... 479Formation of Catecholamines 479Actions of Catecholamines 481

80. Pancreatic Hormones ............................................................................................................................... 486Pancreatic Functions 486Metabolic Effects 487Glucagon 489Somatostatin 490Diabetes Mellitus 490

SECTION X: REPRODUCTIVE SYSTEM

81. Female Reproductive Organs and Ovarian Cycle ............................................................................. 493Female Reproductive Organs 493Ovarian Cycle 494

82. Menstrual Cycle and Its Hormonal Control ....................................................................................... 498Different Phases of Menstrual Cycle 498Mechanism of Menstrual Bleeding 499Anovular Menstrual Cycle 500

83. Ovarian Function and Female Sex Hormones ................................................................................... 501Ovarian Function 501Female Sex Hormones 501

84. Physiology of Pregnancy and Maternal Changes during Pregnancy ........................................... 505Physiology of Pregnancy 505Maternal Changes During Pregnancy 508

85. Labor, Lactation and Methods of Family Planning .......................................................................... 510Labor or Parturition or Delivery or Childbirth 510Labor 511Lactation 512Methods of Family Planning 514

86. Male Reproductive System .................................................................................................................... 516The Accessory Glands 517Spermatogenesis 518Sertoli Cells 519Factors Regulating Spermatogenesis 519Erection and Ejaculation 520

87. Endocrine Function of Testis ................................................................................................................. 522Hormones of the Testis 522Testosterone in Females 524Bioassay of Androgens 524

SECTION XI: SPECIAL SENSES

88. Vision ......................................................................................................................................................... 527Path of Light Ray 529Receptors 529

Contents xxi

Tears 531Optical System of the Eye 531Reduced Eye 532

89. Accommodation and Optical Defects .................................................................................................. 534Accommodation 534Pupil 536Path of Light Reflex 536Optical Defects and Errors of Refraction 537

90. Physiology of Retina ............................................................................................................................... 541Photochemistry of Retina 541Light and Dark Adaptation 544Visual Acuity 545

91. Color Vision .............................................................................................................................................. 547Chromatic Series 547Achromatic Series 547Photochemistry of Color Vision 548Color Blindness and Anomalies 550

92. The Visual Path ........................................................................................................................................ 552Effects of Injury 554Various Injuries 554

93. Hearing ....................................................................................................................................................... 556Anatomy 556Functions of Muscles 557Function of Ossicles 557Internal Ear 558Elementary Physics of Sound 559Masking 560

94. Physiology of Hearing ............................................................................................................................ 561Functions of External Ear 561Functions of Tympanic Membrane 561Function of Middle Ear 561Physiology of Internal Ear 561Electrophysiology of Ear 562Auditory Pathway 565Deafness 567

95. Taste ............................................................................................................................................................ 569Significance of Taste 569Primary Taste Sensations 569The Path of Taste 572

96. Sense of Smell (Olfaction) ..................................................................................................................... 574Olfactory Mucous Membrane 574Physiology of Olfaction 576Olfactory Path or Olfactory Tract 577Abnormalities of Olfactory Sensation 578

xxii Insights in Physiology

SECTION XII: NERVOUS SYSTEM

97. Nervous System ........................................................................................................................................ 579Structural Organization 579Functional Organization of CNS 581Motor Organization 582

98. Structure and Functions of Nervous Tissue ....................................................................................... 583Cytology of Neurons 583Physiology of Neuron 584Synapse 585

99. Synaptic Transmission ........................................................................................................................... 586Sequence of Events during Synaptic Transmission 586Electrical Events during Neuronal Excitation 587Properties of Synaptic Transmission 589

100. Reflex Action ............................................................................................................................................. 591Reflex Pathway or Arc 591Properties of Reflex Action 592Reflexes of the Body 595

101. Sensations Receptors and Pain ............................................................................................................. 597Classifications of Sensations 597Pain 600Kinesthetic Sensation 602Classification and Properties 604

102. Spinal Cord ............................................................................................................................................... 606The Nerve Cells of the Spinal Cord 607Extent of Spinal Cord 608

103. Ascending or Sensory Tracts ................................................................................................................. 610Tracts 610Major Tracts 610Minor Tracts 614

104. Descending or Motor Tracts .................................................................................................................. 615Pyramidal Tract 615Extrapyramidal Tracts 617Functions 618

105. Upper Motor Neuron Lesion, Lower Motor Neuron Lesion and Internal Capsule .................. 619Lower Motor Neurons 619Upper Motor Neurons 619Effect of Upper Motor Neuron Lesion 619Internal Capsule 620

106. Lesions of Spinal CordHemisection and Complete Section ...................................................... 622Hemisection of Spinal Cord 622Effect of Complete Transverse Section of Spinal Cord 623Incomplete Transection of Spinal Cord 627

107. Brainstem ................................................................................................................................................... 628Medulla OblongataFunctions 628Pons 629Midbrain 629

Contents xxiii

108. Thalamus ................................................................................................................................................... 634The Nuclei of Thalamus 636Connections of Thalamus 637

109. Functional Significance of Thalamus .................................................................................................. 641Functions of Thalamus 641Thalamic Syndrome 643

110. Cerebellum ................................................................................................................................................ 645Cerebellar Cortex 647Cerebellar Nuclei 648Connections of Cerebellum 648

111. Functions of Cerebellum ........................................................................................................................ 651Functions of Archicerebellum 651Functions of Paleocerebellum Excluding Archicerebellum 651Functions of Neocerebellum 652Summary of Function of Cerebellum 653Result of Lesion and Tests for Cerebellar Lesion 653

112. Basal Ganglia ............................................................................................................................................ 655Corpus Striatum 656Function of Basal Ganglia 658Clinical Manifestations Associated with Disease of Basal Ganglia 659

113. Cerebral Hemisphere .............................................................................................................................. 662Subdivisions of Cerebral Hemispheres 662Fine Structure of Cerebral Cortex 664Functions of Different Layers of Cerebral Cortex 666

114. Functional Areas of Frontal Lobe ......................................................................................................... 667Excitomotor Areas 667Area 44 and 45 (Brocas Area) 669Cortical Localization 669Generalized Functions of Excitomotor Cortex 669

115. Prefrontal Lobe or Orbitofrontal Region ............................................................................................ 671Situation 671Experimental Studies 673Frontal Lobe Syndrome 674Functions of Prefrontal Lobe in Summary 674

116. Parietal, Temporal, Occipital Lobes and Dominant Hemisphere ................................................. 676Parietal Lobe 676Temporal Lobe 678Occipital Lobe 680General Interpretative Area or Wernickes Area 681Dominant Hemisphere 682

