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Copyright © 2007, 2001, 1988, 1977 New Age International (P) Ltd., Publishers
Published by New Age International (P) Ltd., Publishers
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ISBN : 978-81-224-2429-4
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The Essentials of Animal Physiology has estabIished itseII with the academia and served (a) as a text
Ior courses in animaI physioIogy Ior B.Sc. (Hons.) and B.Sc.(Pass) courses, and (b) as a sound basis
Ior Iaboratory investigations to anaIyse animaI Iunctions.
PhysioIogy is a synthetic and experimentaI science which appIies physicaI and chemicaI methods
in bioIogy. It requires a combination oI IieId and Iaboratory observations oI organisms, since their IiIe
is inIIuenced by a variety oI environmentaI Iactors. This Iourth edition, whoIIy reset in its new Iormat,
has provided an opportunity Ior detaiIed scrutiny and extensive revision. However, the principIes oI
physioIogy stated in the earIier editions remain sound.
The revision has been impacted by two considerations: these are updating the existing text and
adding exciting deveIopments in the IieId to enhance the utiIity oI the book Ior an enIarged
readership. ConsequentIy, this edition contains new chapters on animaI caIorimetry, membrane
physioIogy and physioIogicaI disturbances emanating Irom organeIIar maIIunctions and genetic
disorders. Besides, certain sections oI metaboIism and physioIogy oI digestion have been revised to
provide new insights. It must be appreciated that physioIogy oIIers rationaI basis Ior much oI
medicine, home science and animaI husbandry.
It must be emphasised that an eIIective way oI administering a physioIogy course is to
simuItaneousIy pIan Iaboratory exercises to unraveI the exciting physioIogicaI phenomena. For this
the reader is advised to reIer 'ExperimentaI PhysioIogy¨ (New Age PubIishers), by the same author.
This edition has been reinIorced by providing more muItipIe choice questions Ior seII-assessment.
I hope the book wiII be more appeaIing to students and instructors in terms oI contents and
presentation.
S.C. Rastogi
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Every year, during one semester, I am engaged in the teaching oI physioIogy to senior students. I have
oIten IeIt the diIIicuIty to cover aII areas oI physioIogy owing to deIiciency in the background
knowIedge oI students. With the resuIt certain IundamentaI topics are IeIt uncovered or inadequateIy
treated. In addition, the subject oI physioIogy has recentIy grown so rapidIy that it is impossibIe Ior
the average student to tread the vast IieId. ThereIore, I IeIt the necessity oI writing this book with the
hope that it wouId cater to the needs oI both the categories oI studentsthose who want to study
physioIogy in its essentiaIs, and aIso those who wish to acquaint themseIves with the major areas and
Iatest deveIopments in the IieId.
WhiIe writing the book, I reaIized that with the deveIopment oI the core curricuIa oI diIIerent
universities at various IeveIs oI instruction, the presentation oI the subject shouId provide aII essentiaI
aspects reIated to it. StiII, Iimits had to be imposed on its treatment since the purpose was not to write
a comprehensive treatise. In Iact, the objective was to initiate the student in the study oI the subject
and at the same time to prepare a book that wouId meet the requirements oI various syIIabi. Human
physioIogy has been surveyed at appropriate pIaces without exhaustive treatment.
The book is divided into 18 chapters which are arranged in a Iashion that the reader can deveIop
his ideas step by step. The subject matter gives a comprehensive coverage to such essentiaI areas as
the structure oI ceIIs and their Iunction, IoodstuIIs, digestion and absorption, bioIogicaI oxidations,
metaboIism, water reIations and ionic reguIations, temperature reguIation, body IIuids and their roIe,
circuIation oI bIood, respiration, excretion, nerve physioIogy, sensory mechanisms, nerve
coordination, eIIector organs, hormonaI reguIation, reproduction, and physioIogicaI genetics. The
discussion oI each area is intended to provide an understanding oI important Iacts drawn Irom
reIativeIy new and up-to-date sources that wiII stimuIate students` interest. The book can be proIitabIy
used by them whether they are speciaIizing in areas oI zooIogy, veterinary or human medicine, or
nutrition.
Perhaps it is not customary to begin a book on animaI physioIogy with a chapter on ceII structure
and Iunction as has been done in the present case. The ceII Iorms the basic unit oI IiIe and aII physico-
chemicaI and vitaI IiIe Iunctions were Iirst discovered at the ceII IeveI and Iater extended to the
organismic IeveI. I consider it diIIicuIt, iI not impossibIe, to understand the Iunctioning oI the whoIe
organism without a good knowIedge oI the IundamentaI processes at the ceIIuIar IeveI. One way oI
trying to understand a compIex system is to IormuIate a modeI that exhibits the same properties as are
Iound in the entire organismthat modeI being the ceII. Keeping this in mind I have decided to
incIude this chapter which, I beIieve, wiII enchance the character oI the book in its broad-based bias.
The chapter on IoodstuIIs is comprehensive and highIights chemicaI detaiIs to emphasize the
important point, viz. the various types oI Iood eaten by animaIs are used as IueIs Ior the generation oI
energy expIainabIe in chemicaI terms. ChemicaI detaiIs are necessary to expIain their IunctionaI
signiIicance. The types oI Iood and their chemicaI composition shouId be an important piece oI
inIormation to the students to enabIe them to know as to how animaIs obtain their energy
requirements Irom the compIex IoodstuIIs. A chapter on bioIogicaI oxidations has been incIuded.
BioIogy students have a tendency to ignore this area which is very much a part oI physioIogy essentiaI
to the strengthening oI the basic concepts. It was thought that the initiaI approach to physioIogy must
be to anaIyse physioIogicaI processes in terms oI chemicaI reactions Irom the point oI view oI
energetics.
ReIevant biochemicaI detaiIs are given to the extent they are necessary. The aim was to expIain
rather than to describe principIes oI animaI physioIogy, and thereIore, in some parts I have Ieaned on
biochemistry to achieve this end. The pertinence oI many areas wiII be quite obvious. At appropriate
pIaces, experimentaI detaiIs have been given in support oI the IactuaI statements and hypotheses. The
bibIiography wiII be heIpIuI to an aIert student interested in more detaiIs about the subject.
In a work Iike this, it is impossibIe to accompIish the task without the encouragement and
invaIuabIe heIp oI many. I, thereIore, wish to thank Dr. C.R. Mitra, Director oI the Institute; ProIessor
V. Krishnamurty and T.S.K.V. Iyer Ior the much needed encouragement through the preparation oI the
book. A text oI this type wouId not be possibIe without the aid oI speciaIists in the IieId. AccordingIy
I wish to thank ProIessors H.S. Chaudhury (Gorakhpur University), R. Nagbhushanam (Marathwada
University) and V.P. AgarwaI (D.A.V. CoIIege, MuzaIIarnagar, Meerut University) who served as
members oI the University Grants Commission editoriaI committee, and the reviewer oI the NationaI
Book Trust. They have read the entire manuscript with meticuIous care and oIIered vaIuabIe
comments and exceIIent suggestions about the subject matter. On the basis oI the reviewers`
comments, substantiaI additions have been made in the textuaI matter resuIting in rewriting a Iarge
part oI the manuscript. With the resuIt, the Iirst draIt has been thoroughIy revised and enIarged.
AIthough I have grateIuIIy adopted many oI their suggestions, yet I have sometimes preIerred my own
viewpoint as weII.
I appreciate Dr. H.L. Kundu`s sincere cooperation which I have aIways enjoyed in abundance. I
aIso acknowIedge the assistance extended by Dr. M. Ramakrishna, who was associated with the
project Ior some time, in writing Chapters 1 to 3.
Most particuIarIy, I am grateIuI to the University Grants Commission Ior IinanciaI assistance
under its Book Writing Project sanctioned to me Ior the duration January 1973 to August 1975,
without which this book couId not have taken shape. However, Chapters 16 to 18 were written aIter
the termination oI the project. My sincere thanks are aIso due to Dr. V.N. Sharma Ior his vaIuabIe heIp
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in the preparation oI bibIiography, index and some diagrams incIuded in the text. I am grateIuI to him
Ior his constructive criticism oI Chapters 17 to 18. My speciaI thanks are due to ProIessor S.C. ShukIa
Ior his advice on speciIic points whiIe checking some sections oI the manuscript.
PiIani S.C. Rastogi
December 1, 1976
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Preface to the Fourth Edition v
Preface to the First Edition vii
1. Cell Structure and Function 1
1.1 GeneraI Structure oI CeII 2
1.2 PIasma Membrane 4
1.3 EndopIasmic ReticuIum 8
1.4 GoIgi Apparatus 10
1.5 The Lysosome System 13
1.6 Mitochondria 16
1.7 CentrioIe 19
1.8 NucIeus 20
2. Foodstuffs 25
2.1 Carbohydrates 25
2.2 Proteins 30
2.3 Lipids 39
2.4 Vitamins 47
2.5 MineraIs and Water 56
3. Biological Oxidations 65
3.1 Bioenergetics 65
3.2 Types oI Reactions 67
3.3 CoupIed Reactions 68
3.4 Energy Expenditure in MetaboIic Processes 70
3.5 Oxidation-Reduction Reactions 71
3.6 The Cytochrome System 72
3.7 The FIavoproteins 73
3.8 Dehydrogenation 74
3.9 Energy ReIease and Oxidative PhosphoryIation 75
3.10 GIucose Oxidation 75
4. Enzymes-The Biological Catalysts 79
4.1 GeneraI Properties oI Enzymes 79
4.2 The Mechanism oI Enzyme Action 82
4.3 CIassiIication oI Enzymes 85
4.4 Factors InIIuencing Enzyme Activity 86
4.5 Isoenzymes 90
4.6 AIIosteric Enzymes 90
4.7 Coenzymes 91
5. Animal Calorimetry 93
5.1 AnimaI CaIorimetry 93
5.2 BasaI MetaboIism 96
5.3 CaIoric Requirement 98
6. Metabolism 100
6.1 Oxidation oI Amino Acids 101
6.2 Urea Synthesis 102
6.3 DecarboxyIation 102
6.4 Reactions oI Some Amino Acids 103
6.5 MetaboIism oI Creatine and Creatinine 104
6.6 SuIphur MetaboIism 104
6.7 MetaboIism oI NucIeoprotein 105
6.8 BIood Sugar 108
6.9 GIycoIysis 109
6.10 GIycogenesis 111
6.11 GIuconeogenesis 111
6.12 MuscIe GIycogen 112
6.13 MetaboIism oI Other Sugars 112
6.14 RoIe oI Liver in Fat MetaboIism 113
6.15 Oxidation oI Fatty Acids 114
6.16 >-Oxidation oI Fatty Acids 115
6.17 MetaboIism oI GIyceroI 118
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6.18 Synthesis oI GIycerides and Fatty Acids 118
6.19 MetaboIism oI PhosphoIipids 119
6.20 MetaboIism oI ChoIesteroI 119
6.21 Ketogenesis 121
7. Digestion and Absorption 124
7.1 Modes oI Nutrition 124
7.2 Intake oI Food MateriaIs 125
7.3 Digestion oI FoodstuIIs 127
7.4 Digestion in MammaIs 132
7.5 Digestion in Other Vertebrates 144
7.6 Digestion in Invertebrates 145
7.7 Carbohydrate Absorption 146
7.8 Protein Absorption 148
7.9 Absorption oI Fat 149
7.10 Absorption oI Other Substances 150
8. Water Relations and Ionic Regulations 154
8.1 RoIe oI Membranes in Osmotic and Ionic ReguIations 155
8.2 Some DeIinitions 162
8.3 Aquatic and TerrestriaI Habitats 164
8.4 ProbabIe Movements oI AnimaIs Between DiIIerent Environments 165
8.5 RoIe oI Body FIuids 168
8.6 Adaptation to Marine Habitat 169
8.7 Adaptations to Brackish Water Habitat 171
8.8 Adaptation to Freshwater Habitat 174
8.9 Adaptations to TerrestriaI Habitat 175
8.10 Return to the Sea 178
9. Membrane Physiology 182
9.1 ChemicaI Composition oI Membranes 182
9.2 Membrane Architecture 186
9.3 Membrane Transport Functions 191
9.4 Mechanisms Ior Transport oI MateriaIs Across Membranes 193
9.5 BuIk Transport Systems 198
10. Temperature Regulation 203
10.1 Habitats oI AnimaIs 203
10.2 NomencIature oI ThermoreguIation 204
10.3 Energy ReIationships oI AnimaIs 205
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10.4 Low Temperature EIIects 206
10.5 Temperature ReIations in PoikiIotherms 207
10.6 Temperature ReIations oI Homotherms 210
10.7 Temperature ReIations oI Heterotherms 212
10.8 ThermoreguIatory ControI Centre 213
10.9 Temperature ReguIation in Endotherms 214
10.10 AccIimatization 218
11. Body Fluids 220
11.1 Major Types oI Body FIuids 220
11.2 BIood 221
11.3 GeneraI Properties oI BIood 222
11.4 Composition oI BIood 223
11.5 Formed EIements oI BIood 226
11.6 BIood Groups and TransIusions 232
11.7 CoaguIation oI BIood 237
11.8 Theories oI CoaguIation 239
11.9 HaemoIysis 240
11.10 HaematoIogicaI AbnormaIities 242
12. Circulation of Blood 244
12.1 The BIood VoIume 245
12.2 The Components oI CircuIatory System 245
12.3 Heart oI Invertebrates 246
12.4 Heart oI Vertebrates 247
12.5 PhysioIogicaI Properties oI Cardiac MuscIes 248
12.6 ReguIation oI the Heart 257
12.7 ChemicaI ReguIation 261
13. Respiration 263
13.1 Respiratory Devices 264
13.2 Mechanism oI Breathing 268
13.3 Respiratory Pigments 270
13.4 Properties oI Respiratory Pigments 272
13.5 Factors AIIecting Oxygen Dissociation 273
13.6 Transport oI Carbon Dioxide 276
13.7 BuIIer Systems oI BIood 277
13.8 Acid-Base Disturbances oI Respiratory Origin 279
13.9 Acid-Base Disturbances oI Non-respiratory Origin 280
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13.10 ReguIatory Processes in Respiration 280
14. Excretion 285
14.1 Organs oI Excretion 285
14.2 Types oI Excretory Products 286
14.3 Patterns oI Excretion 291
14.4 Changes in Nitrogen Excretion with LiIe CycIe 293
14.5 Dietary InIIuence on Nitrogen Excretion 294
14.6 Excretory Devices in Invertebrates 294
14.7 Excretion Devices in VertebratesRenaI PhysioIogy 296
14.8 Composition oI Urine 304
14.9 Countercurrent Mechanism 306
14.10 Acid-Base ReguIation 307
14.11 RenaI ControI Mechanisms 309
15. Nerve Physiology 311
15.1 Units oI the Nervous System 312
15.2 IrritabiIity 315
15.3 EIectricaI Phenomena oI Nerves 316
15.4 Theories oI Excitation 324
15.5 Factors InIIuencing Excitation and Propagation 325
15.6 ImpuIse Propagation 326
15.7 Synaptic Transmission 330
16. Sensory Mechanisms 334
16.1 CIassiIication oI Receptors 334
16.2 Chemoreceptors 335
16.3 Mechanoreceptors 338
16.4 Radioreceptors 347
17. Nervous Coordination 354
17.1 Integration 355
17.2 Synaptic Integration 355
17.3 Types oI ReIIexes 359
17.4 CIassiIication oI ReIIexes 361
18. Effector Organs 371
18.1 AnimaI Movement 371
18.2 Structure oI MuscIes 372
18.3 Composition oI MuscIes 374
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18.4 NeuromuscuIar Junction 377
18.5 ExcitabiIity oI MuscIe Tissue 378
18.6 MuscIe Contraction 379
18.7 Theories oI Contraction 388
18.8 ChemicaI Basis oI Contraction 390
18.9 BioeIectrogenesis 394
18.10 BioIuminescence 395
18.11 Chemistry oI BioIuminescence 396
18.12 CoIour Production 400
18.13 Mechanism oI Action oI Chromatophores 402
19. Hormonal Regulation 404
19.1 The Pituitary 410
19.2 The Pancreas 425
19.3 HormonaI ControI oI Growth 427
19.4 HormonaI ControI oI Ionic and Water BaIance 427
19.5 ProstagIandins 429
19.6 HormonaI ReguIation in Invertebrates 430
20. Reproduction 435
20.1 LeveIs oI Reproduction 435
20.2 Patterns oI Reproduction 436
20.3 MorphoIogy oI the Reproductive Organs 437
20.4 Breeding CycIes 443
20.5 HormonaI ControI oI Sex and Reproduction 444
20.6 HormonaI ControI in FemaIes 444
20.7 GonadaI Hormones 446
20.8 Puberty 448
20.9 Estrous Behaviour 449
20.10 OvuIation 452
20.11 Sperm Transport in the FemaIe GenitaI Tract 453
20.12 ImpIantation 454
20.13 PIacentation 455
20.14 Parturition 456
20.15 Lactation 458
21. The Genetic Code and Protein Synthesis 461
21.1 The Organization oI the Chromosome 462
21.2 RepIication oI DNA 463
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21.3 The Genetic Code 467
21.4 Synthesis oI PoIyribonucIeotides 467
21.5 Protein Synthesis 471
22. Physiologic Disorders 478
22.1 OrganeIIe MaIIunction 478
22.2 MetaboIic Disorders 483
23. Physiological Genetics 486
23.1 The Gene as a FunctionaI Unit 486
23.2 ControI oI MetaboIic Processes 487
23.3 NucIeus-CytopIasmic Interaction 490
23.4 TranspIant Experiments 492
23.5 Genetic ControI oI Eye Pigments 493
23.6 Genic ControI oI DeveIopment 495
23.7 EIIects oI Gene Mutations 497
23.8 Inborn Errors oI MetaboIism: Genic DeIects 498
24. Immune System 502
24.1 Types oI Immunity 502
24.2 What are Antigens? 503
24.3 Types oI ImmunogIobuIins 504
24.4 Lymphocytes and the Lymphatic System 507
24.5 Antigen-Antibody Interaction 509
24.6 TranspIantation Immunity 516
24.7 AIIergy 519
25. Physiology of Aging 521
25.1 Aging at CeIIuIar LeveI 521
25.2 Aging at the MoIecuIar LeveI 523
25.3 Aging oI Connective Tissue 526
25.4 Aging and ImmunoIogicaI SurveiIIance 527
25.5 MentaI Aspects oI Aging 528
25.6 Theories oI Aging 528
Self Assessment Questions (SAQs) 532
Review Questions 550
Bibliography 561
Index 567
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Every muIticeIIuIar organism is composed oI ceIIs, which are the basic units oI IiIe. The ceII can be
Iikened to a Iactory. A Iactory has severaI machines which are Iinked to one another in speciIic order
and each one makes a particuIar component. By sequentiaI operations, the components Irom these
machines are, assembIed to produce the desired products. SimiIarIy the ceIIuIar constituents, each
with their speciIic Iunction, have a deIinite arrangement. They produce the components, in this case
moIecuIes, which are assembIed to synthesize the required products (macromoIecuIes). The Iunction
oI the organism as a whoIe is the resuIt oI the combination oI activities and interactions oI the ceII
units in its body. Hence to understand the essentiaI physioIogy oI animaIs we need to know the
physioIogicaI Iunctions oI the ceIIthe ceII which is a IundamentaI unit oI IiIe.
The Iiving ceII perIorms aII the Iunctions oI IiIe such as intake oI nutrients, metaboIism, growth,
reproduction, etc. To perIorm these IiIe activities the ceII has in it various ceIIuIar constituents or
organeIIes.
Our knowIedge oI the structure and Iunction oI the ceIIuIar constituents has greatIy increased
with the deveIopment oI eIectron microscope by KnoII and Ruska in 1933 and the centriIuge by
Swedberg in 1924.
EIectron microscope became avaiIabIe in 1940. It paved the way Ior a more speciIic knowIedge
oI the ceII structure and the structure oI organeIIes within the ceII. It permits magniIications oI
1,000,000 times or more, i.e. down to the moIecuIar dimensions. It has reveaIed the strict and orderIy
patterns oI arrangement oI macromoIecuIes constituting the organeIIes oI the ceII. Hence with the
eIectron microscope it is possibIe to observe the structuraI pattern oI organeIIes, but the Iunction oI
organeIIes and oI their constituent chemicaI components couId be observed by other instruments and
techniques. The Swedberg centriIuge which gives quantitative data on sedimentation rates has, to
some extent, heIped their observation in the above mentioned aspect. The uItra-centriIuges which are
now avaiIabIe whirI at 65,000 rpm and produce a centriIugaI Iorce which is 425,000 times that oI
gravity. With the heIp oI uItracentriIuge the constituent parts oI the ceIIs Irom macerated tissue can be
CeII 5tructure ond
Function
+ 0 ) 2 6 - 4