117. Conditioned Reflex and Speech ........................................................................................................... 684Conditioned Reflexes 684Speech 686Aphasias 687

xxiv Insights in Physiology

118. Cerebrospinal Fluid ................................................................................................................................. 689Choroid Plexuses 690Mechanism of Formation and Absorption 690Functions of Cerebrospinal Fluid 690

119. Learning and Memory ............................................................................................................................ 693Sites of Learning 693Intercortical Transfer of Learning 694Memory 694

120. The Limbic System .................................................................................................................................. 698Anatomical Considerations 698Limbic Functions 699

121. Hypothalamus and Emotion .................................................................................................................. 705Hypothalamus 705Emotion 710

122. Reticular Formation and Reticular Activating System .................................................................... 711Connections 711The Main Function 712Functions of Reticular Formation 713

123. Electroencephalogram (EEG) ................................................................................................................. 715Origin of Brain Waves or Neurophysiological Basis of EEG 716EEG in Various Diseases 718

124. Sleep ............................................................................................................................................................ 721Basic Theories of Sleep and Wakefulness 724Cycle between Sleep and Wakefulness 725Physiological Effects of Sleep 725

125. Muscle Tone .............................................................................................................................................. 726Decerebrate Rigidity 730

126. Posture ........................................................................................................................................................ 732Postural Reflexes 732Static Posture 732Righting Reflexes 735Dynamic Posture 735

127. Equilibrium ............................................................................................................................................... 736The Vestibular Apparatus (Labyrinth) 736Important Difference between Ampullar and Macular Receptors 741

128. Autonomic Nervous System .................................................................................................................. 742Functional Anatomy 742The Parasympathetic System 745Parasympathetic Afferents 747Effects of Autonomic Stimulation 748Functions of Autonomic Nervous System 749Chemical Transmitter in Autonomic Nervous System (ANS) 749Receptors 751

Index ................................................................................................................................................................. 753

Introduction to

Physiology

1

CHAPTER

The term physiology refers to the functioningof a living organism or its parts.

PHYSIOLOGICAL PROCESSES

In the more complex animals such as birdsand mammals the first characteristics oflife that come to mind are: (i) warmth, and(ii) movement.

By taking food and oxidizing it, the animalobtains energy, which is used to produce heatand movement. The breakdown processes inthe body known as catabolism, obtain energy.The energy obtained by these catabolicprocesses may also be used for anabolic orsynthetic processes such as those necessary forgrowth. Since, both processes occur side bysideit is convenient to use the wordmetabolism, when referring to the total chemicalchanges occurring in the cell or in the body. Solong as metabolic processes continue, however,slowly, the cell is alive. Their arrest is death.

Chemical processes are under control ofenzymes. If the temperature is too high, the cellis destroyed and at low temperature, theenzymic reactions are retarded and finally cease.

Living material is organized. That is, it has adefinite structure and a particular function.The cells and organs, whose structure ispeculiarly fitted to the functions, carry out thefunctions.

For a cell to survive, there must be inte-gration of functions within it. In multicellularorganisms, there must be coordination ofactivities of various cells. This is done bychemical messengers (hormones) or by asystem of nerves.

Growth is a characteristic feature of livingorganism. Growth of a single cell cannot goon indefinitely, because as the cell increases involume, its surface through which oxygen andnutrients are absorbed, becomes so far awayfrom the center that its supply cannot bemaintained. Before, this stage is reached thecell divides into two daughter cells. A processknown as Reproduction.

Because a cell cannot live in isolation, it mustbe capable of reacting to changes in itsenvironment. Such changes are called stimuli. Ifthe stimulus increases the rate of chemicalchanges in the cell it is said to excite, if it decreasesthe metabolic rate it is said to depress or inhibit.

SECTION I: GENERAL PHYSIOLOGY

2 Section I: General Physiology

Homeostasis

All cells of the body except those on the sur-face are provided with a fluid environmentof relatively constant: (i) temperature,(ii) hydrogen ion concentration, (iii) electrolytecomposition, and (iv) osmotic pressure. Thispermits many bodily activities to be carriedout under optimum conditions. Small changesin the composition of the extracellular fluid,produces reactions, which quickly restore theinternal environment to its original state. Themaintenance of constant environment for thecells is known as Homeostasis.

The first requirement for homeostasis is adetector of deviation from the standardconditions. The appropriate regulator mustthen be instructed to reduce the deviation. Thenew state of affairs is continuously assessedby the detector and the regulator is given freshinstructions. In other words, the activity of theregulating device is constantly modified, onthe basis of information fed to it from thedetector. Such systems are termed feedback orcontrol mechanisms, for example:1. Sensory receptors in muscles and joints

send information to central nervoussystem (CNS) about length of muscles andangle of joints, and movement and posturesare regulated.

2. Cells sensitive to osmotic changes in theblood regulate the loss of water from thebody.

3. Receptors in blood vessels detect changesin blood pressure and allow appropriateadjustments in the output of heart andcaliber of blood vessels.Thus, the study of physiology may be of great

practical importance in leading to methods ofdiagnosis and treatment of disease.

Diseases are regarded as disordered bio-chemical or physiological processes, which the

homeostatic mechanisms have been unable tocorrect.

The bodily activities depend so closely onone another so we need to consider briefly thesubject as a whole before beginning a moredetailed description of its various parts.

OUTLINE OF HUMAN PHYSIOLOGY

Nutrition

The source of all the energy required by thebody is food. This consists mainly of:1. Proteins, fats and carbohydrates which are

oxidized in the body.2. In addition, food must contain inorganic

substances which are necessary for example,to provide material for formation of bloodand bone. Ca is required for formation ofbone and Fe is required for blood. So,calcium and iron must be provided in food.

3. Food must supply certain substances whichthe body cannot synthesize such as vitaminsand essential amino acids.

4. Since fluid is lost continuously from thebody, by way of the kidneys, lungs andskin, water must be drunk to make goodthis loss.

Digestive System

When food is swallowed, it reaches thestomach and small intestine, where it is brokendown by enzymes into substances of simplerchemical composition, which are absorbedthrough the lining of the small intestine intothe blood and distributed throughout thebody.

Respiration

Oxygen required for combustion of foodstuffreaches blood through lungs. During breathingthe chest expands and air flows into the lungs,which are richly supplied with capillary blood

Introduction to Physiology 3

vessels. Oxygen diffuses readily through verythin walls of blood vessels and becomesattached to hemoglobin (Hb) contained in thered cells, in which it is distributed throughoutthe body by circulation. CO2 produced incombustion in the tissues is taken up by theblood and carried to the lungs where it escapesfrom the blood and is breathed out.

Blood

Blood is circulating in the blood vessels andacting as a transport system of the body,providing nutrients, oxygen and othersubstances (like hormones, immunologicalsubstances), to the cells and carrying away thewaste products of their metabolism and CO2is also carried away.

Excretion

Byproducts of oxidation not needed by thebody reach the kidneys via the blood and areexcreted into the urine.

Circulation

The heart is a two sided muscular pump whichdrives the blood along the blood vessels. Theleft side pumps blood to: (i) the heart muscleitself, (ii) to the skeletal muscles, (iii) to thebrain, and (iv) other organs.

The blood from these parts return to the rightheart, which sends blood to the lungs, whereoxygen is taken up and CO2 is eliminated.

ArteriesThe blood is conveyed away from the heart ata fairly high pressure in thick walled tubesthe arteries, which branch repeatedly andbecome smaller in diameter, with thinner andthinner walls. In the tissues, the smallest bloodvesselthe capillaries are bound by a singlelayer of cells, through which the gases, water

and chemical substances of small moleculemove easily.

VeinsThe blood is drained away from the tissues, atlow pressure in the veinswhich are widevessels with relatively thin walls.

William Harveys great discovery ofcirculation of the blood is the basis of modernphysiology.

Nervous System

The skeletal muscles are the main effectortissues. By their contractions the position ofbones is altered during: (i) movement,(ii) respiration, and (iii) speech.

The highly complex movements of thelimbs in walking and of the tongue in speechare coordinated by central nervous system(CNS) consisting of Brain and Spinal cord.

Nerves called efferent or motor leave thissystem and pass to all the structures of thebody and control: (i) muscular movement aswell as, (ii) secretion of some glands, (iii) theheartbeat, and the (iv) caliber of blood vessels.

Central control is of no use unless the CNShas full information about events in the bodyand around it. This information is conveyedto the central nervous system by sensory orafferent nerves, which convey impulses from:(i) eye, (ii) ear, (iii) skin, (iv) muscles, (v) joints,(vi) heart, (vii) lungs, and (viii) intestines.

The sensory nerves are much more numerousthan motor nerves.

Although many of the activities occurringin the CNS are exceedingly complex relativelyfew rise to consciousness. We are quiteunaware for example of the: (i) muscularadjustments needed to maintain balance or (ii)to move our eyes so that images of the externalworld are kept fixed on the retinae. Theseadjustments are called reflexes and the


pathways involved are called reflex arc, whichinclude: (i) sensory nerve, (ii) CNS, and (iii)motor nerve.

Endocrines

In addition to the rapidly acting coordinatingmechanism of nervous system, the bodypossesses a chemical (humoral) system whichoperates more slowly. For example, during thedigestion of food a chemical substance(hormone) called secretin is produced in themucous membrane of duodenum, is absorbedinto the blood and carried to the pancreaswhich responds by pouring out its digestivejuices.

Reproduction

Reproduction are the processes necessary forthe maintenance of the species. The malecellsthe spermatozoa are produced by testisand when deposited in female genital tract,one of them may fertilize an ovum producedin the ovary. This sets off a series ofcomplicated changes, mainly under hormonalcontrol, to provide for the nutrition of thefertilized cell in the uterus.

At the end of the pregnancy, the muscularwalls of the uterus contract, the fetus isdelivered and then acquires oxygen directlyby breathing air into its lungs instead ofindirectly through placenta.

Internal Environment

Homeostasis and Feedback

Mechanisms2

CHAPTER

INTERNAL ENVIRONMENTHOMEOSTASIS

The cell is a structural and functional unit oflife.1. It ingests nutrients from environment

(a) by diffusion, (b) by phagocytosis (= celleating), and (c) by pinocytosis (= celldrinking).

2. It gets rid of waste products (Fig. 2.1) (a)by diffusion, and (b) by exocytosis.

3. It can synthesize all the enzymes requiredfor optimal utilization of the ingestednutrients.

4. It can reproduce by simple dividing intoidentical daughter cells.But it functionsonly within the limited

range of(a) temperature, (b) pH, (c) osmo-larity, and (d) electrolyte composition.

Therefore, survival of the cell requiresimmediate environment of the cell be relativelyconstant and uniform in these characters.1. For unicellular organisms this poses no

problem, because they exist surrounded bylarge body of sea water.

2. The process of evolution led to the develop-ment of multicellular organism (Fig. 2.2).Cells in the interior no longer remained indirect contact with external environment.

3. In the course of evolution, this problem wasinitially solved by having sea water runthrough the organism to bring sea water indirect contact with every cell. But thissimple solution could not work if thenumber of cells in organism increasedbeyond a certain limit.

Fig. 2.2: Multicellular organismFig. 2.1: Single cell


4. When the organisms became more complexa thin layer of fluid resembling sea wateraround each cell was developed. Thus, if seawater could not be carried to each cell, eachcell was furnished with a small private seaof its own. This private sea or intercellularfluid or interstitial fluid persists in highlyevolved organism such as man. Itscomposition is reminder of origin in the sea.This environment surrounding each cell iscalled internal environment. It is part ofextracellular fluid (= fluid outside the cells).It is from this fluid the cells receive oxygenand nutrients and cells excrete their wasteinto it. But the interstitial fluid is smallquantity so that:i. Nutrients in it must be replenished.ii. Waste products should be removed

continuously and promptly otherwiseits pH will change, and its compositiondoes not remain suitable for optimalfunctioning of the cell.

Therefore, a set of tubes called capillariesare developed:

1. Fluid in the capillaries is in constantexchange with interstitial fluid.

2. Interstitial fluid is doing same thingwith the cells.

The fluid in capillaries must be in constantmotion, so that:

1. Continuous replenishment of nutrientsis there.

2. Prompt removal of waste products takeplace.

This motion was possible by evolution ofpump to provide the force for motionthe heart.

The capillaries at least at few points incirculatory system must come in close contactwith external environment for fresh supply ofnutrients and disposal of waste and suchstructures were evolved. They are:1. Lungs: Where oxygen is taken up and CO2

is disposed off.2. Kidneys: Nitrogenous waste products are

disposed off.3. Gut: Where nutrients are picked up.

Thus, digestive system, excretory systemand respiratory systems establish link betweeninternal and external environment (Fig. 2.3).

Blood supplies nutrients and oxygen to alltissues and removes waste. While passingthrough lungs, gut and kidney it does some-

Fig. 2.3: Elaborates link between internal andexternal environment

Internal Environment Homeostasis and Feedback Mechanisms 7

thing in addition. For example: (i) in lungs, itabsorbs large quantity of oxygen and gives outlarge quantity of CO2, (ii) in gut, it absorbsnutrients and water, and (iii) in kidney, itexcretes nitrogenous waste products andabsorbs water, glucose, etc.

Ultimate aim of the work of all the systemsis to maintain constancy in the characteristicsof thin layer of fluid surrounding every cell ofthe body or internal environment or in otherwords all the systems work for homeostasis.

Importance of constancy of the internalenvironment was first stressed by ClaudeBernard in 1857. It is also called Milieu Interieur(= French word for internal environment).