Animal Physiology
separated into Iayers depending upon their weights. Under the microscope, these Iayers can then be
identiIied with the constituent parts and studied Ior their activities.
The eIectron microscope and the uItracentriIuge have heIped in the merger oI cytoIogy and
biochemistry, and soIved many physioIogicaI intricacies oI the ceII.
3.3 GENERAL STRUCTURE DF CELL
The various ceIIuIar organeIIes as seen in eIectron microscope are incorporated in Fig. 1.1 to give a
comprehensive view oI their arrangement in the ceII. The detaiIed structure and Iunction oI each
organeIIe is deaIt with under separate headings.
FIg. 1.1 Ceneralized structure of a cell (adapted from J. Brachet. Sci. Amer. 205:3 (l96l)).
Region containing
microtubules and microfibrils
Pinocytotic
vesicles
Golgi
apparatus
Centrosomes
Secretion
vacuole
Ribosomes
attached to
reticulum
Endoplasmic
reticulum
Cytoplasmic
matrix
Mitochondrian
Plasma membrane
Nuclear
membrane
Phospholipid
storage granule
neutral lipid
storage granule
Lysosome
Nucleus
Nucleolus
Cell Structure and Iunction !
The ceII contains cytopIasm which is an active IIuid medium that heIps carry out its IiIe activities.
The cytopIasm is a coIIoidaI soIution mostIy containing water. About 30 per cent oI the totaI mass oI
this soIution consists oI various substances. OI these substances, about 60 per cent are proteins, and
the remainder consists oI carbohydrates, Iipids, other organic substances, and inorganic materiaIs. The
cytopIasm is enveIoped by a membrane known as pIasma membrane. The pIasma membrane is oIten
termed as cytopIasmic membrane.
CytopIasmic matrix is a ground substance and usuaIIy it is poIyphasic in nature. Some authors
reIer to this matrix as groundpIasm. It is the internaI environment oI the ceII. Suspended in the
cytopIasm, i.e. matrix, are the various organeIIes and incIusions. The organeIIes are the Iiving
materiaIs and the incIusions are IiIeIess and oIten temporary materiaIs. The Iatter comprise pigment
granuIes, secretory granuIes, and nutrients, whiIe the Iormer are the endopIasmic reticuIum, the
mitochondria, the GoIgi compIex or apparatus, the ribosomes, the Iysosomes, the centrioIes and the
nucIeus.
Three decades ago onIy the cytopIasm and the nucIeus were known to be enveIoped by
membranes. With the advent oI eIectron microscope it was Iound that the various organeIIes and
incIusions IIoating in the cytopIasm are aIso enveIoped by membranes and separated Irom the
cytopIasm.
The commonIy represented organeIIes as weII as incIusions which are covered by membranes are:
the pIasma-membrane, rough and smooth endopIasmic reticuIum, GoIgi apparatus, Iysosomes,
mitochondria, nucIear enveIope, centrioIes, phagosomes, pinocytic vesicIes, etc. There does not exist
a typicaI ceII in any tissue that is represented by a set oI aII these organeIIes. Based on the IunctionaI
requirements, the ceIIs in various tissues have one or the other oI these organeIIes, i.e. the
endopIasmic reticuIum is dense in ceIIs oI pancreas; the Iysosomes are weII deveIoped in
macrophages; pinocytic vesicIes are common in Iiver ceIIs; GoIgi vesicIes are conspicuous in storage
and secretory tissues; and mitochondria are numerous in the ceIIs oI aII tissues which expend high
energy.
WhiIe many ceIIuIar organeIIes consists oI a singIe unit membrane (vide page 6) certain
organeIIes, such as mitochondria and nucIear enveIope, have two such membranes, one enveIoped by
the other. The ceIIuIar membranes oI the ceII heIp reguIate the passage oI substances through them
and such a passage may be by passive diIIusion, or by active transport invoIving the aid oI enzymes
(see Chapters 3 and 7) which are Iocated in the membranes. Another important Iunction oI the
membrane is to provide a surIace Ior harbouring the enzymes.
NucIeus is the most conspicuous structure in a ceII. UsuaIIy each ceII has one nucIeus, but ceIIs,
such as Iiver ceIIs, and skeIetaI muscIe ceIIs contain more than one. The IIuid matrix oI the nucIeus is
known as karyopIasm or nucIeopIasm. It is enveIoped by a doubIe Iayered nucIear membrane. The
karyopIasm has denseIy staining particIe caIIed the nucIeoIus. It is Iarge in growing ceIIs and
disappears during ceII division. Sometimes the nucIeus may have more than one nucIeoIus. The
karyopIasm is not greatIy diIIerent Irom the physicaI and chemicaI properties oI cytopIasm. The most
important content oI karyopIasm is the chromatin, which is a combination oI protein and
deoxyribonucIeic acid (DNA). It is granuIar in nature but during ceII division it is transIormed to Iong
strands caIIed ?DHIAI.
Animal Physiology "
3.E PLASMA MEMBRANE
There aIways exists a state oI imbaIance in the concentration oI ions and moIecuIes between the ceII
and its environment. This diIIerence is maintained by the pIasma membrane which is the Iimiting
Iayer oI the ceII. In order to maintain this dynamic reIationship, nutrients must IIow in and reaction
products Irom the ceII must IIow out through the pIasma membrane constantIy but in a controIIed
manner. Once inside the ceII the nutrients, i.e. carbohydrates, proteins, Iipids, mineraIs, and vitamins
can participate in the metaboIic processes. How is this dynamic reIation maintained? To answer this
we need to know the moIecuIar architecture oI the membrane. Such an architecture was conjectured
Iong beIore the avaiIabiIity oI eIectron microscope. However, it is cIear that the perIormance oI
pIasma membrane is inIIuenced by three Iactors; one oI them is its own capabiIity, second is the
supporting ceIIuIar activity, third is degree oI stress by the environment upon the membrane. The Iirst
point, i.e. pIasma membrane`s own capabiIity in transporting substances, can best be understood by
studying its structure.
Structure
PIasma membrane is essentiaI Ior the IiIe oI the ceII. It is a bio-membrane that Iies cIose to the
cytopIasm. The structure oI aII bioIogicaI membranes was deduced Irom the knowIedge oI their
IunctionaI roIe. AII bioIogicaI membranes have many properties in common. This Ied to the
assumption that they aII have the same basic moIecuIar structure. Since IipophiIic substances
preIerabIy permeate through the membrane, it was conceived that the ceII has a Iipid covering. But
how are the Iipid moIecuIes arranged in the membrane? For this an understanding oI the behaviour oI
Iatty acid moIecuIes with water medium is required because the Iipid moIecuIes in the bio-membrane
behave much in the same way. Each Iatty acid moIecuIe contains a hydrophiIic carboxyI group known
as poIar head, and a hydrophobic hydrocarbon chain caIIed nonpoIar taiI. The carboxyIic group oI the
Iatty acid is the charged end. This group dissociates Iorming hydrogen bonds when it comes in
contact with water. Thus at the water Iace severaI Iatty acid moIecuIes arrange themseIves in a singIe
Iayer with their hydrophiIic poIar heads in contact with water and the hydrophobic hydrocarbon
chains away Irom water surIace (Fig. 1.2). Fatty acid moIecuIes wouId be arranged as doubIe Iayers in
apertures separating two water compartments. In this case the hydrocarbon, chains oI the two
moIecuIar Iayers being hydrophobic, extend inwards Iorming a hydrocarbon phase, whereas the poIar
heads being hydrophiIic Iie in contact with aqueous medium (Fig. 1.2).
The ceII has aqueous medium inside as weII as outside. Hence the Iipids in the pIasma membrane
are arranged in two Iayers, each Iayer being one moIecuIe thick. The inner Iayer with poIar heads
Iacing the ceII, the outer Iayer with poIar heads Iacing away Irom the ceII, and the hydrocarbon chains
oI both the Iayers Iacing each other in the same way as in Fig. 1.2. Thus the poIar heads oI inner and
outer Iayers are in contact with intra-ceIIuIar and extra-ceIIuIar aqueous media respectiveIy. Further
prooI as to the bimoIecuIar nature oI Iipids was provided by the measurements oI the amount oI Iipid
present in the ceII membranes oI red bIood ceIIs. The measurements suggested that the quantity oI the
Iipid present was just suIIicient to cover the surIace oI the ceII with a bimoIecuIar Iayer. It has been
Iound that the Iipid portions oI the membranes are either phosphoIipids, cerebrosides, or choIesteroI.
When Iipids are phosphoIipids, the poIar heads have charged phosphates. Measurements oI the
Cell Structure and Iunction #
surIace tension oI membranes have indicated that it is Iower than that oI the Iipid surIace. Such a Iow
surIace tension is interpreted to be due to the existence oI a protein coating on either side oI the Iipid
biIayer oI the ceII membrane. Based on the physicaI properties oI the ceII membranes, such as
preIerentiaI permeabiIity to Iipid soIubIe substances, occurrence oI Iow surIace tension, and high
eIectricaI resistance, DanieIIi and Davson (1935) deduced the structure oI the membranes. They
suggested the existence oI a continuous Iayer oI Iipid moIecuIes with their poIar groups directed
towards the exterior and interior oI the ceII; and a coating oI a singIe Iayer oI protein moIecuIes on the
poIar surIaces; the protein Iayer consisting oI poIypeptide chains or meshworks oI such chains (Fig.
1.3).
Robertson (1959) suggested the structure oI a membrane which nearIy corresponds to the one
proposed by DanieIIi and Davson. He caIIed it a unit membrane. However, the structure oI this unit
membrane was evoIved by the studies based on eIectron microscopy, X-ray diIIraction and chemicaI
techniques. According to him the unit membrane has a centraI core oI bimoIecuIar IeaIIet oI Iipid on
either side by a singIe Iayered IuIIy spreadout hydrophiIic protein or nonIipid materiaI.
AIter examining the ceII membranes oI a variety oI tissues Irom pIants and animaIs, Robertson
(1960) postuIated the probabiIity oI its universaI occurrence in animaIs and pIants. The unit
membrane may act as a barrier between the ceII and its environment, and between the ceII-organeIIes
and the ceII-matrix. In Iater studies Robertson observed that the outer and inner protein Iayers oI
pIasma membranes diIIer in chemicaI reactions. This Ied Robertson to amend the concept oI the
universaIity oI unit membrane. In such asymetricaI pIasma membranes he suggested that the Iayers on
one side oI the Iipid core is made up oI protein and the other is made up oI carbohydrate perhaps in
the Iorm oI mucopoIysaccharide (Fig. 1.3).
It is weII known that the membranes have diverse physioIogicaI Iunctions. In accordance to the
requirements oI organeIIes, ceII and tissues, the membranes seIect and aIIow the admission oI
nutrients. Such diversities in the membranes may be due to: (=) the assortment oI Iipid constituents in
FIg. 1.2 Behaviour of the fatty acid molecules at the water surface.
(a)
Water
Hydrocarbon chain
Polar head (hydrophilic)
Hydrocarbon phase
(b)
Water Water
Animal Physiology $
the centraI core; (>) the character oI non-Iipid monoIayer on either side oI the Iipid biIayer; (?) the
chemicaI speciIicity oI certain areas oI a continuous membrane.
To expIain certain aspects oI membrane permeabiIity, DanieIIi suggested the existence oI poIar
pores Iined by protein moIecuIes. According to SoIomon (1960) these are not the Iixed pores but act
as and when required by the intra-and extra-ceIIuIar conditions. These conditions cause some pores to
open and the rest to cIose. He supposed that a Iarge part oI traIIic IIows through these pores in the
membrane.
The membrane is a barrier to the intra-ceIIuIar protein anions whereas it aIIows water, sodium,
potassium, and chIoride. Thus the membrane is semipermeabIe in its nature. As a resuIt oI
semipermeabiIity oI the membrane, chemicaI and eIectricaI gradients are created (see aIso Chapter 7).
FIuid-mosaic ModeI of Membrane
RecentIy Singer and NicoIson (1972) have proposed a working modeI which has been wideIy
accepted. Robertson`s modeI envisages a uniIorm structure oI the pIasma membrane but according to
FIg. 1.3 Membrane models proposed by (a) Danielli and Davson (l935), (b) Davson and Danielli (l9+3), (c) Robertson
(l965).
(a)
Danielli and Davson
1935
(c)
Robertson
1961/1965
(b)
Davson and Daneilli
1943
Cell Structure and Iunction %
The membrane proteins pIay a very active roIe in the structure and Iunctions oI the membrane.
They are oI two types: peripheraI (extrinsic) and integraI (intrinsic). The peripheraI proteins are
superIiciaIIy Iocated and many oI these are enzyme proteins. The integraI proteins associated with the
biIayer oI phosphoIipids penetrate into the interior oI the membrane aIong with the Iatty acid side
chains. They are tightIy bound to the Iipids and constitute the IunctionaI proteins not easiIy separabIe.
AII membrane bound enzymes, carriers etc. are incIuded in this category. PeripheraI proteins have a
Ioose aIIinity and can be easiIy dispIaced. Such a membrane is dynamicaIIy more stabIe and can
expIain the intricate transport phenomena across the membrane.
ChemicaI Gradient
The ceII has in it, higher concentrations oI potassium, protein and reIated anions whereas outside it
has sodium and chIoride in higher concentrations. Hence a chemicaI gradient exists between a region
oI high concentration and a region oI Iow concentration. SoIutes Irom higher concentration tend to
diIIuse through the pIasma membrane towards Iow concentration. The movement oI potassium ions
Irom the ceII to the exterior is said to be passive and down the concentration gradient. The movement
oI sodium and chIoride into the ceII is said to be down in the gradient. To maintain the gradients the
substances moving passiveIy aIong the gradients must be counter-baIanced by active transport, which
restores the extruding potassium ions to the ceII and the intruding sodium ions to the environment.
the proposed modeI, in most oI the membranes, the Iipids are in the Iorm oI a IIuid biIayer and the
proteins do not Iorm a sandwich covering oI hydrophiIic biIayer Iipid covering. The membrane
proteins are Iound to be embedded in the biIayer (Fig. 1.4). The Iipids, which are mostIy
phosphoIipids and gIycoIipids in nature, when suspended in water give rise to aggregates oI many
Iorms and shapes by Iorming miceIIes. These aggregates stiII preserve the hydrophiIic and
hydrophobic characteristics oI the phosphoIipids, but the hydrophobic regions are internaIIy arranged
in such a way so that water is expeIIed out oI them, whiIe the hydrophiIic regions remain in contact
with the outer aquatic phase.
FIg. 1.4 Fluid mosaic model of the plasma membrane as proposed by Singer.
Hydrophilic
area
lntegral
protein
Peripheral
protein
Phospholipid
bilayer
Hydrophilic
area
Animal Physiology &
EIectricaI Gradient
The membranes oI aII Iiving ceIIs exhibit a diIIerence oI eIectricaI potentiaI. The potentiaI diIIerence
oI most membranes is Iound to be oI the order oI 100 mV. Such a potentiaI diIIerence strongIy
inIIuences the movement oI charged materiaIs, particuIarIy inorganic ions, across the membranes.
UsuaIIy the interior oI the ceII is eIectricaIIy negative. The chIoride, which is negativeIy charged,
is known to exist in high concentration outside the ceII. II it diIIuses down the concentration gradient
into the ceII, it wouId promptIy be Iorced back down the potentiaI gradient.
3.3 ENDDPLASMlC RETlCULUM
EndopIasmic reticuIum is a membranous system oI canaIs extending Irom pIasma membrane to the
nucIear membrane. These canaIs have the same environment that exists around the ceII because they
are in direct connection with extraceIIuIar medium. In other words, the network oI canaIs provide
extraceIIuIar environment deep inside the ceII and surrounding the nucIeus. The advantage oI such an
environment within the ceII is that it provides opportunity Ior a rapid transIer oI substances between
extraceIIuIar and intraceIIuIar environments. The endopIasmic reticuIum suppIies nutrients to the
organeIIes in the cytopIasmic matric and removes Irom them the products oI synthesis and
degradation. In a three dimensionaI view (Fig. 1.5) the endopIasmic reticuIum exhibits cavities oI
varying sizes and shapes. These appear as vesicIes and tubuIes or as IIattened sacs. For Iaboratory
studies, Iragmentation oI the endopIasmic reticuIum is brought about by uItracentriIugation.
Ribosomes
Matrix
Membranes
FIg. 1.5 The three-dimensional view of the endoplasmic reticulum.
Cell Structure and Iunction '
The endopIasmic reticuIar membrane, Iike pIasma membrane is a unit membrane oI the type
described by Robertson. The surIace Iayers oI two membranes are connected by protein septa. The
endopIasmic reticuIum exists in aII ceIIs oI higher animaIs except in mature erythrocytes. The
compIexity oI reticuIum increases with an increase in the degree oI protein synthesis activity within
the ceII. AccordingIy, in secretory ceIIs the reticuIum is weII deveIoped. The absence oI both the
nucIeus and the endopIasmic reticuIum is expIained to be the reason Ior the absence oI enzymatic
synthesis in mature erythrocytes.
The endopIasmic reticuIum is subdivided into areas with speciaIized Iunctions. These areas
incIude the granuIar or rough endopIasmic reticuIum, the agranuIar or smooth endopIasmic reticuIum,
the nucIear enveIop, and the GoIgi apparatus. The IunctionaI signiIicance oI these various speciaIized
areas is discussed under the titIe GoIgi apparatus.
GranuIar or Rough EndopIasmic ReticuIum
Growing ceIIs as weII as those engaged in protein synthesis are rich in granuIar or rough
endospIasmic reticuIum. The membrane oI this reticuIum, aII aIong its outer surIace Iacing the
cytopIasmic matrix, is studded with uniIorm size oI particIes caIIed ribosomes. High density oI
ribosomes wouId mean greater protein synthetic activity.
AgranuIar or Smooth EndopIasmic ReticuIum
The outer membrane oI this reticuIum is devoid oI the ribosomes and hence it is termed agranuIar or
smooth endopIasmic reticuIum. It is continuous with rough endopIasmic reticuIum and with GoIgi
apparatus. It is present in ceIIs synthesizing steroids, in voIuntary muscIe ceIIs and in Iiver ceIIs.
The NucIear EnveIope
The nucIear membrance is covered over by a Iarge cisternaI unit oI granuIar endopIasmic reticuIum.
At intervaIs the nucIear and recuIar membranes join Iorming pores. These pores are continuous with
the cytopIasmic matrix oI the endopIasmic reticuIum. These pores aIIow the moIecuIes Irom the
nucIeus to the cytopIasmic matrix (Moses, 1964). Some investigators suggest that the pores are
covered and open onIy when traIIic is warranted. In protein synthesis, the mRNA, tRNA, and rRNA
(as ribosomes) traveI Irom the nucIeus to the cytopIasmic matrix. The direct route Ior such a traIIic
wouId be through the nucIear pore. Through these pores the nucIeus receives the nutrients Irom the
intraceIIuIar environment. The channeIs oI the endopIasmic reticuIum act as extraceIIuIar environment
and extend Irom the pIasma membrane to the nucIear enveIope. In other words the nucIeus is
surrounded by the extraceIIuIar medium. Thus the nucIeus aIso receives nutrients direct Irom the
extraceIIuIar environment.
Functions
EndopIasmic reticuIum carries out speciaIized Iunctions. These Iunctions are IocaIized in various
substructures:
(i) One oI the important Iunctions, viz. the transport, is carried out by the channeIs.
(ii) Protein synthesis is associated with the ribosomes oI the granuIar endopIasmic reticuIum.
Animal Physiology
(iii) Concentrating and packaging oI enzymes is IocaIized in the GoIgi apparatus.
(iv) Steroid synthesis takes pIace in the smooth reticuIum.
(v) The intraceIIuIar stabiIity, movement and the activation oI amino acids Ior protein synthesis,
and IinaIIy the gIycoIysis, are IocaIized in the cytopIasmic matrix.
3.4 GDLGl APPARATUS
The GoIgi apparatus, endopIasmic reticuIum, membrane bound vesicIes and Iysosomes constitute a
part oI the membrane system present in the cytopIasm oI the ceII. The constituents, though aIways
present, exist in a state oI constant changeIormation, transIormation, breaking down, and
reIormation. They aIso move within the cytopIasm. The ceIIuIar organeIIes such as, nucIear enveIope,
the rough and smooth endopIasmic reticuIum, the GoIgi apparatus, the Iysosomes, the pinocytic
vesicIes, aII have membranous covering. These organeIIes or membrane bound spaces have been
connected either by IunctionaI continuity or by morphoIogicaI connection and consequentIy
IaciIitating transport oI substances not onIy within the ceII but aIso to the exterior, and in some ceIIs
Irom the exterior into vesicIes and Iysosomes.
In this membrane bound transport system, the GoIgi apparatus occupies a position where the
nucIeus and endopIasmic reticuIum are at one end, and the vesicIes, Iysosomes and pIasma membrane
at the other end. In this system, proteins, poIysaccharides, gIycoproteins, and probabIy Iipids and
Iipoproteins are Iormed and transported. NucIeus acts as a centraI controI site Ior transport oI
substances.
Form of GoIgi Apparatus
The Iorm oI GoIgi apparatus varies Irom a compact discrete granuIe or mass to a weII dispersed
IiIamentous reticuIum. It is pIeomorphic and a variation in shape can be observed with the metaboIic
and deveIopmentaI state oI the ceII. It occurs in aImost aII ceIIs oI animaIs and pIants. It is easiIy
recognizabIe and consists oI 3 to 12 disc-shaped cisternae or saccuIes arranged compactIy one above
the other Iike a stack oI neatIy arranged saucers. The cisternae are sIightIy curved and Ior this reason
the entire GoIgi apparatus appears concave at one surIace and convex at the other (Fig. 1.6). The
materiaI between the cisternae is known as intercisternaI structure. A network oI tubuIes arises Irom
the edge oI each cisternae and sweII to Iorm various types oI vesicIes.
Formation of GoIgi Apparatus
GoIgi apparatus is Iormed by conversion oI the membrane. The deveIopment and Iormation oI GoIgi
apparatus in the ceII takes pIace in a series oI processes. These processes are: (1) the synthesis oI a
piIe oI cisternae in the absence oI pre-existing GoIgi apparatus; (2) the aIteration in the type and
number oI vesicIes; and (3) the increase in number oI piIes or stacks, in the number and size oI
cisternae, and in the number oI tubuIar and vesicuIar regions oI the stack. Another way oI Iormation
oI individuaI stacks oI cisternae is by Iragmentation oI the preexisting stacks. CytoIogicaI,
biochemicaI and chemicaI evidences indicate a IIow oI membrane materiaI Irom the rough
endopIasmic reticuIum via the GoIgi apparatus to the pIasma membrane. This suggests that Ior the
Cell Structure and Iunction
Iormation oI the cisternaI membrane, the necessary membrane materiaI come Irom the rough
endopIasmic reticuIum. To achieve the Iormation oI cisternaI membranes oI the GoIgi apparatus, it is
beIieved that Iirst the rough endopIasmic reticuIum changes to smooth endopIasmic reticuIum.
Smooth endopIasmic reticuIum then becomes the GoIgi cisternae and these cisternae break down to
Iorm vesicIes. The vesicIes can Iuse with the pIasma membrane in order to extend it (Fig. 1.7).
In the absence oI nucIeus or in the presence oI actinomycin D, the GoIgi apparatus graduaIIy
decreases in size and IinaIIy disappears. The renucIeation oI enucIeated amoebae restores the smooth
cisternae within haII an hour to one hour, and within 6-24 hours the GoIgi compIexes increase in size
and number.
During this time dense materiaI can be observed both in the Iumen oI endopIasmic reticuIum and
in the Iumen oI cisternae which participates in the membrane production.
Autoradiographic studies by G.E. PaIade and his co-workers (1964-1967) showed that dense
materiaI Irom the rough endopIasmic reticuIum was transIerred to proximaI cisternae oI the GoIgi
apparatus with the aid oI smaII vesicIes. In other words the endopIasmic reticuIum is in continuity
with GoIgi apparatus.
WhiIe the vesicIes derived Irom the reticuIum Iuse constantIy Iorming the proximaI cisternae, the
distaI cisternae oI the stack give oII vesicIes, i.e., GoIgi apparatus is conceived as having a newIy
Iorming Iace at one surIace and mature secreting Iace at the other surIace.
The membranes oI GoIgi apparatus have a chemicaI composition intermediate to that oI
endopIasmic reticuIum and pIasma membrane (Keenan and Morre, 1970). The GoIgi cisternae occupy
an intermediate position (centraI position) with precise unit membranous structures such as the pIasma
membrane and the vesicIes at the distaI or mature Iace, and with the nucIear enveIope and the
endopIasmic reticuIum membranes at the other extreme. Being thin (25 40A) the Iatter group oI
FIg. 1.6 Structure of the Colgi apparatus.
Granule
Forming pole
Pores
Cisternae
Inter-cisternal
structure
Secreting pole
Vesicles
Ribosomes
Animal Physiology
membranes are IaintIy stained, whereas the Iormer group being thick (75A) are brightIy stained
(Grove, Bracker, and Morre, 1968). The membrane system within the GoIgi apparatus exhibits
diIIerence, i.e. the cisternaI membranes at the Iorming Iace are simiIar to the membranes oI
endopIasmic reticuIum and the nucIeus; the membranes at the mature Iace are simiIar to pIasma
membrane; and the membranes between these two Iaces are intermediate in nature. The membranes in
the GoIgi apparatus are thus modiIied. The Iunction oI GoIgi apparatus is to aIter the membranes oI
endopIasmic reticuIum Ior the Iormation oI pIasma membrane.
The IoIIowing scheme iIIustrates the reIationship oI the GoIgi apparatus with the rest oI the
membrane system:
Functions
GoIgi apparatus serves as part oI an internaI transport system oI the ceII. It carries out secretory and
digestive processes. It synthesizes the Iipoprotein membranes. The GoIgi apparatus is concerned with
the Iormation and packaging oI materiaI Ior export across the pIasma membrane. The process oI
exporting is reverse oI pinocytosis. The ceII structures such as the acrosome oI the maturing
spermatids (Fawcett, 1966) and the tubuIar incIusions oI endotheIiaI ceIIs (SengeI and Stoebner, 1970)
are Iew among severaI exampIes oI secretions derived Irom the GoIgi apparatus. It is now known that
there are severaI materiaIs which are packaged and passed through the GoIgi apparatus and its
FIg. 1.7 Formation of the Colgi Apparatus
I. Material is transferred from endoplasmic reticulum to the Colgi apparatus. The endoplasmic reticular vesicles
fuse to form cisternae at the proximal end of the Colgi apparatus.
II. Cisternal contents and membranes are transferred as the cisterna is displaced distally.
III. Cisternae at the distal pole give rise to secretory vesicles.
Iv. Secretory vesicles migrate to the plasma membrane at the apex. Some increase in size while others fuse with
other vesicles.
v. vesicles fuse with the plasma membrane of the apex liberating their contents on to the surface of the cell.
Plasma membrane
Secretory
vesicle
Cisternae
Endoplasmic
reticular vesicles
Endoplasmic
reticular
R
v
iv
iii
ii
i
Cell Structure and Iunction !
associated vesicIes. Such materiaIs are mostIy poIysaccharides or proteins or Iipids in the Iorm oI
gIycoproteins or gIycoIipoproteins, and such a conjugation with carbohydrates is a prerequisite Ior
subsequent transport across the pIasma membrane.
PaIade and coworkers (1964 and 1967) have shown that the digestive enzymes (e.g. =amyIase)
or their precursors (e.g. =chymotrypsinogen) synthesized on ribosomes at the outer surIace oI the
rough endopIasmic reticuIum are passed into the Iumen across the reticuIum membrane. They are then
transIerred to the smooth endopIasmic reticuIum. Here they are packed into smaII granuIes and sent
into the Iorming surIace oI the GoIgi apparatus. Then they are concentrated as zymogen granuIes into
the vesicIes which are detached Irom the cisternae. The granuIe containing vesicIes then migrate to
the ceII apex, where the materiaI is passed out oI the ceII by reverse pinocytosis. In this process the
membrane oI the vesicIes Iuses with the ceII membrane and becomes a part oI it.
In case oI pancreatic ceIIs, the materiaI thus ejected out oI the ceII Iinds its way into the
pancreatic duct and eventuaIIy into the intestine. SimiIar events have been observed Ior the mucous
production in the gobIet ceIIs oI the coIon oI rats.
3.5 THE LYSDSDME SYSTEM
Present in the cytopIasm are smaII membrane-bound vesicIes containing a group oI hydroIytic
enzymes. BiochemicaI studies reveaI that aII the enzymes in these vesicIes show an acid pH optimum.
These enzymes serve to destroy certain parts not required by the ceII. For this reason de Duve (1955)
named the vesicIes containing these enzymes as Iysosomes. The Iysosomes aIso digest the
macromoIecuIes taken in across the pIasma membrane. Hence the Iysosomes can be described as the
digestive system oI the ceII.
Large numbers oI Iysosomes are present in white bIood ceIIs, macrophages, and in the ceIIs oI
Iiver, kidney, thymus and spIeen. They were biochemicaIIy separated by NovikoII et aI. (1956). They
observed these as surrounded by a unit membrane containing acid phosphatase. This is a
characteristic enzyme oI Iysosome.
The Iysosome is the seat Ior a minimum oI tweIve hydroIytic enzymes. AII these act in acid pH
and spIit the bioIogicaI substances such as proteins, nucIeic acids, and poIysaccharides. The
Iipoprotein oI the unit membrane prevents these enzymes Irom being harmIuI to the ceII. Inspite oI
this, the substances can be digested by the action oI enzymes iI they come to a reasonabIe distance
Irom the IysosomaI membrane. The Iysosome may be described as a packet containing enzymes
inaccessibIe to the rest oI the ceII. However, the enzymes are reIeased within the ceII, iI the membrane
is injured. In such a case the ceII wouId be digested.
FIg. 1.S The relationship of Colgi apparatus with other organelles.
Nuclear envelope
Endoplasmic reticulum
Plasma membrane
Golgi apparatus
Lysosome
º
º
º
Animal Physiology "
Structure
The Iysosome is smaII in size, Iacks uniIorm appearance, and has no characteristic Iine structure. It
diIIers not onIy among the ceII types but aIso within the ceII types. Some oI the diIIerences have
aIready been known whiIe much awaits investigation. According to de Duve, the Iysosome exists in
Iour IunctionaI Iorms, viz. storage granuIe or protoIysosome, phagoIysosome or digestive vacuoIe,
autophagic vacuoIe, and residuaI body (Fig. 1.9). The IoIIowing paragraph deaIs with the Iormation oI
these Iysosome types and their inter-reIationships.
Some oI the substances required to nourish the ceII may be in the Iorm oI Iarge moIecuIes,
bacteria, or other ceIIs. Such particuIate materiaIs cannot be absorbed through the ceII membrane.
FIg. 1.9 Lysosome: (a) biochemical nature, (b) formation of the lysosomal types.
Phagosome Autophagic vacuole
Early autolysosome
Early phagolysosome
Phagolysosome
(digestive vacuole)
Residual body
Autolysosome
Proteases Proteins
Nucleases and related enzymes Nucleic acids
Polysaccharides Glycosidases
Organic linked sulphates Aryl sulfatases
Lipids Lipases phospholipases
Phosphatases Organic linked phosphates
(a)
(b)
Cell Structure and Iunction #
ThereIore, these particIes are enguIIed by the ceII through a process known as endocytosis. In this
process Iirst, the required susbtance or particuIate materiaI attaches itseII to a portion oI the ceII
membrane (Fig. 1.9). Then at the region oI attachment, the particIe aIong with the membrane is drawn
inward to Iorm a smaII internaI pocket. This pocket is then pinched Iree Irom the ceII membrane and
taken inside the ceII. The structure thus Iormed consists oI particuIate materiaI surrounded by ceII
membrane, and this structure is caIIed the phagosome or Iood vacuoIe. The autophagic vacuoIe is
Iormed Irom intraceIIuIar materiaI. The enzymes required Ior the Iormation oI protoIysosomes are
synthesized by the ribosomes. These enzymes then Iind their way into the GoIgi apparatus aIong with
the endopIasmic reticuIar vesicIes (Fig. 1.7). The GoIgi apparatus reIeases them packed in the Iorm oI
protoIysosomes. The phagosome and the autophagic vacuoIe merge with the protoIysosomes to Iorm
phagoIysosome or digestive vacuoIe and autoIysosome respectiveIy. The Iourth type, i.e. the residuaI
body contains substances undigested by the Iysosome enzymes.
The onIy one and important characteristic Ieature oI Iysosome is the presence oI a singIe unit
membrane (NovikoII, 1963). The unit membrane oI Iysosome serves as the semipermeabIe
membrane. Neither the inner structure nor the Iipoprotein membrane oI Iysosome binds the hydroIases
within them. ConsequentIy, they are Iree to move and escape iI IysosomaI membrane is injured.
The membrane is unaIIected by the highIy active hydroIytic enzymes, Ior the simpIe reason that
none oI them is Iipase or phosphoIipase. The Iysosome, however, contains enzyme acting on proteins,
gIycogen, nucIeic acids, and mucopoIysaccharides. Inspite oI the presence oI these enzymes,
destruction oI the ceIIuIar organeIIes does not take pIace. OnIy when a substrate comes within the
boundaries oI the Iysosome, the digestive action is initiated.
The membrane, according to de Duve (1963), is responsibIe Ior the inactivity oI the enzymes.
Koeing (1962) suggested that the enzymes are ionicaIIy bound to the acidic gIycoIipids, which makes
them inactive. The existence oI a Iine structure inside the Iysosome is yet to be reveaIed, and when
discIosed it wouId be possibIe, perhaps, to pinpoint its roIe in Iatency.
The stabiIity oI the IysosomaI membrane is important to carry out its normaI physioIogicaI
activity. There are two agents inIIuencing the stabiIity and disruptivity oI the IysosomaI membrane.
Those Iavouring membrane stabiIity are termed stabiIizers; and those disrupting it are termed
IabiIizers. The agents which disturb ceIIuIar pH, osmotic reIations, chemicaI stabiIity, and eIectricaI
charge oI the membrane are the IabiIizers and they wouId interrupt the orderIy course and Iiberate the
enzymes into the ceII. A baIanced proportion oI stabiIizers and IabiIizers is maintained to keep the
membrane intact. Since the organeIIes depend on nutrients avaiIabIe in the intraceIIuIar environment,
it is beIieved that nutrients have stabiIizing and IabiIizing eIIect on the IysosomaI membrane.
Vitamin A is a IabiIizer oI the IysosomaI membrane. It is suggested that the vitamin A penetrates
the membrane and causes the expansion oI the Iipoprotein constituent. Thus expanded membrane is
weak to retain the enzymes and hence reIeases them into the ceII. UItravioIet Iight and ionizing
radiations are the other IabiIizers oI the membrane. The water in the ceII absorbs the ionizing
radiations and decomposes to give rise to Iree radicaIs such as hydroxyI, perhydroxyI radicaIs. AIong
with these radicaIs oxidizing compounds such as hydrogen peroxide and organic peroxides aIso are
Iormed. The membrane is sensitive to the damage by these Iree radicaIs. As a resuIt, the enzymes
escape through the damaged membrane. However, the toxic eIIects by peroxides are counteracted by
Animal Physiology $
the iron containing enzyme cataIase which decomposes hydrogen peroxide to water and oxygen. But
iI the production oI Iree radicaIs exceeds the capacity oI the cataIase reaction, the toxicity is
inevitabIe.
Vitamin E is a membrane stabiIizer in that it prevents the Iormation oI Iree radicaIs due to Iipid
peroxidation. DeIiciency oI vitamin E wouId aIIow the Iormation oI Iree radicaIs which disrupt the
IysosomaI membrane. Rabbits and chicks deIicient in vitamin E are prone to muscuIar distrophy.
Functions
The enzyme containing Iysosome and the substrate containing phagosome merge to perIorm the
digestive process within the encIosed membrane. The worn out, damaged or other unwanted
accessory structures in the ceII may be disposed by means oI an autophagic vacuoIe. Even the
outIived whoIe organs, such as tadpoIe taiI and MuIIerian ducts in maIe chick embryo, are disposed in
this way. During starvation, the digestion oI ceIIuIar contents by Iysosome provides essentiaI nutrients
to carry out important Iunctions in the ceIIs.
3.8 MlTDCHDNDRlA
In order to carry out IiIe processes the organisms are equipped with dependabIe machinery to perIorm
two basic Iunctions; to reproduce themseIves by deoxyribonucIeic acid (DNA) and to generate energy
by adenosine triphosphate (ATP). DNA is the genetic materiaI responsibIe Ior the repIication oI key
substances oI IiIeproteins and nucIeic acids. ATP moIecuIe is as important as the DNA and acts as
a kind oI storage battery. It suppIies energy Ior aII processes oI IiIe incIuding repIication. The
enzymes which cataIyze the process oI gIycoIysis, and the subceIIuIar particIes, nameIy the
chIoropIasts (a pIant ceII organeIIe) and the mitochondrion are the three systems responsibIe Ior
generating energy in the Iorm oI ATP. OI these, the process oI gIycoIysis which is the breakdown oI
sugars by enzymes in the absence oI Iree oxygen is the most primitive. In this process onIy one
moIecuIe oI ATP is produced Ior each pair oI eIectrons reIeased. The chIoropIast in the green pIants,
and the mitochondrion in the animaI kingdom produce three moIecuIes oI ATP Ior each pair oI
eIectrons reIeased. The ATP is the universaI intraceIIuIar carrier oI chemicaI energy. From the singIe
ceII oI the protist to each oI the myriad ceIIs oI the compIex organisms, mitochondrion is the site Ior
a series oI integrated enzymaticaIIy controIIed reactions which end in the Iormation oI ATP.
There are other Iunctions which the mitochondrion perIorms, besides generating energy. One oI
them is the metaboIism. There are two distinct Iorms oI metaboIism in the mitochondrion, one Iorm oI
metaboIism invoIves the oxidation oI metaboIites Ior the purpose oI energy gain to the ceII and the
synthetic reactions. The other Iorm oI metaboIism is invoIved in the biogenesis oI mitochondrion
itseII. Krebs cycIe, Iatty acid oxidation sequence, and enzymes responsibIe Ior ketone body oxidation
and Iormation are some oI the metaboIic pathways present within the mitochondrion. Through these
cycIes, the mitochondrion yieIds Iarge number oI reduced enzymes and hydrogens. The hydrogens are
then taken into the eIectron transport chain.
The mitochondrion has the abiIity to synthesize and cataboIize proteins with the mediation oI
ribosomaI particIes. They aIso participate in ionic reguIation in the ceII and change the permeabiIity oI
Cell Structure and Iunction %
its membranes to make new substrate avaiIabIe. Another property oI mitochondrion, as observed in
some ceIIs, is the production oI mitochondria Irom pre-existing mitochondria by growth and division.
Shape
There is variation in the shape oI mitochondria. They may be minute gIobuIes, vesicIes, straight or
curved rods, straight or branched threads, chain oI granuIes, nets and other irreguIar bodies. However,
the major variation is among ceII types but not among ceIIs oI the same type. MostIy they are sausage
shaped, but with aItered conditions the mitochondria are observed changing their Iorm, hence
pIeomorphic.
The number oI mitochondria per ceII varies depending on the ceII type but within a kind oI ceII
the number remains IairIy constant. In numbers they vary Irom 500 in case oI some Iiver ceIIs, to
more than 100,000 in case oI some singIe ceIIed organisms.
Location
Mitochondria are situated cIose to the source Irom where metaboIities enter the ceII. They are
generaIIy Iound oriented with their Iong axes indicating the direction oI IIow oI materiaIs in the ceIIs
perIorming active transport. Mitochondria are Iound in those areas oI the ceII which depend on the
ATP they contain. In neurons they accumuIate at the internodes where the passage oI nervous impuIse
is supposed to take pIace. In secretory ceIIs they accumuIate at the basaI regions, and in retina at one
end oI the rod ceIIs. The mitochondria oI some ceIIs can move about IreeIy and passiveIy, whiIe in
other ceIIs they are stationary.
Structure
A striking simiIarity exists in the IundamentaI structure oI mitochondria in aII Iorms Irom protozoa to
primates. In most cases it is a sausage shaped object measuring 15,000 A units in Iength and 5,000 A
units in diameter. The compIex uItra-structure oI the mitochondria as reveaIed by eIectron microscope
was Iirst described by PaIade (1952). It has a two Iayered wrapping constituting an outer and an inner
membrane and in this respect it resembIes a thermos bottIe (Fig. 1.10). The outer membrane is eIastic
and at times it may be stretched to 200 times its originaI dimensions. AII over the surIace it is covered
by staIkIess particIes. The outer membrane is separated Irom the inner membrane by a IIuid matrix
which is structureIess. This matrix provides communication between the two membranes and suppIies
FIg. 1.10 Structure of the mitochondrion.
Inner wall
Outer wall
Crista
Animal Physiology &
coenzymes to the enzymes present in the membrane. The inner membrane encIoses another matrix
which is not in contact with the IIuid between the two membranes. The membrane contains some
protein and Iipid materiaI and as a resuIt may be semirigid. The surIace oI the inner membrane is
much expanded and thrown into numerous transverse IoIds or cristae which oIIer an increased surIace
area to this membrane. WhiIe this is the generaIized structure, there are mitochondria which do not
bear cristae aII aIong their Iength but are Iimited to a smaII part oI it. In some they are tubuIar. The
outside surIace oI the outer membrane and the inside surIace oI the inner membrane are sprinkIed
with thousands oI smaIIer particIes. These particIes are the eIementary units which carry out the
chemicaI activities oI the mitochondrion. The two membranes are the structuraI back bones oI the
mitochondrion and have three propertiesgood tensiIe strength, stabiIity, and IIexibiIity. In other
words, the mitochondriaI membranes are strong enough to hoId a structuraI shape, stabIe enough to
aIIow membrane phenomena to occur and IIexibIe enough to aIIow movement.
The Iine structure oI the mitochondrion is better understood than beIore, as a resuIt oI speciaI
staining methods and very highIy magniIied eIectron-micrographs. The permanganate Iixed
mitochondrion reveaIed the two membranes as separated Irom each other by a width oI about 100 A.
Each mitochondriaI membrane cIoseIy resembIes the membrane oI the ceII itseII. It is about 75 A
thick. It is made up oI two materiaIs apart Irom the particIes attached to it. Under the eIectron
microscope each membrane can be seen as a three Iayered unit. Each oI the two protein Iayers oI the
membrane is about 20 A thick. The inner Iayer is sandwiched by two protein or other nonIipid outer
Iayers (darker Iayers). The inner Iayer (Iighter Iayer) is made up oI two rows oI Iipid moIecuIes with
their nonpoIar ends Iacing each other (Robertson, 1959) and is 35 A thick. Thus the two membranes
together measure about 250 A thick.
The principIe materiaI is the structuraI protein which is insoIubIe in water and accounts Ior Iour
IiIths oI the weight oI the membrane. The remainder oI the materiaI is Iipoid, primariIy phosphoIipid.
The protein oI the membrane is oI two types. StrucutraI and the mitochondriaI actomyosin. The
structuraI protein is a poIymer, composed oI basic subunits oI a smaII protein. HaII oI the amino acid
content in these moIecuIes have hydrocarbon side chains which are insoIubIe in water and Iorm
hydrophobic bonds. The mitochondriaI actomyocin, in reaction with ATP, is presumed to transIorm
the chemicaI energy into mechanicaI energy (Lehninger, 1962).
The beIieI that the outer surIace oI the membrane has IooseIy attached to it thousands oI gIobuIar
particIes, is not universaI. Logistics suggest, however, that the enzymes responsibIe Ior providing
'energetic¨ eIectrons by carrying out the oxidation reactions such as those oI the Krebs and the Iatty
acid cycIes are Iocated in the outer membrane.
The uItrastructure oI the inner membrane and its extensions are oI great interest. The inner
surIace oI the inner membrane is Iined by thousands oI particIes (Fig. 1.11). These are eIementary
particIes as termed by Fernandez Moran (1962). Each particIe has a terminaI gIobuIar head oI about
80 A in diameter and a staIk oI about 50 A Iong and 30 A width. The base with which it is connected
to the membrane has the same diameter as does the head piece. These eIementary particIes are the
respiratory assembIies. They are muIti-enzyme aggregates and serve in transporting the eIectrons over
a chain oI compIexes that synthesize ATP. Hence they are convenientIy known as eIectron transport
particIes. They are composed oI a protein cortex with a phosphoIipid core and thus regarded as
enzyme (protein) Iipid compIexes.
Cell Structure and Iunction '
FIg. 1.11 Ultrastructure of the membrane of mitochondrion.
Functions
The carbohydrates, Iats, and proteins are oxidised, via tricarboxyIic acid (TCA) or Krebs citric acid
cycIe which is the common pathway in the conversion oI the energy Irom IoodstuIIs to a Iorm that the
ceIIs can use. This usabIe Iorm oI energy, i.e. the currency oI the ceII, is Adenosine triphosphate
(ATP). The energy or ATP producing system is the eIectron transport system or respiratory chain and
it is present in the eIectron transport particIes. The eIectron transport system transIorms the energy oI
oxidation oI TCA cycIe substrates to Iorm phosphate bond energy that is needed Ior the ceIIuIar
processes.
3.7 CENTRlDLE
CentrioIe is a minor ceII organeIIe and in Iight microscopy it appears as a singIe dot encIosed in a tiny
vesicIe. It is situated in the region oI the nucIeus and GoIgi apparatus. EIectron microscopic studies
reveaIed that it consists oI a pair oI bundIes and each bundIe consisting oI nine IiIaments. At mitosis
the IiIaments in the bundIe subdivide Iirst, and then the bundIes. As a resuIt two pairs oI bundIes, each
pair with nine IiIaments are Iormed. SubsequentIy each pair moves to either side oI the nucIeus to
mark the two poIes oI the spindIe.
O
2
Complex 1V
Complex III
Complex II Succinate
NADH
Complex I
Animal Physiology
3.8 NUCLEUS
The nucIeus contains karyopIasm which is covered by a doubIe Iayered membrane. It has in it a
denseIy stained area caIIed nucIeoIus, which consists oI a rich concentration oI RNA and certain
proteins. NucIeus aIso contains chromatin which is a combination oI nucIear protein (either
protamines or histones) with deoxyribonucIeic acid (DNA). During ceII division the chromatin takes
the Iorm oI Iong strands which are caIIed chromosomes.
Among mineraIs, the caIcium, magnesium, sodium and the phosphates are Iound in the nucIeus.
CaIcium is bound to the protein, and magnesium to DNA. Sodium ions are required Ior the active
transport oI amino acids through the nucIear membrane Ior which energy is suppIied by ATP.
The nucIeus is covered by a doubIe membrane. The space between the outer and inner membrane
is in continuation with the endopIasmic reticuIum thereby Iorming a continuous channeI. Through this
channeI, materiaIs which are reIused transport through by the pIasma membrane, reach the nucIear
enveIope Irom the extraceIIuIar medium and get seIectiveIy absorbed through the nucIear membrane.
The two nucIear membranes, at intervaIs, join to Iorm pores which IaciIitate communication between
karyopIasm and cytopIasm. These pores aIIow the escape oI three Iorms oI ribonucIeic acid (RNA) to
the cytopIasm.
Chromosomes
The nucIeus oI the resting ceII contains Iong chromatin reticuIum which is in combination oI DNA
and proteins. During the process oI mitosis, the chromatin reticuIum condenses into compact bodies
caIIed chromosomes. The typicaI chromosome has bands which are known as euchromatic, and
heterochromatic bands. The Iormer are composed oI DNA associated with histones. The Iatter, i.e.
heterochromatic bands are Iormed oI both DNA and RNA.
During mitosis the chromosome is IongitudinaIIy sub-divided into two chromatids. Each oI the
two chromatids is composed oI paired IiIaments caIIed chromonema.
The chromosome has a region oI constriction caIIed kinetochore. Based on its position the
chromosomes can be identiIied as acrocentric, metacentric and submetacentric types. During ceII
division the kinetochores are subjected to the puIIing inIIuence oI the spindIe Iibres.
There are severaI hypotheses over the Iine structure oI the chromosome. Some beIieve the
chromosome as containing a singIe strand oI doubIe heIicaI DNA supported by a backbone oI protein.
According to another hypothesis, the chromosome consists oI a continuous non-DNA backbone to
which the DNA moIecuIes are attached at reguIar intervaIs. Yet another hypothesis is that severaI
DNA moIecuIes get attached end to end to Iorm a continuous strand.
The arrangement oI the proteins in the chromosome is unknown. AIthough the histones seem to
bound cIoseIy to DNA, some histone moIecuIes mereIy run aIong the doubIe heIix.
A discussion oI the chromosome is incompIete unIess the concept oI gene is considered. The
generaIIy accepted view is that the genes are Iragments oI DNA moIecuIe. Each gene is abIe to exert
its activity which is diIIerent Irom that oI other gene. The reason Ior the diIIerence in the activities oI
the genes is now beIieved to be due to the sequence oI the nucIeotides in the DNA or in the spatiaI
reIationship oI the nucIeotides to each other. Such genes are Iocated in a Iinear sequence on the
Cell Structure and Iunction
chromosomes and when the chromosomes divide during meiotic division the hereditary inIormation
oI the organism is carried into the germ ceIIs.
NucIeic Acids
NucIeic acids are compIex moIecuIes and consist oI a number oI nucIeotides joined chainwise. Each
nucIeotide is a monomer and is made up oI three parts, a purine or pyrimidine, a pentose sugar and a
phosphate group. The purines are adenine and guanine, whiIe pyrimidines are thymine, cytosine and
uraciI (Fig. 1.12). Both the purines and pyrimidines are bases.
FIg. 1.12 Chemical structure of purines and pyrimidines.
The pentose sugar moIecuIes Iorm a part oI the nucIeic acids and they exist in the Iorm oI a ring.
The sugar gets attached either to a purine, or to a pyrimidine base Iorming a nucIeoside. The base
attaches to the carbon oI the pentose sugar.
The third part, i.e. the phosphate group gets attached with one arm to the IiIth position oI the
pentose sugar to Iorm a nucIeotide. For the Iormation oI a nucIeic acid chain severaI nucIeotides join,
each by its phosphate group binding to the third position oI the pentose sugar beIonging to the other.
Thus the phosphate group in the nucIeic acids is known to bind to the IiIth position oI the pentose
sugar oI a nucIeotide with one arm, and with another arm to the third position oI the pentose sugar oI
O
C
CH
CH
N
H
Uracil
HN
C
C
C—CH
3
CH
N
O
HN
C
CH
CH
N
C
C
NH
2
PYRIMIDINES
PURINES
NH
2
C
C
C
C
C
N
N
N
N H
H
Adenine
H
H
H N
2
OH
C
C
C
C
C
C
N
N
H
Guanine
H
Thymine
N
H
Cytosine
N
O
O
O
Animal Physiology
the adjacent nucIeotide beIonging to the same chain. The sugar and phosphate Iorm the backbone oI
the nucIeic acid and the bases (purines or pyrimidines) are attached perpendicuIar to it.
The nucIeic acids are oI two kindsthe ribonucIeic acid (RNA) and the deoxyribonucIeic acid
(DNA). The RNA has a characteristic pyrimidine, the uraciI, in its structure instead oI thymine which
is present in DNA. In addition, the RNA has a Iive carbon ribose sugar whiIe the DNA has the
deoxyribose sugar in its structure.
DNA: The deoxyribonucIeic acid consists oI adenine, thymine, cytosine, and guanine as bases. In
an intact nucIeic acid moIecuIe these bases are attached to a Iive carbon sugar deoxyribose, thus
Iorming a deoxynucIeoside. As described above, the phosphate group heIps Iinking the deoxyribose
oI the deoxynucIeoside to Iorm a strand oI poIynucIeotide chain. A DNA moIecuIe has two such
poIynucIeotide chains arranged in a heIicaI structure and heId together by hydrogen bonding between
bases. Bonding occurs between the purine base oI one strand and the pyrimidine base oI the partner
strand. ChemicaI data reveaIs onIy two base pair combinations, i.e. adenine-thymine, and cytosine-
guanine (Fig. 1.13). Pairing occurs by the sharing oI two hydrogen bonds between adenine-thymine,
and by sharing three hydrogen bonds between cytosine-guanine. Since pairing occurs aIways between
FIg. 1.13 Base pairing: (a) Thymine-Adenine, (b) Cuanine-Cytosine.
C H
C
C
C
C
N
N
N
N
N
T
o
c
h
a
i
n
H
H
O
H
H
H
H
B
H
N H
C
C
C
C O
Guanine
T
o
c
h
a
i
n
Cytosine
T
o
c
h
a
i
n
H
C
N
C
C
C
C
N
N
H
H
N
N
H H
C
C
C
C
C
N
N
H
H H
H
O
O
Adenine
T
o
c
h
a
in
Thymine
N
Cell Structure and Iunction !
adenine-thymine, cytosine-guanine, the estabIished bases oI one strand in DNA wiII determine the
sequence on the partner strand. For instance, iI the order oI bases in one strand are A G C A G G T,
the base sequence on the compIementary strand wiII be T C G T C C A. This property oI speciIic base
pairing in DNA is very important in the repIication process oI DNA, and in the preservation and
transIer oI species characters to the oIIspring.
WhiIe DNA is heIicaI in aII organisms, it diIIers Irom species to species due to changes in the
sequence oI nucIeotides in the strand and aIso due to the variation in the Iength oI the strand. Because
oI these diIIerences in DNA, the genes and consequentIy the characters oI species diIIer.
One oI the important Iunctions oI the DNA is the repIication oI the genetic inIormation coded in
its strands. RepIication process is initiated at one end oI the heIix by the separation oI its
poIynucIeotide strands in a Iinear and unidirectionaI Iashion. Each one oI the separating strands acts
as a tempIate and captures the corresponding bases Irom the nucIear IIuid. The bases thus picked up
are simiIar to those Iost in the separation. These newIy acquired bases are
joined together Iengthwise to Iorm a strand, and Ior this process energy-
rich phosphate oI the nucIeotide is required. The energy-rich phosphates
are triphosphates. Since there are Iour types oI bases which are required
to be connected Iengthwise, evidentIy Iour types oI triphosphates exist.
These are coIIectiveIy known as nucIeotide triphosphates and individuaIIy
they are deoxy ATP, TTP, GTP and CTP. Each oI these nucIeotide
triphosphates is joined to its neighbour, in the presence oI speciIic
nucIeotide poIymerase, with the Iiberation oI two inorganic phosphate
moIecuIes. With the Iinking oI the bases the Iormation oI a
compIimentary strand is compIeted.
Another Iunction oI DNA moIecuIe is, it acts as a tempIate in the
Iormation oI messenger RNA (mRNA).
RNA: The inIormation required to carry out ceIIuIar activities is
codiIied in DNA. Most oI the ceIIuIar activities, such as metaboIic and
synthetic processes take pIace in the cytopIasm under the inIIuence oI
enzymes. Since the code Ior the proteins is in the DNA (genes), it must
be brought to the cytopIasm by a Iorm that can carry out protein
synthesis. This is accompIished by a Iorm oI ribonucIeic acid, which
because oI its Iunction is caIIed messenger RNA.
There is yet another major type oI RNA known as tRNA, or soIubIe
RNA. The Iunction oI tRNA is to carry and assembIe the amino acids Ior
the synthesis oI poIypeptide chains. KnowIedge oI the structure oI both
the RNAs is necessary Ior an understanding oI their roIe in the
poIypeptide synthesis. The structure oI tRNA has been described in
chapter 5. BeIore we go in Ior the mRNA structure Iet us know how an
RNA diIIers Irom the DNA.
mRNA
FIg. 1.14 Formation of the
messenger RNA.
Animal Physiology "
The RNA diIIers Irom DNA in that, its pentose sugar is ribose instead oI deoxyribose; one oI its
bases is uraciI* instead oI thymine; the poIynucIeotide is singIe stranded chain rather than doubIe
stranded heIix as in DNA. RNA strand contains onIy hundreds oI nucIeotides whiIe DNA has them in
thousands. DNA contains genetic code and is present in the ceII nucIei whereas RNA contains
message encoded Irom DNA tempIate, and migrates to cytopIasm to be associated with the synthesis
oI proteins with the aid oI ribosomes.
MESSENGER RNA: The process oI Iormation oI mRNA in the nucIeus is not compIeteIy cIear.
However, it is presumed that mRNA is Iormed using one oI the strands oI DNA as a tempIate
(Fig. 1.14), IirstIy because it has a base sequence compIimentary to one oI the DNA strands, and
secondIy because much oI the newIy synthesized RNA is cIoseIy associated in the Iorm oI a hybrid
with DNA. It shouId be remembered that uraciI oI RNA is, compIimentary to adenine oI DNA.
Enzyme RNA poIymerase, and Iour, triphosphates (ATP, UTP, CTP, and GTP) are, oI course, required
in the synthesis oI RNA.
WhiIe the enzyme is needed in making the compIimentary copies oI bases Iine up in sequence
with those oI DNA, the energy rich phosphates are required to join the RNA nucIeotides together to
Iorm a strand. The mRNA with a transcribed nucIeotide copy oI the message Irom the DNA traveIs to
the protein Iorming sites. i.e, the ribosomes.
NUCLEOLUS: NucIeoIus is very Iarge and conspicuous in growing ceIIs but disappears during ceII
division. It can be seen as a dense area within the nucIeus and has no membrane separating it Irom
karyopIasm. It is thus exposed Ior interaction with nucIear materiaI. The RNA and proteins which
make up ribosomaI particIes are Iormed in the nucIeoIus. WhiIe some ribosomaI particIes remain
within the nucIeus to synthesize nucIear proteins, the other migrate to the cytopIasm. These nucIear
ribosomes synthesize enzymes required in the nucIeus, such as DNA-poIymerase, etc.
*The structure oI uraciI is very much Iike that oI thymine but Ior the Iack oI CH
3
(methyI) group which thymine possesses.
As we know weII, Iood is a matter other than oxygen and water which animaIs take into their body. It
has three principaI uses: First as IueI to suppIy energy, second as a materiaI Ior buiIding new tissues
(i.e. in growth) and Ior repair, and third as substances which with IittIe or no change take part in the
various biochemicaI reactions without being part oI the structure oI the body.
The Iood oI animaIs chieIIy consists oI varied compIex organic substances such as carbohydrates,
Iats and proteins. These basic IoodstuIIs get oxidized to meet most oI the energy requirements oI the
animaIs. The amino acid units oI proteins are required Ior growth and repair oI tissues, and aIso Ior
the synthesis oI various secretions oI the body. Besides these, there are a number oI substances such
as vitamins and inorganic compounds, which the animaIs cannot synthesize and stiII essentiaI in
carrying out both energy yieIding and anaerobic growth promoting reactions. Such substances Iorm
part oI the Iood and are obtained Irom outside. FinaIIy the body aIso obtains through Iood, mineraIs
required Ior the reguIation oI osmotic pressure and acid-base baIance, Ior incorporation in the
structure oI certain tissues, and Ior the activation oI severaI enzyme reactions. AII the above
mentioned substances are taken in by the animaIs through the Iood. Since they are the constituents oI
the Iood they are convenientIy caIIed IoodstuIIs or nutrients. The ensuing portion oI this chapter gives
an account oI the nature oI various IoodstuIIs.
E.3 CARBDHYDRATES
Carbohydrate is the chieI nutrient Ior the animaI kingdom. AnimaIs procure carbohydrates Irom
pIants. PIants synthesize carbohydrates through a process oI photosynthesis, a process in which the
chIorophyII wouId utiIize soIar energy to synthesize carbohydrates Irom the carbondioxide oI the air
and the water Irom the soiI. Carbohydrates serve as main source oI energy. Their energy vaIue is Iour
kiIocaIories per gram oI carbohydrate nutrient and it is provided to the various synthetic needs oI a
ceII. Carbohydrates incIude sugars and starches.
.@IJKBBI
+ 0 ) 2 6 - 4