His concepts were further supported byextensive experimental work of WalterCannon in early 20th century. Cannon coinedthe word Homeostasis to describe constancyof internal environment (homios = similar;stasis = position).

All systems contribute to homeostasis:1. Systems such as digestive, respiratory and

excretory contribute directly.2. Role of blood and cardiovascular system

is obvious.3. Endocrines and NS work for coordination

of activities of other systems.Like this every part of the body makes some

contribution to the survival of whole organismby doing something to maintain: (i) tempera-ture, (ii) pH, (iii) osmolarity, and (iv) electro-lyte composition of internal environment atoptimal level. Optimal level is that at whichthe enzymes function best.

FEEDBACK MECHANISMS

Control systems: Principles on which they workto maintain homeostasis.

They work on the basis of feedback. There-fore, they are called feedback systems orfeedback mechanism (Fig. 2.4).

For feedback systems to work there mustbe: (a) a detector (or sensor), (b) a regulator(or control systems) and for most variablesthere is, (c) a set point. For example, for bodytemperature or blood glucose there is a fixedset point at which level is maintained.

Current value of the variable minus set point= deviation or error. This error is corrected bycorrecting measures which work in oppositedirection. Therefore, these mechanisms arecalled as negative feedback mechanism, as theeffector response is negative to initiatingstimulus. For example, for body temperatureset point is 37C. When temperature increases,the correcting processes decrease the bodytemperature.

Positive feedback would be disastrous.Therefore, most of the control systems in thebody are of negative feedback type.

However, there are some situations in thebody in which control system operates on thebasis of positive feedback.

For example:1. Sex hormones normally inhibit gonadotro-

pins by negative feedback. But one to twodays before ovulation, estrogen level

Fig. 2.4: Scheme of control system feedback mechanism


increases the level of LH, and FSH. This LH,and FSH, surge is essential for ovulation(Fig. 2.5).

2. During laboruterine contractions pushthe fetus down towards the cervix. It causesstretching of cervix. This stimulates uterinecontraction by positive feedbackstretching the cervix still more resulting inmore strong uterine contraction (Fig. 2.6).Like this stronger contractions continue tillbaby is delivered.

Fig. 2.6: Strong uterine contraction inlabor positive feedback

Fig. 2.5: FSH and LH surge positive feedback

3. Some blood coagulation reactions are autocatalytic in nature. Once a small amount ofthrombin is formed it acts on prothrombinto form still more thrombin.

Prothrombin

Thrombin

Prothrombin

Thrombin

Body Fluid Compartments,

Extracellular Fluid and

Intracellular Fluid3

CHAPTER

Maintenance of a relatively: (a) constantvolume, and (b) stable composition of bodyfluid is essential for homeostasis.

Fluid intake and output must be balancedduring steady state conditions inspite ofvariable intake that must be matched carefullyby equal output from the body to prevent bodyfluid volumes from increasing or decreasing.

DAILY INTAKE OF WATER

1. Ingested in the form of liquids or water willadd about 2100 ml/day to body fluids, and

2. It is synthesized in body as a result ofoxidation of carbohydrates will add 200ml/day.Thus, total water intake is 2300 ml/day

water intake varies in different persons, alsoin same person on different days dependingon: (a) climate, (b) habits, and (c) levels ofphysical activity.

DAILY LOSS OF BODY WATER

1. Insensible fluid loss includes:i. Evaporation from respiratory tract

(300-400 ml/day): Water is lost byevaporation from respiratory tractbecause vapor pressure of inspired airis less, in cold it becomes zero. Expiredair is saturated with moisture.

ii. Diffusion through skin (300-400 ml/day)more loss is prevented by cholesterolfilled cornified layer of skin. In burns,skin is denuded which leads to more lossof water and more fluids should be givenintravenously.

Insensible fluid loss cannot becontrolled. Total amount lost is 700 ml/day. It is also called invisible water loss.

2. Fluid loss in sweat: The amount of fluid lostby sweating is highly variable dependingon physical activity and environmentaltemperature.For example: Normal loss100 ml/dayhot temperature or heavy exercise1 to 2L/hour.

3. Water loss in faeces: Small amount is lostnormally100 ml/day.

It is increased to several liters per dayin severe diarrhea.

4. Water loss by the kidneys: Remaining waterloss is by urine, excreted by the kidneys.Various mechanisms control this loss ofwater.For example: Normal urine output is 1.5 L/day.

It can be as low as 0.5 L/day in dehydratedperson or 20 L/day, in person who is drinkingtremendous amount of fluid.


BODY FLUID COMPARTMENTS

Compartments are because of the presence ofbarriers and properties of barriers determinethe movement of substances and fluid betweencontiguous compartments.

In normal 70 kg adult human (Physio-logical man) the total body water averagesabout 60% of the body weight (= 42 liters).Percentage can change depending on (a) age(b) sex, and (c) degree of obesity, because totalbody water depends on fat content.

Total body fluid is distributed among twomajor compartments:1. Extracellular fluid (ECF): Fluid outside the

cell (1/3 of total body water).2. Intracellular fluid (ICF): Fluid inside the cell

(2/3 of total body water).

Extracellular Fluid

Extracellular fluid is present in two compart-ments:1. Intravascular: Fluid inside blood vessels =

Plasma (20% of total ECF).2. Extravascular: Fluid outside blood vessels.

(80% of total ECF).

Extracellular fluid includes:1. Interstitial fluid2. Blood plasma3. Transcellular fluid

This includes:i. Synovial fluidii. Peritoneal fluidiii. Pericardial fluidiv. Intraocular fluidv. Cerebrospinal fluid (CSF).

4. LymphExtracellular fluid is 20% of body weight

in 70 kg man or 14 L in 70 kg man.Its two largest compartments are:1. Interstitial fluid2. Plasma: It is noncellular part of blood.

Interstitial fluid and plasma are in commu-nication through large pores in capillarymembrane which is freely permeable to almostall solutes of plasma except protein (Fig. 3.1).

Constituents of ECFIonic composition of plasma and interstitialfluid are similar because they are separatedby highly permeable capillary membrane.Important differences between the two is:1. Higher concentration of protein in the

plasma because capillaries have lowpermeability to plasma proteins, thereforeonly small amount of protein leaks ininterstitial spaces.

2. Concentration of positively charged ions isslightly greater (2%) in plasma than ininterstitial fluid because proteins arenegatively charged therefore attractpositively charged ions.

Fig. 3.1: Body fluid compartments(values for average 70 kg man)

Body Fluid Compartments, Extracellular Fluid and Intracellular Fluid 11

But for all practical purposes concentrationof ions in interstitial fluid and plasma areconsidered to be equal.

ECF Contains (Fig. 3.2)1. Large amounts of sodium and chloride

ions.2. Reasonably large quantity of bicarbonate

ions.3. Small quantity of potassium, calcium,

magnesium, phosphate and organic ions.Composition of ECF is carefully regulated

by various mechanisms, but especially bykidneys.

Intracellular Fluid

Intracellular fluid is 40% of body weight in 70kg man or 28 L in 70 kg man.

Composition is reasonably similar in allcells of our body. Therefore, considered as onelarge fluid compartment.

ICF is separated from ECF by selectivelypermeable cell membrane which is highlypermeable to water but not to most of theelectrolytes of the body. Cell membranemaintains a fluid composition inside the cellsthat is similar among different cells of thebody.

ICF Contain (Fig. 3.2)1. Small quantities of sodium and chloride

ions.2. Almost no calcium.

3. Large amount of potassium and phosphateions.

4. Moderate amount of magnesium andsulfate ions, and

5. Reasonably large amount of protein ions.

Blood VolumeBlood is plasma with cells suspended in it.They are: (i) RBC, (ii) WBC, (iii) platelets.

Blood is present in separate fluid compart-ments of its own. Therefore, considered asseparate fluid compartment. It contains ECFand ICF both. Average blood volume ofnormal adult is 5 L. Out of which 55-60% isplasma and 40-45% is blood cells. Volumeoccupied by blood cells is known as packedcell volume or hematocrit. It is determined bycentrifuging blood in a hematocrit tube untilthe blood cells become tightly packed in thebottom.

Measurement of the Volume of the BodyFluid CompartmentVolume of a compartment is measured byusing dilution principle. If a known quantityof substance is added to a compartment and ifit is evenly distributed throughout thecompartment the extent to which the addedsubstance is diluted can be determined and thevolume of the compartment can be found out.If Q = Quantity of substance added

C = Concentration of the substancewhen evenly distributed.

and V = Volume of the compartment.

then V = QC

Requirements1. Marker must be freely diffusible and must

be confined to the compartment to bemeasured.Fig. 3.2: Composition of ECF and ICF


2. If it is excreted it should be at a constantmeasurable rate.

3. The marker must be nontoxic, neithersynthesized nor metabolized.

4. Accurate measurement of the concen-tration of the marker must be possible.

5. A representative sample must be easilyobtained from the compartment.

TOTAL BODY WATER

To measure total body water the markershould diffuse freely in the water outside thecells, but also cross the cell membranes.Three substances are used:

i. Tritiated water (3H2O): Radioactive waterwhere tritium is use.

ii. Heavy water (D2O): Radioactive waterwhere deuterium is use.

iii. Antipyrine: A lipid soluble substance,therefore crosses the cell membrane.

1. A known quantity of labeled water isinjected intravenously as an isotonicsolution of NaCl.

2. It mixes freely with the water of the bodyin a few hours.

3. At the end of this period the blood sampleis taken and concentration of labeled wateris measured.

4. Some marker is lost in the urine, so this lossis allowed for.For example: 100 ml of D2O was infused into

a 70 kg man. After 2 hours when equilibriumhas occurred a sample of blood was taken andconcentration of D2O was found to be 0.0025ml/ml of plasma.

At the same time of plasma sample, urinewas voided and was found to contain 0.5 mlD2O.

TBW =100 ml 0.5 ml0.0025 ml/ml

= 39.81 L or 57% of body weight

ECF Volume

The marker for ECF must be a substance thatdiffuses readily through ECF space but doesnot enter the cells.

Number of substances are used but allcross the cell membrane to some extent. It isusual to use: (a) radioactive isotopes ofsodium, chloride, bromide, thiosulfate,thiocyanate. (b) sucrose and inulin.

Sucrose and inulin penetrate the cellmembrane to a smaller extent than otherstherefore, give a more accurate estimate ofECF. Since all the markers give slightlydifferent values, because of their varyingability to penetrate cell membrane, the resultsare often quoted as 'sodium space', thethiocyanate space, the inulin space, etc.

For inulin spacea known quantity ofinulin (Polysaccharide) inulin is injectedintravenously.1. Plasma inulin concentration is determined

at 30 min interval.2. Plasma concentration falls with time.

Graph is plotted of plasma concentrationof inulin against time (Fig. 3.3). A curvedline is obtained. It is converted to straightline when plasma concentration is plottedagainst log of time. After a period of mixingthe concentration of inulin falls off in apredictable manner because of loss of inulinin urine. If a straight part of the curve isextrapolated back to cut concentration axis,the value of the intercept is the concentr-ation of inulin that would have beenachieved had it been distributedinstantaneously. This method allows for thelosses in urine. For example, 4 gm inulin isinjected intravenously, extrapolation ofconcentration time graph cuts the concen-tration axis at 0 time (that is the time ofinjection) at 0.275 g/L.

Body Fluid Compartments, Extracellular Fluid and Intracellular Fluid 13

Volume of ECF =4 g

0.275 g/L

= 14.5/L for a 70 kg man

Plasma Volume

Markers used to measure plasma volume are:1. Vital dye Evans blue (T 1824) or2. Iodinated albumin.

Normal value3 L in 70 kg man, 2.4 L inwoman.

Interstitial Fluid Volume

There is no method to measure interstitial fluidvolume, which has to be calculated bysubtracting the plasma volume from ECFvolume.

ECF volume Plasma volume =Interstitial fluid volume

Intracellular Volume

Cannot be measured directly, thereforedetermined by subtracting the ECF volumefrom total body water.

TBW ECF = Intracellular volume

Measurement of Blood Volume

1. If you know plasma volume and hemato-crit value, one can determine bloodvolume.

2. Another way to measure blood volumeis to inject into circulation red cells thathave been labeled with radioactivematerial.After these mix in the circulation the

radioactivity of mixed sample can bemeasured and the total blood volume can becalculated.

Fig. 3.3: Graph of inulin concentration against time

Formation of

Interstitial Fluid and Lymph

4

CHAPTER

FORMATION OF INTERSTITIAL FLUID

Exchange of water and dissolved substancesthrough capillary wall depends upon the typeof capillary.

In general, three types of capillaries havebeen described.

Type 1

These capillaries have uninterrupted mem-branes with pores of 4-5 nm in diameter. Theyoccur in muscle, pulmonary circulation andadipose tissue.

Type 2

These capillaries have fenestrated membranes.Fenestration being of the order of 0.1 micro-meter.

Typical sites are glomeruli of the kidneysand intestinal epithelium.

Type 3

Capillaries have discontinuous membranes.They are interrupted by large intercellularspaces through which not only fluids but cellscan pass. These capillaries are found in thebone marrow, spleen and liver.

Two processes are involved in the transferof fluid, nutrients and waste products acrossthe capillary membrane:1. Diffusion2. Filtration/reabsorption.