Animal Physiology $
Carbohydrates are organic compounds in which most oI the carbon atoms carry the eIements oI
water. In a simpIe carbohydrate unit, there are six carbon atoms arranged in a chain with atoms oI
hydrogen and oxygen attached to the carbons in the same ratio as Iound in water, (Figure 2.1). In
other words, in carbohydrates carbon, hydrogen and oxygen are generaIIy Iound in the proportion oI
1 : 2 : 1.
CIassification of Carbohydrates
Compounds oI carbohydrates are cIassiIied into the IoIIowing simpIe groups, viz. monosaccharides,
disaccharides, oIigosaccharides and poIysaccharides, each group containing one, two or more
carbohydrate units respectiveIy.
Glucose Sucrose Starch
+
more
Fructose Maltose Dextrin
+
more
+
more
Fructose Maltose Glycogen
+
more
Cellulose
Monosaccharides
(one sugar compounds)
Disaccharides
(two sugar compounds)
Polysaccharides
(many sugar compounds)
FIg. 2.1 Figure showing the structural moieties of monosaccharides, disaccharides and polysaccharides.
From the above iIIustrated chart it is apparent that the three monosaccharidesgIucose, gaIactose
and Iructose are the units contained in the structure oI di-and poIysaccharides. Mono-and
disaccharides have common characters in that they are soIubIe in water, crystaIIine, and sweet. They
are sugars and their names end with characteristic-ose. In contrast to this the poIysaccharides are
insoIubIe in water, and are neither crystaIIine nor sweet. Their names do not have a characteristic
ending.
MONOSACCHARIDES: The monosaccharides are grouped according to the number oI carbon atoms
in their structure, i.e. trioses (C
3
H
6
O
3
), tetroses (C
4
H
8
O
4
), pentoses (C
5
H
10
O
5
), hexoses (C
6
H
12
O
6
),
Ioodstujjs %
heptoses (C
7
H
17
O
7
). OI these onIy the pentoses and hexoses pIay IundamentaI roIes in ceIIuIar
nutrition. GIucose, Iructose and gaIactose are the hexoses. The gIucose and the gaIactose are aIdoses
(aIdehydes} whiIe Iructose is a ketose (ketones). Though pentoses and hexoses are oIten depicted as
open chain compounds they are normaIIy arranged in a continuous ring in their bioIogicaIIy active
state caIIed hemiacetaIs.
DISACCHARIDES: As aIready mentioned these are compounds joined with two monosaccharide
units. Disaccharides are Iormed by a chemicaI reaction caIIed condensation. In this process an OH
group oI one monosaccharide joins with one oI the carbon atoms oI the other to Iorm a glycoside
bond with the eIimination oI water.
Sucrose, Iactose and maItose are the common disaccharides. Disaccharides are spIit into their
constituent monosaccharides in the process oI digestion beIore being absorbed. Both beet and cane
sugars are known as sucrose and consist oI gIucose and Iructose units. Lactose which is present in
miIk has in it gIucose and gaIactose monosaccharides. MaItose contains two moIecuIes oI D-gIucose
and is not avaiIabIe Iree in nature. It is present in maIt products. It is produced in the body as a resuIt
oI the action oI maItase on starch.
POLYSACCHARIDES: PoIysaccharides consist oI a Iong chain oI monosaccharide units.
PoIysaccharides are aIso accompIished by condensation. PoIysaccharides have a generaI IormuIa
(C
6
H
10
O
5
)nwhere n is the number oI groups that a moIecuIe may incIude. Because oI the
insoIubiIity and Iarge size, they Iorm coIIoidaI soIutions and soIids, and wiII not pass across naturaI
animaI membranes. They are chemicaIIy inert and do not ionize and Ior this reason very much suited
as reservesas starch in pIants and gIycogen in animaIs. Starch, dextrin, gIycogen and ceIIuIose are
the Iour poIysaccharides that are important as nutrients. PoIysaccharides consisting oI onIy one type
oI monosaccharide units are caIIed homopolysaccharides, whiIe, those with diIIerent types oI
monosaccharides or monosaccharide derivatives are hetero-polysaccharides.
HOMOPOLYSACCHARIDES
Starch: PIant products such as roots, tubers, Iruits and seeds contain primariIy starch. Starch is Iound
in the ceIIs oI pIants in the Iorm oI granuIes. The size, shape and markings oI starch granuIes are
typicaI oI the pIant in which they occurovaI shaped in case oI wheat starch; smaII, rounded and
anguIar in case oI corn starch. The composition oI starches aIso diIIers to some extent, however, aII
P¡ng sIru¿Iurø ø/ gIu¿øsø, gaIa¿Iøsø anø /ru¿Iøsø. GIu¿øsø anø gaIa¿Iøsø arø ¡sømørs.
C
H
C
CH
2
OH
HO
C
H
C
H
C
H
H O
C
H
O
H
C
HO
C
H
H
C
OH
C
H
C
OH
O
H
C
CH
2
OH
HO
C
H
C
HO OH
H
OH
C
H
O
CH
2
OH
H
H
HO
H O
H O
D-glucose D-galactose D-fructose
Animal Physiology &
types have both amyIose and amyIopectin. The Iormer is a straight chain poIymer and the Iater a
branched chain. Starch is hydroIyzed in the intestinaI tract yieIding dextrins and maItose, and
eventuaIIy gIucose.
In animaIs, starches are digestibIe poIysaccharides whereas ceIIuIoses are indigestibIe ones. The
end product oI starch hydroIysis in the body is gIucose. Unwanted or excess gIucose is stored in Iiver
and muscIes as gIycogen. When the ceII need gIucose, the gIycogen (aIso known as animaI starch) is
hydroIyzed by amyIase to Iorm maItose, which is Iurther hydroIyzed by maItase to Iorm gIucose.
Dextrins: They are the intermediate compounds Iormed as a resuIt oI hydroIysis oI starch to
maItose and IinaIIy to gIucose, both in the process oI preparing Iood (heating) and digestion oI starch.
They are avaiIabIe particuIarIy in the germinating seeds. The presence oI dextrin medium in the
aIimentary canaI is IavourabIe Ior the growth oI acidophiIic organisms.
Glycogen (or Animal Starch): GIycogen is present in invertebrates as weII as vertebrates. It is a
branched chain poIymer having 6,000 to 30,000 gIucose units. It gives a brown to red coIour with
iodine. On hydroIysis both yieId gIucose as the end product.
Cellulose: The ceII waIIs oI pIants are made up oI ceIIuIose which consists oI a Iinear chain oI
gIucose units. These units may range Irom 900-2000 in diIIerent ceIIuIoses. It is not acted upon by
digestive enzymes secreted by mammaIs, but bacteria break it down. Cotton has a pure Iorm oI simpIe
ceIIuIose.
HETEROPOLYSACCHARIDES
These are compIex poIymers containing severaI diIIerent monosaccharides or monosaccharide
derivatives. In combination with proteins poIysaccharides Iorm mucopoIysaccharides. They occur in
mucous. Many mucopoIysaccharides tend to be highIy viscous and are responsibIe Ior the viscosity oI
body mucous secretions. These are oI no dietary signiIicance.
FunctionaI Significance of Carbohydrates
Carbohydrates serve variety oI Iunctions. They suppIy energy Ior the body Iunctions and Iorm part oI
the structure oI the mucous membranes, supporting tissues, and the centraI nervous system.
Carbohydrates are antiketogenic and aid in the utiIization oI body Iats. Carbohydrates have aIso
protective Iunction.
The main Iunction oI carbohydrate is to suppIy energy Ior the body processes. GIucose, a
monosaccharide sugar, is the uItimate product into which the entire starch (poIysaccharide) and haII
oI the sucrose and Iactose (disaccharides) are converted. The other products Iormed in this conversion
are Iructose and gaIactose, but they are present in smaIIer quantities. The Iructose and most oI the
gaIactose are converted into gIycogen by the Iiver and a Iarge amount oI it is stored in it. SimiIarIy it
is aIso stored in other tissues notabIy muscIes. GIycogen is broken down to gIucose by the process oI
gIycogenoIysis and the gIucose is carried out by bIood and gets burnt to provide energy Ior the body
processes.
StructuraI Function of Carbohydrates
GaIactose, which is present in smaII quantities in the bIood oI miIk drinking peopIe, serves an
important structuraI Iunction, i.e. Iorming a covering to nerve Iibres.
Ioodstujjs '
At the time oI birth oI a chiId its nerve Iibres, especiaIIy those oI the spinaI cord Iack the
necessary covering oI the myeIin sheath. The chiId needs gaIactose in its bIood in order to synthesize
myeIin, which is a compIex Iat Iike compound. MyeIin sheath acts as an insuIator around nerve Iibres
and prevents the nerve impuIses Irom the Ieakage Irom one Iibre to another.
Thus smaII amounts oI carbohydrates and their derivatives Iorm the structuraI eIements in certain
tissues.
Pentoses are constituents oI nucIeic acids. Various carbohydrates are present in many conjugated
proteins. CartiIage, bones and tendons have an aminopoIysaccharide. The Iormation and the
destruction, oI these carbohydratecontaining structuraI eIements is a phase oI carbohydrate
metaboIism.
Formation of Fats from Carbohydrates
When excessive carbohydrates are absorbed into the body, the Iiver transIorms the excess amount into
gIycogen and stores them. However, iI the carbohydrate intake is more than the Iimited transIormation
capacity oI the Iiver, they are then converted to Iats and stored in the tissues. Formation oI Iats Irom
gIucose is brought about by the synthesis oI two components, i.e. Iatty acids and gIyceroI. AcetyI
coenzyme A (acetyI CoA), the Iast compound in the gIycoIytic pathway acts as a starting substance in
the synthesis oI Iatty acids. In case oI gIyceroI synthesis, the dihydroxyacetone phosphate, aIso a
compound oI the gIycoIytic pathway acts as a starting substance. Though the mechanism invoIved in
the Iormation oI Iats is a compIicated one, it may be summarised in the IoIIowing two paragraphs.
The Iirst reaction requiring energy Irom ATP, is the carboxyIation oI acetyI CoA to maIonyI CoA
in the presence oI coenzyme, biotin. AIter this maIonyI CoA compIex reacts with another moIecuIe oI
acetyI CoA to Iorm butyryI CoA. Thus by a series oI repeated condensations the Iong chain Iatty acids
are Iormed.
For the synthesis oI gIyceroI, the starting substance is dihydroxyacetone phosphate. In the Iirst
step this substance is reduced to >-gIyceroIphosphate. The >-gIyceroIphosphate is then esteriIied by
two acetyI CoA moIecuIes resuIting in phosphodigIycerides. Next to this trigIycerides are produced
under the action oI another acetyI CoA moIecuIe.
Antiketogenic RoIe
Ketones are Iormed Irom the degradation oI Iipids when the organism suIIers Irom carbohydrate
starvation or diabetes. In such circumstances sugar which provides energy is not avaiIabIe to the
organism, and hence the energy is suppIied by extensive oxidation oI Iipids. The ketones (acetone,
acetoacetic acid, >-hydroxybutyric acid) Iormed during the cataboIism oI Iipids are so Iarge that they
exceed the oxidative capacity oI the tissues, hence they get accumuIated in the bIood (ketonemia) and
pass into the urine (ketonuria). Since some oI the ketones are strong acids their excessive production
aIters akaIinity oI bIood to acidity, thus producing hyperacidemia. In normaI conditions hyperacidemia
does not occur because the smaII amounts oI ketones Iormed can be neutraIized by the aIkaIine
reserve oI the bIood, but during carbohydrate deIiciency ketone bodies become overIoaded.
GIucose has an antiketogenic roIe because it is Iound that the administration oI carbohydrates in
the case oI carbohydrate starvation reduces ketogenesis. SimiIarIy, carbohydrates and insuIin
administration prevents diabetic ketogenesis.
Animal Physiology !
Protection of Proteins
Another important Iunction oI carbohydrates is to spare protein Ior buiIding and repairing oI body
tissue which is its primary duty. The energy need oI body is to be Iirst satisIied beIore the nutrients are
used Ior other Iunctions. When the carbohydrate and Iat content oI the diet is beIow the desirabIe
caIoric IeveI, protein stops its primary duty oI tissue buiIding and repairing and starts degradation.
Certain amino acids, Ieucine, phenyIaIanine, tyrosin, which are products oI this degradation are
considered to be ketogenic since they can Iorm acetoacetic acid. NormaIIy acetoacetic acid is utiIized
in Iipogenesis but during carbohydrate starvation this does not happen.
E.E PRDTElNS
The term protein was suggested by Gerardus MuIder in 1840. This term is taken Irom Greek and it
means 'to come Iirst¨. TruIy enough the proteins Iorm the most important constituents oI the animaI
body and account Ior about one haII oI the totaI dry weight oI the body. A IiberaI suppIy oI protein is
necessary to the body and without it no IiIe is possibIe. It must be constantIy suppIied to the body Ior
growth and repair.
There are diIIerent types oI proteins. These types are cIoseIy reIated yet they are distinct
physioIogicaIIy. PIant proteins diIIer Irom each other and are convertibIe to animaI proteins. Each
species in animaIs has its speciIic proteins. Further, a given animaI has many diIIerent proteins within
its organs, IIuids and tissues. No two proteins are exactIy aIike in their physioIogicaI behaviour. Some
proteins serve as structuraI components, some others are important components oI extraceIIuIar IIuids.
The proteins Iunction within the Iiving ceIIs as bioIogicaI cataIysts. AImost every reaction taking
pIace within the ceII requires a speciIic cataIyst. Such cataIysts are caIIed enzymes and account Ior
about 90° oI the totaI IunctionaI protein in the ceII. A singIe ceII may contain in it as many as 1,000
diIIerent enzymes.
Carbon, hydrogen, oxygen and nitrogen are the eIements which are present in each protein
moIecuIe. Many proteins aIso contain suIphur, a Iew others contain, phosphorus, iron iodine and
cobaIt. Nitrogen is the distinguishing eIement in the proteins because it is present in these compounds
whereas it is absent in carbohydrates and Iats.
The individuaI moIecuIes oI proteins have high moIecuIar weight and Ior this reason they are
oIten reIerred to as macromoIecuIes. Since a Iarge number oI simiIar units, known as
macromoIecuIes, are joined to Iorm chain-Iike moIecuIes they are characterized as bio-poIymers.
Amino Acids
A compIete hydroIysis oI various proteins yieIds about 20 diIIerent amino acids, showing thereby that
the proteins are made up oI amino acid subunits. AII these amino acids are =-amino acids, i.e. the
amino group is attached to the =-carbon. Each amino acid has one part which is same Ior aII and one
part which is speciIic onIy to that particuIar amino acid. Taking these points in view the generaI
IormuIa oI an amino acid is sketched as IoIIows:
Ioodstujjs !
The part IabeIIed R varies Ior each amino acid: whereas rest oI the moIecuIe is the same Ior aII.
The simpIest oI the amino acid is amino-acetic acid or gIycine.
H
R
C
H
H
C N
OH
O
C
H
C H
O
O
H
H
H
C
H
C N
O
O
H
H
H
Acetic acid Amino acetic acid (Glycine)
AIanine, the next simpIest amino acid, is amino-propionic acid. There are two amino derivatives
oI propionic acid and their Iormation is based on the attachment oI the amino group either to =- or
>-carbon atom.
In the same way three possibIe amino acids can be derived Irom butyric acid. But the proteins are
constituted onIy with =-amino acids and not with other amino acids.
In aII amino acids, with the exception oI gIycine, the =-carbon atom is attached to Iour diIIerent
atoms or groups. The =-carbon atom is thereIore asymmetric. The amino acids containing asymmetric
=-carbon are opticaIIy active and can exist in two stereo-isomeric Iorms (Fig. 2.2).
The naturaIIy occurring ones beIong to L-Iorm. But some amino acids such as aIanine are
dextrorotator aIthough they beIong to L-Iorm. They are amphoteric eIectroIytes because they have
both amino, and carboxyI groups which react as acids in the presence oI bases and as bases in the
presence oI acids.
H C
C
H
C
OH
O
H
H
H
H C
C
H
C
H
H
H
N
H
H C
C
H
C
NH
2
H
H
C
H
C
H
H C
H
H
C
NH
2
C
H
H C
H
H
C
NH
2
C
H
H C
H
H
OH
O
OH
O
OH
O
OH
O
OH
O
Propionic acid a-amino-propionic
acid (alanine)
b
b
-amino-propionic
acid ( -alanine)
or or or
Animal Physiology !
STRUCTURE AND CLASSIFICATION OF AMINO ACIDS AVAILABLE IN PROTEINS: The cIassiIication oI
amino acids, obtained by the hydroIysis oI proteins is given beIow and it is based upon the
composition oI the side chain, i.e. R-group which varies Irom, one amino acid to another.
TabIe 2.1 Amino Acids and Their Structural Formulate
Namø SIru¿IuraI /ørmuIa
I. Side chains with no functional groups-simple amino acids.
Clycine (Cly)
C
2
H
5
NO
2
Alanine (Ala)
C
3
H
7
NO
2
valine (val)
C
3
H
ll
NO
2
Leucine (Leu)
C
6
H
l3
NO
2
Isoleucine (Ilc)
C
6
H
l3
NO
2
C
OH
C
O
R
C H
OH
C
O
R
H NH
2
NH
2
FIg. 2.2 Two isomeric forms of typical amino acid.
C
OH
O
H C
H
NH
2
C
H
C
H
H C
NH
2
H
OH
O
C C
H
H C
3
C
NH
2
H
H C
3
OH
O
C C
H
H C
3
C
NH
2
H
H C
3
C
H
H
OH
O
C C
H
H C
3
C
NH
2
H
C
H
CH
3
H
OH
O
(CønIø.}
Ioodstujjs !!
(CønIø.}
II. S¡øø ¿na¡ns with hydroxylic (OH) groups-Hydroxy-amino acids.
Serine (Ser)
C
3
H
7
NO
3
Threonine (Thr)
C
+
H
9
NO
3
III. Side chains with sulfur atoms.
Cystine (Cys)
C
6
H
l2
N
2
O
+
S
2
Methionine (Met)
C
5
H
ll
NO
2
S
Iv. Side chains with a basic group.
Lysine (Lys)
C
6
H
l+
N
2
O
2
Hydroxylysine (Hyl)
C
6
H
l+
N
2
O
3
Arginine (Arg)
C
6
H
l+
N
2
O
2
Histidine (His)
C
6
H
9
N
3
O
2
C C
H
C
NH
2
H
OH
H
OH
O
C
H
C
NH
2
H
C
H
OH H
H C
OH
O
C
OH
O
C
H
C
NH
2
H
S
H
C
H
C
NH
2
S
H
H
C
OH
O
C
OH
O
C
H
C
NH
2
H
C
H
H S
H
CH
3
C
H
H C
NH
2
H
C
H
NH
2
H
C
H
H
C
H
H
OH
O
C
C C
H
H C
NH
2
H
C
H
NH
2
H
C
H
OH
C
H
H
OH
O
C C
H
H C
NH
2
H
C
H
H
C
H
H N C HN
NH
2
H
OH
O
(CønIø.}
NH
C
H
N NH
2
CH C CH
2
CH CHOOH
Animal Physiology !"
v. Side chains with a carboxyl group-Acidic amino acids-or their amides
Aspartic acid (Asp)
C
+
H
7
NO
+
Asparagine (Asn)
C
+
H
8
N
2
O
3
Clutamic acid (Clu)
C
5
H
9
NO
+
Clutamine (Cln)
C
5
H
l0
N
2
O
3
vI. Side chain with aromatic (Benzene-like) group.
Phenylalanine (Phe)
C
9
H
ll
NO
2
Tyrosine (Tyr)
C
9
H
ll
NO
3
Tryptophan (Trp)
C
ll
H
l2
N
2
O
2
Proline (Pro)
C
5
H
9
NO
2
Hydroxyproline (Hyp)
C
5
H
9
NO
3
The amino acids are described as the buiIding bIocks oI proteins, and may be convenientIy
grouped under two broad categories, i.e. essentiaI and nonessentiaI. The essentiaI amino acids are to
be obtained by the animaI through its diet. The nonessentiaI amino acids are, however, synthesized by
the animaI tissues.
(CønIø.}
C C
H
H C
NH
2
H
HOOC
OH
O
C C
H
O C
NH
2
C
H
NH
2
H
OH
O
C C
H
H C
H
COOH
C
H
NH
2
H
OH
O
C C
H
C
NH
2
C
H
NH
2
H
C
H
H
O
OH
O
C C
H
C
H
NH
2
H
HO
OH
O
C C
H
C
H
NH
2
H
OH
O
N
CH NH
2
H
C CH
2
CH COOH
H C
2
CH
N
H
H C
2
CH
2
C
OH
O
H C
2
CH
HO HC CH
2
N
H
C
OH
O
Ioodstujjs !#
Peptides: The amino acids (subunits) are joined together in the IoIIowing manner.
NH
2
— C — C — OH + NH — C — C— OH
2
R
1
O R
2
O
H H
NH
2
— C — C — N — C — C — OH + H O
2
R
1
O R
2
O
H H
H
The above reaction shows the amino acids as Iinked through the carboxyI
(C )
OH
O
and amino
groups. The carbon and nitrogen bond between each pair oI amino acids shown above is a speciaI
kind oI amide bond and is reIerred to as a peptide bond. The compound Iormed is a dipeptide. Like
amino acid, it stiII has an amino group at one end and a carboxyI group at the other end. ThereIore it
can stiII react with another amino acid to Iorm a Ionger chain (tripeptide), which in turn can react in
this way to accept amino acid again and again in order to Iorm poIypeptides. These compIex
poIypeptides have properties resembIing that oI proteins. Each poIypeptide has in it about 100 to 200
various amino acids in the Iorm oI amino acid residues. A protein may have two or more oI such
peptide chains. SeveraI such chains join to Iorm macromoIecuIes oI proteins.
Protein Structure
For a better understanding oI the structure oI protein the IoIIowing inIormation is essentiaI.
(a) MoIecuIar size oI protein.
(b) ReIative proportions oI various amino acids.
(c) Amino acid sequence in the chain.
(d) Three-dimensionaI arrangement oI the chain.
MoIecuIar Size
The estimation oI the size or moIecuIar weight oI protein is made Irom the accurate measurements oI
osmotic pressure, or oI sedimentation veIocity and sedimentation equiIibrium in the uItracentriIuge.
Primary Structure of Proteins: the Sequence of Amino Acids
The term primary structure is used to designate the sequence in the arrangement oI amino acids in
proteins. The sequence remains same in a speciIic protein and it is an important character in protein
Iunction. Any change in sequence oI amino acid is enough to disquaIiIy the protein Irom discharging
its Iunction. The substitution oI onIy one amino acid Ior another in the haemogIobin moIecuIe is
suIIicient to cause sickIe-ceII anemia. The sequence oI amino acids in insuIin moIecuIe was Iirst
estabIished in the year 1955. The moIecuIe has two poIypeptide chains, and arranged in them are 51
amino acids. The two chains, one with 21 and other with 30 amino acid, are joined by suIphide bond.
Animal Physiology !$
The compIete amino acid sequence oI severaI other proteins is known. These incIude enzymes
such as ribonucIease, Iysoyme and the subtiIisin oI Bacterium subtilis, etc.
Thus, under the primary structure we have considered the amino acid sequence. Each amino acid
is Iinked with its immediate neighbour by peptide bonds. The peptide bonds are the primary and
strongest Iinkages.
Secondary Structure of Proteins
In addition to the above mentioned primary structure the bioIogicaI activity oI protein aIso depends on
the secondary structure. Under the secondary structure oI protein we consider the structuraI aspects
Iike IoIding oI the poIypeptide chains into a speciIic coiIed structure arising as a resuIt oI the Iinkage
oI amino acid units which are not Iar Irom each other, as in the =-heIix. These amino acid units are
Iinked by means oI hydrogen bonds and disuIphide bonds (Fig. 2.3).
Tertiary Structure of Proteins
Tertiary structure deaIs with the arrangement and interreIationship oI twisted chains oI proteins. Such
a structure enabIes the proteins to Iorm speciIic Iayers, crystaIs or Iibres. This tertiary structure is
maintained by weak hydrogen bonds and eIectrostatic Iorces. The tertiary structure is important and
Iound in gIobuIar proteins. II this structure is disrupted, the bioIogicaI activity oI protein wouId be
Iost. The tertiary structure oI the myogIobin which was estabIished is iIIustrated in Fig. 2.4.
0uaternary Structure of Protein
In addition to the above three structures, a Iourth IeveI oI structure has been recognized in some
proteins. This structure is essentiaI Ior the activity oI enzyme protein. There are aIso a number oI
gIobuIar proteins having the quaternary structure, i.e. they are composed oI subunit peptide chains
FIg. 2.3 Alpha-helix (after Pike and Brown, NuIr¡I¡øn, l967, p.+0).
CH
2
CH
2
CH
2
CH
C
O
CH
N
H C
O
C
O
N
H
CH
O
C
H
N
N
O
O
CH — CH — R
2
COOH
CH — CH — R
2
N
H
O
C
O
C
H
N
CH
H
NH
2
N
H
CH
CH
Ioodstujjs !%
linked together by any or all of the forces that can act betveen amino acid side chains. HaemogIobin,
a protein capabIe oI carrying oxygen, is a Iine exampIe oI quaternary structure. It has Iour peptide
chains and each chain (subunit) is compIexIy IoIded and resembIes myogIobin to some extent. Chains
IaII under two types, each type consisting oI one pair. These peptide pairs oI haemogIobin interact
with each other resuIting in a quite stabIe and compact bundIe, which is the active protein.
CIassification
During the earIy stages oI the protein chemistry a number oI operationaI cIassiIication systems were
suggested. The situation is not much diIIerent even today. PresentIy there are three cIassiIications oI
proteins. They are as IoIIows:
A. CIassiIication based on the composition oI proteins.
B. CIassiIication based on the shape oI the protein moIecuIe.
C. CIassiIication based on the soIubiIity oI proteins.
StiII none oI the above systems oI cIassiIication is satisIactory. The present inIormation on the
precise structure oI proteins is insuIIicient. A precise system oI cIassiIication aiming at correIating
structuraI characteristics with biochemicaI Iunction shouId be possibIe with the avaiIabiIity oI more
and more inIormation on the exact nature oI protein. TiII that time, to Iessen conIusion it is necessary
to IoIIow one. Given beIow is an arbitrary cIassiIication Ior descriptive purposes. The proteins are
mainIy cIassiIied into two broad groupings, viz. (a) simpIe proteins, and (b) conjugated proteins. The
simpIe proteins wouId give rise to onIy amino acids on hydroIysis. In case oI conjugated proteins
some other substancea prosthetic groupis attached to the protein.
(a) 1he simple proteins: Proteins such as aIbumins, gIobuIins, gIuteIins and gIiadins, scIeroproteins,
protamines and histones come under this group.
(i) Albumins: They are soIubIe in water, diIute acids and bases. They coaguIate when heated. II a
soIution oI aIbumin is heated near the isoeIectric point the protein gets denatured and then
FIg. 2.4 (a) Tertiary of the myoglobin, (b) the course of the polypeptide chain.
COOH
Fe
NH
2
(a) (b)
Animal Physiology !&
precipitates as coaguIum. This property is utiIized to test the presence oI aIbumins in urine.
AIbumins are precipitated (usuaIIy without denaturation) by saturating the soIution with
ammonium suIphate. In naturaI state they are IrequentIy associated with smaII quantities oI
mucopoIysaccharides (reIer to mucopoIysaccharides under the titIe poIysaccharides). Common
exampIes are aIbumins oI egg-white and, oI bIood serum, and IactaIbumin.
(ii) Globulins: They are insoIubIe in water but soIubIe in diIute soIutions oI saIts. They are aIso
coaguIabIe when heated. From soIutions they are precipitated by haII-saturating with
ammonium suIphate. Common exampIes are the gIobuIins oI egg-white; oI bIood serum; oI
variety oI seeds, incIuding squash, soybean, hemp, and others.
(iii) Glutelins: They are soIubIe in diIute acids and aIkaIies, and insoIubIe in neutraI soIvents
(distiIIed water and aIcohoI), but when pressed and squeezed (kneaded) with water they Iorm a
tenacious sticky mass. They are coaguIabIe when heated. They are pIant proteins and Iound in
the cereaIs. GIuteIin Irom wheat is one oI the exampIes.
(iv) Scleroproteins: They are chieIIy the Iibrous proteins, insoIubIe in water or in other common
soIvents. They are partiaIIy or highIy resistant to digestive enzymes. They are the important
constituents oI the connective tissue and externaI coverings oI animaIs. Keratin, coIIagen,
eIastin are exampIes oI scIeroproteins. Keratins are the principaI constituents oI skin, hair,
bones; coIIagens are present in tendons, bones and aIso in the skin. EIastins are the main
constituents oI arteries, eIastic tissues and aIso tendons.
(v) Protamines: They have reIativeIy Iow moIecuIar weights ranging Irom 2,000 to 4,000. They
are very soIubIe, smaII, stabIe proteins and cannot be coaguIated by heat. They contain onIy a
Iew amino acids but a Iarge proportion oI them are basic in nature. The protamines are
exceptionaIIy rich in arginine, hence strongIy basic in nature. By virtue oI this basic, character
they readiIy Iorm saIts with mineraI acids, acidic proteins, and nucIeic acids. These saIts are
either insoIubIe or partiaIIy soIubIe. During the process oI puriIication oI proteins in order to
eIiminate the unwanted nucIeic acids, they are made to combine with protamines to Iorm
insoIubIe nucIeic acid saIts. InsuIin in the Iorm oI protamine-insuIin is Iess soIubIe and more
stabIe towards heat. Further, it is absorbed more sIowIy and hence eIIective over a Ionger
period oI time. Protamines are Iound in the ripe sperm ceIIs oI certain Iish.
(vi) Histones: Like protamines, histones have Iow moIecuIar weight, are basic in nature and very
soIubIe in most common soIvents. However, histones greatIy diIIer Irom protamines in that
they (histones) are somewhat weaker bases and are insoIubIe in ammonium hydroxide
soIutions. Histones are Iound associated with nucIeic acids in the nucIeoproteins. They are
obtainabIe Irom the spIeen, thymus; nucIeated R.B.C. oI birds.
(b) Confugated proteins: Phosphoproteins, gIycoproteins, chromoproteins, and Iipoproteins are
incIuded under this major group.
Phosphoproteins: In these the protein moIecuIe is Iinked to phosphoric acid. The phosphoproteins
when treated with diIute sodium hydroxide yieId inorganic phosphate. ExampIes oI phosphoproteins
are casein oI miIk and viteIIin oI egg-yoIk.
Ioodstujjs !'
Glycoprotein: They contain smaII quantity oI carbohydrate, bound to protein moIecuIe. The
carbohydrate in these is usuaIIy the mucopoIysaccharide. Mucin oI saIiva, chorionic gonadotropins
and some oI the pituitary hormones such as IoIIicIe stimuIating hormone (FSH) and the Iuteinizing
hormone (LH) are gIycoproteins.
1he nucleoproteins: These are Iormed by the combination oI nucIeic acid with protein.
1he chromoproteins: These are the compounds consisting oI protein and the coIoured materiaIa
non-protein. HaemogIobin contains protein gIobin and red pigment haem. Other exampIes are
haemocyanins, IIavoproteins and cytochromes. Haemocyanins are the respiratory pigments Iound in
the bIood oI invertebrates and they have copper content.
1he lipoproteins: They are compounds oI protein and Iipids. Lipoproteins have soIubiIity properties oI
proteins, hence the Iipid portion is insoIubIe in ether. Extraction oI Iipid portion is possibIe onIy when
the protein is denatured. LipoviteIIine oI egg-yoIk is a Iipoprotein.
E.3 LlPlDS
Lipids are important group oI organic compounds extractabIe Irom bioIogicaI materiaIs with usuaI Iat
soIvents such as (ether-aIcohoI mixtures, chIoroIorm, benzene, acetone, etc.). They are insoIubIe in
water. Lipids, Iike carbohydrates, aIso contain carbon, hydrogen, and oxygen, the Iormer two in Iarger
quantity than oxygen. Some Iipids contain phosphorus and nitrogen. The Iipids in the body, serve as
condensed reserve oI energy. Some have structuraI Iunctions yet others are hormones essentiaI Ior
various reactions in intermediary metaboIism. Lipids pIay very signiIicant roIes in nutrition and
physioIogy. Lipids are transported in bioIogicaI IIuids when they are in combination with proteins
(e.g., Iatty acids with pIasma aIbumin in vertebrates) or when they exist as derivative oI a protein (e.g.
Iipoproteins).
CIassification of Lipids
A brieI cIassiIication presented beIow is Iimited to Iipids oI importance in animaI nutrition.
A. SIMPLE LIPIDS: These are esters oI Iatty acids with various aIcohoIs.
1. Fatty acids.
2. NeutraI Iats (mono-, di-, and trigIycerides)
3. Waxes (esters oI Iatty acids with higher aIcohoIs)
(a) SteroI esters (choIesteroI esters with Iatty acids)
(b) NonsteroI esters (i.e. vitamin A esters, etc.)
B. COMPOUND LIPIDS OR COMPLEX LIPIDS: These are Iipids with additionaI group mentioned beIow.
1. Phospholipids: Any Iipid containing phosphorus is incIuded under phosphoIipids
(a) Phosphatidic acids (phosphogIycerides) Iecithins, cephaIins. etc.
(b) PIasmaIogens
(c) SphingomyIins
Animal Physiology "
2. Glycolipids: These are carbohydrate containing Iipids.
(a) Cerebrosides
(b) GangIiosides
3. Lipoproteins: These are Iipids in combination with proteins.
C. DERIVED LIPIDS (aIcohoIs, incIuding steroIs, hydrocarbons).
These are products derived by hydroIysis oI above mentioned groups, and stiII having some
generaI properties oI Iipids.
SlMPLE LlPlDS
FATTY ACIDS: Fatty acids are the simpIest oI aII the Iipids. These are constituents oI most oI the Iipids.
Fatty acids are monocarboxyIic acids. The moIecuIe oI a Iatty acid has a poIar carboxyI group soIubIe
in water and a non-poIar hydrocarbon chain soIubIe onIy in common organic soIvents. They have
greater soIubiIity in organic soIvents than in water. The Iatty acids with short chain Iength (under 12
carbon atoms) have greater soIubiIity in water whiIe the soIubiIity decreases appreciabIy with the
increase in their chain Iength (more than 16 carbon atoms). The short chain Iatty acids are present in
coconut oiI, miIk Iat and butter Iat. Most oI the Iong chain Iatty acids (16 to 18 carbon atoms) are
Iound in the average diet. Fish oiIs, peanut oiI contain Iatty acids having more than 20 carbon atoms.
H
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
O
C OH
CH – (CH ) –COOH
3 2 16
Stearic acid (saturated) C H O
18 36 2
H
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
C
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
O
C OH
H
2
C – (CH ) –CH
2 7
Oleic acid (monounsaturated) C H O
18 34 2
H
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
C
H
C
H
H
C
H
C
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
O
C OH
Linoleic acid (polyunsaturated) C H O
18 32 2
HC – (CH ) –CHOOH
2 7
HC–(CH ) –CH
2 4 3
HC–CH –CH
2
HOOC–(CH ) –CH
2 7
Ioodstujjs "
The Iatty acids Iound in Ioods are cIassiIied under three groups based on their degree oI
saturation or unsaturation. A saturated Iatty acid contains as many hydrogen atoms as its carbon chain
can hoId. The saturated Iatty acids have the generaI IormuIa C
n
H
2n1
O
2
or C
n
H
2n1
COOH.
CHEMICAL STRUCTURE OF SATURATED AND UNSATURATED FATTY ACIDS Certain other Iatty acids
have a singIe doubIe bond in their carbon chain resuIting in the Ioss oI two hydrogen atoms. These are
caIIed monounsaturated fatty acids and their generaI IormuIa is C
n
H
2n2
O
2
or C
n
H
2n1
COOH.
There are yet other Iatty acids, viz. polyunsaturated fatty acids, which have 2, 3, 4 or more doubIe
bonds in the carbon chain with the consequent absence oI 4, 6, 8 or more hydrogen atoms. The
poIyunsaturated Iatty acids, IinoIeic, IinoIenic and arachidonic are oIten termed as essential fatty acids
since they must be suppIied in adequate amounts in the diet oI mammaIs. The absence oI IinoIeic acid
in diet oI rats, pigs and the Iike deveIops the characteristic dermatitis.
A Iimited types oI unsaturated Iatty acids can be synthesized by the animaI ceII. For this purpose
addition oI any new doubIe bonds must be carried out between the carboxyI group and the Iirst doubIe
bond oI the Iatty acid moIecuIes. The conversion oI IinoIeic acid into arachidonic acid in animaI ceIIs
is an exampIe oI this.
The existence oI diIIerent isomeric Iorms oI unsaturated Iatty acids is due to the occurrence oI
doubIe bonds in its moIecuIe.
In the modern chemicaI nomencIature, the names oI the Iatty acids have suIIixes which denote the
state oI saturation, i.e. -anoic, saturated; -enoic, one doubIe bond; -dienoic, two doubIe bonds and so
Iorth. These names are given in parenthesis in the IoIIowing tabIe.
TabIe 2.2 A Few Common Fatty Acids Found in Lipids
FaII) a¿¡øs FørmuIa
Saturated acIds
Butyric (butanoic) C
+
H
8
O
2
Caproic (hexanoic) C
6
H
l2
O
2
Palmitic (hexadecanoic) C
l6
H
32
O
2
Stearic (octadecanoic) C
l8
H
36
O
2
Arachidic (eicosanoic) C
20
H
+0
O
2
Unsaturated acIds
Oleic (hexadecenoic) C
l8
H
3+
O
2
Linoleic (octadecadienoic) C
l8
H
32
O
2
Linolenic (octadecatrienoic) C
l8
H
30
O
2
Arachidonic (eicosatetraenoic) C
20
H
32
O
2
As regards properties, the saturated Iatty acids have higher meIting points and are Iess reactive
than the unsaturated ones having equaI number oI carbon atoms. For exampIe, stearic acid (saturated)
meIts at 70°C, whereas oIeic, IinoIeic and IinoIenic acids are Iiquid at room temperature in spite oI the
Iact that they aII have 18 carbon atoms. These characteristics are important in physioIogy as they
inIIuence the properties oI Iats and other media in which the Iatty acids are combined.
NEUTRAL FATS: The chemicaI term Ior a neutraI Iat is trigIyceride. TrigIycerides are esters Iormed
by a combination oI the trihydroxy aIcohoI (gIyceroI) with three moIecuIes oI Iatty acids. The
Animal Physiology "
trihydroxy aIcohoI bears three side groups each oI which terminates in an OH radicaI. In the
iIIustrated reaction given beIow the R in the generaI IormuIa oI Iatty acid stands Ior the side chain;
whereas the carbon at the other end bears a group which is typicaI oI aII organic acids, i.e. COOH.
As a resuIt oI reaction, the carboxyI group oI three moIecuIes oI Iatty acid units with the aIcohoIic
group in the gIyceryI moIecuIe to Iorm a moIecuIe oI trigIyceride on one hand, whiIe on the other
hand, the hydroxyI groups Irom the three arms oI the gIyceroI units with each oI the hydrogen atom in
the acid radicaI oI the three moIecuIes oI Iatty acid to Iorm three moIecuIes oI water.
CH
2
OH H OOC — R
CH OH H OOC — R
CH
2
OH H OOC — R
CH
2
— OOC — R
CH — OOC — R
CH
2
— OOC — R
+ 3H O
2
One mol. glycerol Three moles
of fatty acid
One mol. of
triglyceride
+
The trigIycerides may be esters oI one, two, or three Iatty acids with gIyceroI. II aII the 3 moIes oI
the Iatty acids that go in the Iormation oI a trigIyceride are the same, it is known as simpIe
trigIyceride. A mixed trigIyceride is one, in the Iormation oI which, diIIerent Iatty acids are invoIved.
The commonest Iatty acids Iound in Iats are paImitic, oIeic and stearic acids.
As aIready stated trigIycerides are neutraI Iats; neutraI, because the acid ions are neutraIized
during their uniIication with gIyceroI; Iats, because the buIk oI the moIecuIe is devoid oI eIectro-
negative eIements which can unite with hydrogen to Iorm water moIecuIes. Because oI neutraI and
inert nature oI trigIycerides, they mainIy serve as a storage medium Ior carbon compounds such as
Iatty acids and gIyceroI. These Iatter compounds can be broken down in order to Iiberate energy to be
used by the ceII.
Whether a trigIyceride is a Iiquid or soIid is based on the kind oI Iatty acid residues in its
structure. The trigIyceride which is Iiquid beIow 20°C is termed oiI in industriaI cIassiIication and
contains residues, more oI the unsaturated Iatty acids; whereas the gIyceride which is soIid above this
temperature is caIIed a Iat and contains more oI the saturated Iatty acid residues in its structure. The
oiIs are predominant in pIants, and the Iats are predominant in animaIs.
The Iats oI animaIs diIIer Irom species to species. Even within the same species Iats in the
diIIerent parts exhibit variation. For exampIe, meIting point oI Iard (the typicaI body Iat oI swine) is
28°C, whereas the Iat oI its kidney meIts at 43°C. This indicates that the kidney Iat has Iirmer
consistency and higher saturated Iatty acid composition. Because oI this diIIerence in the property, the
Iat around the kidneys acts Iike cushions to protect them Irom shock injuries. The Iats in the more
active parts oI organisms have Iower meIting point and are more unsaturated. This means they wouId
be more easiIy oxidized and constantIy utiIized than those stored as Iatty tissues eIsewhere.
BODY FATS: AnimaIs Iiving in coId zones generaIIy possess Iats having more unsaturated
components than those oI animaIs Irom tropicaI regions. Further, there is variation in the type oI Iat
present in poikiIotherms and homeotherms. The poikiIotherms, i.e. coId bIooded animaIs, are soIter
and thus have more unsaturated Iats than warm-bIooded animaIs. The meat eating animaIs have soIter
Iats than the vegetabIe Ieeders.
Ioodstujjs "!
Fats are hydroIized into gIyceroI and Iatty acids by diIute mineraI acids, enzymes such as Iipase,
or steam. Enzymatic hydroIysis takes pIace during digestion by pancreatic Iipases.
SAPONIFICATION: BoiIing the Iats with aIkaIi such as sodium hydroxide wouId yieId gIyceroI and
the aIkaIi saIt oI the Iatty acid, which is known as soap.
CH .O.CO.C H
2 17 35
CH.O.CO.C H
17 35
+ 3NaOH CHOH + 3C H COONa ®
17 35
CH .O.CO.C H
2 17 35
CH OH
2
CH OH
2
Tristerin Glycerol Sodium stearate
This process is known as saponiIication, and it occurs during the digestion under the action oI
sodium saIts in the biIe. Fats are aIso hydroIyzed by superheated steam.
The saponiIication vaIue oI a Iat is the number oI miIIigrams oI aIkaIi, the potassium hydroxide,
required to saponiIy one gram oI Iat.
HYDROGENATION: The Iats (trigIycerides), Iiquids at ordinary temperature; are mentioned as oiIs
containing a Iarge proportion oI unsaturated Iatty acids. The oiIs may be hardened to make soIid
trigIycerides or soIt Iats may be hardened to increase the meIting point by a chemicaI process known
as hydrogenation. In this process the trigIycerides are treated with hydrogen under certain pressure, in
the presence oI IineIy divided nickeI as a cataIyst. As a resuIt, the hydrogen is added on the doubIe
bonds oI the unsaturated Iatty acids to Iorm a more saturated Iat. The process oI hydrogenation is not
aIIowed to reach compIetion as it makes the Iat too hard and brittIe making it undesirabIe.
The saturation oI doubIe bonds due to hydrogenation, makes the Iat Iess reactive and thus tends to
prevent the oxidative changes. Thus, the hydrogenation is used Ior improving the storage quaIities
especiaIIy oI certain vegetabIe oiIs.
ROLE OF FATS AND OILS: The Iats and oiIs are important constituents oI the dietary requirements
because they have higher energy vaIue. By caIorimetric studies it is Iound that one gram oI
carbohydrate wouId yieId 4.1 caIories, whereas one gram oI Iat yieIds 9.3 caIories. Lipids contain Iat
soIubIe vitamins and the essentiaI Iatty acids which are Iound in the naturaIIy occurring Iats. The Iat
reserves (adipose tissue) in the body are the rich store houses oI energy and it wouId be reIeased when
the body needs energy. The adipose tissue Iound in the subcutaneous tissues serves as an insuIating
materiaI. As aIready mentioned, they serve as protective cushions Ior the viscera and certain organs in
the body such as the kidneys.
EssentiaI Iatty acids, viz. IinoIeic, IinoIenic and arachidonic heIp preventing certain disorders in
mammaIs Iike mouse, dog and man. LinoIenic acid has an essentiaI roIe in reproduction and Iactation.
It aIso serves as a protective agent against radiation eIIects and prevents heavy Ioss oI water Irom the
body by acting against the deveIopment oI permeabiIity oI skin capiIIaries.
WAXES: The wax is an ester oI a Iatty acid with one oI the higher monohydroxy or dihydroxy
aIcohoIs. The waxes have high meIting points. The Iat spIitting enzyme Iipase cannot react on waxes
and Ior this reason these are not suitabIe as Iood. However, many animaIs, insects in particuIar,
synthesize and secrete the waxes. Beeswax is an ester oI paImitic acid with myricyI aIcohoI.
Animal Physiology ""
Spermaceti is an ester oI paImitic acid with cetyI aIcohoI. It is Iormed Irom the head oI the sperm
whaIe.
STEROIDS: These are oIten associated with Iat and are separabIe Irom it by a process oI
saponiIication. The steroids occur in unsaponiIiabIe residue. Like Iipids they are soIubIe in Iat
soIvents and generaIIy insoIubIe in water. AII steroids have simiIar cycIic nucIeus oI the type shown
beIow. The rings A, B, and C in the Iigure represent phenanthrene and to this structure the ring D
representing cycIopentane is attached.
A B
D C
It shouId be noted that this cycIic nucIeus is not uniIormIy unsaturated, but the actuaI parent
substance is compIeteIy saturated and is termed as perhydro-cycIopentanophenanthrene. Steroid
compounds are the derivatives oI this ring. The steroids incIude such substances as choIesteroI and
other steroIs, the biIe acids, the maIe and IemaIe sex hormones, the hormones oI the adrenaI cortex,
etc.
STEROLS: Certain steroids are characterized by a Iree hydroxyI group and as such behave
chemicaIIy Iike aIcohoIs. Such aIcohoI-Iike steroid compounds which do not contain carboxyI or
carboxy groups common to other steroids are reIerred to as sterols (the term sterols means soIid, and
ol represents the ending, oI` oI aIcohoI). The steroIs are cIassiIied into: (i) zoosteroIs, iI they are
avaiIabIe Irom the animaI tissues, i.e. choIesteroI, corticosterone, etc., (ii) phytosteroIs, iI avaiIabIe
Irom vegetabIe tissues; (iii) mycosteroIs, iI avaiIabIe Irom Iungi, yeast, etc.
Functions: SteroIs Iorm esters with Iatty acids and act as carriers oI Iats Ior absorption and
transport. They go into the Iormation oI nerve sheaIth (myeIin), and ceII membrane. The steroIs,
which are present as esters in the Iatty secretions oI the sebum, cerumen, etc., act as Iubricants to skin
and hair.
CDMPDUND LlPlDS
PHOSPHOLIPIDS: Lipids containing phosphorus are phosphoIipids. They are aIso reIerred as
phosphoIipins and phosphatides. They diIIer Irom the neutraI Iats in containing phosphoric acid and
an organic nitrogenous base. The phosphoIipids are wideIy distributed in animaI and pIant ceIIs. They
are abundant in brain and nervous tissues. They have a poIar group which can combine with protein to
Iorm bioIogicaIIy important Iipoproteins.
The diIIerent types oI phosphoIipids described beIow have the same essentiaI structure but they
vary onIy in the nature oI one oI the groups Iinked to the phosphate portion oI the moIecuIe. Further,
Ioodstujjs "#
most oI the compounds are oI phosphodiesters nature. One type oI phosphoIipid, viz. phosphatidic
acid is indicated beIow with a generaI IormuIa.
PHOSPHATIDIC ACIDS: Phosphatidic acids are compounds consisting oI gIyceroI, two Iatty acids,
and a phosphate group.
H C — O — C — R
2 1
O
O
H C — O — C — R
2 2
O
H C — O — P — OH
2
OH
The R
1
and R
2
in the above IormuIa represent the residues oI the moIecuIes oI Iatty acids. The
phosphatidic acids shouId be viewed as Iats in which one oI the Iatty acids is repIaced by phosphoric
acid. The structure suggests, these acids couId easiIy give rise to trigIycerides or to phosphoIipids.
The phosphatidic acids are not present in signiIicant amounts in the tissue extracts. They pIay
important roIe as active intermediates in the biosynthesis oI other Iipid compounds.
Lecithins (phosphatidyI choIines): Lecithins are choIine esters oI phosphatidic acid. They are Iats
in which one oI the Iatty acids is repIaced by phosphoric acid and the nitrogenous choIine. They are
best known and probabIy the most common Iorm oI phosphoIipids in animaIs. On hydroIysis,
Iecithins break up into gIyceroI, Iatty acids, phosphoric acid and choIine.
Lecithins are soIubIe in the Iat soIvents except acetone and by this property they are distinguished
Irom the Iats. These are required Ior the transport, and utiIization oI other Iipids especiaIIy in the Iiver.
II the synthesis oI choIine, an important component oI Iecithin is interrupted, the synthesis oI Iecithin
aIso wiII be stopped. With the resuIt, the transport oI Iat to and Irom the Iiver is interrupted.
ConsequentIy, the Iipids accumuIate in the Iiver giving rise to a condition caIIed fatty liver. The Iack oI
dietary choIine aIso Ieads to a variety oI troubIes such as growth IaiIure, hemorrhagic kidneys, and
sIipped tendons, etc.
H C — O — C — R
2 1
O
O
HC — O — C — R
2
O
H C — O — P — O — CH CH
2 2 3 2
— —N (CH )
+
3
O

The enzyme, Iecithinase A, present in the venoms oI snakes attacks Iecithins and removes one oI
the Iatty acid residues Ieaving a product known as IysoIecithin. This product has the abiIity to
haemoIyze the red bIood corpuscIes.
Cephalins (PhosphatidyI ethanoIamines): These are phosphoIipids which resembIe Iecithins in
most properties, but diIIer in containing aminoethyI aIcohoI (NH
2
CH
2
CH
2
OH) in pIace oI
choIine.
Animal Physiology "$
H C — O — C — R
2 1
O
O
HC — O — C — R
2
O
H C — C — P — O — CH CH N
2 2 2 3
H
O

+
PhosphatidyIserine is a cephaIin Iike compound and contains the amino acid serine in pIace oI
ethanoIamine.
H C — O — C — R
2 1
O
O
HC — O — C — R
2
O
H C — O — P — O — CH CH NH
2 2 3
O

+
COOH
Phosphatidyl inositol is a phosphoIipid simiIar in structure to the Iecithin but has inositoI in pIace
oI choIine.
H C — O — C — R
2 1
O
O
HC — O — C — R
2
O
H C — O — P — O — C
2
OH
C
C
C
C
OH
H H
H OH
C
H
OH
OH H
OH
These are mainIy Iound in pIants and in nervous tissues.
Plasmalogens: These phosphoIipids are abundant in brain and muscIe. They resembIe Iicithins
and cephaIins in structure but possess an aIdehyde group in pIace oI one oI the Iatty acids in typicaI
phosphoIipid moIecuIe. The structure shown beIow represents a typicaI pIasmaIogen. The portion oI
the IormuIa encIosed by Iine is an ethonoIamine residue.
Ioodstujjs "%
H C — O — CH = — R
2 1
CH
O
HC — O — C — R
2
O
H C — O — P — O — CH CH NH
2 2 2 3
O

+
Structure of plasmalogen (phosphatidal ethanolamine)
Sphingosine lipids: These are more compIicated phosphatides containing sphingosine, a Iong-
chain amino aIcohoI in pIace oI gIyceroI.
Sphingomyelins (sphingosine phosphatides): These phosphoIipids contain sphingosine and a Iatty
acid attached in the Iorm oI amide Iinkage to the nitrogen oI carbon 2, and phosphorychoIine attached
to the terminaI carbon atom oI sphingosine. On hydroIysis they yieId Iatty acids, phosphoric acid,
choIine and sphingosine. The sphingomyeIins are Iound in Iarge quantities in the nerve tissue,
particuIarIy in the myeIin sheath oI the nerve.
GLYCOLIPIDS: Cerebrosides and gangIoisides are the chieI gIycoIipids.
CH (CH ) CH=CH
3 2 12
HO — CH
H N — CH
2
CH OH
2
CH (CH ) CH=CH
3 2 12
H — CH O
R — C — N — CH
H
CH — O — P — O — CH
2 2
O
O

CH N (CH )
2 3 3
+
Sphingosine Sphingomyelins
O
These are particuIarIy abundant in the brain and in the myeIin sheath oI nerves. There are the
Iipids containing carbohydrate radicaIs and nitrogen in the moIecuIe. In structure these are reIated to
sphingomyeIins, but contain a hexose instead oI phosphorychoIine. On hydroIysis they give rise to
Iatty acids, sphingosine and gaIactose.
E.4 VlTAMlNS
In the year 1911 Funk, a PoIish biochemist, coined the term 'vitamine¨ to designate the antiberiberi
Iactor. In the term vitamine vita suggests the essentiaI nature oI the Iactor, and amine indicates the
chemicaI structure. Later the same term was used Ior severaI unknown dietary Iactors. Not aII the
known Iactors have the amine structure. ThereIore in 1919 the Iast 'e¨ Irom the vitamine was
discontinued Irom use thereby removing the impIication oI chemicaI structure.
Vitamins can be described as accessory Iood Iactors which are essentiaI Ior some metaboIic
reactions within the ceII and which must be provided in the diet in minute amounts. In many animaIs
Animal Physiology "&
they cannot be synthesized by the body. Certain animaIs do synthesize a Iew vitamins in very minute
quantities but they IaII short oI the requirements. In any case, the animaIs shouId procure them
through Iood. Vitamin deIiciency resuIts in severaI diseases characteristic oI each vitamin deIiciency.
Vitamins are a speciaI group oI organic substances which are chemicaIIy unreIated. They may be
organic acids, amines, amino acids, esters, aIcohoIs, steroids, etc. These vitamins are traditionaIIy
divided into two subgroups on the basis oI their soIubiIity properties, such as water soIubIe vitamins
and Iat soIubIe vitamins.
Water-soIubIe Vitamins
Vitamins C and B compIex are water soIubIe substances.
ASCORBIC ACID OR VITAMIN C: Ascorbic acid is a hexose derivative and is properIy cIassiIied as
a carbohydrate. It is a white crystaIIine substance highIy soIubIe in water. It is easiIy oxidized in
soIution and cooking destroys it. The vitamin is highIy unstabIe in aIkaIine soIutions.
This vitamin is required by primates and the guinea pig. AII other vertebrates and some
invertebrates as weII as pIants and most micro-organisms can synthesize ascorbic acid Irom
carbohydrates. It is an essentiaI dietary Iactor, the deIiciency oI which causes painIuI disease oI the
joints and gums caIIed scurvy.
O = C —
HO — C
HO — C
H — C —
HO — C — H
CH OH
2
O
L–Ascorbic acid
(reduced form)
O = C —
HC —
CHOH
CH OH
2
O
L–Dehydroascorbic acid
(oxidized form)
O = C
O = C
HydroxyproIine is an unusuaI amino acid Iound in the coIIagen and is essentiaI Ior maintenance
oI normaI tissues. It is Iormed by hydroxyIation oI proIine and this process requires vitamin C. In the
absence oI this vitamin the hydroxyproIine production is very much reduced. ThereIore, the coIIagen
Iormed during ascorbic acid deIiciency, contains negIigibIe amount oI hydroxyproIine and this brings
about structuraI abnormaIities observed in scorbutic tissues.
Vitamin C is contained in Iresh vegetabIes and Iruits.
VITAMIN B GROUP: Vitamin B group contains about tweIve known vitamins. Each one perIorms
speciIic Iunction. They are coIIectiveIy caIIed vitamin B compIex and are generaIIy Iound together.
1hiamine or vitamin B: This vitamin is contained in yeast, miIk, egg, peas and beans hence richIy
distributed in pIants, animaIs and certain microorganisms. A deIiciency oI this vitamin causes a
serious disease known as beriberi. Its symptoms are inIIammation oI nerves, muscuIar weakness and
paraIysis oI Iimbs.
Ioodstujjs "'
NH
2
CH
2
N
H C
3
— N
+
C1

CH
3
(CH )
2 2
S
N
OH



— —
Thiamine
Thiamine Iunctions as part oI the coenzyme cocarboxyIase which is the coenzyme Ior pyruvic
decarboxyIase and Ior severaI other enzymes which are necessary Ior the oxidation oI pyruvic acid to
acetyICoA and =KetogIutaric acid to succinyI CoA (see Chapter 4).
Riboflavin or vitamin B
2
: This vitamin is wideIy distributed and the rich sources are Iiver, yeast,
wheat germ, miIk, eggs, and green IeaIy vegetabIes. Its deIiciency causes cracks in the corners oI the
mouth and dermatitis oI the Iace. The eyes become inIIamed and there is dimness in vision. This
vitamin is a part oI two coenzymes, IIavin mononucIeoide (FMN) and IIavin adenine dinucIeotide
(FAD) which are Iinked to proteins as IIavoproteins.
H
OH
C CH
2
H
OH
C
H
OH
C CH
2
OH
N
N CH
3
CH
3
O
N
NH
O
Riboflavin
Nicotinic acid or niacin: Nicotinic acid is an essentiaI dietary requirement. Tryptophan is its
precursor which is converted into nicotinic acid through a series oI biochemicaI reactions. Its
deIiciency in diet causes a disease peIIagra which is characterized by dermatitis diarrhoea and nervous
disorders. This vitamin (niacin) is a component oI coenzymes Iike DPN and TPN which take part in
oxidation-reduction oI carbohydrates, Iats, proteins and nucIeic acid metaboIism.
This vitamin is widespread, but the chieI sources are meat, Iiver, yeast, beans and wheat germ.
C
OH
N
Nicotinic acid
O
Jitamin B
6
: This vitamin occurs in three Iorms; pyridoxine, pyridoxaI and pyrodoxamine. It is an
essentiaI component oI the coenzyme pyridoxaI phosphate which is an important coIactor in the
transmination and decarboxyIation oI aII naturaIIy occurring amino acids. The dietary requirement oI
vitamin B
6
; in human beings is not yet IuIIy estabIished. It is synthesized by green pIants and a
number oI microorganisms. The vitamin is Iound in many Ioods Iike Iiver, pork, kidney, yeast, egg-
yoIk, grains and various seeds.
N
CH OH
2
CH OH
2
HO
CH
3
CH OH
2
CH
2
HO
CH
3
CH OH
2
H O
CH
3
NH
2
Pyridoxine Pyridoxamine Pyridoxal
C
H
O
N N
Animal Physiology #
Pantothenic acid: The requirement oI this vitamin in human beings has not been estabIished so
Iar, aIthough it is essentiaI Ior many other animaIs. Pantothenic acid is essentiaIIy a portion oI the
coenzyme. A moIecuIe which has a key roIe in the metaboIism oI Iats, carbohydrates and amino acids.
Its roIe has been IuIIy determined in rats where the Iack oI this vitamin induce retardation oI growth,
reproduction impairment and greying oI bIack hair. The rich sources oI this vitamin are Iiver, yeast,
eggs and royaI jeIIy. This is synthesized by green pIants and some microorganisms.
HOC
H
H CH
3
C
H
OH
C
O
C
H
N
H
H
C
H
H
C COOH
Pantothenic acid
CH
3
Biotin: Biotin requirements in man have not been determined so Iar, but its importance in other
animaIs has been ampIy demonstrated. However, recentIy it has been shown that this vitamin is
necessary in Iatty acid synthesis. It is aIso necessary Ior growth and respiration oI certain species oI
bacteria. Rich sources oI biotin are Iiver, yeast, kidney and egg-yoIk. Some animaIs obtain their biotin
requirements Irom the biosynthetic activity oI their intestinaI bacteria.
HN NH
HC CH
H C
2
CH – CH
2
– CH – CH – CH – COOH
2 2 2
S
Biotin
C
O
Folic acid: This vitamin exists in severaI diIIerent Iorms depending upon the bioIogicaI source.
Its importance has been estabIished in a number oI animaIs. SimpIest type is the IoIic acid moIecuIe
caIIed pteroyIgIutamic acid, which is isoIated Irom Iiver. This contains gIutamic acid, para-
aminobenzoic acid and peteridine. The importance oI IoIic acid is Iound in the enzymatic synthesis oI
serine Irom gIycine. It is aIso necessary in the metaboIism oI tyrosine, ascorbic acid, biotin and
vitamin B
12
. It is chieIIy Iound in green IeaIy vegetabIes, Iiver, yeast and kidney.
C
COOH
CHNH
CH
2
COOH
O
NH CH
2
N N
N
N
OH
NH
2
Glutamic
acid
Pter yl (pteroic acid) o
p-Aminobenzoic acid Pteridine
Folic Acid (Folacin)
CH
2
Jitamin B
12
. This vitamin occurs in nature in a variety oI Iorms. Its chemicaI structure is compIex
and contains a metaI cobaIt, cyanide, ribose sugar and other components. This vitamin has been
Ioodstujjs #
shown as a very important growth Iactor Ior many animaIs, man and microorganisms. A deIiciency oI
this vitamin causes a bIood disease caIIed pernicious anaemia in higher animaIs. The vitamin is Iound
in Iiver, kidney, meat and miIk, etc., and takes part in the metaboIism oI proteins, Iats, carbohydrates
and nucIeic acids.
Other B vitamins: ChoIine, inositoI, Iipoic acid, carnitine and pantothenic acid are important
constituents oI group B vitamins. ChoIine is a portion oI Iecithin, one oI the ceII phosphoIipids. A
dietary deIiciency oI choIine produces symptoms Iike deposition oI excess oI Iat in the Iiver oI
mammaIs and shortening and thickening oI bones in birds. One oI the most important Iunctions oI
choIine is to provide a source Ior methyI groups (CH
3
) in ceII metaboIism. It is abundantIy Iound in
egg, Iiver, meat, kidney and Inositol is a growth Iactor Ior severaI yeasts and Iungi and aIso Ior human
ceII brain when in cuIture medium. In the intact organism (man) its necessity has not been determined
so Iar. This is usuaIIy Iound in substances rich in caIcium, phosphorus and magnesium. Its rich
sources are miIk, cereaIs, Iiver, sharks, etc.
CH
3
CH
3
N — CH
+
2
—CH OH
2
CH
3
Choline
OH
H
HO
H OH
H
OH
H
OH
H OH
H
Inositol
Lipoic acid has not been shown to be required by animaIs in their diets aIthough it is a growth
Iactor Ior certain microorganisms. It is an 8-carbon compound containing suIphur. However, it
Iunctions in pIants, animaIs and microorganism as hydrogen carrier in the metaboIism oI pyruvic acid.
CH
2
CH—(CH ) —COOH
2 4
S—S
CH
2
CH
2
CH—(CH ) —COOH
2 4
CH
S
H
S
H
Lipoic acid (reduced fo m) r
Lipoic acid (oxidized form)
Animal Physiology #
Carnitine is Iound to be necessary in certain insects and is responsibIe Ior the compIetion oI their
IiIe cycIe. Its Iunctions are stiII not known.
Fat-soIubIe Vitamins
Vitamins A,D,E and K are Iat-soIubIe vitamins. Their enzymatic roIe has not been eIucidated so Iar
due to their Iat-soIubIe nature.
VITAMIN A: It is avaiIabIe in severaI chemicaI Iorms and was recognized as earIy as 1913 by
McCoIIum and Davis. It is determined to be a growth Iactor in rats. The carotenes oI pIants upon
ingestion are converted into this vitamin. In most oI the animaIs, a deIiciency oI this vitamin causes
retardation oI growth, drying out oI epitheIiaI ceIIs and deposition oI horny substances in the corner
oI the eye. The Iatter symptom Ieads to conditions oI bIindness (xeropthaImia). In man, its deIiciency
causes night bIindness causing depIetion oI a red pigment caIIed rhodopsin. Fish, Iiver, miIk, cheese
and vegetabIes are rich sources oI this vitamin.
CH
3
CH
3
CH
3
—CH=CH—C=CH—CH=CH—C=CH—CH OH
2
CH
3
CH
3
Vitamin A
1
VITAMIN D: The vitamins D are aII steroIs and in nature they are chieIIy Iound in animaI
organisms. These vitamins are Iormed Irom their provitamins which are aIso steroIs. In mammaIs
vitamin D can cure or prevent ricketsa disease in which bones IaiI to caIciIy. For this reason they
are aIso caIIed antiricketic vitamins.
The provitamin D
2
(ergosteroI) occurs in pIant kingdom (i.e., ergot and in yeast) and as such is
avaiIabIe to animaIs through Iood. Man and other animaIs can synthesize provitamin D
3
(i-dehydrochoIesteroI). The provitamins D
2
and D
3
are then activated to Iorm vitamin D
2
(caIciIeroI)
and vitamin D
3
(choIcaIciIeroI) when the animaI is exposed to uItravioIet rays. The activation takes
pIace in the skin and the vitamins are subsequentIy transIerred to various organs Ior utiIization. A part
oI the vitamins D is stored chieIIy in the Iiver, though skin, brain, Iung, spIeen, and bones aIso contain
smaII amounts oI stored D-vitamins.
Pure vitamins D are white, crystaIIine, odourIess substances soIubIe in Iats and Iat soIvents such
as ether, chIoroIorm, acetone and aIcohoI. They are resistant to oxidation, aIkaIi and to temperatures
beIow 140°C. In acid media these vitamins D are reIativeIy unstabIe.
Functions of vitamins D: Vitamin D is essentiaI Ior the normaI growth oI the bone. In case oI
deIiciency oI this vitamin, deposition oI inorganic bone mineraIs IaiI to occur in the newIy Iormed
bone matrix, but the matrix continues to Iorm. The provisionaI zone oI caIciIication wouId no Ionger
be cIearIy demarcated, but is irreguIar and deIormed. In chiIdren rickets is a skeIetaI deIormation and
Ioodstujjs #!
can be noticed in the Iorm oI bowIegs, knock-knees, rachitic rosary (beaded appearance on ribs at the
juncture oI the rib bones and the costaI cartiIage), and pegion-breast. In aduIts it Ieads to Iate rickets
(osteomaIacia).
Another important Iunction oI vitamin D is to increase the intestinaI absorption oI caIcium. To
expIain the mechanism by which the vitamin aids caIcium absorption, two expIanations have been
given. According to the Iirst, the vitamin is invoIved in active transport oI caIcium. The second
expIanation is that the vitamin increases permeabiIity oI ceIIs oI the mucosa to the mineraI. It is
beIieved that the vitamin aids not onIy absorption oI caIcium but aIso that oI various other mineraIs
such as magnesium, beryIIium, zinc, iron, etc. Later these wouId be deposited in the bone.
In parathyroidectomized animaIs, vitamin D IaciIitates the excretion oI the phosphate by the
kidney and consequentIy the high serum phosphate IeveI is Iowered.
Sources of vitamin D: The main sources oI vitamin D are Iish, Iiver, oiIs and miIk. Vitamin D is
not wideIy distributed in nature but both provitamins are wideIy distributed. AIthough provitamin D
2
is a common occurrence in vegetation, vitamin D
2
is not present in Iiving pIants. AnimaIs are the onIy
source oI 7-dehydrochoIesteroI. These provitamins require sunIight, to be transIormed into active
Iorm.
VITAMIN E: Vitamin E was discovered in the year 1922 and it has been known as antisteriIity
vitamin. First discovered as an essentiaI compound Ior the normaI reproduction in maIe and IemaIe
rats. Its absence causes death and resorption oI Ioetuses, and testicuIar degeneration in rats.
Compounds possessing vitamin E activity are chemicaIIy known as tocopheroIs. This name is derived
Irom the Greek in which tokos means chiId birth; perhos means to bear; and the suffix-ol signiIies an
aIcohoI.
There are seven Iorms oI tocopheroIs and each Iorm, despite its diIIerence due to the position oI
methyI groups, is caIIed vitamin E. AII these diIIerent E-vitamins are derived Irom the compound -
tocol
O
CH
3
HO
(CH )
2 3
C
H
CH
3
(CH )
2 3
C
H
CH
3
(CH )
2 3
C
H
CH
3
CH
3
The diIIerence between the various Iorms oI tocopheroIs is in the structure oI the moIecuIe. The
various tocopheroIs are:
=-tocopheroI: 5, 7, 8-trimethyItocoI
>-tocopheroI: 5, 8-dimethyItocoI
C-tocopheroI: 7, 8-dimethyItocoI
@-tocopheroI: 8-methyItocoI
-tocopheroI: 5-methyItocoI
-tocopheroI: 5, 7-dimethyItocoI
D-tocopheroI: 7-methyItocoI
OI these tocopheroIs, the =-tocopheroI is most wideIy distributed among animaIs.
Animal Physiology #"
O CH
3
HO
(CH )
2 3
C
H
CH
3
(CH )
2 3
CH
3
CH
3
H
2
CH
3
C
CH
3
(CH )
2 3
C
CH
3
CH
3
H H
-Tocopherol 5,7,8, – Trimethyltocol a
Function of vitamin E: The absence oI vitamin E in the diet hampers the normaI reproduction in
both the sexes in rats. In IemaIes it causes death and resorption oI Ioetuses and in maIes it brings
degenerative changes in the testes. In the mouse, onIy the IemaIe seem to suIIer Irom this vitamin
deIiciency resuIting in death and resorption oI Ioetuses. However, in case oI hamsters onIy the maIes
aIIected and resuIt in testicuIar degeneration. In cattIe, sheep, or goats neither the deIiciency nor the
concentrated doses oI this vitamin seem to have inIIuence on the reproductive perIormance.
Vitamin E has a powerIuI antioxidant property and protects vitamin A, carotene and ascorbic acid
Irom oxidative destruction both in the digestive tract and in the body tissues. As a resuIt oI this
protection these vitamins retain their properties Iong enough to IaciIitate the body to use them more
eIIicientIy.
Vitamin E Iunctions as a coIactor in the eIectron transIer system operating between cytochromes
b and c. Its deIiciency Ieads to uncoupIing oI oxidative phosphoryIation.
In some species oI animaIs vitamin E deIiciency produces muscuIar distrophy primariIy in the
skeIetaI muscIes. Intake oI trocopheroI-rich diets cures this troubIe. The diets deIicient in both
suIphur-containing amino acids (particuIarIy cystine) and vitamin E produced hepatic necrosis in
experimentaI animaIs. Such a dietary Iiver necrosis can be prevented by providing the animaIs with
adequate amounts oI suIphur-containing amino acids, and vitamin E aIong with seIenium.
Vitamin E increases the nucIeic acid turnover rate in skeIetaI muscIes.
There is no cIear evidence to suggest that vitamin E is essentiaI to man. Even though its IeveI in
the serum is considerabIy reduced Ior 10 to 22 months, no signiIicant cIinicaI or physioIogicaI eIIects
have been noticed. In human beings the administration oI this vitamin neither brought any reIieI Irom
steriIity, nor cured human muscuIar distrophy.
A deIiciency oI vitamin E is unIikeIy to occur because oI the abiIity oI the body to store it.
Storage is mostIy in the Iiver though smaII quantities do exist in other organs and tissues.
Sources of vitamin E: Richest sources oI this vitamin are vegetabIe oiIs such as wheat germ oiI
and cotton seed oiI. LeaIy-green pIants and vegetabIes as weII as whoIe grain cereaIs are aIso rich
sources oI vitamin E. Among animaI products Iiver, heart, kidney, miIk, and eggs are the best sources
oI vitamin E.
VITAMINS K (NAPHTHOQUINONES): In 1929 Dam, a Danish scientist observed that the chicks raised
on synthetic diet suIIered Irom hemorrahage under the skin. In the year 1935 he identiIied this as due
to the absence oI an antihemorrhagic Iactor. When these chicks were Ied with green Ieaves, the
hemorrhagic syndrome disappeared. He thereIore reasoned that these Ioods contained the
Ioodstujjs ##
antihemorrhagic Iactor and named it as vitamin KsymboIizing the Danish term, 'KoaguIation
Faktor¨. The vitamin was isoIated in a puriIied Iorm Irom aIIaIIa by Dam and his associates in the
year 1939. In nature it occurs in two Iormsas K
1
in green Ieaves and as K
2
when produced by
bacteriaI synthesis. These K
1
and K
2
are derivatives oI 2-methyI-I, 4-naphthoquinones and soIubIe in
oiIs.
CH
3
CH —CH= C—CH (CH —CH —CH—CH ) H
2 2 2 2 2 3
=
CH
3
CH
3
O
O
Vitamin K
1
The compound 2-methyI-1, 4-naphthoquinone is a synthetic Iorm oI this vitamin and is caIIed
menadione. It is aIso termed as vitamin K
3
. It is water soIubIe and is more potent than the naturaIIy
occurring vitamins K.
Functions of vitamin K: The parenchyma in normaI Iiver produces prothrombin which is one oI
the Iactors required Ior bIood cIotting. The Iunction oI vitamin K is to cataIyze the synthesis oI
prothrombin. In the absence oI vitamin K, hypoprothrombinemia occurs and this greatIy deIays the
bIood cIotting. Administration oI vitamin K aIIeviates hypoprothrombinemia iI the hepatic
parenchyma is heaIthy enough to produce prothrombin. In cirrhosis the parenchyma IaiIs to produce
prothrombin and in such a case vitamin K has no eIIect.
CH
3
O
O
(2–methyl–1, 4–naphthoquinone
Vitamin K ;(menadione)
3
It is known that vitamin K Iunctions in eIectron transport and oxidative phosphoryIation system in
mitochondria. The exact Iocation oI vitamin K in the eIectron transport chain is not cIear. Martius
(1956-1961) suggests that Iirst the cytochrome b oxidizes vitamin K and the Iatter, then, is reduced by
a speciIic enzyme caIIed the vitamin K reductase.
The vitamin K
1
is aItered by the action oI uItravioIet radiation. Rats when Ied with steriIized Iood
deveIoped vitamin K deIiciency and as a resuIt the activity oI oxidative phosphoryIation was
impaired. When suppIied with vitamin K, oxidative phosphoryIation was restored as usuaI. This
suggests the important roIe oI this vitamin in oxidative phosphoryIation.
Animal Physiology #$
NormaIIy, dietary vitamin K deIiciency is unIikeIy to occur IirstIy, because it is IairIy weII
distributed in Ioods and, secondIy because the microorganisms in the intestinaI tract synthesize
considerabIe amounts oI it. However, deIiciency oI this vitamin can occur when Iiver or gaII bIadder
IaiI to secrete or pass biIe IIuid, the vitamin K Iike other Iat soIubIe vitamins, cannot be absorbed
through the intestine and this resuIts in deIiciency oI vitamin K. Excessive use oI suIpha drugs can
destroy intestinaI microorganisms heIpIuI in synthesizing considerabIe vitamin K.
Sources of vitamin K: Green IeaIy tissues oI pIants are a good source oI vitamin K.
E.5 MlNERALS AND WATER
In addition to proteins, carbohydrates and Iipids animaI body requires mineraI eIements which serve
structuraI and physioIogicaI Iunctions. CaIcium, phosphorus, sodium, potassium, magnesium, iron,
seIenium, moIybdenum, manganese, copper, cobaIt, zinc, suIphur, chIorine and iodine are the mineraI
eIements which conduct certain essentiaI Iunctions in the animaI body. A nutrient is said to be
essentiaI iI its absence in the diet oI the concerned animaI prevents its growth, survivaI or the normaI
Iunctioning. The essentiaIity oI the above eIements has not been tested Ior aII species; however, aII
these are required by aII higher animaIs. Besides the above mentioned, there are aIso other mineraI
eIements in the body tissues. AII these are avaiIabIe to animaIs through diet. Some oI the eIements are
mereIy retained in the body whiIe the essentiaI Iunction oI a Iew others is yet to be discovered. Recent
investigations have been bringing to Iight the useIuI Iunctions oI IIourine and chromium. These two
eIements may aIso be entitIed to be cIassiIied under essentiaI eIements.
Though aII these eIements are needed by the animaI body, the quantity oI requirement oI certain
eIements such as caIcium, phosphorus, sodium, potassium, magnesium, suIphur and chIorine is IairIy
Iarge. Iron, manganese, copper, cobaIt, zinc, iodine and moIybdenum are required in minute
quantities. EIements Iike seIenium and chromium appear to serve certain Iunctions in metaboIic
systems.
MineraIs Irom organic compIexes can be removed either by dry ashing or by wet ashing. In the
Iormer process the materiaI is heated to high temperatures in muIIIe Iurnace, and in the Iatter process
materiaIs are dissoIved in strong acids. In addition, there are other techniques Ior assaying trace
mineraIs in organic compIexes (SandeII 1959, AOAC 1960, and Oser 1965).
CaIcium
CaIcium goes in the Iormation oI hard structures Iike bones and teeth and about 90 per cent oI aII
body caIcium is concentrated in these structures. SmaII amounts oI caIcium are present in bIood, inter-
and intra-ceIIuIar IIuids, pIaying a IundamentaI roIe. About haII oI the caIcium in these IIuids is
present in the Iorm oI Iree ions and this is essentiaI Ior a variety oI processes. A major roIe oI caIcium
is in the reguIation oI ion transport across the ceII membranes. CaIcium exerts a proIound eIIect upon
neuromuscuIar irritabiIity. High concentration oI caIcium stimuIates the contraction oI heart muscIe.
CaIcium IeveI in the bIood is maintained independent oI its intake through diet. Serum caIcium is
maintained at the normaI IeveI by the parathyroid. II caIcium IeveI is Iow, the caIcium Irom the bones
is added into the bIood. Certain enzymesIipases, ATPase oI actomyosin and myosin choIinesterase,
Ioodstujjs #%
and succinic dehydrogenaserequire caIcium Ior their activation. CaIcium is necessary Ior bIood
coaguIation.
Phosphorus
Phosphorus accounts Ior 12 gm/kg oI Iat Iree tissue in the human body. Out oI this about 85 per cent
is present in skeIetaI tissues in the inorganic Iorm. The totaI phosphorus content in both the pIasma
and the RBC may range Irom 30 to 45 mg/100 mI bIood.
Organic phosphates are very much invoIved in the ceIIuIar Iunctions in aII ceIIs. The high energy
compound ATP suppIying energy to aII ceIIuIar activities contains phosphorus. PhosphoIipids in
ceIIuIar membranes heIp in the permeabiIity.
Phosphorus is a wideIy distributed mineraI in the IoodstuIIs. Hence dietary deIiciency oI it is
unIikeIy to occur in the human body. Grazing Iivestock depending on grass and herbage oI the
phosphorus deIicient soiIs, Iose appetite and appear emaciated. Such animaIs resort to eating materiaIs
such as bones, wood, cIothing, etc. depending on accessibiIity.
Magnesium
The body magnesium is about 0.5 gm/kg oI Iat-Iree tissue. OI this, bones hoId about 60 percent.
SmaII amounts oI magnesium is present in the extraceIIuIar IIuid. The normaI amount oI magnesium
is 1-3 mg/100 mI oI serum.
Next to potassium, the concentration oI magnesium is greater in the ceIIs oI the soIt tissues, and
a Ioss oI magnesium wouId mean tissue breakdown and ceII destruction. Magnesium is necessary in
oxidative phosphoryIation Ieading to the Iormation oI ATP.
AII enzymatic reactions requiring thiamine pyrophosphate (TPP) and the various reactions in the
Iipid and protein metaboIism aIso need magnesium. Magnesium deIiciency does not appear to occur
in human beings because oI their universaI distribution in IoodstuIIs. Green vegetabIes contain IairIy
good amounts oI magnesium. Severe diarrhoea or excessive vomiting however, cause magnesium
deIiciency in human beings.
Magnesium deIiciency brings about personaIity changes, muscIe tremor, gastro-intestinaI
disturbances. Decrease in magnesium aIso brings down the IeveIs oI serum caIcium and potassium.
Sodium, Potassium and ChIorine
These, unIike the previousIy described mineraIs, are IargeIy present in the IIuids and soIt tissues.
Maintenance oI osmotic pressure and acid-base equiIibrium, reguIation oI the movement oI nutrients
into the ceIIs, and participation in the water metaboIism are some oI the Iunctions carried out by these
mineraIs. These mineraIs need to be reguIarIy taken through diet because the body has Iimited storage
capacity. When the avaiIabiIity oI these mineraIs to the body is Iimited, they are excreted in Iesser
quantities. The body thus conserves them. The deIiciency oI any one oI these eIements is IoIIowed by
Iack oI appetite, Ioss oI weight and production in the aduIt, reduction in growth, and decreased bIood
IeveIs.
Animal Physiology #&
SODIUM: The body contains approximateIy 1.8 gm oI sodium per kg Iat-Iree body weight.
AIthough a Iarger proportion oI it is Iound in the extraceIIuIar IIuids, studies indicate that some oI the
sodium is bound in the bones. Sodium together with caIcium, magnesium and potassium in the
extraceIIuIar IIuid are basic in reaction. Sodium Iorms about 93 percent oI the bases in the bIood
serum and hence is highIy concerned in maintaining neutraIity.
Sodium is capabIe oI passing across the ceII membrane. During the process oI nerve transmission
and muscIe contraction, a temporary exchange oI extraceIIuIar sodium and intraceIIuIar potassium
takes pIace. SubsequentIy this sodium is pumped out oI the ceII.
A dietary deIiciency oI sodium does not occur in human beings. His diet generaIIy contains more
sodium than necessary. Sodium is readiIy absorbed and it circuIates through the entire body. It is
excreted through the kidneys as chIorides and phosphates. AIdosterone, a hormone oI the adrenaI
cortex is responsibIe Ior the reabsorption oI sodium Irom kidney tubuIes. Absence oI this hormone
increases sodium excretion and brings out deIiciency symptoms. A major portion oI sodium is Iost in
man at hard work, particuIarIy in summer. Vomiting, diarrhoea, or proIuse sweating wouId resuIt in
increased Ioss oI sodium. A Iack oI this mineraI wouId aIso reduce the utiIity oI digested protein and
energy and prevents reproduction.
POTASSIUM: The human body contains about 2.6 gm oI potassium/kg Iat-Iree body weight. UnIike
sodium a Iarger proportion oI potassium is present as a chieI cation in the intraceIIuIar IIuid. The body
conserves more potassium than sodium. Potassium is concentrated mainIy within the ceIIs. Potassium
aids in the maintenance oI osmotic pressure and acid-base baIance in the ceIIs-sodium and chIoride
mostIy Iocated outside the ceIIs, potassium inside the ceIIs.
Potassium is required in carbohydrate and protein metaboIism, in the Iormation oI gIycogen, and
in the degradation oI gIucose. Investigations suggest that potassium is an activator oI enzymes. It may
pIay an important roIe in the amino-acid uptake by the ceII.
Potassium transIer across the membrane takes pIace more easiIy than that oI sodium. Most oI
excessiveIy absorbed potassium is normaIIy excreted through urine and sweat.
Like that oI sodium, the potassium deIiciency does not occur in human beings under normaI
conditions oI heaIth. Hypopotassiemia resuIts due to excessive excretion oI potassium through the
kidney. Body burns, excessive vomiting and diarrohea aIso resuIt in the Ioss oI potassium. Such a Ioss
is suppIemented by the depIetion oI body potassium.
Potassium deIiciency is characterized by muscuIar weakness; and weakness oI skeIetaI muscIe
resuIts in paraIysis. Its deIiciency in chicks retards growth, incapacitates Iegs and IinaIIy Ieads to
death.
CHLORINE: UnIike sodium and potassium, chIorine is distributed in Iarge concentrations both in
intraceIIuIar and extraceIIuIar IIuids. It is the chieI anion oI the extraceIIuIar IIuid and a greater part oI
it occurs in combination with sodium. A smaII amount. i.e. about 15 to 20 percent oI the chIorine is in
combination with protein and other organic substances. ChIorine with phosphate and suIphate groups,
and protein is acidic in reaction. The chIorine transIer between the serum and erythrocytes is easiIy
perIormed and this phenomenon is termed as the chIoride shiIt (Chapter 10). This is an exampIe oI
homeostatic mechanism by which the pH oI the bIood is maintained. In addition, chIorine is an
Ioodstujjs #'
essentiaI component oI the gastric hydrochIoric acid, and activates the amyIase oI saIiva Ior the starch
spIitting process.
Dietary deIiciency oI chIorine is unIikeIy to occur owing to its abundance in the normaI diet.
Moreover, the body is capabIe oI storing certain amount oI chIorine in the skin and subcutaneous
tissues. The chIoride content oI a teaspoon IuII saIt is about 4.2 gm. The chIorine transIer across the
membranes generaIIy takes pIace by passive diIIusion. However, in gastric and intestinaI mucosa the
transIer is by active transport.
The same Iactors causing sodium Ioss are responsibIe Ior chIoride Ioss. However, its Ioss due to
vomiting is high because oI excessive Ioss oI hydrochIoric acid Irom the stomach.
lron
The iron content in human body is about 75 mg per kg oI Iat-Iree body weight. It is wideIy distributed
throughout the body. Though this eIement is present in smaII quantities, it pIays a key roIe in IiIe
processes. It is a constituent oI the respiratory pigment, the haemogIobin. The haeme moIecuIe is
composed oI Ierrous or Ierric iron at the centre oI a porphyrin ring. Four porphyrin units are bound to
the protein gIobin Iorming haemogIobin. The haeme moIecuIe is aIso a component oI cytochrome C
peroxidase, cataIyse, and other enzymes. Iron is aIso present in the pIasma bound to a speciIic
gIobuIin caIIed transIerrin. About 55 to 60 percent oI the body iron is in the bIood.
Some iron is aIso present in the myogIobin-a compound present in skeIetaI and heart-muscIe; and
it has greater aIIinity to oxygen. A considerabIe amount iron (about 26 per cent oI totaI body content)
is stored in the Iiver and secondariIy, in the spIeen, in the kidneys and in the bone marrow.
Intestine, excepting the coIon part, is capabIe oI absorbing iron. The absorption is highest in the
duodenum and it decreases progressiveIy towards iIeum (Brown, 1963; Moore and Dubach, 1962).
The absorption is eIIicient in the Ierrous (reduced) state. The absorbed iron goes directIy into the
bIood. Once iron enters the bIood stream it wouId be heId by the body. The excretion oI iron through
the bIood in the intestine is very minute. Iron excretion through urine is Iess than 0.2 mg per day. The
iron reIeased Irom the breakdown oI RBC is saved and reused.
The absorbed iron wouId Ieave the body in signiIicant quantities as a resuIt oI Ioss oI bIood. Iron
deIiciency anemia occurs in women and chiIdren due to the Iack oI buiIding stone necessary Ior
haemogIobin synthesis. Iron deIiciency anemia is the commonest oI the nutritionaI anemias. Its
deIiciency may be due to dietary inadequacy or due to poor absorption, or due to excessive Ioss oI
bIood. The haemogIobin IeveI oI a person with iron deIiciency is Iower than the normaI, and the size
oI the RBCs are smaIIer than normaI (hypochromic nicrocytic anemia). As a resuIt oI this condition
the oxygen carrying capacity is Iessened, and the tissues receive Iess oxygen resuIting in Iatigue.
Iron requirement through diet varies in various animaIs. Chickens require 80 mg per kg oI diet,
whiIe pigs need 80 mg per kg. Ruminant`s requirement varies between 25 to 40 mg per kg. Young
peopIe between 15 and 18 years oI age and women between 18 and 55 oI age require an intake oI 15
mg oI iron per day. AduIts require 10mg per day.
Liver, as Iood, is an exceIIent source oI iron. Meat products and eggs aIso obtain iron in generous
amounts. Iron content oI IeaIy-green vegetabIes is IairIy good.
Animal Physiology $
SuIphur
The body has about 0.15 percent oI suIphur. SuIphur is principaIIy Iocated in the suIphur-containing
amino acids, i.e. cystine and methionine. This eIement is aIso present in saIiva, biIe, gIutathione and
insuIin, but these are synthesized in the body with the heIp oI cystine and methionine.
SuIphur is present as chondroitin suIphate in the cartiIage. It is aIso present in minute quantities in
the bIood. Thiamin and biotin aIso have smaII quantities oI suIphur but these vitamins are not
synthesized inside the body.
SuIphur is excreted through Iaeces and urine. In urine it is present as inorganic suIphates, ethereaI
suIphur and neutraI suIphur. NeutraI suIphur occurs in the Iorm oI cystine, thiosuIphates, and other
compounds.
LittIe is known about the eIIects oI suIphur deIiciency in man and animaIs. WooI contains about
13 percent oI cystine. However, cystine Ieeding did not, improve the wooI production in sheep. There
is aIso no evidence oI any reIationship between the dietary deIiciency oI suIphur and the Iack oI hair
growth in humans.
Body acquires suIphur in the Iorm oI organic compIexes, i.e. amino acids. These amino acids are
constituents oI proteins and hence avaiIabIe to the body through protein diet. Wheat germ, cheese,
kidney beans are very rich in suIphur.
Trace EIements
Body contains many trace eIements, oI which onIy a Iew are known to take part in ceIIuIar
metaboIism. Dietary deIiciency oI iodine and cobaIt are known to obstruct normaI physioIogicaI
Iunctioning. Trace eIements are required in minute quantities. They are wideIy distributed in most oI
the Ioods and hence are avaiIabIe to the body in suIIicient quantities. The very Iact that these trace
eIements are in smaII amounts in the body suggests that they pIay primariIy cataIytic roIes in the
ceIIuIar metaboIism.
DeIiciencies oI some trace eIements have been reported in cattIe grazing on pastures grossIy
deIicient in these eIements. Excess intake oI certain trace eIements may resuIt in toxic eIIects. Studies
on trace mineraI metaboIism were handicapped by two basic probIems. First being the precise
determination oI inIinitesimaI quantity oI trace eIement in Ioods, bIood and other tissues. Second
being the totaI puriIication oI the diet Irom the trace eIement. EssentiaI nutrient is that substance
which by its absence in the diet oI experimentaI animaIs wouId aIIect growth, survivaI or the normaI
Iunctioning.
Copper
The human body has about two mg oI copper per kg oI Iat-Iree body weight. Though present in aII
body tissues, copper is observed in highest amounts in brain, heart and kidneys.
Copper deIiciency causes an anemia in which the erythrocyte synthesis and the IeveI oI totaI body
iron is reduced. Inadequate copper in sheep, cattIe and pigs resuIts in abnormaIities in bone structure.
Extreme Ioss oI protein under certain pathoIogicaI conditions wouId resuIt in Iow copper IeveI in
serum. Evidence on speciIic dietary deIiciency oI copper in human body is Iacking. However, there
are reports when anemia in chiIdren has responded to the administration oI copper but not to iron.
Ioodstujjs $
Manganese
Very Iow concentrations oI this mineraI are Iound in aII animaI tissues, but high concentration oI it is
present in pituitary, Iiver, pancreas, skin, bones and muscIes. Highest concentration oI manganese is
in the bone.
Manganese is required in the body since it can repIace magnesium as coIactor Ior certain
phosphoryIations. It is probabIy aIso required to incorporate acetate into Iatty acids, and in the
conversion oI mevaIonic acid to squaIene in the choIesteroI synthesis.
Dietary deIiciency oI manganese is unIikeIy to occur in humans, but such a deIiciency has been
demonstrated in rats, chicks, pigs, etc. In rats, its deIiciency eIIects the normaI process oI
reproduction and Iactation. In such cases the IemaIes IaiI to suckIe their young, and the maIes suIIer
degeneration oI reproductive organs. In chicks the deIiciency resuIts in an abnormaIity oI Ieg bones
known as perosis or sIipped tendon. The Ieg bones shorten and undergo physicaI and chemicaI
changes.
High intake oI manganese retards growth in rats; and in dogs it causes onIy gastric disturbances.
Men inhaIing ore dust containing manganese oxide deveIop manganese toxicity, the symptoms oI
which are a pecuIiar mask-Iike expression oI the Iace, invoIuntary Iaughing, Iow voice with indistinct
speech, spastic gait, and tremors oI the hands.
Manganese requirement in man is not known. The average diet oI man contains about 4 mg oI
this substance per day. Wheat bran, bIueberries, whoIe wheat are the richest sources oI manganese.
lodine
Iodine is an important dietary nutrient required Ior a normaI Iunctioning oI thyroid gIand. Body
contains inIinitesimaIIy smaII quantity oI iodine. The quantity oI totaI iodine in the body varies Irom
20 to 30 mg. One-third oI this is concentrated in the thyroid gIand. Next to thyroid, highest
concentrations oI iodine have been Iound in ovary, muscIes, and bIood. SmaII quantities oI the
remaining iodine are present in the other tissues.
Though this eIement is observed as iodine, in the thyroid gIand it quickIy gets oxidized to iodine
and goes in the Iormation oI thyrogIobuIin. The thyroid gIand serves as a store house Ior iodine. The
body conserves some iodine when thyroxine, one oI the iodine containing compounds breaks down in
the normaI process. This is again reused by the body. Iodine is excreted chieIIy through the kidney. It
is aIso excreted through intestine, and through the skin by way oI perspiration. Iodine is secreted into
the miIk during Iactation.
Thyroxine and other compounds oI thyroid gIand which contain iodine as an essentiaI
component, serve important physioIogicaI Iunctions. The Iunction oI thyroxine is thereIore attributed
to that oI iodine. Increase in the secretion oI thyroid hormone wouId speed up the rate oI oxidation in
the ceIIs. In the absence oI thyroxine, the rate oI energy metaboIism is retarded. Thus the rate oI
metaboIism or the basaI metaboIic rate is an indicator oI the normaIity oI thyroid Iunction.
Hypersecretion oI the hormone increases the basaI metaboIic rate and hyposecretion resuIts in Iow
rate.
Thyroxine is aIso essentiaI Ior the normaI growth and deveIopment. Undersecretion oI thyroxine
retards growth and a proIonged undersecretion prevents physicaI and mentaI maturity. In chiIdren
Animal Physiology $
thyroxine deIiciency causes cretinism. Its symptoms are retarded growth; arrested deveIopment;
coarse and swoIIen IaciaI Ieatures; thick, dry wrinkIed skin; enIarged tongue; thickened Iips and partIy
opened mouth. In aduIts the deIiciency causes myxoedema which is symptomized by the thickening
oI subcutaneous tissues, in particuIar that oI Iace and extremities. The Iace is expressionIess and the
person becomes Iethargic. Besides, iodine is aIso necessary Ior normaI reproduction. Absence oI
iodine suppIy Ior a proIonged period may resuIt in steriIity or the birth oI deIormed progeny. Lack oI
iodine in the Ioods is due to deIiciency oI this mineraI in the regionaI soiI where they are grown. This
causes simpIe goiter which is endemic. Endemic goiter can be cured by constantIy providing iodized
tabIe-saIt in the Iood.
Iodine content in Ioods is extremeIy smaII and a quantitative determination oI this eIement is
possibIe onIy by sensitive chemicaI method. Its content in Ioods varies greatIy and is dependent on the
soiI condition. Marine or deep-sea Iishes and sheII Iishes have high iodine content. Anadromous
Iishes (saImon, sea trout, etc.) have higher iodine content than those Iishes that Iive aII the time in
Iresh water. The Ieaves oI vegetabIes such as spinach, turnip, and broccoIi have higher iodine content
than in their roots.
Zinc
AnimaIs and pIants have smaII quantities oI zinc in their body. Most oI this mineraI is present in the
Iiver, bones, and bIood. The exact Iunction oI this eIement in the body is unknown, though its
presence is reported in severaI enzymes and hormones. The respiratory enzyme carbonic anhydrase
present in the RBCs contains zinc. The zinc in this enzyme hastens the breakdown oI carbonic acid in
Iungs in the process oI exchanging carbon dioxide Ior oxygen. Zinc is an essentiaI component oI one
oI the protein spIitting enzymes oI the pancreas. SeveraI dehydrogenases present in the Iiver aIso have
zinc in their structure. Zinc is present in the crystaIIine structure oI insuIin. OI the severaI types oI
insuIins manuIactured, the protamine-zinc insuIin is in wide use, because in this Iorm the insuIin is
absorbed more sIowIy into the tissues.
Zinc deIiciency in rats and mice resuIts in the reduction oI growth rate, and Ioss oI hair around
neck and shouIders. In pigs it causes parakeratosisthe symptoms oI which are retarded growth, a
Iesion oI the horny Iayer oI the skin, and Iowered Ieed utiIization. In chicks its deIiciency symptoms
are sIow growth, shortened and thickened Ieg bones and poor Ieathering. CaIves suppIied with Iow
zinc ration deveIop aIopecia, parakeratotic skin Iesions.
High IeveI oI zinc in the body wouId cause zinc toxicity, the symptoms oI which are growth
depression, anemia, and decreased copper IeveI in the Iiver. When in excess, it interIeres with the
Iunction oI copper in the Iormation oI iron-porphyrin compounds, and thus Ieads to anemia.
Excessive amounts oI zinc aIso interIere in the iron metaboIism. Zinc deIiciency is unIikeIy to occur
in animaIs and man, IirstIy because oI its presence in most naturaI diets and secondIy because oI its
retention power. Oysters, wheat germ, and brain are richest in zinc. Fruits and vegetabIes contain onIy
smaII amounts.
CobaIt
AnimaI body requires cobaIt in smaII amounts and gets it through the diet. CobaIt is present as a part
oI the vitamin B
12
and this is synthesized in the rumen with the heIp oI bacteria. This vitamin is not
Ioodstujjs $!
present in the pIant Ioods consumed by the ruminants. Since vitamin B
12
is synthesized in the body it
is not a dietary essentiaI vitamin and thus cobaIt is necessary in the Iormation oI RBCs.
The cobaIt requirement in animaIs varies. The requirement oI cobaIt in mg per kg oI ratio is 0.05-
0.07 in cattIe; 0.08 in sheep and 5-8 in the case oI horses. AnimaIs grazing in deIicient soiIs do not
get cobaIt and consequentIy they IaiI to synthesize vitamin B
12
. In case oI cattIe and sheep, absence oI
vitamin B
12
Ieads them to restIessness, Ioss oI appetite and weight, weakness and anemic, and IinaIIy
to death.
II cobaIt intake exceeds the normaI requirement, the RBC number in bIood increases. This
increase is caIIed polycythemia and has been observed in rats, guinea pigs, rabbits, dogs, pigs,
chiIdren and man. PoIycythemia is a normaI occurrence in peopIe Iiving at high aItitudes and this
heIps them cope with the Iower percentage oI oxygen there. The daiIy need oI cobaIt in diIIerent
animaIs has not been estabIished. The average diet normaIIy suppIies the required amounts oI cobaIt
to man.
MoIybdenum
MoIybdenum is another trace eIement which is Iound essentiaI in nutrition. MoIybdenum is an
essentiaI Iactor Ior the Iormation and maintenance oI xanthine oxidase oI some animaIs. In man the
Iunction oI this mineraI is yet to be known. This enzyme, essentiaI in the oxidation oI aIdehydes and
purines, is present in Iiver and intestinaI tissue, and aIso in miIk. MoIybdenum is an essentiaI nutrient
and is aIways avaiIabIe to the animaIs through their diet. For this reason neither animaIs nor man
show the symptoms oI moIybdenum deIiciency. However, excess intake oI this eIement causes
reduced growth rate and death in rats; retarded growth, Ioss oI weight, Iow haemogIobin and RBC
counts, aIopecia and maIIormed Ieg bones in rabits; Ioss oI weight and change in hair coat in caIves.
Legumes, cereaI grains, dark green vegetabIes Iiver and kidney, are rich in moIybdenum.
SeIenium
Dietary intake oI traces oI seIenium is required in certain animaIs.
An unidentiIied Iactor Iound in certain Ioods (miIk, brewer`s yeast, meat, and some kinds oI
cereaIs) is capabIe oI preventing iII eIIects caused by vitamin E deIiciency in rats and chicks. This is
termed Iactor 3. From this Iactor, Schwarz and FoItz (1957) isoIated seIenium. Minute amounts oI
sodium seIenite are Iound to be as eIIective as the vitamin E in the prevention oI Iiver necrosis in rat,
mouse, and pig. SeIenium saIts are aIso eIIective in the prevention oI exudative diathesis in chicks,
and the muscuIar distrophy in Iambs.
The mechanism oI seIenium Iunction is not compIeteIy estabIished, but it cIearIy has a roIe in
metaboIism oI tocopheroI compound.
SeIenium toxicity in Iarm animaIs grazing on seIenium rich soiIs is weII known. The symptoms oI
seIenium poisoning are emaciation, Ioss oI hair and hooIs, cirrhosis oI Iiver, and skeIetaI erosions.
The toxicity seems to be due to inhibition oI certain enzyme systems. Linseed oiI meaI, arseniIic
acid, and organic arsenicaIs eIIectiveIy counter the seIenium toxicity.
Animal Physiology $"
Chromium
Schwarz and Mertz (1959) suggested that trivaIent chromium is an essentiaI dietary requisite in rats.
Chromium probabIy acts as a coIactor with insuIin in carrying out the gIucose metaboIism. Chromium
deIiciency retards growth in maIe and IemaIe rats and resuIts in a syndrome simiIar to that caused by
diabetes meIIitus (Schroeder, 1966).
Water
Water is an essentiaI Iiquid present in aII ceII structures. About 65 percent oI the body weight is water.
Two-thirds oI this is contained within the ceIIs and the remaining is present in spaces outside the ceII.
It is the medium in which chemicaI reactions required in ceIIuIar metaboIism take pIace and hence it
is the most essentiaI oI the nutrients in aII animaIs.
Water is avaiIabIe to the body through the mineraI water and soIid Ioods taken in by the animaIs.
About 15 percent oI the daiIy requirements oI water is gathered by the body as a resuIt oI the
oxidation oI IoodstuIIs within its ceIIs.
Water is the soIvent Ior more substances than any other Iiquid. It is an ideaIIy suited medium Ior
the transportation and distribution oI nutrients to aII the ceIIs in the body. Water reguIates the body
temperature by conducting and distributing heat energy to the entire body. It removes, by
vaporization, the excess heat oI the body generated by metaboIic reactions.
Water is Iost Irom the body due to proIuse sweating, diarrhoea, and proIonged and Irequent
vomiting. As a resuIt oI water Ioss, dehydration and Ioss oI eIectroIytes wouId resuIt. AnimaIs can Iive
Ionger periods without Iood, but without water they die soon.
AII Iiving systems require energy to carry out IiIe processes. The most common and cheapest source
oI energy is the sun. The soIar energy is initiaIIy utiIized by the chIorophyII oI green pIants and some
bacteria to synthesize carbohydrates in the Iorm oI starch. This process is known as photosynthesis.
Green pIants are eaten by animaIs and the stored carbohydrates serve as the basic source oI energy.
CeIIs oI pIants, animaIs and bacteria are primariIy composed oI poIymers such as carbohydrates,
proteins, Iats and Iatty acids. These biopoIymers are Iarge moIecuIar compIexes which upon oxidation
yieId energy. The maintenance and growth oI ceIIuIar structures is dependent upon the energy-
requiring or endergonic reactions by which these Iarge poIymer compIexes are synthesized.
Endergonic reactions store up energy in a potentiaI Iorm in the products oI the reaction.
Photosynthesis is an ideaI exampIe oI such endergonic reactions. Energy is, however, required Ior
other Iunctions as weII, such as endergonic chemicaI reactions. BioIogicaI systems aIso require
exergonic reactions which are energy-yieIding processes. Energy thus Iiberated is used up Ior growth,
chemicaI synthesis, muscIe contractions, maintenance and repair oI body parts and other protopIasmic
activities. ThereIore, a bioIogicaI system must provide the energy necessary Ior its maintenance,
growth, and various other processes. BioIogicaI oxidations are the most important exergonic reactions
oI the Iiving matter which Iurnish chemicaI Iorm oI energy to buiId and maintain structure.
3.3 BlDENERGETlCS
Energy is deIined as the capacity to do work. It is a common knowIedge that energy can neither be
created nor destroyed, but can be transIormed Irom one Iorm to the other. Various Iorms oI energies
exist, such as thermaI, mechanicaI, eIectricaI and chemicaI and it is the transIer oI energy through one
oI these means that work can be perIormed. MuscuIar work, conduction oI nerve impuIse and
synthesis oI compIex Iood moIecuIes are some oI the exampIes in which energy transIer is invoIved.
Living organisms, thereIore, cannot consume energy, but they can transIorm it invoIving oxidation,
ßioIogicoI Oxidotions
+ 0 ) 2 6 - 4
!
Animal Physiology $$
reactions. Such transIormations are accompIished at rather constant temperature and under constant
pressure-voIume reIationships.
BeIore discussing energy in bioIogicaI systems, it wouId be appropriate to discuss the generaI
Iaws oI thermodynamics which govern aII energy transIormations. The Iaws which govern the
behaviour oI aII energy in the universe are the Iirst and the second Iaws oI thermodynamics. The
physicaI and chemicaI events taking pIace in the universe are under the controI oI energy contained in
the universe. Both matter and energy must be exchanged between the system and surroundings.
The Iirst Iaw oI thermodynamics states that the energy content of the universe must remain
constant since it can neither be created nor destroyed. BioIogicaI systems absorb Irom their
environment useIuI Iorm oI energy under constant temperature and pressure and return the same
amount oI energy oI Iess useIuI Iorm to the environment. Thus useIuI Iorm oI energy absorbed by
bioIogicaI systems is caIIed the free energy which is capabIe oI doing work.
BioIogicaI systems have a high moIecuIar compIexity and orderIy structure, whereas the non-
Iiving matter is in a state oI disorder or randomness. The second Iaw oI thermodynamics states that
the randomness or entropy of the universe alvays increases. Living organisms maintain their
orderIiness at the expense oI their environment and in return increase its entropy.
Living organisms are caIIed open systems since they exchange both matter and energy with the
environment. AIthough apparentIy a Iiving system may seem to be in equiIibrium, but it is not; it is
actuaIIy in a steady state. Steady state is that condition oI an open system in which the rate oI transIer
oI matter and energy Irom the environment into the system is baIanced by the rate oI transIer oI matter
and energy out oI the system.
Living organisms are unabIe to use heat as a usabIe energy, since they are essentiaIIy isothermaI.
In man-made machines, such as steam engines, heat energy is transIormed into work. This may be
expressed as IoIIows:
,E ÷ q v
Where ,E is the change in the energy oI the system, q is the increase in heat and v is the amount
oI work done by the system. The energy change accompanying a chemicaI reaction may be measured
in the Iorm oI heat gained or Iost and is caIIed enthalpy change. This can be expressed as H or the
heat oI reaction. In Iiving ceIIs heat is not used as a source oI energy because heat can do work at
constant pressures onIy. II in a reaction there is no change in pressure, no work is accompIished, then
,H ÷ , E
Organic moIecuIes Iike carbohydrates have a heat oI combustion which is characteristic oI any
given moIecuIe. II 1 moIe oI gIucose is compIeteIy oxidized aerobicaIIy, the heat evoIved or the moIar
enthaIpy can be measured. This is expressed as
,H ÷ 686,000 caI/moIe
In this case ,H is negative since heat is Iost during the reaction
C
6
H
12
O
6
¹ 6O
2
6CO
2
¹ 6H
2
O ¹ 686 kcaI
We have discussed earIier that the entropy content oI the universe aIways Increases. II the entropy
oI a system increases during a process, the amount oI useIuI energy contained in the system decreases.
Biological Oxidations $%
Thus higher the degree oI order, Iower the entropy. The Iree energy which does useIuI work is
designated is ,G aIter WiIIard Gibbs, who deveIoped the concept. The equation representing
reIationship among Iree energy, enthaIpy and entropy may be expressed as:
,G ÷ ,H 1 , S
where
,G is change in Iree energy.
,H is change in enthaIpy.
,S is change in entropy.
1 is absoIute temperature.
A drop in Iree energy is IoIIowed invariabIy by an increase in entropy. The change in Iree energy
oI a reaction is an index oI its abiIity to do useIuI work. Exergonic reactions proceed spontaneousIy
and have a negative ,G vaIue. Endergonic reactions do not proceed spontaneousIy, require chemicaI
energy input and have a positive ,G vaIue.
3.E TYPES DF REACTlDNS
A most accurate deIinition oI oxidation is rather impossibIe. However, a compound is said to be
oxidized iI the IoIIowing take pIace:
(a) when it Ioses one or more eIectrons, Ior exampIe
Fe
¹¹