Diffusion

1. The capillary membrane is very leaky. Itspermeability is high but its selectivity islow. Substances of molecular weight lessthan about 70,000 cross freely down theirconcentration gradient to reach equalconcentration on both sides of capillary,therefore, do not contribute to an osmoticpressure difference across the wall.

2. Plasma proteins are largely retained andcreate osmotic pressure or oncotic pressurewhich is 25 mm Hg (3.3 kpa).

3. Diffusion is fast process and most cells arewithin 5-10 micrometer of capillary anddiffusion distance between adjacent cellsmay be less than 0.1 micrometer.

4. Diffusion is more effective, the greater thecapillary density in a tissue, because thesurface area is greater.

5. An increase in capillary density and surfacearea occurs when a tissue becomes activeduring vasodilatation because morecapillaries open up.

Formation of Interstitial Fluid and Lymph 15

Filtration/Reabsorption AcrossCapillary Membrane

Starling proposed that fluid exchange acrossthe capillary wall between plasma andinterstitial fluid was achieved by a balancebetween two forces (Fig. 4.1).1. Hydrostatic pressure in the capillary -

(caused by action of heart)directs thefluid movement outwards (filtration).

2. This effect is opposed by the colloid osmo-tic pressure of the plasma proteina forcethat is directed inwards (reabsorption).

Thus, at the arterial end of a capillary,the hydrostatic pressure exceeds colloidosmotic pressure and net filtration takesplace.

At the venous end hydrostatic pressurefalls below the colloid osmotic pressure andreabsorption occurs.

Two other factors affect the trans-capillary movement of fluid.

3. There is a small negative hydrostaticpressure in tissues outside the capillary.This increases the outward force.

4. Also the capillaries are not entirely imper-meable to proteins and some escape intothe interstitial fluid where it opposes the

inwardly directed force of the colloidosmotic pressure.

Hydrostatic pressureat the arterialend of the capillary depends on:1. The type of tissue.2. Activity of the tissue, and3. Vasomotor supply.

For example:a. In resting state - the pressure in glomerular

capillary is 70 mm Hg and ultrafiltrationonly occurs.

b. In lungs and liver it is 8 mm Hg andabsorption only occurs. Important, thatfiltration does not occur in lungs otherwiserespiratory exchange would be impeded.

c. In human finger, the pressure at the arterialend of the capillary is about 32 mm Hg andboth filtration and re-absorption occur.

FORMATION OF LYMPH

Distal lymphatics form a closed system of tubesconsisting of endothelial lining supported byfibrous tissue and out of the filtered fluid fromthe capillary 10% enters in these lymphaticswhereas 90% is reabsorbed at the venous end(Fig. 4.2).

Fig. 4.1: Filtration/reabsorption Fig. 4.2: Formation of lymph


Lymphatics are much more permeable toproteins than capillaries. The proteins leakedfrom plasma into interstitial space cannotreturn to capillary because of adverse concen-tration gradient. Their accumulation ininterstitial space will upset starling equili-brium and proteins diffuse into the verypermeable lymphatic capillaries together withlarge molecules produced by cells such as: (a)hormones, (b) enzymes, (c) lipoproteins, (d)chylomicrons.

Large lymphatics have muscle fibers intheir walls, lymphatic vessels posses num-erous valves and the flow of lymph fromperiphery to thoracic duct and right lymphaticduct is brought about by muscular andrespiratory movement in the same way asblood flows in the veins.

Right lymphatic duct opens in rightsubclavian vein and thoracic duct opens in leftsubclavian vein.

The lymphatics of intestine (lacteals) showrhythmic contraction which, because of the manyvalves propel lymph into the thoracic duct. Thiscontractile activity is an intrinsic property of thelymphatics and is not coordinated by NS.

Lymph

1. Has same concentration of salts as inters-titial fluid and plasma.

2. Has lower concentration of proteins thanplasma.

3. Has slightly higher concentration ofproteins than interstitial fluid.Before reaching the blood lymph passes

through at least one or more, usually 8-10 lymphnodes. Lymph nodes are placed at strategic pointsalong the routeaxilla, elbow, groin, abdomen,thorax and neck where several lymphatic vesselsjoin. During its passage through a lymph nodethe lymph is altered in composition.

i. Small molecules pass into the blood.ii. Large molecules are retained.

iii. Newly formed antibodies (immuno-globulins) are added.

iv. Lymphocytes enter.

Functions of Lymph

1. Return of proteins to blood from tissuespaces.

2. Role in fluid distribution in body.It is estimated that in an adult man some

20 L of water are ultrafiltered fromcapillary. Of this some 16-18 L return to thecapillary at venular end by reabsorptionand 2-4 L return to circulation throughlymph.

3. Lymph acts as middle man between bloodand tissue fluid.

4. Fat from intestine are mainly absorbedthrough lymph.

Lymphedema

Complete obstruction of lymphatic vesseldraining a part of the body leads to edema ofthe area known as lymphedema.

Edema

Edema can be explained by starling hypo-thesis. It means accumulation of excessiveamounts of salt and water in interstitial space.

In this condition the tissuesusually independent parts become swollen with fluidthat resembles plasma but has a low proteincontent.Edema accumulates when:1. The hydrostatic pressure in the veins is

increased, e.g. congestive heart failure.2. Colloid osmotic pressure of plasma is

reduced (because albumin level is low).Edema from hypoalbuminemia arises in (a)

malnutrition (famine edema) (b) chronic liverdisease (cirrhosis) when albumin synthesis islow and (c) in nephrotic syndrome in whichexcessive amounts of albumin are lost in urine.

Fig. 5.1: Danielli-Davson model

Cell Membrane and Principles

of Biological Transport

Across Cell Membrane5

CHAPTER

The structural and functional unit of life is acell. Initially only cell had a membrane aroundit, its contents floated freely within. Bacterialcells are still like that and are called Prokaryoticcells.

In the next step of evolution the nucleicacids were packed in membrane boundstructurethe nucleus and various organelles,which are also membrane bound, appeared.

Thus, a cell is bound with: (a) cellmembrane and contains, (b) protoplasm, (c)nucleus, and (d) organelles.

CELL MEMBRANE

Cell membrane is a vital and dynamicstructure. It is also called as plasma membraneto distinguish it from other membranesurrounding organelles. Structure of both themembranes is similar. Hence, the term unitmembrane includes both.

Under electron microscope the cellmembrane is a three layered structure 8-10 nmin thickness.

Structure

I. Simplest interpretation of the structure isprovided by Danielli-Davson model (Fig.5.1).

It consists of:i. Outer most layer of protein molecules.

ii. Layer of lipid molecule.iii. Further layer of lipid molecules, andiv. Innermost layerthe fourth layer is

again made up of protein molecules.Thus, there are two layers of lipid molecules

sandwiched in between two layers proteinmolecules.

The lipids of the cell membrane are mostlyphospholipids. These individual phospholipidmolecules are elongated structures looking likebamboos.