e
Fe
¹¹¹
(b) when the compound Ioses one or more atoms oI hydrogen, Ior exampIe
CH
3
CH
2
OH

2H
CH
3
CHO
(c) When one or more atoms oI oxygen are added to the compound, Ior exampIe
CH
3
CHO

O
CH
3
COOH
Reduction reactions are reverse oI oxidations.
AII the chemicaI reactions in the ceIIs are varied and IrequentIy compIex, but are restricted to
these three simpIe cIasses. In order to understand them better, we may cIassiIy them into Iive generaI
groups: digestion, synthesis, transIer, oxidation and reduction.
(a) A digestion reaction is actuaIIy a hydroIytic reaction in which compIex moIecuIes are broken
down to smaIIer sub-units. Degradations oI carbohydrates, Iats and proteins are common
exampIes oI such digestion reactions.
H O
2
(b) In synthetic reactions smaIIer moIecuIes are combined into Iarger ones with Ioss oI water:
H O
2
Animal Physiology $&
(c) In transIer reactions a portion oI one moIecuIe is transIerred to another moIecuIe.
(d) Oxidation and reduction reactions aIways occur together invoIving change in the number oI
eIectrons. II the number oI eIectrons decreases, the atom is said to be oxidized, whereas
increase in the number oI eIectrons indicates reduction. II oxidation occurs, reduction must
IoIIow it. An exampIe oI this reaction is when metaIIic zinc is added to an aqueous soIution oI
copper suIphate. The zinc is oxidized to zinc ions at the expense oI copper ions which are
reduced to metaIIic copper.
(Ox: oxidized)
(red: reduced)
Zn Cu
++
Zn
++
Cu
B ox A red
A ox B red
or
3.3 CDUPLED REACTlDNS
The bioIogicaI systems are dependent upon coupIing oI energy between oxergonic and endergonic
reactions. In coupIed reactions there is aIways a moIecuIar Iorm which donates energy and another
moIecuIar Iorm which accepts energy. It is necessary that we examine some oI the exergonic reactions
which provide usabIe energy to the Iiving system to derive endergonic reactions.
It shouId be stated here that the carbohydrates, Iats and proteins are not the immediate IueIs that
run the Iiving system, instead ATP (adenosine triphosphate) perIorms this Iunction. ATP is the most
common and universaI energy donor beIonging to the cIass oI nucIeoside triphosphates. The chemicaI
structure oI ATP is given in Figure 3.1. ATP consists oI a nucIeoside (adenine 5-carbon D-ribose) and
three phosphate moIecuIes attached to it. The phosphate ester Iinkage (POP) between the two
terminaI phosphate groups oI ATP is reIativeIy weak. This terminaI phosphate group breaks
spontaneousIy Irom the kinetic energy oI the moIecuIe when ATP is in compIex with an enzyme. The
breakage oI the phosphate bond reIeases chemicaI energy causing an immediate shiIt in the bond
energies within, giving rise to ADP (adenosine diphosphate). About 10 kcaI/moIe oI energy is
reIeased.
DG = –10 kcal/mole
DG = +10 kcal/mole
ADP + Pi ATP
When the terminaI bond oI ATP is broken down, the phosphate becomes inorganic phosphate (Pi)
which is endowed with Iow energy. The reaction is reversibIe and the Iormation oI ATP requires ADP
Biological Oxidations $'
FIg. 3.1 Structure of ATP.
and inorganic phosphate. The regeneration oI ATP requires 12 kcaI/moIe and occurs in the coupIed
reactions.
ATP is universaI energy donor, hence it shouId be regenerated constantIy when any mechanicaI
work is done. In the coupIed reaction as shown above, 10 kcaI/moIe oI energy is reIeased Irom one
NH
2
N
N
N
N
CH
Adenine
H
P P P
O O O
O O O CH
2
H
OH OH
O

O

O

O

H
D-Ribose
H H
O
Adenosine Triphosphate (ATP)
CO + 2NH
2 3
+ 13800 calories
E
n
e
r
g
y
Enzyme catalysed reaction
H Catalysed reaction
+
Uncatalysed reaction
Urea
H O
2
Reaction coordinate
FIg. 3.2 Enzyme catalysed reaction.
Animal Physiology %
ATP moIecuIe, showing thereby a Ioss oI 2 kcaI/moIe oI energy during regeneration. When a
phosphate bond is broken, 10 kcaI/moIe oI energy is reIeased, but onIy 8 kcaI/moIe is converted to
work and the rest is Iost. Thus ATP can derive most oI the metaboIic reactions requiring 8 kcaI/moIe
or Iess.
3.4 ENERGY EXPENDlTURE lN METABDLlC PRDCESSES
The ceII machinery Iunctions on maximum economy basis, hence the energy expenditure is to be
minimized in a metaboIic process. This is achieved by the use oI enzymes which heIp in Iowering the
energy oI activation (Fig. 3.2). Enzymes are reIerred as bioIogicaI cataIysts which obey certain
generaI ruIes. The enzyme-cataIyzed reactions take pIace at physioIogicaIIy Iow temperatures and
require extremeIy smaII amounts oI enzymes.
II a gIucose moIecuIe is subjected to a series oI enzyme-cataIyzed reactions, the moIecuIe is
broken down with minimum expenditure oI energy. Sometimes the energy required Ior the reaction is
present in the kinetic Iorm in the reaction itseII, but more IrequentIy, the enzyme acts in combination
with ATP requiring Iow activation energy. Both synthetic and degradative pathways require the use oI
ATP. In synthetic reactions the ATP moIecuIe combines with the enzyme at one oI the active sites and
the substrate combines with other sites. This can be shown as:
Substrate ¹ enzymes ¹ ATP ATP enzyme substrate
ADP ¹ Pi ¹ enzyme ¹ product
Since the reaction is enzyme mediated, it can be simpIiIied thus:
ATP ADP + Pi
Enzyme
B
(Product)
A
(Substrate)
In degradation reactions, the terminaI phosphate group oI ATP (A P P P) is usuaIIy
transIerred to the substrate which gets phosporyIated. This may be shown as:
ATP ADP
Enzyme
B
(Phosphorylated
substrate)
A
Since ATP is used both in synthetic and degradative reactions, its regeneration is essentiaI Ior
eIIicient Iunctioning oI the bioIogicaI systems (Fig. 3.3). Regeneration oI ATP is possibIe in two
ways: (i) by transIer oI a phosphate group Irom a high-energy moIecuIe (substrate-IeveI
phosphoryIation) and (ii) by eIectron transport system.
Biological Oxidations %
3.5 DXlDATlDN-REDUCTlDN REACTlDNS
One oI the major cIasses oI reactions is the oxidation-reduction reaction in which eIectrons are
transIerred Irom one atom to another. We have aIready noted that oxidation invoIves Ioss oI eIectrons
whereas reduction invoIves gain oI eIectrons. This may be shown as:
Fe
++
Oxidation
Reduction
Fe
+++
+ e

In some oI the redox reactions, the vaIues oI ,G are very high, hence they may serve as ATP
regeneration reactions. In aII redox reactions, a reducing agent (eIectron donor) and an oxidizing
agent (eIectron acceptor) are present. During the reaction, reducing agent gets oxidized and the
oxidizing agent gets reduced and this is dependent upon the abiIity oI reducing agent to Iurnish
eIectrons and the tendency oI oxidizing agent to accept them. This reIative abiIity to donate and
accept eIectrons is caIIed redox potential. It is represented by the IoIIowing equation:
E
h
÷ E
o
¹
R1
nF
In
(oxidant)
(reductant)
where
E
h
÷ the redox potentiaI
E
o
÷ the standard emI oI the system
R ÷ gas constant in jouIes/moIe/degree
1 ÷ absoIute temperature
n ÷ vaIence oI the ion or number oI eIectron equivaIents
FIg. 3.3 ATP cycle in energy-transfer processes.
Muscle contraction
ADP
+
Pi
Nerve conduction
Glucose absorption
Protein synthesis
Energy
requiring
reaction
Energy
yielding
ATP
Oxidation of glucose
Fatty acid oxidation
Oxidation of amino acids
Photosynthesis
Animal Physiology %
F ÷ Faraday (96,500 couIombs)
In ÷ Iogarithm to the base e
When the concentration oI oxidant and reductant are equaI, In (oxidant/reductant) becomes 0 and
E
h
÷ E
o
. The redox potentiaI vaIues as cited above are appIicabIe when the pH vaIue is 0, otherwise it
wouId vary with the change in pH. The E
o
oI the hydrogen at pH 7.0 is 0.420 V (redox potentiaI oI
hydrogen at pH 0 is 0.000).
3.8 THE CYTDCHRDME SYSTEM
The transIer oI eIectrons occurs on an atomic IeveI. Whether the atom shouId act as a reducing or
oxidizing agent depends on the structure oI the moIecuIe. The cytochromes are a group oI compIex
types oI moIecuIes beIonging to the cIass oI porphyrins. They have an atom oI iron (Fe) heId in the
porphyrin ring structure. An important property oI the cytochromes is their abiIity to undergo
reversibIe oxidation invoIving a change in the vaIency oI iron.
A variety oI cytochromes have been identiIied Irom pIants and animaIs. In mammaIian ceIIs, Iive
types oI cytochromes have been identiIied: Cytochromes b, c
1
, c, a and a
3
. These have important roIes
in the oxidation reactions. In bioIogicaI systems, reactions invoIving the removaI oI hydrogen atom
occur most IrequentIy and this hydrogen atom is transIerred to the hydrogen acceptor. NAD
(nicotinamide adenine dinucIeotide) is the common hydrogen acceptor which acts as an oxidizing
agent. In the conversion oI pyruvate to CO
2
and acetate, roIe oI NAD can be indicated:
COOH
C
NAD NADH + H
+
O
CH
(Pyruvate)
3
(Acetyl CoA)
O CO + CoA C CH
2 3
In the above reaction, the carboxyI group is Iost by the pyruvate and the remaining 2-carbon
portion is joined to coenzyme A. When NAD accepts a hydrogen, it aIso invoIves ionic bonding to a
second hydrogen, giving rise to product NADH ¹ H
¹
:
NAD ¹ pyruvate NADH ¹ H
¹
¹ 2e

¹ CO
2
¹ acetate
Regeneration oI ATP is dependent upon reactions invoIving removaI oI hydrogen. The oxidizing
agent NAD has an E
o
value of 0.320, whereas the reducing agent pyruvate has an E
o
vaIue oI
0.700. There are many compounds in bioIogicaI systems which have more positive redox potentiaIs
than NAD and NADH. When NAD reacts with such compounds, it serves as a reducing agent in its
NADH ¹ H
¹
Iorm. NADH (reduced Iorm) enters into a series oI reactions invoIving transIer oI
eIectrons. In the course oI reactions great deaI oI energy is generated. Series oI such reactions are
caIIed eIectron transport system. In the scheme oI reactions, oxygen is the IinaI hydrogen acceptor
(Fig. 3.4).
Biological Oxidations %!
EIectron transport system in diIIerent organisms may diIIer in certain steps. However, the major
components oI the system are:
(a) an enzymeNAD (nicotinamide adenine dinucIeotide)
(b) a IIavoprotein
(c) coenzyme Q
(d) cytochrome compounds
3.7 THE FLAVDPRDTElNS
In bioIogicaI systems, many metaboIites undergo oxidation by the Ioss oI hydrogen through cataIyzed
reactions. The speciIic enzymes invoIved are known as dehydrogenases and the reaction can proceed
with the aid oI a hydrogen acceptor. Dehydrogenation oI a substrate depends upon the avaiIabiIity oI
NAD
¹
or NADP
¹
. The oxidized Iorms oI these enzymes are present in the system in minute
quantities, and in order to maintain a constant suppIy, NADH and NADPH are reoxidized to NAD
and NADP. The mechanism to reoxidize these enzymes is Iurnished by certain flavoproteins. These
are proteins and act as coenzymes. They contain a prosthetic group FMN (IIavin mononucIeotide) or
FAD (IIavin adenine dinucIeotide). These coenzymes cataIyze oxidation-reduction reactions:
FP
+2H
2H
FPH
2
Two co-enzymes oI this group, NADH
2
and NADPH
2
reoxidize NADH and NADPH. This can
be shown as:
NADH + H
+
NAD
FP
FPH
2
NADPH + H
+ +
NADP
FP
FPH
2
FIg. 3.4 Electron transport system.
ATP
A-H
2
2e
NAD
NADH
2
2e 2e
FADH
2
FAD
quinone
hydro-
quinone
ADP + P Coenzyme
Q
ADP +
2e 2e 2e 2e 2e
2 Fe
2+
cyt. b
2 Fe
3+
2 Fe
2+
2 Fe
3+
2 Fe
3+
2 Fe
2+
2 Fe
3+
2 Fe
2+
H O
2
1/2O
2
cyt. c cyt. a cyt. a
3
A
Reduced
substrate
P ADP + P
ATP ATP
Animal Physiology %"
The IIavoprotein enzymes act upon certain metaboIites that Iunction as substrates. FIavoproteins
take hydrogen Irom NAD and thereby get reduced. The same IIavoprotein moIecuIe is reoxidized to
become active again to participate in Iurther reactions. This can be shown as:
AH
2 NAD
A
(Substrate)
FP
(Flavoprotein)
FP-H
2
NADH
+
H
+
Reoxidation oI IIavoproteins is accompIished by cytochrome system.
3.8 DEHYDRDGENATlDN
The initiaI step oI the eIectron transport system is the oxidation oI the organic substrate by NAD, and
in turn NAD gets reduced to NADH. It may be shown as under:
MetaboIite ¹ NAD oxidized metaboIite ¹ NADH ¹ H
¹
In the above reaction, the oxidizing agent NAD is reduced to NADH by accepting two eIectrons
and one hydrogen, the other hydrogen atom is reIeased as hydrogen ion (H
¹
). Such reactions
invoIving Ioss oI hydrogen and two eIectrons by the moIecuIe to be oxidized are caIIed
dehydrogenations. The enzymes which cataIyze such reactions are caIIed dehydrogenases. SpeciIic
dehydrogenases are required Ior diIIerent organic moIecuIes.
The NADH thus Iormed is reoxidized to NAD by a IIavoprotein enzyme. FIavin Iunctions as a
coenzyme. The NADH is oxidized to NAD and IIavin accepts two eIectrons, a hydrogen atom and the
H
¹
Irom the soIution.
H
¹
¹ NADH ¹ FIavin FIavin H
2
¹ NAD
Thus IIavin is reduced, and Iurther undergoes reoxidation by coenzyme Q. The reaction invoIves
oxidation oI reduced IIavin by the transIer oI two eIectrons and two hydrogens to a moIecuIe oI
coenzyme Q.
Flavin H
2
Flavin
Coenzyme Q
In the next reactions, reoxidation oI coenzyme Q takes pIace by cytochromes which act as
eIectron carriers. There are a number oI such compounds which occur in the mitochondria oI the
ceIIs, and diIIer Irom each other on the basis oI their structure with respect to the protein moIecuIe.
Owing to their structuraI diIIerences, they aIso diIIer with respect to their abiIity to accept or donate
eIectrons. They react in a particuIar order, cytochrome b cytochrome c cytochrome a
Biological Oxidations %#
cytochrome a
3
. Cytochrome b accepts an eIectron Irom coenzyme Q and thus gets reduced. Since one
eIectron is accepted by one moIecuIe oI cytochrome b, two moIecuIes are necessary to reoxidize
coenzyme Q. The hydrogens oI the reduced coenzyme Q are not accepted by cytochromes and they
are reIeased as hydrogen ions in the medium.
An eIectron thus accepted by cytochrome b is next passed on to c, then to a, and IinaIIy to
cytochrome a
3
with aIternate oxidation and reduction oI the iron atom oI the cytochromes.
Cytochrome a
3
is commonIy known as cytochrome oxidase which is capabIe oI undergoing direct
oxidation by moIecuIar oxygen. Cytochrome oxidase is an important enzyme showing a speciIic
behaviour. In the presence oI oxygen it works eIIicientIy and continuousIy transIers eIectrons in one
direction, that is to oxygen. In the absence oI oxygen, it becomes inactive. The sequence oI reactions
is shown in Fig. 3.4.
3.8 ENERGY RELEASE AND DXlDATlVE PHDSPHDRYLATlDN
II one moIe oI gIucose is compIeteIy oxidized, 686 kcaI oI energy is reIeased. This can be shown thus:
C
6
H
12
O
6
¹ 6O
2
6CO
2
¹ 6H
2
O ¹ 686 kcaI
In order to produce ATP Irom ADP and Pi in a bioIogicaI system, about 10 kcaI oI energy per
moIe oI ATP is required. It is apparent Irom the above equation that 68 moIes oI ATP wouId be
produced Ior each moIe oI gIucose aerobicaIIy oxidized. However, it is not true. ActuaIIy, 38 moIes oI
ATP are produced per each moIe oI gIucose oxidized. One might ask as to what happens to the rest oI
energy?
Rest oI the energy is Iost in the Iorm oI heat. The typicaI reaction oI gIucose oxidation can be
shown as IoIIows:
C
6
H
12
O
6
¹ 6O
2
¹ 38 ADP ¹ 38Pi 6CO
2
¹ 6H
2
O ¹ 38 ATP ¹ 310 kcaI (heat)
The above equation summarizes the oxidation oI gIucose in one step. In actuaI oxidation process,
however, severaI steps are invoIved so that the energy is reIeased bit by bit in a stepwise Iashion. Thus
onIy one moIe oI ATP is synthesized in one singIe reaction. In bioIogicaI systems gIucose is the chieI
IueI to be oxidized Ior the production oI ATP. A series oI oxidation reactions are empIoyed by the ceII
to oxidize gIucose to CO
2
and water. We shaII describe these reactions with respect to oxidative
phosphoryIation.
3.30 GLUCDSE DXlDATlDN
Carbohydrates are IueIs which are Iirst broken down to 6-carbon sugars beIore they are oxidized.
GIucose is the simpIest 6-carbon sugar which must be Iirst converted into gIucose-6-phosphate
through phosphoryIation by ATP. This is the common earIy stage oI glycolysis. It is Iurther
transIormed to pyruvic acid as summarized in Fig. 3.5.
In the next reaction gIucose-6-phosphate is converted to Iructose-6-phosphate under enzymatic
controI. Fructose-6-phosphate is phosphoryIated again on the Iirst carbon and Ieads to the Iormation
oI Iructose-I, 6-diphosphate. This conversion is accompIished by ATP which acts as both energy and
Animal Physiology %$
phosphate donor. In the next series oI reaction, the 6-carbon diphosphoryIated sugar is spIit into two
3-carbon phosphoryIated sugar, phosphogIyceraIdehyde (PGA) and dihydroxy acetone phosphate
(DHAP). Next reaction is very important Ior two reasons. FirstIy, one more moIecuIe oI phosphate is
added, and secondIy in the course oI this reaction a hydrogen is removed Irom the aIdehyde group
which is picked up by NAD. In the next reaction transIormation oI the two moIecuIes oI 1, 3-
diphosphogIyceric acid and 2 moIecuIes oI ADP to two moIecuIes oI 3-phosphogIyceric acid and 2
moIecuIes oI ATP takes pIace. This is an enzyme cataIyzed reaction. Up to this stage the energy yieId
has been baIanced by the energy expenditure. Any energy derived Irom the process aIter this step wiII
be the net gain.
The next two reactions rearrange the phosphate group oI 3-phosphogIyceric acid resuIting in the
Iormation oI 2-phosphogIyceric acid which is then converted to phosphoenoI pyruvate by Iosing one
hydrogen. For each gIucose moIecuIe oxidized, two phosphoenoI pyruvates are Iormed. The
phosphate group oI phosphoenoI pyruvate is transIerred to ADP moIecuIe to Iorm ATP. AIter
transIerring the phosphate Irom phosphoenoI pyruvate, the resuIting compound pyruvic acid or
pyruvate is Iormed. Four ATP moIecuIes are Iormed in this gIycoIytic process, two pay back Ior the
two expended in the beginning oI gIycoIysis. ThereIore the net gain is oI 2 ATP moIecuIes.
The importance oI gIycoIysis can be enumerated as IoIIows:
1. About 10 per cent oI Iree energy avaiIabIe in gIucose moIecuIe is reIeased.
2. GIucose moIecuIe is changed to Iorm pyruvic acid which can enter the citric acid cycIe to
reIease more energy.
3. A net synthesis oI 2 moIecuIes oI ATP takes pIace.
4. Two moIecuIes oI NADH are generated by dehydrogenase action.
The remainder oI energy contained in the gIucose moIecuIe is reIeased during the course oI citric
acid cycIe and oxidation by the eIectron transport system. The product oI gIycoIysis, pyruvic acid
enters the mitochondria where it undergoes oxidative phosphoryIation with the heIp oI eIectron
transIer chain to generate more oI ATP. The compIex reactions, their sequence and products are
summarized in Fig. 3.6.
At the beginning oI the cycIe, pyruvic acid is acted upon by an enzyme pyruvic dehydrogenase
and acetyI CoA is Iormed. The enzyme aIso transIers hydrogen Irom pyruvic acid to NAD which
FIg. 3.5 Scheme of glucose oxidation (glycolysis).
(1 mole)
glucose
ATP ADP
glucose 6-phosphate fructose 1, 6-diphosphate
(2 moles)
3-phospho-
glycoraldehyde
(2 moles)
3-phosphoglyceric
acid
(2 moles)
1, 3-diphosphoglyceric
acid
(2 moles)
2-phosphoglyceric
acid
(2 moles)
phosphoenol pyruvate
(2 moles)
pyruvate
2ATP 2ADP
H O
2
2NAD.H
2
2NAD
2P
2ADP ATP
ATP ADP
Biological Oxidations %%
Iorms NADH, a reduced compound. The compound acetyI CoA enters the citric acid cycIe by
reacting with a 4-carbon moIecuIe, oxaIoacetic acid, Iorming citric acid.
In the next reaction isocitric acid is Iormed invoIving minor changes in the citric acid moIecuIe.
In the next step dehydrogenation oI isocitric acid to oxaIosuccinic acid takes pIace. The coenzyme
which acts as the eIectron acceptor is NADP. OxaIosuccinic acid is a keto-acid and is capabIe oI
undergoing decarboxyIation. The product oI this reaction is =-ketogIutaric acid. =-ketogIutaric Iurther
undergoes decarboxyIation and Iorms a high energy compIex, succinyI CoA. NAD acts as an
oxidizing agent removing the hydrogen. SuccinyI CoA is rapidIy cIeaved to succinic acid and CoA
becomes Iree. This reaction Ieads to the synthesis oI one moIecuIe oI ATP.
In the next reaction, an enzyme succinic dehydrogenase oxidizes succinic acid to Iumaric acid. In
this reaction 2 moIecuIes oI ATP are Iormed. An addition oI a water moIecuIe to Iumaric acid yieIds
maIic acid. MaIic acid is then IinaIIy oxidized by NAD to oxaIoacetic acid, thus compIeting the cycIe.
There ATP moIecuIes are Iormed in this step. The most important concIusion drawn Irom the cycIe is
the entrance oI an acetyI group which is oxidized to CO
2
, and H
2
O, by Iour oxidation reactions. The
baIance sheet oI the ATP yieId Irom gIycoIysis and various steps oI oxidative phosphoryIation is
given in TabIe 3.1.
FIg. 3.6 The citric acid cycle (Krebs cycle).
2
1
10
3
4
5
6
7
8
9
Pyruvic acid
NAD
CoA
CO
2
CoA
3ATP NADH
2
CoA
Acetyl
Oxaloacetic
acid
a-ketoglutaric
acid
Citric acid 3ATP NADH
2
NAD
Malic acid
H O
2
Fumaric acid
2ATP FADH
2
FAD
Succinic acid
CoA
GTP
1ATP
GDP
Pi
H O
2
Succinyl
acid
NADH
2
3ATP
NAD
CoA
CO
2
CO
2
Oxalosuccinic acid
3ATP
NAD
NADPH
2
Isocitric
acid
CITRIC ACID CYCLE
Animal Physiology %&
TabIe 3.1 Net ATP Gain During Complete Glucose Oxidation
Søquøn¿ø ø/ røa¿I¡øns NøI ATP )¡øIø
l. l glucose 2 pyruvic acid moles 2
2. NADH + H
+
from conversion of 3-phosphoglyceraldehyde to l, 3-diphosphoglyceric acid
(electron transport system) 6
3. 2 pyruvic acid 2 acetyl-CoA + 2CO
2
6
+. 2 acetyl-CoA +CO
2
(citric acid cycle) 2+
Glucose 6CO
2
38
In the previous chapter it has been mentioned that the enzymes cataIyze metaboIic reactions in a
precise way by Iowering the energy barrier (see section 3.4 oI Chapter 3). In Iiving systems chemicaI
reactions proceed at physioIogicaI temperatures which are quite Iow (in most cases 37°C). The same
reactions in vitro wiII proceed at considerabIy higher temperatures and pressure. But the remarkabIe
property oI the ceII to carry out its reactions at miId temperatures, Iow pressure, and in diIute soIutions
is due to the inIIuence oI enzymes.
ChemicaIIy, enzymes are compIex protein moIecuIes synthesized in the ceIIs where they act as
biocataIysts in carrying out various physico-chemicaI reactions. These proteins have their own
speciIicity and kinetics. By deIinition a cataIyst is a substance which speeds up the rate oI a given
reaction and at the end oI the reaction it remains unaItered. Further, the cataIyst heIps in attaining a
reaction in a state oI equiIibrium. Many noncataIyzed reactions remain in a nonequiIibrium condition
since their rate oI reaction to reach the state oI equiIibrium is very sIow. For exampIe, gIucose and
oxygen may remain together in a soIution Ior years without reacting with each other. However, iI a
suitabIe cataIyst is added to the soIution, both wiII react readiIy to attain the state oI equiIibrium by
Iorming carbondioxide and water. This may be represented as,
6CO
2
¹ C
6
H
12
O
6
6CO
2
¹ 6H
2
O
The above reaction has an equiIibrium Iavouring the product Iormation since no detectabIe
amount oI gIucose wiII be Iormed iI CO
2
and H
2
O are mixed together.
4.3 GENERAL PRDPERTlES DF ENZYMES
AII enzymes are proteins and synthesized within the ceII. Owing to their protein nature their physicaI
and chemicaI properties conIorm to the nature oI proteins. Action oI strong acids, bases, organic
soIvents, heat and agitation wiII denature and render them bioIogicaIIy inactive. An essentiaI property
Enzymes~The ßioIogicoI
CotoIysts
+ 0 ) 2 6 - 4
"
Animal Physiology &
oI these bioIogicaI cataIysts is to speed up the rate oI chemicaI reactions and whiIe doing so they
remain unchanged without Ioss oI activity. An enzyme recognizes its speciIic substrate and reacts
with it to Iorm product and gets regenerated at the end oI the reaction. The enzyme Iowers the
activation energy and aIIows a Iarger number oI moIecuIes to react at a given temperature. The
eIIiciency with which an enzyme acts on its substrate is known as its turn over rate which is the
number oI substrate moIecuIes converted into the product by a singIe moIecuIe oI enzyme per unit
time.
Enzyme cataIysis IoIIows the same generaI ruIes as observed Ior nonenzymatic cataIysis. Both
cataIyze Iorward and backward reactions to reach a state oI equiIibrium. However, the main
diIIerence Iies in the Iact that the enzyme deIicateIy controIs and reguIates the ceIIuIar processes at
considerabIy Iow temperatures with maximum economy.
Enzyme Specificity
Enzymes have a preIerence Ior their speciIic substrate on which they act. The phenomenon is known
as enzyme speciIicity. Some enzymes have absoIute speciIicity, i.e. the enzyme can act on onIy one
substrate. Urease hydroIyzes urea and any modiIication in urea moIecuIe wiII render it ineIIective Ior
enzyme attack:
CO
NH
2
NH
2
¹ H
2
O


2NH
3
¹ CO
2
Certain enzymes are capabIe oI acting on a speciIic organic group, thus showing group
speciIicity. For exampIe, aIcohoIic dehydrogenases act onIy on aIcohoIs. SimiIarIy, carboxyI esterases
wiII act on carboxyIic acid esters onIy.
R OH ¹ NAD
¹
R CHO ¹ NADH ¹ H
¹
In the above reaction the R and H groups are immateriaI.
Some enzymes act on a range oI substrates showing a broad specificity. Trypsin wiII attack
peptide bonds in a protein chain onIy between certain amino acid residues invoIving Iysin and
arginine.
Certain enzymes show optical specificity, i.e. they are abIe to discriminate between their opticaI
isomers. An L-amino oxidase wiII not act on D-amino acids or vice versa.
Enzyme-substrate lnteraction
An enzyme reacts with its substrate at various concentrations. When the rate oI enzymes cataIyzed
reaction is studied at various substrate concentrations, a hyperboIic curve is obtained (Fig. 4.1). When
the initiaI substrate concentration is Iow, the rate is directIy proportionaI to the substrate
concentration. As the substrate concentration is increased the veIocity oI reaction reaches a maximum
J
max.
At high concentrations the rate oI reaction becomes independent oI substrate concentration
(Fig. 4.1).
Enzymes~The Biological Catalysts &
The enzyme cataIyzed reaction is a two-step process which can be shown thus:
|E| ¹ |S|
k
k
1
2
º |ES| (1)
|ES|
k
k
3
4
º |E| ¹ |P| (2)
In this process the enzyme Iirst combines with the substrate |S| to Iorm enzyme-substrate |ES|
compIex. This compIex breaks down into the product |P| and the enzyme |E|. The enzyme cataIyzed
process was quantiIied by MichaeIis and Menten who appIied the Iaw oI mass action to the Iormation
oI ES compIex. FoIIowing equation was obtained to express the reIationship:
J ÷
J S
K S
m
max
| |
| |
where
J ÷ veIocity oI reaction
|S| ÷ substrate concentration
J
max
÷ maximum veIocity
K
m
÷ MichaeIis-Menten`s constant
FIg. 4.1 Effect of substrate concentration on the velocity of enzyme catalyzed reaction.
B
A
V
2
C
S Km O
V
2
V
V
max
Animal Physiology &
K
m
represents the substrate concentration at which the veIocity oI reaction is haII oI the maximum
veIocity (J
max
).
4.E THE MECHANlSM DF ENZYME ACTlDN
Activation Energy
An exergonic reaction wiII take pIace very sIowIy, but the rate oI reaction is determined by how many
moIecuIes have the activation energy (E
A
) to react together at anyone moment. In a sIow reaction onIy
a smaII percentage oI the moIecuIes invoIved have the necessary amount. The activation energy
thereIore represents a kind oI barrier which must Iirst be overcome beIore the reaction can proceed
(Fig. 4.2).
FIg. 4.2 Activation energy: enzyme lowers the energy barrier. Heat produces a secondary effect, increasing the kinetic
energy of the reactants.
In principIe, reactions can be speeded up in two ways:
(a) by suppIying the reactants with more energy, Ior exampIe by heating;
(b) by Iowering the activation energy by means oI a cataIyst.
In Iiving organisms heat Irom any externaI source cannot be appIied, because oI Iimitations.
Besides, heat aIso denatures proteins which incIude enzymes aIso. However, enzymes are biocataIysts
Energy content
of reactants
Enzyme lowers energy barrier
so that E < E ¢
A A
E
(without
heat or
enzyme)
A E (with heat) ²
A
E (with enzyme) ¢
A
Products
6CO + 6H O
2 2
DG°
Reactants
C H O + 6O
6 12 6 2
Heat raises energy
content of reactants
so that E < E ¢¢
A A
Progress of reaction
U
V
|
W
|
U
V
|
W
|
U
V
|
|
W
|
|
U
V
|
|
|
|
W
|
|
|
|
Heating
This difference equals
(E – E
A
¢
A
) since heating
raises the energy content
of the products as well
as that of the reactants
Enzymes~The Biological Catalysts &!
which Iower the activation energy barriers dramaticaIIy. How these enzymes Iower the energy barrier?
BeIore we answer this question, Iet us have a cIoser Iook at the concept oI the active site or the
catalytic site.
Lock and Key Hypothesis
Fischer postuIated a Iock and key hypothesis to expIain the interaction between the enzyme and the
substrate. The modeI visuaIizes the enzyme moIecuIe as a rigid structure having a Iixed substrate
binding site (Fig. 4.3). For a key to work it must be provided with the right Iock and so is with
enzyme and substrate.
FIg. 4.3 Fischer´s lock and key hypothesis to explain the formation of enzyme-substrate complex.
1he concept of active site. The active site oI an enzyme moIecuIe is the cataIytic site which reacts
with the substrate. It has been suggested that there must be one or more active sites oI an enzyme
which are the centres oI cataIytic activity. Enzymes are huge moIecuIes with a high moIecuIar weight,
but substrates are oIten smaII. It has been suggested that one or two substrate moIecuIes bind at a time
to speciIic points on an enzyme, showing that enzymes possess speciIic active sites Ior cataIysis. II
the active site is onIy a smaII part oI the enzyme moIecuIe, what is the Iunction oI the rest oI the
moIecuIe? In 1963, KoshIand suggested that an enzyme consists oI essentiaIIy Iour categories oI
amino acids (Fig. 4.4):
E S E + S Complex
FIg. 4.4 Amino acid residues in an enzyme molecule showing four sites: catalytic site, binding site, structural residues
and non-essential residues.
Non essential
residues
Structural
residues
Catalytic residues
Active site
Binding residues
Active site
Enzyme
Animal Physiology &"
(i) Catalytic residues: These are the amino acids at the cataIytic site which make and break
chemicaI bonds. They participate in the cataIytic activity.
(ii) Binding residues: These amino acids hoId the substrate in pIace whiIe cataIysis is taking pIace.
(iii) Structural residues: These amino acids hoId the active site in the correct shape so that it can
Iunction properIy.
(iv) Non-essential residues: These amino acids have no speciIic Iunction. They are oIten near the
surIace oI the enzyme and can be removed or repIaced without Ioss oI Iunction.
lnduced-fit Theory
The idea oI an enzyme wrapping around` a substrate to Iorm a more stabIe structure is caIIed
induced-fit hypothesis. These and other considerations Ied KoshIand to postuIate that essentiaI
IunctionaI groups on the active site oI the Iree enzyme moIecuIe are not in their optimaI positions Ior
promoting cataIysis when the active site is unoccupied, but when the substrate moIecuIe is bound by
the enzyme, the binding aIIinity Iorces the enzyme moIecuIe into a conIormation in which the
cataIytic groups assume a IavorabIe geometric position to Iorm the transition state. This is the
induced-Iit modeI oI enzyme-substrate interaction (Fig. 4.5).
FIg. 4.5 Induced fit model of enzyme molecule as proposed by Koshland.
MoIecuIar Basis of Enzyme Action
According to thermodynamic considerations, enzymes Iower the energy barrier or activation energy
through severaI steps, each step with reduced activation energy, incIuding the Iormation oI ES-
compIex. On the other hand, in moIecuIar terms, Iew major Iactors appear to participate and probabIy
Enzymes~The Biological Catalysts &#
operate simuItaneousIy at the active site, aII oI which contribute to a Iowering oI activation energy,
and hence to the Iarge rate acceIerations produced by the enzyme (TabIe 4.1).
TabIe 4.1 Nechanisms which Contribute to the Catalytic Efficiency of Enzymes
Mø¿nan¡sms Døs¿r¡pI¡øn ø/ ¿aIaI)s¡s
Proximity effects Temporary binding of reactants close to each on an enzyme increases the chance
of a reaction.
Orientation effects Reactions are held by the enzyme in such a way that the bonds are exposed to
attack and a transition state is readily achieved.
Strain effects Enzyme may induce strain or distortion in the susceptible bond of the substrate
molecule, making the bond easier to break.
Acid-base catalysis Acidic and basic amino acids in the enzyme facilitate transfer of electrons to and
from the reactants.
Covalent catalysis Enzyme may combine with the substrate to form an unstable covalent
intermediate that readily undergoes reactions to form the products.
Nicroenvironmental effects Hydrolytic amino acids create a water-free zone in which non-polar reactants
may react more easily.
4.3 CLASSlFlCATlDN DF ENZYMES
The InternationaI Enzyme Commission has adopted a system oI cIassiIication oI enzymes recognizing
six major cIasses (TabIe 4.2).
TabIe 4.2 Na]or Classes of Enzymes and the Types of Reactions Catalyzed by Them
Enz)mø ¿Iass NaIurø ø/ røa¿I¡øn Ma)ør I)pø ø/ ønz)møs w¡In Inø¡r spø¿¡/¡¿ røa¿I¡øns
l. Oxido-reductase Biological oxidation and reduction l. Dehydrogenases: catalyze removal of 2 atoms of
hydrogen
2. Oxidases: these catalyze reduction of O
2
3. Oxygenases: which catalyze incorporation of molecular
O
2
into the substrate
+. Oxidative deaminases: catalyze the oxidation of amino
compounds with the formation of NH
3
5. Hydroxylases: these introduce OH groups
6. Peroxidases: they use H
2
O
2
as oxidant
2. Transferases Effecting exchange of groups l. Aminotransferases: catalyze exchange of amino
groups between two substrates: & Keto group between amino and Keto acid
AB + CD AC + BD 2. Kinases: catalyze the transfer of a PO
+
radical
3. Acyltransferases: catalyze the transfer of acylfacetyl
group to a suitable acceptor
+. Clycosyltransferases: they transfer glycosyl groups
CønIø.
Animal Physiology &$
4.4 FACTDRS lNFLUENClNG ENZYME ACTlVlTY
There are many Iactors which inIIuence the activity oI enzymes. These may be physicaI or chemicaI in
nature.
A. Substrate and Enzyme Concentration
An enzyme cataIyzed reaction is dependent on the enzyme concentration.
UsuaIIy the enzyme is present in much Iower concentration than the substrate. In vitro experiment
iI we take increasing enzyme concentration in the presence oI an excess oI the substrate, a Iinear
reIationship is observed showing increased utiIization oI the substrate (Fig. 4.6). However, with Iixed
enzyme concentration and increasing substrate
concentration a diIIerent reIationship is observed (Fig.
4.7). First oI aII a rapid rise in veIocity oI reaction is
observed and subsequentIy the reaction rate sIows down
untiI no change in veIocity is observed. The enzyme at this
stage is saturated with the substrate. Three situations are
observed at points A, B and C.
1. At point A (Fig. 4.1) the |S| is much Iess than K
m
,
hence the veIocity J is dependent upon the substrate
concentration.
2. At point B the substrate concentration is equaI to
K
m
, hence the veIocity is haII oI J
max
.
3. At point C the substrate concentration is much
greater than the K
m
vaIue, hence the veIocity oI
reaction is maximaI (J
max
).
3. Hydrolases They catalyze hydrolysis reactions: l. Peptidases: catalyze hydrolysis of peptide bonds
AB + H
2
O A OH + HB 2. Clycosidases: catalyze glycosidic bonds
3. Esterases: carry hydrolysis of carboxylic esters
+. Phosphatases: hydrolyse phosphoric acid esters
5. Phosphodiesterases:
6. Deaminases: catalyse hydrolysis of amines
7. Deamidases: catalyze hydrolysis of amides
+. Lyases Remove groups from substrates l. Decarboxylases
non-hydrolytically:
2. Aldolases
AB A + B
3. Dehydratases
5. Isomerases Catalyze isomerization of l. Racemases
substances (substrates) 2. Epimerases
6. Ligases Synthetases, bring about the formation of C-O, C-S, C-
N or C-C bonds.
Reactions require expenditure of energy with
simultaneous cleavage of ATP.
Catalyze ]oining together of two
molecules coupled with the break
down of a pyrophosphate bond in
ATP
CønIø.
Enzyme concentration
V
e
l
o
c
i
t
y
o
f
r
e
a
c
t
i
o
n
O
FIg. 4.6 Effect of enzyme concentration on
the rate of reaction.
Enzymes~The Biological Catalysts &%
B. Temperature
Temperature has a marked eIIect on enzyme-cataIyzed reactions as enzymes are very sensitive to
eIevated temperatures. At high temperatures the enzymes undergo denaturation resuIting in compIete
Ioss oI their bioIogicaI activity. For most enzymes, optimaI temperatures are cIose to that oI the
ambient temperature oI the ceII. In homeotherms this temperature is around 37°C. However, the
enzymes show their activity over a Iimited range oI temperature.
According to vant HoII Iaw, a rise oI 10° in temperature wiII doubIe the veIocity oI a reaction. II
we assume that at a given temperature 1
o
the rate oI reaction is J, the Iatter becomes 2J at
temperature 1 10°. This is expressed in terms oI the ratio oI veIocities oI the reaction at two
temperatures 10° apart and is indicated by Q
10
. This hoIds true Ior an enzyme-cataIyzed reaction at
Iow temperatures. The temperature range Ior most oI the enzymes Iies between 30° and 50°C.
C. pH
The enzymes are inIIuenced by pH changes since they are
proteins and have an ionic character due to amino and
carboxyIic groups. Each enzyme has an optimum pH at
which the veIocity is maximaI provided aII other
conditions Iike temperature, substrate concentration etc,
are ideaI. In a typicaI curve showing the eIIect oI pH on
an enzyme-cataIyzed reaction it is observed that the
maximaI cataIytic activity is seen at the optimum pH,
whiIe on either side oI the curve it is Iow (Fig. 4.7).
Within a narrow range oI pH (i.e. sIightIy aIkaIine or acid
condition), the changes in the reaction are reversibIe.
However, iI the pH is either too Iow or too high, the
changes are irreversibIe due to denaturation oI the
enzyme protein.
D. Redox PotentiaI
Many enzymes are sensitive to oxidizing and reducing agents and the comparative abiIity oI oxidation
or reduction oI an enzyme is known as redox potentiaI. It is the eIectromotive Iorce (measurabIe in
miIIivoIts) deveIoped by the soIution when in physicaI contact with the pIatinum eIectrode as
compared to the normaI hydrogen eIectrode at zero potentiaI. The redox potentiaI oI an enzyme is
either positive or negative owing to its reIative oxidizing or reducing abiIity in comparison to
hydrogen.
E. lnhibitors
There are certain compounds, aIso known as antimetaboIites, which when added to the substrate
combine with the enzyme reversibIy or irreversibIy to bIock the production oI end products. Such
substances are known as inhibitors which incIude drugs, antibiotics, poisons and certain metaboIites.
Inhibition occurs in a variety oI ways, but broadIy they may be cIassiIied into two categories:
reversibIe and irreversibIe inhibitions.
Optimum pH
O Low pH High
V
e
l
o
c
i
t
y
o
f
r
e
a
c
t
i
o
n
FIg. 4.7 Effect of pH on the enzyme
catalyzed reaction.
Animal Physiology &&
(a) Irreversible Inhibition: Some enzymes have a thioI (SH) group at the active site. The
compounds Iike iodoacetate (CH
2
I .COOH) or mercuriaIs react with the IunctionaISH group
oI the enzyme and Iorm covaIent derivatives. This kind oI binding with the active site oI the
enzyme moIecuIe causes more or Iess inactivation oI the enzyme. The inhibitor cannot be
reIeased by any means, hence caIIed irreversibIe inhibitor. The inhibition is proportionaI to the
concentration oI the inhibitor.
ESH ¹ ICH
2
COOH ESCH
2
COOH ¹ HI
(b) Reversible Inhibition: Many inhibitors reversibIy bind with the enzyme moIecuIe aIIecting
the equiIibrium constant oI the reaction. Three types oI reversibIe inhibitions are known.
(i) Competitive Inhibition: In this type oI inhibition both the inhibitor and the substrate
compete Ior the same active site oI the enzyme, but the inhibitor has greater aIIinity. The
eIIect oI inhibition can be overcome by increasing the substrate concentration. In such
cases the inhibitor is structuraIIy reIated to the substrate and bind with the enzyme
decreasing the eIIective concentration oI the enzyme. An exampIe oI this type oI inhibition
is succinic dehydragenase which converts succinate to Iumaric acid. II maIonic acid (it is
anaIogous to the structure oI succinic acid) is added to the reaction, the activity oI succinic
dehydrogenase IaIIs but the activity can be restored by increasing the concentration oI
succinic acid (Fig. 4.8).
FIg. 4.S Craphical representation showing competitive inhibition.
(ii) Noncompetitive Inhibition: In this case there is no competition between substrate or
inhibitor and the inhibitor either combines with the enzyme with the ES compIex (Fig. 4.9).
Noncompetitive inhibition cannot be IuIIy reversed even at high substrate concentrations.
Noncompetitive inhibitors Iower the J
max
but do not aIIect the K
m
vaIue. From the Fig. 4.10
1/V
– 1/Km
O
+ Inhibitor
No inhibitor
1/v
1/(S)
Enzymes~The Biological Catalysts &'
FIg. 4.9 Nechanism to show binding of inhibitor with enzyme or with ES complex.
EI
ES
EIS EI + P
E
E + P
+ I
+ S
+ I
+ S
FIg. 4.1û A plot showing non-competitive inhibition.
it can be seen that the substrate has an aIIinity both Ior enzyme and Ior EI compIex. When
the resuIts are pIotted with 1/J against I/S at various concentrations oI the inhibitor J
max
is
Iowered (Fig. 4.10).
(iii) Uncompetitive Inhibition: Some inhibitors combine with ES compIex, hence are caIIed
uncompetitive inhibitors. Such inhibitors have no aIIinity with the substrate and bear no
resembIance with it. This type oI inhibition can never be reversed. A variety oI poisons
such as iodoacetamide and metaI ions (Ag, Hg) cause this type oI inhibition.
M
o
r
e
i
n
h
i
b
i
t
o
r
I
n
h
i
b
i
t
o
r
N
o
in
h
ib
ito
r
1/V
1/V
max
–1/K
m
Animal Physiology '
4.5 lSDENZYMES
Certain enzymes occur in muItimoIecuIar Iorms in the same organism. These enzymes have diIIerent
physicaI properties but cataIyze the same type oI reactions. Lactate dehydrogenase (LDH) is an
exampIe oI an isoenzyme which can be distinguished into 5 distinct types. These Iive diIIerent Iorms
diIIer in their behaviour, amino acid composition and reIative rates oI reaction. They have been
reported Irom diIIerent organs oI vertebrates, chieIIy Irom the heart and skeIetaI muscIes. Two basic
subunits oI LDH enzymes are known, the H type predominant in the heart and the M type in the
skeIetaI muscIes. Both have same moIecuIar weights (35,000) and both are produced in the same ceIIs
by two, separate genes. LDH is composed oI M and H subunits in 5 diIIerent combinations. These
are: H
4
, H
3
M, H
2
M
2
, H
1
M
3
and M
4
. M
4
and H
4
are pure tetramers. Besides LDH, many other
enzymes Iike aIkaIine phosphatase, gIutamate-oxaIoacetate transaminase and creatinine
phosphokinase aIso occur in the Iorm oI isoenzymes.
4.8 ALLDSTERlC ENZYMES
There is an important cIass oI enzymes usuaIIy known as aIIosteric or reguIatory enzymes. They have
distinct reguIatory and cataIytic sites and their activity can be enhanced or inhibited by organic
compounds that occur as intermediates in the sequence oI reactions. The inhibitor oI the reguIatory
enzyme bears no structuraI simiIarity with that oI the substrate and usuaIIy occurs at the end oI the
pathway.
AIIosteric enzymes do not IoIIow MichaeIis-Menten kinetics and behave atypicaIIy in their
reIationship with the substrate concentration. NormaIIy, an enzyme possessing independent binding
sites wiII yieId a hyperboIic curve to represent
their veIocity oI reaction. However, in case oI
aIIosteric enzymes, binding oI one substrate
moIecuIe wiII induce structuraI changes in the
enzyme to IaciIitate aIIinity oI the substrate
with the remaining binding sites. In such cases
the enzyme-substrate reIationship yieIds a
sigmoidaI curve (Fig. 4.11). This is aIso known
as positive cooperativity. In order to expIain
this behaviour exampIe oI haemogIobin may be
cited. HaemogIobin moIecuIe is composed oI 4
poIypeptide chains Iinked to the haeme
moIecuIe and the binding oI a moIecuIe O
2
wouId induce structuraI changes in the
haemogIobin moIecuIe which wouId IaciIitate
Iurther binding oI O
2
to reach saturation
point. The reIationship is sigmoidaI. On the
other hand, myogIobin, which has onIy one
FIg. 4.11 Effect so substrate concentration on the velocity
of (l) an enzyme showing Nichaelis-Nenten
kinetics and, (2) allosteric enzyme.
20
40
60
80
100
20 40 60 80 100
(1)
(2)
0
Allosteric enzyme
V
max
Enzymes~The Biological Catalysts '
poIypeptide chain, can bind with one moIecuIe oI oxygen and shows a hyperboIic curve. MichaeIis-
Menten kinetics is not appIicabIe to aIIosteric enzymes, hence Km has no meaning. Sometimes the
binding oI substrate moIecuIe to one cataIytic site obstructs the binding at another site and this
behaviour is known as negative cooperativity.
Two types oI aIIosteric responses are known, homotropic and heterotropic, In case oI homotropic
response the substrate (eIIector) is a second moIecuIe. Many, enzymes have severaI active sites per
moIecuIe. When the substrate is bound at one site, the aIIinity at other sites changes markedIy due to
conIormationaI change in the enzyme moIecuIe. In case oI heterotropic response, the eIIector or the
co-substrate (other than the substrate) binds at the reguIatory site aIIecting the aIIinity oI other vacant
binding sites. Most heterotropic eIIectors that bind with the reguIator sites are unreIated to substrates
or products, but are usuaIIy identiIied as terminaI products oI the metaboIic pathway exhibiting a
Ieedback controI.
4.7 CDENZYMES
Some enzymes such as pepsin and ribonucIease occur as pure proteins, whiIe others have a non-
protein component associated with the protein moIecuIe. This non-protein component oI the enzyme
moIecuIe is known as prosthetic group and the protein moiety is caIIed the apoenzyme which together
constitute holoenzyme.
The prosthetic group may be either in the Iorm oI a metaI ion (coIactor) or as a coenzyme which
may be IirmIy or IooseIy bound to the apoenzyme. Enzyme activity depends upon the coenzyme
which is oIten regarded as a second substrate. Some important coenzymes aIong with their IunctionaI
characteristics are given in TabIe 4.3.
TabIe 4.3 Coenzymes and Their Functional Characteristics
Namø ø/ ¿øønz)mø Fun¿I¡øns
Nicotinamide adenine dinucleotide (NAD) Transfer of hydrogen atoms (electrons)
Nicotinamide dinucleotide phosphate (NADP) Transfer of hydrogen atoms
Thiamine pyrophosphate (B
l
) Decarboxylation and aldehyde group transfer
Flavin mononucleotide (FNN) Transfer of hydrogen atoms
Flavin adenine dinucleotide (FAD) Transfer of hydrogen atoms
Lipoic acid Transfer of acyl groups
Biotin Transfer of CO
2
Pyridoxal phosphate (B
6
) Participates in transamination, decarboxylation and racemization,
reactions of amino acids
Tetrahydrofolate Transfer of methyl, methylene, formyl or formimino groups.
Cyanocobalamine (vitamine B
l2
) Transfer of alkyl groups in alkylation reactions
Coenzyme Q Transfer of hydrogen atoms
Coenzyme A Transfer of acyl groups
Animal Physiology '
ReguIation of Enzymes
CeIIs contain a Iarge number oI enzymes aII oI which do not Iunction simuItaneousIy. They have to be
reguIated and their Iunctioning coordinated according to the requirements oI the ceII. Some enzymes
remain in inactive Iorm and unIess they are activated by proper conditions they wiII not participate in
cataIytic activity (exampIes: pepsin and chymotrypsin). A Iew hydroIytic enzymes are Iound to be
trapped in Iysosomes, and iI Iound Ioose in the cytopIasm they may cause seII destruction oI the ceII
machinery.
A number oI enzymes Iorm enzyme compIexes
and have spatiaI arrangement in the ceII. These are
known as muItienzymes and cataIyze a series oI
reactions. The enzymes within the mitochondria and
chIoropIasts are so organized in the membrane
system oI the organeIIe that they estabIish a chain oI
reactions. Enzymes oI the respiratory chain are
membrane bound and transIer eIectrons Irom the
substrate to oxygen.
A number oI enzymes remain in physicaI
association with each other in Iorm oI cIusters (Iatty
acid synthetase). So Iong the enzymes are physicaIIy
bound together, their cataIytic activity remains intact.
Some enzymes occur as independent moIecuIar
entities in the cytopIasm and convert a substrate to an
end product by producing a number oI intermediate
metaboIities and iI the product oI the system
accumuIates in the ceIIs, it speciIicaIIy inhibits the
activity oI the Iirst enzyme oI the reaction system.
The Iirst enzyme oI the sequence which is inhibited is
known as the reguIatory enzyme and the product is
known as the moduIator (Fig. 4.12). On the other
hand, iI the initiaI substrate accumuIates in the ceII it
activates the enzyme E5 so that the conversion oI
initiaI substrate (A) continues.
A
B
C
D
E
P
E1
E2
E3
E4
E5
S
u
b
s
t
r
a
t
e
A
c
t
i
v
a
t
i
o
n
F
e
e
d
b
a
c
k
I
n
h
i
b
i
t
i
o
n
Initial substrate
FIg. 4.12 Feedback inhibition showing self-regulation
to control concentration of metabolites.
The organisms shouId be considered as chemicaI Iaboratories where energy transIormations are
continuaIIy taking pIace. LiIe oI organisms is intricateIy woven with their environment and as Iong as
they Iive, they continuaIIy exchange matter and energy with their environment. Thus, the organisms
constitute a dynamic system exhibiting bioIogicaI activity at ceIIuIar and organismic IeveIs. The
compIex pattern oI activity invoIves capture oI Iood, digestion and absorption oI Iood, transport oI
nutrients and eIimination oI wastes.
The Iood suppIies the energy needed Ior the maintenance oI body temperature, Ior muscuIar
movements oI the heart and respiration, and Ior other physicaI activities. The packets oI energy
Iiberated Irom utiIisation oI various Ioods are diIIerent. The quantity oI energy avaiIabIe Irom 1 g oI
carbohydrate is 4.1 kiIocaIories: Irom 1 g oI Iat, 9.3 kiIocaIories are Iiberated, and Irom 1 g oI protein
onIy 5.3 kiIocaIories are obtained in the Iorm oI heat oI combustion.
5.3 ANlMAL CALDRlMETRY
To maintain normaI physioIogicaI Iunctions, physicaI activity, growth, and tissue repair, the body
needs an ongoing suppIy oI energy Irom oxidation oI IoodstuIIs. Oxidation oI dietary carbohydrates,
Iats and proteins suppIies the required energy Ior these body Iunctions. Recommended dietary
aIIowances (RDA) have been estabIished Ior required energy needs, incIuding vitamins and mineraIs.
However, RDA does not appIy to peopIe with conditions such as chronic iIIness, inIections or
metaboIic disorders. In these cases nutritionaI requirements are determined on individuaI basis.
AnimaI caIorimetry deaIs with the measurement oI energy requirement oI the body under various
physioIogicaI conditions and the IueI vaIue oI Ioods which suppIy the energy. In animaIs the chemicaI
source onIy need be considered and we may conIine our attention to that Iorm oI combustion in which
the substance IinaIIy appears in the compIeteIy oxidised Iorm.
AnimoI CoIorimetry
+ 0 ) 2 6 - 4
#
Animal Physiology '"
Unit of Heat
Since oxidation oI Iood invoIves combustion in the body, heat is evoIved as recognised by
temperature which is due to the energy oI moIecuIar motion. In animaI caIorimetry the unit oI heat is
the Iarge caIorie (kiIocaIorie), which is deIined as the amount oI heat necessary to raise the
temperature oI 1 Iitre oI water Irom 15°C to 16°C.
When certain substances are combusted in a bomb calorimeter (an apparatus Ior measuring
heat), we can obtain the vaIues oI heat oI combustion:
1 g oI H
2
gas produces 34.5 kiIocaIories
1 g oI charcoaI produces 8.0 kiIocaIories
1 g oI gIucose produces 3.7 kiIocaIories
1 g oI sucrose produces 3.96 kiIocaIories
1 g oI starch produces 4.2 kiIocaIories
FueI VaIue of Foods
The potentiaI energy oI diIIerent Ioods is determined by combusting them in an atmosphere oI
oxygen in a metaI chamber known as bomb calorimeter. The amount oI heat produced in the
instrument is measured in terms oI caIories, which is sIightIy more than the Iood actuaIIy oxidised in
the body. The caIoric content oI the three principaI IoodstuIIs measured in a bomb caIorimeter is
given in TabIe 5.1.
Carbohydrates and Iats are compIeteIy oxidised in the body to CO
2
and water. However, proteins
do not undergo compIete oxidation, thereIore the energy obtained is a bit Iess.
TabIe 5.1 Fuel values of Food Obtained by Burning 1 g of Food
1n DømD ¿aIør¡møIør 1n Inø Døø) MøIaDøI¡¿ waIør
Carbohydrates +.2 kcal +.1 kcal 0.55 g
Proteins 5.6 kcal +.1 kcal 0.+1 g
Fats 9.3 kcal 9.3 kcal 1.07 g
Types of CaIorimetry
The amount oI heat produced in the body is dissipated and is measured as the amount oI energy
expenditure in the animaI. There are two methods oI measuring energy expenditure.
Direct CaIorimetry
Direct caIorimetry measures the totaI heat production in a Iiving organism. The animaI is pIaced
inside a Iarge chamber having doubIe insuIated waIIs with a provision to remove water evaporated
Irom the Iungs and skin, and exchange oI oxygen and carbondioxide. A constant IIow oI air is needed
which enters through a saturator and then passes through a heat exchanger. The air then circuIates in
the caIorimeter and comes out through another heat exchanger. The IIow rate oI both the exchangers
is identicaI. The circuIating water in heat exchangers is warmed by absorbing the heat given out by
Animal Calorimetry '#
the animaI. The temperature oI water is recorded which gives an indication oI the body heat
production. Though direct caIorimetry is a cumbersome process requiring expensive equipment, it
permits precise and continuous measurement oI heat produced.
lndirect CaIorimetry
When carbohydrates are oxidised in the body, oxygen is consumed invoIving heat production and
carbondioxide Iormation. In such a case, the rate oI oxygen consumption can be measured to Iind out
the heat evoIved. The equipment used Ior the purpose is known as spirometer The spirometer is IiIIed
with oxygen and aIso contains a vesseI IuII oI soda Iime. The animaI is pIaced inside the respiratory
chamber. When the animaI inhaIes oxygen, water and carbondioxide are expired, which are absorbed
by soda Iime. The chamber is airtight but since it is not insuIated, heat production cannot be obtained
directIy. The animaI remains in the oxygen chamber Ior severaI hours and its oxygen consumption
and carbondioxide output are measured at reguIar intervaIs. A writing pen is attached to the
spirometer connected with a revoIving drum. There is an upward stroke Ior inspiration and a
downward stroke Ior expiration. The sIope indicates the rate oI oxygen consumption. The
reIationship between oxygen consumption and heat production varies with the type oI Iood consumed,
hence with the heIp oI a caIibration chart one can Iind out the amount oI heat produced in reIation to
the oxygen consumed. To know heat production oI the body Irom the oxygen consumed, it is
necessary to know the nature oI Iood (carbohydrate, Iat or protein) being consumed. The inIormation
can be obtained Irom the respiratory quotient (TabIe 5.2).
Respiratory 0uotient IR0¡
The respiratory exchange oI gases is dependent upon the type oI Iood consumed and the physioIogicaI
state oI the animaI. For this purpose, the amount oI O
2
consumed and the amount oI CO
2
evoIved are
used as a measure oI the extent oI the type oI IueI oxidized by a particuIar animaI. The ratio oI the
voIume oI CO
2
produced to the voIume oI oxygen absorbed is known as the respiratory quotient
(RQ). This has diIIerent vaIue Ior each oI the major Iood components and serves to determine what
substances are being burned.
TabIe 5.2 Energy Relationships and Respiratory Quotients
Carbohydrate Fat Protein
O
2
utilisedfg (in litres) 0.75 2.03 0.97
CO
2
producedfg (in litres) 0.75 1.+3 0.78
RQ 1.00 0.71 0.80
Kcal yieldfg +.10 9.30 +.10
kcal equivalent of 1 litre of O
2
5.+7 +.60 +.23
We can Iurther expIain the concept oI RQ by taking an exampIe oI gIucose oxidation where the
quantity oI CO
2
evoIved is equaI to the amount oI O
2
consumed:
C
6
H
12
O
6
¹ 6O
2
6CO
2
¹ 6H
2
O
The RQ Ior gIucose (carbohydrate) ÷
voIume oI CO evoIved in time
voIume oI O consumed in time
2
2
t
t
÷ 6/6 or 1.0
Animal Physiology '$
1 Iitre oI oxygen represents a Iiberation oI 5.011 kcaI. In animaI caIorimetry the heat equivaIent oI 1
Iitre oI oxygen is generaIIy accepted as 5.047 kcaI when carbohydrates are burned in the body.
As noted above, the ratio is known as RQ, which is diIIerent Ior diIIerent IoodstuIIs. In other
Ioods, however, this RQ is Iess because reIativeIy Iess oxygen is consumed. In case oI Iat (tristearin
Ior exampIe), the RQ is about 0.71:
C
57
H
110
O
6
¹ 163O
2
114CO
2
¹110H
2
O
÷
CO
O
2
2
÷
114
163
÷ 0.71
Proteins too have a Iower RQ vaIue ranging between 0.8 and 0.82. Based on the anaIyticaI Iigures
Ior the average protein, it is estimated that 1 g oI urinary nitrogen represents the metaboIism oI 6.25
g oI protein, the absorption oI 5.91 Iitres oI oxygen, the production oI 4.76 Iitres oI carbondioxde, and
the Iiberation oI 26.51 kiIocaIories.
5.E BASAL METABDLlSM
Energy requirement oI the animaI body may be studied with the heIp oI two IunctionaI parameters:
energy required Ior basaI metaboIism and the energy needed Ior active work. BasaI metaboIism
incIudes the energy expended in respiration, bIood circuIation, intestinaI contractions, activities oI
various organs, maintenance oI muscuIar work, thermaI equiIibrium, etc. The basaI metaboIic rate
(BMR) is inIIuenced by the amount oI protopIasmic mass, height, weight, surIace area, age, sex,
composition oI the tissues, generaI heaIth etc., and is governed by endocrine organs, particuIarIy the
thyroid and pituitary gIands.
The energy consumed in active work and indeed aII Iorms oI voIuntary activity, imposes an
additionaI requirement Ior IueI over the basaI metaboIism, which depends upon the nature and extent
oI the muscuIar work. OrdinariIy an average man expends about 100 kcaI per hour whiIe sitting at
rest, his metaboIism may increase to about six times with extreme physicaI eIIort. In a heaIthy person,
energy requirements are determined by basaI energy expenditure, physicaI activity, and the energy
used Ior digestion. Digestion reIated energy expenditure is known as calorigenic effect of food, which
generaIIy equaIs about 10° oI the basaI energy expenditure.
BasaI MetaboIic Rate IBMR¡
BasaI metaboIic rate is a measure oI the heat production oI the body in compIete mentaI and physicaI
repose, and in the post absorptive state. It represents the Iowest energy expenditure consonant with
minimaI physicaI activity and reIIects the amount oI energy needed to maintain basic physioIogic
Iunctions and is expressed as the heat produced per hour per meter square. It is determined 12 hours
aIter the Iast meaI. The subject shouId have had compIete rest at 20°C beIore the BMR estimation is
done. The BMR is expressed in kcaI/hr per surIace area (in sq metre) and is determined Irom the RQ
vaIues obtained over a known period oI time.
Animal Calorimetry '%
Factors Affecting BMR
The BMR vaIues diIIer with age, sex, surIace area, cIimate, raciaI variations, state oI nutrition, disease
and hormonaI baIance. SmaIIer individuaIs have higher rate oI metaboIism. It is Iower in women and
higher in chiIdren (TabIe 5.3). From birth to the age oI one and a haII years the basaI metaboIism
increases at a remarkabIe rate, and is IoIIowed by a graduaI decIine untiI IuII growth and deveIopment
is reached. Constancy characterises the rate in aduIt IiIe, with a sIight decIine as oId age advances. In
normaI heaIthy maIes around 20 years oI age, the BMR is about 40 kcaI/hr/m
2
. In women the BMR
averages about 12° beIow that oI men.
TabIe 5.3 Oxygen Consumption (in litres) and Heat Production CaloriesfHourfN
2
(in Humans)
Agø
MaIøs FømaIøs
()rs} O
2
¿ønsumøø CaIør¡øs O
2
¿ønsumøø CaIør¡øs
1+-15 9.53 +5.9 8.91 +2.9
16-17 8.91 +2.9 8.29 39.9
18-19 8.50 +0.9 7.88 37.9
20-29 8.19 39.+ 7.67 36.9
30-39 8.19 39.+ 7.57 36.+
+0-+9 7.98 38.+ 7.+6 35.9
50-59 7.77 37.+ 7.25 3+.9
60-69 7.57 36.+ 7.05 33.9
In many diseased states such as Ieukemia, hypertension, anaemia and Iever, which invoIve
increased ceIIuIar activities, the BMR is increased. Thyroid maIIunctioning inIIuences BMR to a
great extent, hyperthyroidism increases BMR due to excessive O
2
consumption, whiIe
hyperthyroidism Iowers it. The rate oI heat production is aIso inIIuenced by epinephrine. It is Iowered
in conditions oI under-nutrition, deIiciency oI adrenaI cortex and in some pituitary disorders.
Measurement and CaIcuIation of BMR
The BMR is expressed in kiIocaIories per sq meter oI the body surIace area per hour. SurIace area
may be obtained Irom the Du Bois` standard chart. However, the average surIace area oI women is
about 1.6 m
2
, and Ior men about 1.8 m
2
. A simpIe method Ior caIcuIating surIace area is
circumIerence oI midthigh (in cm) height (in cm). A simpIe method to caIcuIate BMR Irom the
oxygen consumption is IargeIy in use. The diet consists oI a mixture oI carbohydrates and Iats, and
the RQ oI this mixture oI Ioods is taken to be 0.82, a vaIue obtained aIter 12 hours oI Iasting by the
subject. II the O
2
consumption over a period oI 10 minutes is 2.5 Iitres, then the hourIy heat
production under deIined conditions at RQ 0.82 wiII be:
2,500 4.825 60/10, i.e. 72.36 kcaI.
II this subject has a surIace area oI 1.8 m
2
, the heat production wouId be 72.36/1.8 ÷ 40.2 kcaI/
m
2
/hr. The surIace area oI the body bears a reIationship with height and weight.
AIthough there are diIIerent systems avaiIabIe Ior caIcuIating normaI heat production, Du Bois
system is more Iavoured which is based on the height and weight:
Animal Physiology '&
A ÷ Wt
0.425
Ht
0.725
71.84
where A equaIs the area in m
2
, Wt is in Kg and the height (Ht) in cm.
5.3 CALDRlC RE0UlREMENT
CaIoric Requirements in Man
The heat production oI normaI individuaIs under basaI conditions IargeIy depends upon the Iactors oI
age, height and weight. The normaI standards are based upon thousands oI determinations (TabIe 5.4).
TabIe 5.4 Standard values for Energy Production in Relation to Age and Sex
Agø
K¡Iø¿aIør¡øs,m
2
,nøur
)øar MaIøs FømaIøs
6 53.0 50.6
7 52.+ +9.1
8 51.8 +7.0
10 +8.5 +5.8
12 +6.8 ++.3
1+ +6.+ +1.5
16 +5.7 38.9
18 +3.3 37.0
20 +1.8 36.2
25 +0.+ 35.9
30 39.6 35.8
35 38.9 35.7
+0 38.2 35.0
50 37.0 3+.5
60 35.8 33.0
The above tabIe is kg intervaIs Ior the height range oI 110 to 200 cm and the weight range oI 20
to 110 kg.
CaIoric Requirements of AnimaIs
The energy requirements oI animaIs are varied depending upon their metaboIic capacities. In coId-
bIooded animaIs most oI the energy reIeased Irom Iood is used to perIorm physicaI activities.
GeneraIIy they need greater amounts oI oxygen with increasing ambient temperature. ThereIore, in
such animaIs the metaboIic rate is measured under speciIic conditions. This is known as standard
metabolic rate (SMR). In warm-bIooded animaIs such as birds and mammaIs, a high constant internaI
temperature is maintained. Their energy requirements vary with the change in ambient temperature in
either direction. There is greater consumption oI oxygen at Iow temperature associated with muscuIar
activities. Thus in homeotherms, the basaI metaboIic rate represents the minimaI metaboIic energy
required and is determined by measuring oxygen uptake by a resting animaI.
Animal Calorimetry ''
AIter Iood ingestion the metaboIic rate oI an animaI is enhanced resuIting in more heat
production. Increase in metaboIism above the basaI IeveI is due to caIorigenic eIIect oI Iood and is
caIIed specific dynamic action (SDA) oI Iood and its eIIect is known as specific dynamic effect
(SDE).
There is undoubtedIy a cIose reIationship betwen body surIace and the metaboIism. In this regard
greater attention has been paid to mammaIs as compared to other animaIs. In mammaIs oxygen
consumption and thereIore heat production varies with the body weight, approximating to about two-
thirds. The reIationship between weight and voIume is 1:1, hence the heat Ioss is directIy proportionaI
to the surIace area, because body surIace determines heat Ioss.
GeneraIIy the BMR vaIues have not been Iound to be reIated to cIimatic conditions. This is weII
iIIustrated by the Iact that birds and mammaIs Iiving in Iow temperatures oI arctic, when exposed to
temperatures much beIow their core body temperatures (50°C), do not show signiIicant diIIerence in
the BMR as compared to birds and mammaIs oI tropicaI regions.
DaiIy rhythm is another parameter which can hardIy be over-emphasized in energy reIationships.
PhysioIogic measurements show striking reIationship with the daiIy cycIe. Factors such as oxygen