Individual lipid molecule has two ends:1. Hydrophilic end which is polar end. They

are facing the protein layer.2. Hydrophobic end which is nonpolar end.

They meet the hydrophobic ends of theirfellows. These molecules are placed side by


2. It is the first point of contact with any agentwhich is capable of influencing the cell.

3. It is selectively permeable barrier.4. It acts as receiver and transducer of

information.5. It incorporates:

i. Several enzymes.ii. Transport proteins.

iii. Receptors for hormones and neuro-transmitter.

iv. Antigens.v. Several channels for passage of Na, K,

etc.Since all these functions differ from cell-to-

cell, time-to-time and on the inside ascompared to outside the surface membrane,the cell membrane is: (i) heterogeneous, (ii)dynamic, and (iii) asymmetrical structure.

Cell Junctions

In multicellular organisms the adjacent cellsare joined to each other (Fig. 5.3). Their pointsof contact show varying degrees of: (a) fusion(Fig. 5.4), and (b) specialization depending onthe requirements of the tissue.

Junctions found in various tissues areclassified into three types:1. Tight junctions.2. Gap junctions.3. Desmosomes.

Fig. 5.2: Diagrammatic fluid mosaic model

side in a row due to: (a) their polarity, and(b) electrical charges.

II. Currently accepted interpretation of thestructure is the fluid mosaic model ofSinger and Nicolson, first proposed in 1972(Fig. 5.2). Similarity with previous modelisthe lipid bilayer is intact in this modelas well.

Distinguishing features are:1. Dynamic nature of membrane.2. Presence of transmembrane proteins or

integral proteins, which span entire widthof the membrane, instead of being confinedto the surface.

3. Presence of peripheral proteins confined tosurface also known as extrinsic proteins.

4. Surface carbohydrates: (a) phospholipids(b) cholesterol, and (c) glycolipids form themajor lipids of the cell membrane. Com-position is affected to some extent by natureof dietary lipids. Transmembrane proteins form hydro-

phobic linkage with fatty acyl chain. Peripheral proteins are attached to polar

end of lipids through electrical linkage.

Functions and Characteristics of CellMembrane

1. It is responsible for guarding the contentsof the cell, which are unique as comparedto outside.

Cell Membrane and Principles of Biological TransportAcross Cell Membrane 19

1. Tight junctions : The cell membranesbetween the adjacent cells are fusedtogether. No molecules can pass through.They are found in gastrointestinal tract andprevent passage of substances from thelumen to the interior of the gut by theintercellular route.

2. Gap junctions: The cells are very close toeach other but there is a small gap of 2 nmbetween adjacent cells and cytoplasm of thetwo cells are connected with each other bysort of channels. So, molecules can passfrom cytoplasm of one cell to cytoplasm ofother cell without coming in contact withECF.

It is widespread in distribution. Evencells with tight junctions show gapjunction below. It is important whererapid communication between adjacentcells is required. For example:

i. Smooth musclegap junction iscalled nexus.

ii. Cardiac musclegap junction formsa part of intercalated disk.

3. Desmosomesi. Gap of 25-30 nm between the cells is

filled with carbohydrate rich material.ii. On cytoplasmic side of the membrane

there are electron-dense plaques.iii. In the electron dense plaques are

fine fibrillar structure called tono-filaments.

iv. Function of desmosomes is to providestructural support.

v. Most abundant where firm support isessential, as in epidermis.

The same tissue may have tight junctionsnear the surface in order to provide animpermeable surface, gap junction at anintermediate depth to allow intracellulartransport and communication and desmo-somes at a still greater depth to keep the cellstogether.

PRINCIPLES OF BIOLOGICAL TRANSPORT

Cells utilize nutrients and produce wasteproducts continuously, rate may vary fromtime-to-time. Nutrients are picked up fromimmediate surroundings and waste productsare dumped into the surroundings. Both aretransported across the cell membrane.

Transport may be governed only byphysical processes, membrane acting as semi-permeable membrane. Such transport isknown as passive transport or transport mayinvolve expenditure of biologically producedenergy. Such transport is known as activetransport.

Passive TransportPassive transportacross the cell membranedepends on (a) physical factors such as:1. Concentration gradient2. Electrical gradient

Fig. 5.3: Cell junctions

Fig. 5.4: Cell junctions (Fusion)


3. Pressure gradient, and (b) permeability ofmembranepermeability of a substancedepends on:

i. Its molecular size.ii. Lipid solubility, and

iii. Whether a carrier is available toshuttle the substance across themembrane.a. Lipid soluble substance is trans-

ported faster because such sub-stance can dissolve in the lipidbilayer of cell membrane and crossit.

b. For some special important sub-stancesa carrier protein isavailable in cell membrane whichcarries it across cell membrane.

Major Processes

Major processes by which passive transport isaccomplished are:1. Simple diffusion.2. Facilitated diffusion.3. Osmosis, and4. Ultrafiltration.

Simple Diffusion1. Dissolved substances are in a state of random

molecular motion. Molecules therefore, strikethe membrane. Frequency is more on the sideon which concentration is more. Therefore,there is greater possibility of striking a porethrough which they can go to the other sideof the membrane.

2. Or if lipid solublehigher the concen-tration greater is the possibility of particlesstriking the membrane and dissolving init. Therefore, substances diffuse from theside on which they are present in a largerconcentration to the side of lower concen-tration (Fig. 5.5).

3. If there is electrical charge across themembranea charged particle will have atendency to diffuse towards oppositelycharged side.

4. Pressure gradient = sum total of collisionson a given side of the membrane. Pressurehas nonspecific effect of driving substancesout. Hence, diffusion is increased from theside with higher pressure to that of lowerpressure.

5. Molecular size also affect simple diffusion.Respiratory gases are transported acrossthe alveolar membrane in the lungs bysimple diffusion.

Facilitated DiffusionTransport by diffusion may be made fastereven if molecular size is large, if a suitablecarrier is available in cell membrane.

Since, the carrier merely facilitates diffusionthe process is called facilitated diffusion

Fig. 5.5: Lipid soluble substances diffuse fast


Fig. 5.7: Graph showing relationship of increased conc.and rate of transport

(Fig. 5.6), because it occurs in such a way thatmolecule moves from a region of higherconcentration to a region of lower concen-tration. For example, in small intestine fructoseis absorbed by facilitated diffusion.

Note1. Molecule must fit in the receptor on the

carrier.2. Substances with similar molecular

structure compete with one another fortransport.

3. Transport can be blocked by specificagents, if the blocking agent binds to thecarrier but does not get transported, itblocks the carrier irreversibly.

4. Concentration of a substance and rate atwhich it is transported bear linearrelationship only up to a limit. After whicheven if concentration increase, rate doesnot increase.