consumption, body temperature, Iocomotor activity and bIood sugar, etc., show variations in a cycIic
manner. These daiIy cycIes, caIIed circadian rhythms, inIIuence heat production to an appreciabIe
extent.
MetaboIism can be deIined as the sum totaI oI chemicaI reactions necessary Ior the IoodstuIIs to be
utiIized by the body. We have aIready seen in Chapter 2, the IoodstuIIs IaII under six categories:
proteins, carbohydrates, Iipids, water, mineraIs, and vitamins. These are broken down to simpIer
substances beIore being absorbed by the body tissues. During the process oI biochemicaI reactions a
number oI intermediate products are Iormed which participate in a variety oI interactions. The subject
oI metaboIism is very vast and IaIIs in the purview oI biochemistry. However, we shaII attempt to
describe in brieI such reactions that have reIevance to the understanding oI physioIogicaI processes.
MetaboIism is absoIuteIy essentiaI to the maintenance oI homeostasis oI the body chemistry.
During metaboIism energy is required to breakdown the IoodstuIIs, which in turn yieId more energy
to derive other vitaI IiIe processes. Some oI the energy is evoIved as heat necessary to maintain a
constant body temperature (especiaIIy in warmbIooded animaIs). A good deaI oI energy is utiIized in
the synthesis oI new protopIasm during growth and tissue repair, in impuIse transmission, in muscIe
contraction, etc. In generaI, these processes IaII under two categories: (a) anabolism, in which simpIe
substances are converted into compIex substances; and (b) catabolism, invoIving degradation
reactions converting compIex substances into simpIer moIecuIes during which energy is reIeased.
A. PRDTElN METABDLlSM
Protein metaboIism consists essentiaIIy oI transIormations oI amino acids which are more readiIy
absorbed Irom the intestine into the portaI bIood to be conveyed to the Iiver. Some proteins can be
synthesized in the body Irom amino acids ingested in Iood as proteins, whiIe a number oI them are
synthesized Irom amino acids not present in the diet. Amino acids are aIso oxidized Ior energy and
utiIized Ior non protein nitrogenous compounds. The body is not capabIe oI storing Iarge amounts oI
amino acids and proteins, hence interconversion oI amino acids to other compounds Iike
carbohydrates, Iats, etc., takes pIace. Most oI the absorbed amino acids are removed Irom the bIood
MetoboIism
+ 0 ) 2 6 - 4
$
Metabolism
by the Iiver and the muscIes so that the average concentration oI amino nitrogen is about 6 mg per 100
mI. This IeveI is maintained aImost constant, aIthough the bIood urea nitrogen may be somewhat
increased.
Proteins a re indispensabIe and suppIy the required amino acids Ior growth, repair and
maintenance oI the body. In aII, there are about 20 naturaIIy occurring amino acids which IaII under
two categories: essentiaI and non-essentiaI (TabIe 5.1).
TabIe 6.1 Essential and Non-essential Amino Acids
EssønI¡aI Nøn-øssønI¡aI
Threonine Clycine
valine Alanine
Leucine Serine
Isoleucine Aspartate
Methionine Clutamic acid
Phenylalanine Proline
Histidine Hydroxyproline
Tryptophan Arginine
Lysine
Arginine
*Cysteine
*Cystine
*Tyrosine
*Replaceable amino acids.
8.3 DXlDATlDN DF AMlND AClDS
The process oI deamination takes pIace in the Iiver, kidney and intestinaI mucosa, aIthough urea
Iormation is conIined to the Iiver onIy. In this process ammonia is Iiberated in the intestine and the
kidney, and goes into circuIation in the Iorm oI gIutamine. Very IittIe amount oI ammonia is Iound in
the systemic circuIation. The ammonia produced as a resuIt oI deamination oI amino acids is
converted into urea in the Iiver which is then excreted out.
NH
2
R. CH
– 2H
COOH
NH
R. C
COOA
O
R. C
+ NH
3
COOH
H O
2
amino acid imino acid keto acid
1ransamination invoIves interconversion oI a pair oI amino acids and a pair oI keto acids
cataIyzed by transaminases or amino-transIerases. The reactions are reversibIe.
Various amino acids enter the citric acid cycIe in diIIerent ways. VaIine, threonine and aIanine can
be converted to pyruvic acid. The conversion oI aIanine takes pIace in the IoIIowing way:
Animal Physiology
FIg. 6.1 Transamination reaction.
FIg. 6.2 Conversion of glutamic acid to =-ketoglutaric acid by glutamate dehydrogenase.
8.E UREA SYNTHESlS
Ammonia is Iormed in the tissues by oxidative deamination, some oI which is excreted in the Iorm oI
ammonium saIts (ammonium saIts are excreted in metaboIic acidosis). However, much amount oI
ammonia is excreted in the Iorm oI urea. The conversion oI ammonia into urea takes pIace in the
Iiver. The Iormation oI urea is a compIex process and takes pIace via ornithine cycIe as proposed by
Krebs. In the scheme oI urea Iormation arginine is hydroIyzed by an enzyme arginase to yieId one
moIecuIe oI urea and one oI ornithine. The detaiIs oI the process are described in Chapter 14.
8.3 DECARBDXYLATlDN
DecarboxyIation is a process in which certain amines are Iormed by the removaI oI CO
2
Irom the
COOH (carboxyIic group) oI amino acids. Amines are physioIogicaIIy important. DecarboxyIation is
cataIyzed by amino acid decarboxyIases in the presence oI coenzyme pyridoxaI phosphate. The
resuIting amines, Ior exampIe, histidine yieIds histamine, tyrosine tyramine, and serine yieIds ethanoI
amine. Tyramine gives rise to adernaIine.
Aspartic acid is converted to oxaIoacetic acid, whiIe gIutamic acid is changed to aIpha
ketogIutaric acid.
R.CH (NH ) COOCH
2
a-ketoglutarate NH -to urea cycle
3
R.CO.COOH
(keto acid)
Glutamate
Transamination
CH
3
CH
COOH
NH
2
Transmination
CH
3
CO +NH
3
COOH
alanine pyruvic acid
COOH
CH
2
CH
2
CH
COOH
NH
2
H O
2
COOH
CH
2
COOH
NADH
+ H
+
NAD
+
CH + NH
2 3
glutamic acid a-Ketoglutaric acid
CO
Metabolism !
8.4 REACTlDNS DF SDME AMlND AClDS
AIthough gIycine is the simpIest amino acid, it is a precursor oI the ring systems in purine and
porphyrins. GIycine can be converted into serine when it combines with IormaIdehyde (HCHO), a
singIe carbon compound. GIycine, serine, aIanine and gIucose are interconvertibIe (Fig. 6.3).
FIg. 6.3 Interconversion of glycine, serine and alanine (schematic).
Some amino acids have tremendous physioIogicaI importance. PhenyIaIanine and tyrosine IaII in
this category which have aromatic nucIei. These two amino acids Iorm the precursors oI the hormones
thyroxine, noradrenaIine and adrenaIine. PhenyIaIanine can give rise to tyrosine in the body, but this
is an irreversibIe reaction. DeIective metaboIism oI these amino acids causes a disease alcaptonurea
which is due to an inborn gene error. In this disease the urine turns bIack when exposed to air. A gene
mutation causes the absence oI homogentisate oxygenase Irom the ceIIs, with the resuIt, homogentisic
acid accumuIates in the ceIIs and appears in the urine. In another disease, phenylketonuria, the
conversion oI phenyIaIanine to tyrosine is bIocked, consequentIy the pigment meIanin is not
produced. ChiIdren deIicient in phenyIaIanine suIIer Irom mentaI imbeciIity (Ior more detaiIs reIer to
chapter on PhysioIogicaI Genetics).
FIg. 6.4 Formation of creatine from arginine in the liver (schematic).
Glycine
+
formaldehyde
Serine Phosphoserine
transamination
3-Phosphohydroxy
pyruvic acid
3-Phospho-
glycerate
Transamination
Pyruvic
acid
Alanine
H O + P
2 1
In muscle
Creatinine
Creatine - P
Glyco-cyamine
(Liver)
Ornithine
Glycine
Arginine
Kidney
Animal Physiology "
8.5 METABDLlSM DF CREATlNE AND CREATlNlNE
Creatine and creatinine are metaboIicaIIy important compounds which are reIated to each other.
Creatine is methyI guanidine-acetic acid, and its IormuIa is:
NH
2
,
C ÷ NH
,
N CH
3
Creatine
,
CH
2
,
COOH
Creatine is Iound abundantIy in muscIe, which is probabIy the site oI its Iormation. It is composed
oI amino acids gIycine, arginine and methionine.
Creatine is useIuI in the body in many ways. HydroIysis oI phosphocreatine in the muscIe
provides energy Ior muscIe metaboIism, Ior resynthesis oI adenyI pyrophosphate, suppIies energy Ior
muscIe contraction. Creatine accepts phosphates during gIycoIysis. When combined with phosphoric
acid, creatine serves as a buIIer.
Creatinine is an anhydride oI creatine. Its structuraI IormuIa is:
NH
,
C ÷ NH
,
N CH
3
Creatinine
,
CH
2
,
CO
Creatinine is an excretory product and soIeIy derived Irom creatine (Fig. 6.4). It is Iound in the
muscIes where it is synthesized and excreted in the urine. About 1.0 to 1.5 gm oI creatinine per day is
excreted in the urine and it is independent oI the protein intake. AIter heavy muscuIar exercise
creatinine output is temporariIy acceIerated which soon stops during the recovery period.
8.8 SULPHUR METABDLlSM
SuIphur is a constituent oI suIphur containing amino acids cysteine, cystine and methionine. It is aIso
Iound in gIycoproteins as mucoitin-suIphuric acid in mucine, suIphoIipids in nervous tissue, or as
inorganic suIphates. SuIphur is present in tissue proteins, in hairs, horns and Ieathers, in mucin as
mucoitinsuIphuric acid, in some gIycoproteins oI tendons, cornea and connective tissues.
SmaII amounts oI suIphur-containing amino acids are utiIized Ior the synthesis oI the insuIin. The
tripeptide gIutathione and the >mercaptoethyIamine, a constituent oI coenzyme A. Important
pathways oI suIphur metaboIism are shown in Fig. 6.5.
Metabolism #
Majority oI suIphur-containing amino acids are cataboIized in the Iiver producing urea, and
suIphur is oxidized as suIphuric acid to be excreted as suIphates in the urine. The suIphur compounds
are useIuI in the IoIIowing ways:
(1) Synthesis oI tissue proteins Iike hair, Ieathers, etc.
(2) Synthesis oI gIutathione, taurine, insuIin, suIphatides, etc.
(3) Production oI suIphuric acid in the Iiver which is used Ior detoxication oI compound Iike
phenoI.
(4) Formation oI heparin.
(5) HeIp in the activity oI severaI enzymes where Iree SH group is avaiIabIe.
8.7 METABDLlSM DF NUCLEDPRDTElN
NucIeoproteins are compIex compounds that are present in the chromosomes oI the nucIeus and the
cytopIasm. ChemicaIIy they are composed oI simpIe proteins Iike protamines, proIamines or histones
conjugated with nucIeic acids and are rich in basic amino acids. They are made up oI basic buiIding
bIocks caIIed nucIeotides containing purine and pyrimidine bases, pentose sugars and phosphoric
acid. The purines are converted to uric acid and pyrimidines are oxidized to produce CO
2
and NH
3
.
The pentose sugars are in the Iorm oI deoxyribose or ribose resuIting in deoxyribose nucIeic acid
(DNA) or ribose nucIeic acid (RNA) respectiveIy. The purine bases comprise adenine and guanine,
and pyrimidines consist oI thymine and cytosine. AII these Iour bases are present in DNA, whereas in
RNA thymine is repIaced with uraciI.
FIg. 6.5 Sulphur metabolism (schematic).
Glutathione b - mercaptoethylamine
Cystine Cysteine
Cysteic
acid
Taurine
— CO
2
Taurocholic
acid
Cysteine
sulphuric acid
H SO
2 3
H SO
2 4
+ Pyruvate
Thiosulphate + Cholic acid
H SO
2 4
H S
2
Thiosulphate
Urea
Pyruvate
Mercapturic
acid
NH
3
— CO
2
Animal Physiology $
NucIeotides are nucIeoside phosphates. NucIeosides are Iormed when the phosphoric acid
component is removed. They are moderateIy or entireIy soIubIe in water.
NucIeoproteins are oI two kinds: exogenous and endogenous. The exogenous sources are muscIes
and tissues Iike pancreas, testis, kidney, thymus, etc. Endogenous sources are various ceIIs that
undergo breakdown during the metaboIic process.
SeveraI nucIeotides Iunction as coenzymes which are derivatives oI 5-adenyIic acid. Some oI the
important coenzyme nucIeotides which take part in the metaboIism are: nicotinamide adenine
dinucIeotide (NAD), nicotinamide adenine dinucIeotide phosphate (NADP) and IIavin adenine
dinucIeotide (FAD).
RibonucIeic Acid
About 80 percent oI the RNA in a ceII, is associated with ribosomes. They are primariIy Iound in the
cytopIasm oI the ceII. Very IittIe RNA is Iound in the nucIeus. RNA pIays the key roIe in protein
synthesis. RNA is IabiIe to aIkaIi and is hydroIyzed by ribonucIease (RNAse).
DeoxyribonucIeic Acid
The nucIeus oI the ceII contains aImost aII the DNA oI the ceII. It is the primary component oI the
genes which are the carriers oI heredity. The amount oI DNA remains constant in the somatic ceIIs;
however, just prior to ceII division this amount is doubIed so that each daughter ceII receives the same
amounts as that oI the somatic ceII. The DNA is a doubIe stranded heIicaI structure, and each strand
is compIementary to the other. These strands Irom the tempIates Ior the transcription oI RNA
moIecuIes. The synthesis oI DNA is Iound to be most active in bone marrow, thymus and embryonic
tissues where the ceII proIiIeration is maximum and rapid.
CataboIism of NucIeic Acid
The ingested nucIeo-proteins are hydroIyzed into protein and nucIeic acid in the digestive tract by the
action oI proteases. The speciIic enzymes, deoxyribonucIease and ribonucIease break the DNA and
FIg. 6.6 Hydrolysis of nucleoproteins (schematic).
Protein Nucleic acid
(DNA and RNA)
Phosphoric acid Nucleosides
Nucleoprotein
Bases
(Purines, Pyrimidines)
Pentose sugars
(Deoxyribose, Ribose)
Nucleotides
Metabolism %
RNA respectiveIy into oIigonucIeotides and tetranucIeotides. NucIeotidases act on nucIeotides and
nucIeosidases act on nucIeosides. The nucIeosides upon hydroIysis Iorm adenyIic and guanyIic acids.
The nucIeotidase acts upon nucIeotides to Iorm adenosine or hypoxanthine and guanosine or xanthine
respectiveIy. By speciIic enzymes, adenase and guanase, adenine and guanine are converted to
hypoxanthine and xanthine respectiveIy. An enzyme oxidase then acts upon hypoxanthine to convert
it to xanthine; xanthine is Iurther converted to uric acid by the action oI xanthine oxidase. The
cataboIism oI purine bases is shown in Fig. 6.7.
The purine bases are absorbed in the bIood and one oI the IinaI wastes in man is uric acid. In
other animaIs, uric acid is converted to aIIantoin. The Iate oI pyrimidines is quite compIicated.
However, it is known that they are cataboIized to CO
2
and NH
3
.
Protein Biosynthesis
Proteins are continuousIy degraded to amino acids, and side by side amino acids continuaIIy
participate in protein Iormation. Proteins are essentiaI Ior the body and Iorm structuraI proteins, and
muItipIe enzyme systems and hormones that are necessary Ior chemicaI reactions. Proteins cannot be
synthesized Irom any other source except amino acids and thus they Iorm an essentiaI component oI
the diet. Protein synthesis is under genetic controI, that is gene directed. As a resuIt oI current
researches, a IairIy good picture has emerged as to how genetic inIormation stored in the DNA is
transIated and expressed in speciIic protein moIecuIes. This aspect IaIIs under the IieId oI
biochemistry. The reader is thereIore advised to Iook Ior this in a textbook on biochemistry.
B. CARBDHYDRATE METABDLlSM
Carbohydrates are the main IoodstuIIs which are synthesized by pIants and utiIized by animaIs Ior
their energy requirements. We have discussed in eIIicient detaiIs the diIIerent cIasses oI carbohydrates
in Chapter 2. In this chapter attention wiII be given to the manner in which carbohydrates are
empIoyed as sources oI energy in diIIerent tissues and the way they are distributed and stored in the
body.
The Iood oI organisms contains Iarge amounts oI carbohydrates in the Iorm sugars and starches
which are hydroIyzed in the course oI digestion into their monosaccharide moieties or simpIe sugars.
These simpIe sugars are absorbed by the smaII intestine and utiIized in many ways which may be
enumerated as IoIIows:
FIg. 6.7 Catabolism of purine bases (schematic).
Animal Physiology &
(1) SimpIe sugars Iike gIucose, Iructose, and gaIactose are absorbed by the intestine and may
circuIate as bIood sugars.
(2) Sugars (gIucose) are absorbed into the portaI bIood and converted into gIycogen Ior storage
and Iuture use.
(3) SimpIe sugars may be changed into gIycogen in the muscIes.
(4) They may be transIormed into Iat and deposited as adipose tissue.
(5) A good portion oI the absorbed gIucose is oxidized as an immediate
source oI energy.
(6) Some amount oI sugars is excreted in the urine.
8.8 BLDDD SUGAR
GIucose is the Iree sugar which circuIates in the bIood. AIter a meaI, the circuIating bIood sugar IeveI
is eIevated quickIy aIter absorption. In a Iasting human being the gIucose concentration in bIood is
about 80 mg per 100 mI. However, the bIood sugar IeveI is maintained aImost constant and varies
within narrow Iimits onIy unIess during abnormaI conditions Iike hypergIycemia or hypogIycemia.
SeveraI reguIatory mechanisms are responsibIe Ior maintaining bIood sugar IeveI. Much oI the
gIucose absorbed Irom the gut is passed on to the tissues Ior oxidation or converted into gIycogen in
the muscIes (Fig. 6.8). Quite a good amount is stiII converted to gIycogen in the Iiver through the
process oI gIycogenesis. In case the bIood sugar IeveI IaIIs beIow the required IeveI, gIycogenoIysis
occurs. Thus these two processes have a marked reguIatory eIIect.
FIg. 6.S Regulation of blood sugar.
Amino
acids
Deamination
Glucocortin
Fat + Glucose + Urea
Blood
glucose
Fats
Insulin
Glucocortin
O
x
i
d
a
t
i
o
n
O
x
i
d
a
t
i
o
n
i
n
c
r
e
a
s
e
d
b
y
i
n
s
u
l
i
n
CO + H O + Energy
2 2
L
o
w
e
r
e
d
b
y
g
l
u
c
o
c
o
r
t
i
n
Excreted
A
d
r
e
n
a
lin
e G
r
o
w
th
h
o
r
m
o
n
e
g
lu
c
a
g
o
n Liver
glycogen
C
o
r
i c
y
c
l
e
Lactic
acid
A
d
r
e
n
a
l
i
n
e
Muscle
glycogen
I
n
s
u
l
i
n
I
n
s
u
lin
Metabolism '
A number oI hormones are responsibIe Ior gIucose reguIation. There are three endocrine organs
invoIved in carbohydrate metaboIism. These are: pancreas, adrenaIs and anterior pituitary. We shaII
discuss in brieI the roIe oI each oI these (Ior more detaiIs see Chapter 19). The isIets oI Iangerhans oI
the pancreas secrete the hormone insulin which is cIoseIy Iinked with carbohydrate utiIization in the
body. Increase or decrease in the amounts oI circuIating gIucose depends upon insuIin eIIiciency.
InsuIin speeds the movement oI gIucose Irom the bIood into tissue ceIIs, thereby Iowering the bIood
gIucose IeveI. II too much oI insuIin is present in the circuIation, the bIood sugar IeveI wiII drop
beIow normaI causing hypogIycemia. On the other hand, iI enough insuIin is not present, then the
transport or mobiIization oI bIood sugar is sIowed down causing rise in bIood sugar IeveI. This
condition is known as hypergIycemia. DeIiciency oI insuIin causes the disease, Diabetes mellitus.
InsuIin may aIso heIp in the process oI phosphoryIation during gIycoIysis by acting as a coenzyme to
the enzyme gIucokinase.
Another hormone that aIIects the bIood sugar IeveI is adrenaIine and produced by the adrenaI
meduIIa. This hormone increases the concentration oI gIucose in the bIood by IaciIitating the
breakdown oI Iiver gIycogen. NoradrenaIine probabIy perIorms the same Iunction to a very Iimited
extent.
The steroid hormone Irom the adrenaI cortex, hydrocortisone, stimuIates the Iiver to convert
proteins and Iats to carbohydrates (gIuconeogenesis) resuIting in an increase bIood sugar IeveI.
The anterior pituitary (adenohypophysis) secretes some hypogIycemic hormones which incIude
thyroid stimuIating hormone (TSH), adrenocorticotropic hormone (ACTH) and growth hormone
(STH). These hormones antagonize the action oI insuIin and eIevate the bIood sugar.
8.8 GLYCDLYSlS
AIter absorption the gIucose moIecuIe is subjected to a series oI reactions and is compIeteIy oxidized
into CO
2
and H
2
O pIus some energy. The spIitting oI gIucose moIecuIe is reIerred to as gIycoIysis.
One moIe oI gIucose when oxidized yieIds 686 kiIocaIories oI kinetic (active) energy. Much oI the
energy reIeased during carbohydrate metaboIism is stored in the Iorm oI high energy phosphate
compounds such as ATP. In the process oI gIucose oxidation severaI chemicaI steps are invoIved and
each step is cataIyzed by speciIic enzyme (Fig. 6.5). In the Iirst step each moIecuIe oI gIucose
produces two moIecuIes oI pyruvic acid:
GIucose ¹ 2ADP ¹ 2PO
4
1 pyruvic acid ¹ 2ATP ¹ 4H
The net yieId oI energy is 2 moIecuIes oI ATP. The series oI reactions invoIved in gIycoIysis are
coIIectiveIy known as Embden-Meyerhof Pathvay. The entire process is an anaerobic process and
does not require oxygen.
AIter gIucose has been converted to pyruvic acid, the next step is the conversion oI pyruvic acid
to acetyI coenzyme A.
Pyruvic acid ¹ Coenzyme A AcetyI coenzyme A ¹ 2H
The reaction neither requires ATP, not is ATP generated. Now acetyI coenzyme A undergoes
another series oI reactions which is reIerred to as citric acid cycle or Krebs cycle. This cyIcIe is
Animal Physiology
aerobic and the end products are CO
2
, H
2
O and energy in the Iorm oI ATP. The detaiIs oI the steps are
given in Fig. 4.6. A totaI oI 38 moIecuIes oI ATP are produced utiIizing onIy about 55 per cent oI
kinetic energy reIeased during the process.
Besides Embden-MeyerhoI Pathway, there is yet another pathway Ior gIycoIysis known as hexose
monophosphate shunt (HMP). This pathway occurs in the Iiver, Iactating mammary gIands and the
adipose tissue oI mammaIs. ConsiderabIe Iraction oI gIucose is oxidized in this way. In the HMP-
pathway, Iirst gIucose-6-phosphate undergoes dehydrogenation and decarboxyIation to yieId ribuIose-
5-phosphate (a pentose). In the next phase ribuIose-5-phosphate is converted back to
gIucose-6-phosphate by a series oI intermediate reactions. In case oI HMP-pathway, NADP
(nicotinamide adenine dinucIeotide phosphate) is used instead oI NAD, as hydrogen acceptor. The
shunt works as a source oI chemicaI rather than energy.
FIg. 6.9 Clycogenesis.
1,4 Glycosyl
units
Branching enzyme
Glycogen
synthetase
Phosphorylase
Debranching
enzyme
UDPG Pyrophosphorylase
Pi
Glucose
from
debranching
enzyme
I
S
Phosphoglucomultase
Glucose-6
phosphate
Glucokinase
Glucogen
(1 , 4 and 1 , 6 glycosyl
units)
Glycogen
primer
UDP
Glucose
Insulin
Uridine
diphosphate
glucose (UDPG)
Touronic
pathway
PPi
Uridine
triphosphate
(UTP)
Cyclic AMP
Glucagon
cpinephrine
Glucose 1– phosphate –
to
HMP
shunt
Mg
++
Pi
ATP
Glucose 6 – phosphate –
Mg
++
ADP
S – Simulation
I – Inhibition
H O
2
Glucose
S
S
S
Metabolism
8.30 GLYCDGENESlS
The Iormation oI gIycogen is caIIed gIycogenesis which occurs both in the Iiver and the muscIes
(Fig. 6.9). First, gIucose is phosphoryIated to gIucose- 6-phosphate, which is then converted to
gIucose-1-phosphate, a reaction cataIyzed by phosphogIucomutase. Then gIucose-1-phosphate reacts
with uridine triphosphate (UTP) to Iorm uridine diphosphate gIucose (UDPG). AIter this, enzyme
gIycogen synthetase reacts with UDPG and Iorms a gIycosidic bond between 1 carbon oI activated
gIucose and 4 carbon oI the gIucose residue oI gIycogen reIeasing uridine diphosphate (UDP). The
reactions showing interconversion oI gIucose and gIycogen in the Iiver are given in Fig. 6.12.
Liver gIycogen is Iormed not onIy Irom simpIe sugars, but aIso Irom the Iactic acid that is
produced in the muscIes (Fig. 6.8). Lactic acid produced during muscIe contraction goes to the Iiver
through the circuIating bIood and is converted into gIycogen. GIycogen in the Iiver can be converted
into gIucose, and gIucose can be changed to muscIe gIycogen which in turn is converted into Iactic
acid, some oI which is Iater transIormed back to Iiver gIycogen. The cycIic pathway invoIved in this
process is known as Cori cycle (Fig. 6.10).
FIg. 6.1û Cori Cycle.
8.33 GLUCDNEDGENESlS
Liver gIycogen is aIso Iormed Irom non-carbohydrate sources such as proteins and Iats. The
conversion oI protein into gIycogen is known as gIuconeogenesis. FormerIy it was beIieved that
gIuconeogenesis occurs onIy in speciaI circumstances. However, IateIy it has been proved that it
occurs simuItaneousIy with gIycogenoIysis. The excess amounts oI protein are metaboIized by the
carbohydrate pathway and can be converted into gIucose or gIycogen by reversaI oI gIycoIysis.
GIuconeogenesis is most important because it usuaIIy occurs when the gIycogen store is exhausted.
Animal Physiology
In the process, the excess oI protein is Iirst hydroIyzed to amino acids which are then deaminated
and Iater metaboIized through either carbohydrate pathway or Iat metaboIism.
In addition to these sources oI gIucose or gIycogen in the Iiver, gIucose may derived Irom Iat aIso,
aIthough this conversion takes pIace to a very Iimited extent. In this conversion the essentiaI part oI
the process consist oI the oxidation oI Iong chain Iatty acids in the mitochondria. Then the gIyceroI
component oI the Iat reacts with ATP to Iorm gIyceroI phosphate which is then oxidized to
gIyceraIdehyde 3-phosphate, This may be Iurther oxidized to pyruvic acid or may be converted to
gIycogen by reversaI oI the part oI the gIycoIytic pathway.
8.3E MUSCLE GLYCDGEN
MuscIes are no Iess important than Iiver in carbohydrate metaboIism. NormaIIy the concentration oI
gIycogen in the muscIe ranges between 0.5 and 1.0 per cent oI the weight oI the muscIe. In this way
muscIe gIycogen is Iar greater in amount than the Iiver gIycogen. Liver is the storage organ Ior
gIycogen, whereas muscIe gIycogen acts as a source oI energy during contraction. Starvation does not
aIIect the muscIe gIycogen. Synthesis oI gIycogen in the muscIe takes pIace in the same manner as in
case oI Iiver. MuscIe cannot convert gIycogen to gIucose since the speciIic enzyme required Ior its
conversion is absent in the muscIe. However, gIycogen is broken down to Iactic acid in the muscIe
Irom where it is carried to the Iiver through the bIoodstream to be converted into gIycogen.
8.33 METABDLlSM DF DTHER SUGARS
GIucose, gaIactose and Iructose are sugars oI great metaboIic importance. These sugars enter the
metaboIic pathways aIter being phosphoryIated. PhosphoryIation oI gIucose has aIready been
described in connection with gIycoIysis. The source oI gaIactose is mainIy the Iactose content oI the
miIk. GaIactose is Iirst phosphoryIated in the presence oI a speciIic enzyme galactokinase,and then it
reacts with uridine diphosphogaIactose to Iorm uridine diphosphogIucose which may participate in
gIycogen synthesis. Large quantities oI gaIactose in bIood are known to be toxic and cause a disease
galactosemia.
Fructose is obtained Irom sucrose and Iruits and is readiIy converted into gIucose or gIycogen in
the Iiver. It is phosphoryIated in the presence oI Iructokinase into Iructose-1-phosphate. The sequence
oI events is shown beIow (Fig. 6.11).
OccasionaIIy gIyceraIdehyde is oxidized to gIyceroI. GIyceraIdehyde can aIso be reduced to
gIyceraIdehyde-3-phosphate (triose), and two moIecuIes oI triose can be converted to Iructose-1, 6-
diphosphate.
C. FAT METABDLlSM
Fats and Iipids are important constituents oI the protopIasm. They may be present in the Ioods or may
be Iormed in the body. We have described the chieI cIasses oI Iats and Iipids in Chapter 2. The
Metabolism !
structuraI Iats are very compIex compounds, whereas reserve Iats
or depot Iats are the ordinary Iats which make up the buIk oI the
body. Depot Iats are in the Iorm oI neutraI trigIycerides which can
be hydroIyzed to Iorm monogIycerides and Iree Iatty acids.
TrigIycerides may be resynthesized Irom the Iatty acids in the
ceIIs oI intestinaI mucosa.
In the metaboIism oI Iat, three major processes are invoIved:
(1) MobiIization oI Iat Irom storage Iat depots oI the body,
which Iater take part in cataboIism.
(2) Absorption oI digested Iats.
(3) Synthesis oI Iats in the Iiver, Irom intestinaI muscosa and
the adipose tissue carbohydrate and protein sources.
MobiIe Iat is in the Iorm oI minute oiIy dropIets known as
chylomicrons which traveI in the bIoodstream. ChyIomicrons are
made up oI neutraI Iats, and aIso consist oI phosphoIipids (Iat
pIus phosphate), choIesteroI and choIesteroI esters oI Iatty acids.
The chyIomicrons are absorbed by the Iiver where they are
hydroIyzed giving rise to Iree gIyceroIs and Iatty acids. MobiIization oI Iats can be convenientIy
observed in case oI starving animaIs. AIter starvation Ior a short period, the gIycogen reserve oI the
Iiver is depIeted. Since no more oI carbohydrates are synthesized (except by way oI gIuconeogenesis),
the Iiver does not receive its carbohydrate suppIy. Under such conditions, Iarge, amounts oI Iats are
transported to the Iiver which take part in metaboIism.
8.34 RDLE DF LlVER lN FAT METABDLlSM
Liver has a key roIe in the metaboIism oI Iats. It has been proved beyond doubt that in conditions oI
carbohydrate depIetion, most oI the Iat oI the body is mobiIized to the Iiver to provide an aIternative
source oI energy. Liver is not normaIIy an accumuIator oI Iats as it is Ior carbohydrates. The Iat
content in the Iiver is maintained uniIormIy constant between 3 and 8 per cent. Thus excess oI Iat
deposits is transIormed by the Iiver into useIuI substances through various interconversions
(Fig. 6.12).
Besides interconversion oI proteins, Iats and carbohydrates, which goes on in the Iiver, it is aIso
responsibIe Ior transIormations oI Iipids into phosphoIipids and choIesteroI, desaturation oI Iatty
acids, oxidation oI Iatty acids, etc. The sIuggish Iunction oI the Iiver resuIts in severaI metaboIic
disorders, which may be normaIIy due to the eIIect oI certain poisons, Iat-rich diet, protein-poor diet,
deIiciency oI vitamins and a host oI other causes. ThereIore, we can say that Iiver is the predominant
organ which maintains the heaIthy state oI an individuaI.
D – fructose
Fructose 1 – phosphate
D – Glyceraldehyde
D – Glycerate
ATP
Fructokinase
Dihydroxyacetone
Aldehyde
dehydrogenase
NAD+H
+
NAD
+
Aldolase
FIg. 6.11 Metabolism of fructose.
Animal Physiology "
8.35 DXlDATlDN DF FATTY AClDS
Fats, especiaIIy trigIycerides, are hydroIysed to their constituents Iatty acids and gIyceroI beIore they
proceed to cataboIic pathway. Much oI the Iat hydroIysis takes pIace in adipose tissue, where Iree
Iatty acids (FFA) are produced to be carried into the pIasma (Fig. 6.13). The FFA acids reach the
tissues (Iiver, kidney, heart, muscIe, testis, brain, and adipose tissue) where oxidation takes pIace. The
Iong chain Iatty acids are systematicaIIy broken down to 2-carbon units in the Iorm oI 'active
acetates¨. The acetate and the Iong chain Iatty acids are metaboIised through a common pathway,
requiring ATP and CoA enzyme (Fig. 6.14).
FIg. 6.12 Interconversion of carbohydrates in the liver.
Galactose Galactose 1 – phosphate
Galactokinase
ATP
Uridine diphosphate
glactose
Uridine diphosphate
glucose
Glucose 6 – phosphate
Glucose
phosphate
Fructose 6 – phosphate
glucose 1 – phosphate
Glycogen
phosphorylase
Fructose
Fructokinase
ATP
Glucose
Glucokinase
ATP
CH
3
CHOH
CH
2
COOH
Oxidation
Reduction
CH
3
CO
CH
2
COOH
Decarboxylation
CH
3
CO
CH
3
+ CO
2
b-Hydroxybutyrate Acetoacetate Acetone
The acetyI CoA can either combine with oxaIoacetate beIore entering the citric acid cycIe, or it
may be directIy oxidised to acetoacetate, the Iirst ketonc body. Acetoacetate may Iurther breakdown
to >-hydroxybutyrate and acetone, which accumuIate in the Iiver in smaII amounts. The Iiver tissue
cannot oxidise acetoacetate. Acetone arises Irom acetoacetate by spontaneous decarboxyIation.
Metabolism #
The utiIisation oI gIyceroI is dependent on the activating enzyme, glycerol kinase, which is Iound
in suIIicient amounts in Iiver, kidney, intestine, brown adipose tissue and Iactating mammary gIands.
8.38 >-0XlDATlDN DF FATTY AClDS
Fatty acids are mainIy oxidised by a process caIIed >-oxidation, a scheme proposed by Knoop in
1904. He postuIated that since majority oI neutraI Iats contain even number oI carbon atoms,
>-oxidation is the more IikeIy process in which the Iatty acid moIecuIe is broken down in a stepwise
manner, removing 2-carbon atoms Irom the carboxyI end in each step, yieIding acetate equivaIents.
FIg. 6.14 Metabolism of fatty acids.
FIg. 6.13 Schematic representation of metabolism of fats and carbohydrates.
Carbohydrates
Triose phosphate
Pyruvate
Fatty acid
Oxidized to
Fats Glycerol
CO
2
+ H O
2
Citrate
Acetyl–CoA
Acetoacetate
Acetone
CO
2
–Hydroxybutyrate
Acetylations
Acetate
O
xaloacetic
acid
b
(Sat. fatty acid)
R – CH CH COOH
(Acetyl CoA)
2 2
(CoA derivative)
R–CH CH CO–CoA
2 2
CoA
ATP 1
Citric
acid
cycle
Throlysis
CH CO ~ CoA
3
(active and acid)
R–CH OH CH CO ~ CoA
2
(Hydroxy fatty acid CoA)
R—CH CH CO ~ CoA
R–CO ~ CoA
5
2
3 4
R–CO CH CO ~ CoA
2
Dehydrogenation
H
y
d
r
o
l
y
s
i
s
(Unsaturated fatty acid)
Enzymes
(1) Thiokinase
(2) Acyldehdrogenase
(3) Enol hydrase
(4) – hydroxy acyldehydrogenase b
(5) Thiolase
D
e
s
a
t
u
r
a
t
i
o
n
,
Animal Physiology $
The acetate moIecuIes can be compIeteIy oxidised via citric acid cycIe or may be utiIised to synthesise
gIucose and other compIex carbohydrates as per needs oI the animaI. Some important steps oI >-
oxidation scheme are shown in Fig. 6.15.
It must be borne in mind that Iatty acid oxidation takes pIace in the mitochondria, but beIore FA
enters the mitochondria it has to be made ready Ior oxidation reactions. The FA in the cytosoI is
activated by a moIecuIe oI ATP in the presence oI acyIcoenzyme A(CoASH). The reaction occurs
either in the endopIasmic reticuIum or at the outer mitrochondriaI membrane, resuIting in the
Iormation oI Iatty acyI CoA derivative. The Iatty acyI CoA derivative is then transported inside the
mitochondria with the heIp oI carnitine, a carrier moIecuIe. This reaction is cataIysed by an enzyme,
acyI CoA transIerase. Once the Iatty acyI CoA enters the mitochondriaI matrix, there IoIIows the
removaI oI 2 hydrogen atoms Irom the = and > carbons, cataIysed by a dehydrogenase, resuIting in
FIg. 6.15 >-oxidation.
R – CH = CH – C~S – CoA
R – R – CH
2
– CH –C–OH
2
O
Fatty acid
CoA SH ATP
Mg
++
AMP + PPi
1
Thiokinase
Acyl – CoA
(Active fatty acid)
R – CH –
2
CH – C~S – CoA
2
Acyl – CoA
Acyl – CoA
A – Unsaturated b
Dehydrogenase
2
Fp(Flavoprotein)
Fp H
2
2 ~ P
H O
2
Respiratory chain
H O
2
Enoyl
hydrase
3
acyl – CoA
b–hydroxy
OH
R–CH–CH –C~S – CoA
2
b–hydroxyacyl
CoA dehydrogenase
NAD
3~ P
H O
2
NADH+H
++
Respiratory chain
4
R–C–CH –C~S – CoA
2
CoA SH
b–Ketoacyl
CoA
Thiolase
– Ketothiolase b
5
R–C~S–CoA + CH –C~S – CoA
3
Acyl–CoA Acetyl–CoA
Citric
acid
cycle
2CO
2
O
O
O
O O
O O
Metabolism %
the Iormation oI unsaturated acyI CoA. The unsaturated Iatty acyI CoA derivative is subsequentIy
hydrated and dehydrogenated at the expense oI speciIic enzymes to Iorm corresponding >-keto-acyI
CoA compound. FinaIIy, >-keto-acyI CoA undergoes thioIytic cIeavage by thiolase producing an acyI-
CoA unit and the remaining acyI-CoA chain containing 2-C Iess than the originaI Iatty acyI CoA
moIecuIe. In this way, a Iong chain Iatty acid may be degraded compIeteIy to acetyI-CoA (2-C
Iragments), which can be oxidised to CO
2
and water through citric acid cycIe.
In case oI Iatty acids with odd number oI carbon atoms, oxidation takes pIace through >-oxidation
scheme, Ieaving behind propionyI CoA, a 3-carbon unit. This compound can enter the citric acid cycIe
aIter conversion to succinyI CoA.
Energetics of >-oxidation
Let us consider the oxidation oI one moIe oI paImitic acid (C
16
H
32
O
2
), entering the mitochondria in
the Iorm oI paImitoyI CoA. InitiaIIy one moIe oI ATP is required to activate the acid, and at the end oI
each oxidative spiraI, one FADH
2
and one NADH are Iormed aIong with an acetyI CoA Iragment. In
order to oxidise paImitoyI CoA, 8 acetyI CoA wiII be Iormed and the energy gained in terms oI ATP
wiII be as IoIIows:
8 acetyI CoA ¹ 7 FADH
2
¹ 7 NADH ¹ H
¹
35 ATP Iormed
8 acetyI CoA oxidised via citric acid cycIe 96 ATP Iormed
ATP initiaIIy used Ior activation 01 ATP consumed
Net gain oI ATP 130 ATP
The overaII equation is represented as:
C
16
H
32
O
2
¹ ATP ¹ 7 FAD ¹ 7 NAD
¹
¹ 8 CoASH ¹ 7 H
2
O AMP
¹ PPi ¹ 7 FADH
2
¹ 7 NADH ¹ H
¹
¹ 8 CH
3
COSCoA.
Since each ATP moIecuIe has 7.6 kcaI oI bond energy, the net gain wouId be 130 7.6 ÷ 988
kiIocaIories. The caIoriIic vaIue oI paImitic acid is 2340 kcaI/moIe, the system receives at Ieast 42°
oI high phosphate bond energy (988/2340 100) oI the totaI energy oI combustion oI the Iatty acid.
Dxidation of Unsaturated Fatty Acids
Body Iipids are rich in unsaturated Iatty acids and these are oxidised more sIowIy. Some exampIes are:
paImitoIeic acid (16:1), oIeic acid (18:1), IinoIeic acid (18:2), IinoIenic acid (18:3) and arachidonic
acid (20:4). AII doubIe bonds in naturaIIy occurring unsaturated Iatty acids are in cis-conIiguration.
PaImitoIeic and oIeic acids are not essentiaI as they can be Iormed in the body, but the remaining three
acids come under the essential fatty acids category and have to be suppIied in the diet. Oxidation oI
unsaturated Iatty acids proceeds the usuaI >-oxidative pathway untiI the doubIe bond is reached. The
doubIe bond in cis-conIiguration is not vuInerabIe to enzymic attack unIess it is isomerised to trans-
conIiguration. PoIyunsaturated Iatty acids, such as IinoIeic, arachidonic etc. are more compIex and
require additionaI enzyme Ior oxidation. They are normaIIy Iound as structuraI components in
association with choIesteroI and phosphoIipids (e.g. membranes and reproductive organs). In
mammaIs, arachidonic and some reIated C-20 Iatty acids are known to give rise to unique compounds
Iike prostaglandins which have hormone-Iike activity.
Animal Physiology &
8.37 METABDLlSM DF GLYCERDL
One oI the hydroIysis products oI trigIycerides is gIyceroI which is metaboIised or utiIised in
organs/tissues where speciIic enzyme gIyceroI kinase is abundantIy present. Certain organs such as
Iiver, kidney, intestinaI mucosa and Iactating mammary gIands are rich in the enzyme, whiIe muscIes
and adipose tissue contain very IittIe activity. GIyceroI is predominantIy converted into carbohydrate
through gIyceroI phosphate, Iormed by a speciIic gIyceroI kinase at the expanse oI ATP.
CH
2
OH
CHOH + ATP
CH
2
OH
CH
2
OH
CHOH + ADP
CH
2
O–P
Glycerol phosphate
(triose phosphate)
Glycerol
GIyceroI phosphate is then oxidised to triosephosphate by a gIyceroI phosphate dehydrogenase
which uItimateIy Iorms gIycogen through gIycogenesis. Triosephosphate may be, however, oxidised
to pyruvic acid by way oI gIycoIysis (Fig. 6.16). In diabetic or phIorrhizinised animaIs, gIyceroI is
converted aImost quantitativeIy to gIucose.
FIg. 6.16 Fate of glycerol metabolism.
8.38 SYNTHESlS DF GLYCERlDES AND FATTY AClDS
It has been known Ior a Iong time that Iats are synthesised Irom metaboIites such as acetate and
acetoacetate. Fats are aIso synthesised Irom protein and carbohydrate sources. AII naturaIIy occurring
Iatty acids possess even number oI carbon atoms; thus it is IogicaI that Iatty acids must be synthesised
Irom 2-carbon Iragments. It has been shown that the starting materiaI is acetyI-CoA which can be
derived Irom pyruvate. AIternativeIy, pyruvate can aIso be derived Irom Iree, acetate when it reacts
with coenzyme A and ATP.
Synthesis of GIycerides
TrigIycerides are Iormed by reactions between acyI-CoA compounds and -gIycerophosphate, which
is Iormed by speciIic gIyceroI kinase. There are other enzymes which cataIyse the Iormation oI
monoand diphosphatidic acids at the expense oI Iatty acyI CoA derivatives:
Metabolism '
CH
2
O—R
1
CHO—R
2
CH
2
O—P O
OH
OH
Phosphatidic acid
In the next stage the phosphate group is removed by a speciIic phosphatase IoIIowed by
repIacement by a third Iatty acyI residue:
CH
2
O—R
1
CHO—R
2
CH
2
O—P O
OH
OH
CH
2
O—R
1
CHO—R
2
CH
2
OH
CH
2
O—R
1
CHO—R
2
CH
2
O—R
3
+H O
2
+ Acyl CoA
Phosphatidic acid Diglyceride Triglyceride
Synthesis of Fatty Acids
Fatty acid oxidation occurs in the mitochondria, but Iatty acid synthesis takes pIace not onIy in
mitochondria but aIso in mitochondria-Iree systems. The pathway Ior synthesis is not exactIy reversaI
oI >-oxidation scheme, but it invoIves, some modiIications. Under anaerobic conditions, mitochondria
cataIyse the incorporation oI acetyI-CoA units into Iong chain Iatty acids (viz. stearic acid, paImitic
acid), requiring ATP, NADH and NADPH. Synthesis in extra-mitochondriaI system, especiaIIy in the
Iiver, brain, kidney etc., acetyI-CoA units are incorporated into Iatty acids, cataIysed by cytosoIic
enzymes and coIactors such as ATP, NADPH and Mg