Reason is when all the available carriermolecules are in use, further increase inconcentration of transported substance cannotincrease the rate of transport (Fig. 5.7).

OsmosisIf selectively permeable membrane (semi-permeable membrane) separates two compart-

Transported substance Carrier molecule

Memb = cell membrane

Fig. 5.6: Facilitated diffusion

ments, the membrane allows water to passthrough but not a solute.

On side A is water. On side B is solutedissolved in water. Membrane is permeableonly to water. Concentration of water is higheron side A. Hence, water diffuses from side Ato B, but in this type of situation water is saidto be transported by osmosis.

Osmosis of water increases the hydrostaticpressure on side Bwhen excess hydrostaticpressure on side B equals osmotic pressureexerted by the solute, osmosis stops whichmeanswhen excess hydrostatic pressure(pushing force) becomes equal to pulling force(osmotic pressure exerted by the solute) thereis no further net movement of water (Fig. 5.8).

UltrafiltrationYou are familiar with filtration. If we try topass a solution through a filter, the solvent andother small molecules pass through the filter.Whether a given substance will pass througha filter depends on: (a) the relative size of itsmolecules, and (b) that of pores of the filter.

The rate of filtration can be increased byapplying pressure. Filtration under pressureis called ultrafiltration. For example, thehydrostatic pressure in renal glomeruli ishigher than hydrostatic pressure in any other


Secondary Active TransportIngenious device used by cells to utilize theactive transport of one substance to drive theuphill transport of one or more othersubstances as well.

Few varieties:1. Coupled transportwhich includes:

(i) cotransport or symport, (ii) countertransport or antiport.

2. Osmosisentry of solute into the cell byactive transport increases the osmoticpressure within the cell, hence water alsoenters the cell by osmosis, e.g. reabsorptionof water from gut.

3. Solvent dragalong with water somesubstances dissolved in water may movein the same direction by bulk flow. This isknown as solvent drag.

Coupled TransportTransport of two substances may be coupledto each other because they bind to the samecarrier in the cell membrane.

1. Cotransport or symport: If the substanceswhose transport is coupled move in thesame direction the phenomenon is calledcotransport or symport (Fig. 5.10). For

Fig. 5.8: Osmosis. Note increase in hydrostatic pressure fromHP to HP1; due to diffusion of water to side B. Whenhydrostatic pressure HP1-HP = osmotic pressure exerted bythe solute osmosis stops

capillaries of the body. As a result, water andsmall molecules filter through glomerulirapidly while proteins and blood cells do not.

Active TransportActive transport utilizes biologically producedenergy. This makes it possible to transport asubstance: (a) at faster rate or (b) even againstthe gradient.

Active transport may also be carriermediated. The carrier may be high affinitycareer or low affinity carrier (Fig. 5.9).1. Active transport is required for main-

taining the difference in electrolytecomposition between intracellular andextracellular fluids.

For example: Inside the cell: (i) sodiumion concentration is much lower thanoutside, (ii) potassium ion concentrationis much higher than outside.

2. Actively transporting cell membranes oftencontain ATPase, which will breakdownATP and liberate energy.

3. Active transport may be inhibited by: i. Inhibitors of ATPasespecifically orii. Nonspecifically by attacking various

processes which are involved information of ATP.

Fig. 5.9: Active transport


example, in small intestine absorption ofsodium ion is coupled with that of glucosebecause they bind to the same carrier incell.

2. Counter transport or antiport: If twosubstances whose transport is coupledmove in opposite direction the pheno-

CP = Carrier protein

Fig. 5.10: Cotransport or symport

CP = Carrier protein

Fig. 5.11: Counter transport or antiport

menon is called counter transport orantiport (Fig. 5.11). For example, inproximal convoluted tubule of kidneyssodium is reabsorbed actively. Simulta-neously for each sodium ion reabsorbedone hydrogen ion is transported by thesame carrier into the lumen of the tubule.

Bioelectricity

6

CHAPTER

MEMBRANE POTENTIAL AT REST ANDDURING ACTIVITY

Concentrations of Biological Substances

Traditionally, the concentrations were expressedin mg/100 ml. It is still used, but molecularweight of different substances are different.Therefore, although concentrations of substanceA and B in blood may be M mg/100 ml each,the number of molecules of each in 100 ml ofblood will be different.

Since, substances interact in terms ofmolecules expressing the concentration interms of mass/volume (e.g. mg /100 ml) is nolonger considered to be best mode ofexpression.

Currently popular modes of expressingconcentrations are:1. Moles/L2. Equivalents/L3. Osmols/L.

For small concentrations suitable units are:i. millimoles/L

ii. milliequivalents/Liii. milliosmols/L

Abbreviations m Mol/L mEq/L mOsm/L.

1. One mole of substance is = to its molecularweight in grams, e.g. 1 mole of NaCl = 58.5 gof NaCl.

2. Equivalent weight of a substance is inrelation to its participation in chemicalreactions, e.g. 1 molecule of HCl willcompletely neutralize one molecule ofNaOH but a molecule of H2SO4 is enoughto neutralize 1 molecule of NaOH.Equivalent weight of HCl will be equal toits molecular weight but that of H2SO4 willbe half its molecular weight.

In case of acids and alkalis, when theconcentration is 1 gram equivalent weight/1L it is called a 'Normal' or 1 N solution.

3. Osmolarity of a substance is in relation tothe osmotically active entities that itsmolecule provides. One molecule of NaClprovides two osmotically active entitiesNa+ and Cl-.

Thus, 180 g/L of glucose (an unionizedcompound) is equal to 1 mole/L and also 1osmols/L.

But 58.5 g/L of NaCl is equal to 1 mole/L, but is= 2 osmoles/L.If instead of volume of the solvent,

concentration is expressed in terms of mass ofthe solvent, the concentration is called molalor osmolal concentration.

Bioelectricity 25

Thus, molality of a solution is its concen-tration in moles/kg and osmolality isconcentration in osmols/kg.

Since volume is affected by temperature butthe mass is not, molality and osmolality areindependent of temperature.

Membrane Potential at Rest

Most living cells show some difference inelectrical potential across the cell membrane.This difference is called membrane potential.

Excitable cells, i.e. muscle and nerve cells -show: (a) membrane potential while at rest, butalso show (b) a dramatic change in thepotential during activity.

GENESIS OF RESTING MEMBRANEPOTENTIAL (RMP)

RMPmay be measured by means of fineintracellular glass electrode filled with solutionof KCl, with a tip diameter less than 1 micron,which can penetrate the excitable tissuewithout causing too much injury (Fig. 6.1).

As compared to the ECF the interior of thecell is electrically negative. In smooth muscle cells Thin nerve fibers

and neurons of CNS

In skeletal muscle cellsand large diameterperipheral nerve fibersRMP is mainly the result of following

insights in physiology 2012

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