or Mn

ions. This system is dependent on
CO
2
suppIied by bicarbonate. Chain eIongation usuaIIy takes pIace in the microsomes.
8.38 METABDLlSM DF PHDSPHDLlPlDS
PhosphoIipids are Iound in aII ceIIs and are synthesised either Irom phosphatidic acid or phosphatidyI
choIine. Lecithin is the most important phosphoIipid in the body and is synthesised in the Iiver.
Synthesis oI phosphoIipids Irom Iats invoIves mobiIisation oI Iats in and out oI the ceIIs. Hence the
actuaI sites are Iiver, intestine and kidney. PhosphoIipids are IargeIy Iound in combination with
proteins and are transported in the bIood in the Iorm oI protein compIexes.
The most common among phosphoIipids are Iecithins and cephaIins, whiIe where are others in
which bases are repIaced by serine or inositoI. CataboIism oI Iecithin is accompIished in the IoIIowing
manner (Fig. 6.17):
SphingomyeIins are phosphoIipids containing a Iatty acid, phosphoric acid, choIine, and a
compIex oI amino aIcohoI, sphingosine, but are devoid oI gIyceroI. AbnormaI quantitities oI phospho-
and sphingoIipids in certain tissues, especiaIIy in the nervous system, cause diseases Iike
sphingoIipidoses, and demyIeinating diseases that are inherited.
8.E0 METABDLlSM DF CHDLESTERDL
ChoIesteroI occurs in various body tissues and in the pIasma either in the Iree Iorm or storage Iorm as
Iong chain Iatty acid esters beIonging to the cIass oI steroIs. It is aIso an important component oI the
Animal Physiology
membrane system oI the ceII and is the precursor oI steroid hormones, excreted Irom the body in the
Iorm oI biIe acids (saIts). The choIesteroI content oI the bIood ranges Irom 150 250 mg/100 mI.
Sources of ChoIesteroI in the Body
WhiIe major part oI the body choIesteroI (about 1 g/day) is synthesized in the body, a smaII portion is
(about 0.3 g/day) provided by various Ioods intake such as egg yoIk, meat, Iiver, and brain and its
uptake is through Iow density Iipoproteins (LDLs). Synthesis occurs Irom acetyI-CoA (two-carbon
units) produced by beta oxidation oI Iatty acids in the Iiver, intestine and aImost aII ceIIs. About 700
mg/d is synthesized by a weII reguIated mechanism. Free choIesteroI is removed Irom the body by
pIasma high-density Iipoproteins (HDLs).
Synthesis of ChoIesteroI
AIthough choIesteroI is synthesized by many tissues such as adrenaI cortex, skin, intestine testes etc.
Iiver is considered to be the main site. Two moIecuIes oI acetyI-CoA condense to Iorm acetoacetyI-
CoA, which again reacts with another moIecuIe oI acetyI-CoA to Iorm 3-hydroxy-3-methyIgIutaryI-
CoA (HMG-CoA), Ieading to the synthesis oI mevaIonate (Fig. 6.18). It must be noted that aII carbon
atoms oI choIesteroI originate Irom acetyI-CoA enzyme. MevaIonate is the cruciaI compound and
through a series oI reactions, gives rise to choIesteroI.
Transport and Excretion of ChoIesteroI
ChoIesteroI, in association with other Iipids, is absorbed in the intestine and thereaIter incorporated
into chyIomicrons and very Iow-density Iipoproteins (VLDLs). A greater part oI choIesteroI (about
80°) in the Iymph undergoes esteriIication with Iong-chain Iatty acids and transported as Iipoproteins
in the pIasma. Highest proportion oI choIesteroI is Iound in the LDL. Free choIesteroI in the pIasma is
FIg. 6.17 Catabolism of lecithin.
Lecithin
R—COOH Phospholipase A
Lysolecithin
R—COOH Lysophospholipase
Glyceryephosphoryl choline
Glycerylphosphoryl
choline esterase
a - Glycerophosphate + Choline
Metabolism
equiIibrated with the choIesteroI esters and about haII oI the Iree choIesteroI is eIiminated by
excretion in the Iaeces, whiIe remainder is excreted as neutraI steroid.
The Iiver contains a pooI oI unesteriIied choIesteroI Irom where it is transported to the intestine
and then back to Iiver through chyIomicrons. ChoIesteroI is excreted Irom the body as choIesteroI or
biIe acids. Coprostanol is the main steroI secreted in the Iaeces, a product oI choIesteroI, arising Irom
the intestinaI bacteria activity. Much oI the choIesteroI secreted in the biIe is either reabsorbed or gets
deposited in the arteries in the Iorm oI esters or may participate in steroid synthesis.
8.E3 KETDGENESlS
During conditions oI starvation and diabetes, oxidation oI Iree Iatty acids is enhanced in the
mitochondria. In vertebrates, the acetyI-CoA originating Irom the >-oxidation can Ieave the
mitochondrion in the Iorm oI citrate. However, a major part oI this acetyI-CoA is used Ior the
synthesis oI ketone bodies in the Iiver (ketosis). There are three types oI ketone bodies: acetone,
acetoacetic acid, and 3-hydroxybutyric acid, which are generated through a process caIIed
ketogenesis, taking pIace in the mitochondria.
Formation of Ketone Bodies
Long-chain Iatty acid are transported to the inner mitochondriaI membrane through carnitine
derivatives. >-oxidation oI Iatty acids takes pIace in the mitochondrion, reIeasing acetyI-CoA, with
2 CH –CO S CoA
(Acetyl CoA)
3
– –
CoA
CH –CO S CoA
(Acetoacetyl CoA)
3
–CH –CO– –
2
CoA
CH –C S CoA
3
–CH –Co– –
2
CH Co–S–CoA
3
OH
CH COOH
2
(3-Hydroxy-3-methylgutaryl CoA)
CoA HMG CoA reductase
2NADPH + H
+
2NADP
+
CH –C OH
3
–CH –CH
2 2
OH
CH COOH
2
(Mevalonic Acid)
To synthesis of cholesterol
FIg. 6.1S Steps in the synthesis of mevalonic acid, the precursor of cholesterol synthesis (steps not shown).
Animal Physiology
the consequent production oI Iarge amount oI ATP. The initiaI steps are simiIar to those oI choIesteroI
synthesis (Fig. 6.19). The 3-hydroxy-3-methyIgIutaryI-CoA Iormed is spIit into acetyI-CoA and Iree
acetoacetic acid.
The acetoacetic acid is either spontaneousIy decarboxyIated to acetone or reduced to 3-
hydroxybutyric acid:
CH CO–CH –COOH CO + CH –CO–CH
3 3 2 2 3
(Acetoacetic acid) (Acetone)
CH –CO–CH –COOH + NADH + H CH –CHOH–CH –COOH + NAD
2
+ +
2 3 3
(3-Hydroxybutyric acid)
Long-chain Iatty acids (even number) produce acetyI-CoA units through beta oxidation, but odd
chain Iatty acids produce acetyI-CoA and propionyI-CoA, which is gIucogenic. Peroxisomes oxidize
Iong-chain Iatty acids.
Ketone Bodies Serve as Energy Source
Acetoacetic acid and 3-hydroxybutyric acid are produced in Iarge amount and are utiIized as energy
source by various tissues such as muscIes, kidney and the brain (extrahepatic tissues). Acetoacetic
acid diIIuses IreeIy across the ceII membranes and cannot be reactivated unIess they reach the cytosoI
where they can participate in choIesteroI synthesis as happens with acetoacetate.
Acetoacetate is reactivated in extrahepatic tissues:
Acetoacetate ¹ SuccinyI-CoA Succinic acid ¹ AcetoacetyI-CoA. AcetoacetyI-CoA spIits by
thioIysis into two moIecuIes oI acetyI-CoA which enters the Krebs cycIe. Ketogenesis is an extremeIy
important physioIogicaI process and is excIusiveIy hepatic.
Ketogenesis is reguIated chieIIy by two hormones: insuIin and gIucagon. When bIood gIucose
IeveIs are decreased, insuIin is depressed, thereby raising gIucagon IeveIs, resuIting in arresting
gIycoIysis, increase in gIuconeogenesis and inhibiting Iatty acid synthesis. As a consequence,
hydroIysis oI trigIycerides is aIIected by hormone-dependent Iipase in adipose tissues. The Iatty acids
thus Iiberated are transported to the Iiver.
The hormonaI imbaIance inhibits acetyI-CoA carboxyIase, depressing maIonyI-CoA
concentration, which is a repressor oI acetyIcarnitine synthetase, hence it gets activated. This Iavours
penetration oI Iatty acids into the mitochondria where they are cataboIized by beta oxidation,
increasing the NADH/NAD ratio. This wiII Iead to reduction oI oxaIoacetate to maIate which Ieaves
mitochondria to participate in gIuconeogenesis. The reduction oI oxaIoacetate prevents transIormation
into citrate oI acetyI-CoA arising Irom >-oxidation. Thus the onIy Iate oI acetyI-CoA is to synthesize
ketone bodies to be transported to other tissues capabIe oI utiIizing them.
Oxidation oI ketone bodies takes pIace in the extrahepatic tissues because oI the absence oI key
enzymes in the Iiver to oxidize them, i.e. 3-oxoacid-CoA transIerase. This enzyme is present in the
kidney, red muscIe, brain and other peripheraI tissues. NormaIIy ketone bodies are continuousIy
oxidized in muscIes, thereIore onIy traces oI these may be Iound in the bIood and urine. In Iasting
mammaIs these accumuIate in bIood and the IeveIs may rise to 20-25 mg/100 mI aIter a week`s
Iasting. 3-hydroxybutyrate apearing in the bIood reaches the muscIes (skeIetaI as weII as the cardiac),
where a mitochondriaI enzyme, 3-hydroxybutyrate dehydrogenase oxidizes the compound to
Metabolism !
FIg. 6.19 Formation of ketone bodies from acetyl CoA.
acetoacetic acid. The Iatter compound in the muscIe mitochondria is activated by 3-oxoacid-CoA
transIerase, cataIyzing the transIer oI CoA Irom succinyI-CoA to acetoacetic acid. Excessive
production oI ketone bodies by the Iiver Ieads to ketonemia.
2 CH –CO–S–CoA
(2 Acetyl CoA)
3
CoA
CH –CO–CH –CO–S–CoA
(Acetoacetyl CoA)
3 2
CoA
H O + Acetyl CoA
2
CH –C
3
–OH
CH –COOH
2
CH CO–S–CoA
2

(3-Hydroxy-3-methylglutaryl CoA)
CH –CO–CH –COOH
(Acetoacetate)
3 2
CO
2
NANDH + H
+
NAD
+
CH –CO–CH
(Acetone)
3 3
CH –C
3
–CH –COOH
2
OH
H
(3-Hydroxybutyrate)
Acetyl CoA
In the previous chapter, we have given an account oI the cIassiIication and nature oI nutrients required
by animaIs. The Iood materiaIs avaiIabIe to the animaIs are, as such, rareIy in a Iorm suitabIe Ior
ceIIuIar consumption and to achieved when the Ioods are subjected to mechanicaI processes such as
mastication, swaIIowing and movements oI gastrointestinaI tract, and chemicaI processes such as the
enzymatic reactions in the digestive tract.
During the process oI digestion, the compIex nutrients are spIit into their simpIer substances, i.e.
the proteins into amino acids; the poIysaccharides into monosaccharides; and the Iats into their
constituent Iatty acids and gIyceroIs. In addition to hydroIysis oI proteins, carbohydrates and Iats, the
process oI digestion renders Iood in a soIubIe Iorm Ior abosrption and heIps in separating the required
Irom those not required.
7.3 MDDES DF NUTRlTlDN
Based on their method oI Iood procurement the Iiving organisms (pIants, animaIs and
microorganisms) are broadIy cIassiIied into two major groups, viz. autotrophs and heterotrophs.
Autotrophs
The autotrophs synthesize aII essentiaI organic compounds Irom inorganic constituents. They incIude
phototrophs and chemotrophs. The phototrophs are chIorophyII bearing pIants and make the essentiaI
organic compounds by photosynthesis. For this process they require sunIight, and inorganic
substances Iike carbon dioxide and nitrogenous compounds. The chemotrophs are bacteria making
their Iood by chemo-synthesis. Since the autotrophs synthesize the required organic substances within
their body, digestion is not required.
,ECAIJE =@
)>IHFJE
+ 0 ) 2 6 - 4
%
Digestion and Absorption #
Heterotrophs
The heterotrophs require organic substances as Iood and their synthesizing capabiIity is Iimited. For
this reason they depend on organic substances Iike carbohydrates, Iats and proteins to carry out their
IiIe processes. They obtain their Iood Irom pIants and animaIs. Such a Iood is in a Iorm unsuitabIe Ior
direct absorption. The Iood may be in the Iorm oI tiny particIes (Iood oI protozoans and other Iower
organisms), Iarge chunks or whoIe animaIs (as in higher animaIs), or in the Iiquid Iorm (Ieeches,
certain insects, etc.). ThereIore these Iood particIes are to be reduced to sizes suitabIe Ior entrance
through the ceIIuIar membranes to take part in metaboIic activities. This process as we have
mentioned earIier is caIIed digestion and onIy in heterotrophs it is a necessary process with the
exception oI certain parasites (cestodes, etc.) and commensaIs. The cestodes directIy absorb the
digested Iood through its body surIace, Irom its surrounding medium in the intestine. The maIe
echiurid derives its nourishment Irom the IemaIe echiurid. Such organisms are devoid oI a digestive
tract oI their own.
The organisms are thus broadIy divided into two groups. However, there are Iiving beings
between the typicaI chemotrophs and the typicaI phototrophs, and aIso between the autotrophs and the
heterotrophs. Such Iiving beings are dependent on both the processes and hence are grouped under
mesotrophs. The Euglena, Ior exampIe, is a mesotroph and can synthesize essentiaI organic
compounds but it stiII requires certain growth Iactors or vitamins Ior which it is dependent on organic
sources.
7.E lNTAKE DF FDDD MATERlALS
In order to capture diIIerent kinds oI Iood and prepare it Ior absorption by the ceIIs oI the body, the
heterotrophs have suitabIe anatomicaI structures and devices.
Among animaIs the Ieeding mechanisms exhibit some reIation to the type oI Iood they take. It is
reasonabIe to presume that Iood oI the most primitive organisms is organic matter in soIution.
SimiIarIy organic matter in dissoIved Iorm is directIy absorbed by protozoan parasites, tapeworms and
a Iew other animaIs. Studies on the absorption oI dissoIved organic substances in bacteria as weII as
in the ceIIs oI higher animaIs reveaIed the existence oI a number oI active sites, each oI which
receives the speciIic compounds to Iead them into the ceII. DissoIved substances are absorbed by yet
another process. In this process minute dropIets oI dissoIved Iood are enguIIed by the ceII through
pinocytosis.
Protozoans prey upon parts oI other organisms smaIIer than or equaI to themseIves. To ingest this
type oI Iood the protozoans have a variety oI mechanisms. Amoeba, Ior exampIe, has a mechanism
which may possibIy be an extension oI pinocytosis and upon coming in contact with its Iood particIe
the amoeba surrounds the particIe and enguIIs it. Another distinct mechanism oI Ieeding can be
observed among ciIiates. The ciIiates produce water currents by ciIiary movements and these currents
carry the impaIed organisms or the particuIate Iood to the mouth or guIIet. From here the Iood is taken
into the body. In sponges the method oI coIIecting Iood particIes by water currents and their
subsequent enguIIing by ceIIs Ior digestion exists in a speciaIized Iorm. In this method the Iood
particIes are carried aIong the water currents into the paragastric cavity through body pores.
Animal Physiology $
There are severaI coeIenterates which, Iike sponges, are sessiIe animaIs. However, they procure
Iood by trapping method rather than the current method noted in sponges. The important structure
invoIved in the trappin mechanism is the cnidobIast (nematocyst). The tentacIes in Hydra and some
other coeIenterates are armed with cnidobIasts and these wouId burst when smaII animaIs brush or
bump over the cnidociI which is a smaII hair-Iike process serving as receptor oI contact stimuIi. As a
resuIt oI this burst a poisonous thread Irom the nematocysts is thrust into the victim to impaIe it. The
impaIed organism is then carried to the mouth by one or more oI the tentacIes.
FiIter Ieeding is characteristic oI sessiIe animaIs and sedentary Ieeders such as bivaIve moIIuscs,
Amphioxus, Ammocoete Iarva, etc. These animaIs have varied types oI IiItering and trapping devices.
CiIia and setae produce water currents which carry the Iood particIes to the the Ieeding surIaces.
These particIes get entangIed in the mucus cord which is carried into the digestive, tract by the aid oI
ciIiary movement. Certain sea-cucumbers have sticky tentacIes which trap smaII organisms. These
tentacIes are then thrust into the pharynx in order to wipe oII Iood Irom them.
AIthough IiIter Ieeding is a characteristic Ieature oI sessiIe and sedentary group oI animaIs, it is
aIso present in a Iew other animaI groups. SmaII active copepods, sock-eye saImon, the huge basking
shark and the whaIebone whaIe are aII IiIter Ieeders. The IiIter Ieeders do not seIect their Iood, hence
they are known as nonseIective Ieeders. However, they respond to certain chemicaIs and stimuIi by
operating, or by preventing the IiIter mechanism, depending on IavourabIe or hazaradous conditions.
In other nonseIective Ieeders such as many anneIids, some echinoderms and hemichordates, Iood
enters the body by water currents. From this whatever is needed by the body is absorbed and the rest
discarded. The animaIs oI this group are omnivorous provided those which come in their way shouId
be suIIicientIy smaII to be coIIected in their IiIters or traps. Thus coIIected Iood is subjected in their
IiIters or traps. The coIIected Iood is subjected to grinding when such organs are present. II absent,
the Iood materiaI is passed directIy Ior chemicaI digestion.
SeIective Ieeders empIoy various methods Ior the capture and eIIective utiIization oI buIky Ioods
or Ior withdrawing the juices Irom animaIs and pIants. Each mechanism is supported by suitabIe
anatomicaI modiIications and physioIogicaI aIterations. WhiIe the Iishes, amphibians, reptiIes and
many birds swaIIow their Iood without chewing, the mammaIs masticate Iood and suppIy it to the
digestive system in the Iorm oI smaII size particIes. For eIIicient mastication, changes have been
brought about in the jaw bones and muscIes. The air passages are separated and guarded by soIt
epigIottis and pharyngeaI IoIds in order to IaciIitate breathing during mastication. These changes are
directIy reIated to the changes in the Ieeding habits.
The dependence oI seIective Ieeders on speciIic types oI Iood is so great that in its absence they
suIIer Irom IunctionaI irreguIarities. The IemaIe mosquito, Ior instance, needs a meaI oI bIood Ior the
deveIopment oI eggs. The rabbit IIea, Spilopsyllus cuniculi, requires the bIood oI breeding, or
pregnant rabbit, containing reproductive hormones, to carry out its own reproductive cycIe.
SeIective Ieeders have neurosensory and neuromuscuIar speciaIizations to enabIe them to Iocate
and capture speciIic Ioods. The neurosensory abiIities may be in the deveIopment oI visuaI, chemicaI
and other stimuIi.
Digestion and Absorption %
A. DlGESTlDN
The digestion is cIassiIied into two main types i.e. the intraceIIuIar, and the extraceIIuIar digestion.
Between these two, there exists a transitionaI type oI digestion known as contact digestion.
lntraceIIuIar Digestion
The digestion is intraceIIuIar in protozoans and sponges. The particuIate Iood matter enters the ceII by
pinocytosis or phagocytosis and both these processes require energy. In these processes a portion oI
the ceII`s pIasma membrane encapsuIates the particIe and the capsuIe is then pinched oII in the Iorm
oI a vesicIe Irom the membrane to Iorm pinosome or phagosome which is then carried into the ceII Ior
digestion. The Iysosomes Iuse with these vesicIes and the digestive enzymes react with Iood to
hydroIyze them to simpIe substances. AIter digestion is compIete the remnants are excreted Irom the
ceII as excretory products.
CONTACT DIGESTION: The digestion in some coeIenterates (such as sea-anemones) shows a
transition between primitive intraceIIuIar type and the highIy speciaIized extraceIIuIar type. When a
sea-anemone swaIIows a Iarge organism or a Iarge Iood particIe, the digestion is carried out in the
gastrovascuIar cavity itseII. The gastrovascuIar cavity contains sea water which makes the enzymes
ineIIective iI secreted into it. To overcome this a speciaIized process oI contact digestion has
deveIoped in sea-anemones. In this process, the IiIaments oI endothermaI ceIIs Iining the coeIenteron
are appIied cIoseIy to the surIace oI the Iarge Iood particIe and secrete digestive enzymes Irom the
attached points directIy on to its surIace. The Iood particIe gratuaIIy disintegrates, and the same ceIIs
absorb the resuIting products as soon as they are Iormed. IntraceIIuIar digestion, however, stiII persists
in coeIenterates when smaII Iood particIes are digested.
ExtraceIIuIar Digestion
AnimaIs with compIete digestive tracts carry on their digestion extraceIIuIarIy aIso. The enzymes in
these animaIs are secreted into the Iumen oI the digestive tract. The muscuIar movements oI this tract
bring about mixing oI the Iood materiaI with the enzymes and direct the entire mass posteriad. As a
resuIt oI these processes, the enzymes spIit the IoodstuIIs within the Iumen to a Iorm suitabIe Ior
absorption.
7.3 DlGESTlDN DF FDDDSTUFFS
The IoodstuIIs are digested into a Iorm suitabIe Ior absorption by the action oI speciIic enzymes.
These enzymes are produced by the organism which consumes the Iood. There are certain IoodstuIIs
the digestion oI which is perIormed by the bacteria present in the digestive tract oI animaIs. In the
IoIIowing paragraphs, some basic enzymatic activities invoIved in the digestion oI major IoodstuIIs
have been described.
Major enzymes, their sources and speciIic actions on diIIerent Ioods are presented in TabIe 7.1.
Animal Physiology &
TabIe 7.1 Principal Enzymes of the Digestive Tract and Their Activity on Specific Foodstuffs
(in mammals)
Søur¿ø ø/ ønz)mø Enz)mø anø øpI¡mum SuDsIraIø Prøøu¿Is ø/ ø¡gøsI¡øn
¿ønø¡I¡øn ø/ a¿I¡v¡I)
Salivary gland Salivary amylase Starches Maltose
pH 6.6-6.8
Ptyalin Maltotriose, dextrin
Stomach: Chief Pepsin Protein Proteoses
cells and parietal pH l.0-2.0 Peptones
cells
Rennin Casein of Coagulates milk
pH +.0 milk proteins
Pancreas Trypsin pH 7.9 Protein, Proteoses Polypeptides, Dipeptldes
Chymotrypsin pH 8.0 Proteoses, Proteins Peptides
Carboxypeptidase Polypeptides having Peptides, amino acids
free carboxyl groups
Amylase pH 7.l Starch Maltose
Lipase pH 8.0 Lipids (primary ester Fatty acids, monogly-
linkages) cerides, diglycerides,
glycerol
Cholesterol esterase Free cholesterol Esters of cholesterol
with fatty acids
Ribonuclease RNA Ribonucleotides
Deoxyribonuclease DNA Deoxynucleotides
Small Intestine: Maltase pH 5.8-6.2 Maltose Clucose
Brunner´s glands &
the glands of
Lieberkuhn Lactase pH 5.+-6.0 Lactose Clucose, galactose
Sucrase pH 5.0-7.0 Sucrose Clucose, fructose
Aminopeptidase pH 8.0 Polypeptides with Peptides, free amino
free amino groups acids
Dipeptidase pH 8.0 Dipeptides Amino acids
Phosphatase pH 8.6 Organic phosphates Free phosphates
Polynucleotidase Nucleic acid Nucleotides
Nucleosidases Purine or Pyrimidine Purine or pyrimidine
nucleosides bases, pentoses
Lecithinase Lecithin Clycerol, fatty acids,
phosphoric acid, choline
Digestion of Carbohydrates
Starch grains are poIysaccharides having a centraI core oI amyIose covered over by a husk oI
amyIopectin. Both amyIose and amyIopectin contain chains oI gIucose units. However, amyIopectin
has branched chains, each branch containing about twenty Iour gIucose units joined to each other.
These chains are not broken by any oI the digestive enzymes. GIycogen is another poIysaccharide
consisting oI branched chains, each containing tweIve gIucose units.
Digestion and Absorption '
The digestive enzymes cannot act on starch unIess it is broken down. The starch grains are
broken down either by boiIing, by chewing, by bacteria or by enzymes. The saIiva oI most mammaIs
is Iree Irom enzymes and hence in these animaIs starches cannot be spIit by saIiva. However, pigs,
eIephants, and primates have an enzyme ptyalin (endoamylase) in their saIiva and this attacks the
simpIe Iinks oI amyIose and amyIopectin. As a resuIt oI this attack a series oI maItose, maItoriose, and
dextrin moIecuIes are Iormed. PtyaIin aIso hydroIyzes gIycogen to Iorm maItoses. The optimum pH
6.2-6.8 required Ior the activity oI digestive amyIases is maintained by chIoride ions.
The digestion oI starch by ptyaIin goes on as Iong as it is in the mouth. When the starch reaches
stomach the gastric acidity stops Iurther action oI ptyaIin; however, in case oI soIid Ioods the starch
hydroIysis continues into the stomach so Iong as the acid diIIusion is not compIete. Acid diIIusion
wouId be compIete in about 40 minutes and by this time the starch wouId be spIit to dextrins and
maItoses.
InuIin is a storage compound oI certain pIants (compositae) and is oIten consumed by mammaIs.
It is not hydroIyzed by ptyaIin. The stomach does not produce any enzymes to digest either inuIin or
other carbohydrates such as cane sugar. However, these are hydroIyzed by the acid in the gastric juice.
The pancreatic juice secreted into the smaII intestine has amylopsin, which is simiIar in action to
ptyaIin oI the saIiva. AmyIopsin attacks to spIit raw starch grains to dextrins, maItotrioses and
maItoses. The ptyaIin aIso hydroIyzes dextrins and maItotrioses, aIready produced by the saIivary
digestion, to yieId maItose. Further, severaI enzymes which hydroIyze various disaccharides to the
appropriate hexoses are Iound in the Iumen oI smaII intestine. These enzymes are caIIed glucosidases
or disaccharases. OI these enzymes, maltase and lactase are brought into the intestinaI Iumen by both
the pancreatic juice and the intestinaI juice. The Iactase which spIits miIk sugar (Iactose) to gIucose
and gaIactose is prominent in young mammaIs. The maItase spIits maItose to Iorm two gIucose
moIecuIes. In addition to maItase and Iactase, another sugar-spIitting enzyme present in the intestinaI
juice in sucrase. Sucrase hydroIyzes sucrose (a storage or transport sugar oI severaI nutritious pIants)
to one moIecuIe oI gIucose and one oI Iructose.
CeIIuIose Digestion in Ruminants
The ruminants ingest Iarge quantities oI Iodder rich in ceIIuIose or Iignin. Neither substances can be
digested directIy by mammaIs. But the ceIIuIose is attacked in the rumen by the enzymes produced by
symbiotic bacteria. Sheep and cattIe initiaIIy swaIIow Iood without masticating. In the rumen Iood is
mixed with water. The rumen has miIIions oI bacteria oI severaI species, some oI which attack the
ceIIuIose waIIs oI the Iodder Iiberating the ceII contents oI the Iood. The bacteria aIso breakdown
carbohydrates and proteins to simpIe substances. In the rumen main products oI Iermentation are
acetic, propionic, butyric, and other acids, aIong with smaII quantities oI other substances such as
ethanoI. Besides, symbiotic organisms in the rumen synthesize much more riboIIavin and pantothenic
acid than is normaIIy procured through diet. In addition to bacteria, a number oI protozoan ciIiates
beIonging to spirotrichida and hoIotrichida have been observed in the rumen. Some oI these can break
down ceIIuIose. The stored carbohydrates and proteins within these ciIiates are beIieved to serve as
reserves Ior a short time when Iodder is not avaiIabIe.
Animal Physiology !
CeIIuIose breakdown by bacteria aIso takes pIace in the stomach oI kangaroo (Stronix
brachyurus), and sIoth (Choloepus). In kangaroo the stomach is enIarged, and in the sIoths it is a
compound stomach. CeIIuIose spIitting bacteria are present mostIy in the caecum and ventraI coIon oI
horses, and in the caecum oI rabbits. The rabbits, Iike other Iagomorphs, and many rodents, have
deveIoped a habit oI reingestion or pseudorumination. When rabbit eats Iresh Iood, it directIy reaches
the caecum, remains there Ior one or two days undergoing Iermentation, and is then expeIIed as soIt
Iaeces. These are then eaten and this time they reach the cardiac stomach, but the IreshIy eaten Iood
goes straight into the caecum as usuaI. AIter digestion and absorption the twice swaIIowed Iood is
excreted as hard IaecaI peIIets without Ietting it in through caecum.
Digestion of Proteins
As a resuIt oI enzymatic action the peptide Iinks oI proteins are hydroIyzed. ConsequentIy the simpIe
proteins yieId amino acids, and the conjugated proteins yieId amino acids as weII as nonamino groups.
The enzymes responsibIe Ior spIitting proteins are caIIed proteoIytic enzymes. OI the most IamiIiar
ones are pepsin, trypsin, chymotrypsin, aminopeptidase, carboxypeptidase, tripeptidase and
dipeptidase. Though these enzymes are present in severaI animaIs they are, Iike proteins, highIy
speciIic. The pepsins Irom various species oI vertebrates are Iound to act diIIerentIy on certain
substances, and have diIIerent reaction optima.
The proteoIytic enzymes oI the digestive tract in vertebrates IaII under two distinct groups; the
endopeptidases and the exopeptidases.
ENDOPEPTIDASES: The endopeptidases, aIso known as proteinases under an oId name, attack
poIypeptide chains at peptide bonds away Irom the ends and preIer very speciIic Iinks in the protein
chain. Pepsin is secreted in the gastric juice as an inactive precursor, pepsinogen. Pepsin hydroIyzes
peptide bonds in which the amino Iunction is contributed by phenyIaIanine, tyrosin, tryptophan,
Ieucine, aspartic acid or gIutamic acid. Pepsin is active in acid medium (optimum pH 1.5-2.5)
depending on the substrate. It is inactivated in neutraI or aIkaIine soIutions and is devoid oI a
prosthetic group. Pepsin, Iike rennin, has the property oI coaguIating miIk by converting caseinogen
to casein which Iorms and insoIubIe compIex with caIcium.
1rypsin is secreted by the pancreas in the Iorm oI an inactive precursor, trypsinogen. Trypsinogen
is activated by the enzyme enterokinase secreted by the intestinaI mucosa and then autocataIyticaIIy
by trypsin itseII. Trypsin cataIyzes the hydroIysis oI peptide bonds in a protein chain in which the
carbonyI Iunction is contributed by Iysine or an arginine residue. Trypsin has no prosthetic group and
its pH optimum Iies between 7-9. It is reIativeIy stabIe to heat in acid soIution and Iess so in aIkaIine
soIution.
Chymotrypsin is secreted Irom the pancreas in an inactive Iorm, chymotrypsinogen. Activation oI
chymotrypsinogen to its active Iorm is brought about by the trypsin. The optimum pH is 7-8.
Chymotrypsin attacks the peptide bonds in which the carbonyI group is Iurnished by the aromatic
amino acids, phenyIaIanine, tyrosine or tryptophan.
The endopeptidases described above hydroIyze Iarge protein moIecuIes to smaIIer peptides which
are Iurther broken down to smaIIer peptides by the action oI exopeptidases and dipeptidases.
Digestion and Absorption !
EXOPEPTIDASES: Exopeptidases, aIso known as peptidases under an oId name, cataIyze the
removaI oI terminaI amino acids and require a metaI ion as activator Ior their cataIytic activity. These
are either secreted by the pancreas or the intestinaI mucosa.
There are two carboxypeptidases which are secreted as precursor procarboxypeptidases and
activated by trypsin. Carboxypeptidase A (Zn
¹¹
containing) hydroIyzes terminaI amino acids with Iree
caboxyI groups with the exception oI Iysine or arginine. Carboxypeptidase B wiII hydroIyze peptide
with Iree carboxyI terminaI oI Iysine or arginine. Both do not attack dipeptides.
Aminopeptidase preIers the terminaI amino acid with Iree amino group. This is rather nonspeciIic
enzyme and does not act on dipeptides.
There are a number oI dipeptidases which are quite speciIic Ior speciIic dipeptides. Prolidase is
an exopeptidase which hydroIyzes proIine peptides derived Irom the breakdown oI coIIagen.
Endopeptidases as weII as exopeptidases are required both Ior intraceIIuIar and extraceIIuIar types
oI digestion. The pepsin, trypsin and chymotrypsin are Ior extraceIIuIar digestion. Their counterparts
in intraceIIuIar digestion are cathepsin A, B and C. Other than the endopeptidases the ceIIs aIso
possess exopeptidases corresponding to those oI extraceIIuIar enzymes. The intraceIIuIar enzymes do
not usuaIIy require an activator.
Digestion of Fats
Because there is no Iipase in the saIiva nor in the gastric juice, the digestive activity oI Iipase in the
stomach is inhibited, aIthough some pancreatic Iipase may be Iound in the gastric contents through
regurgitation. When the chyme passes through duodenum, the biIe and the pancreatic juices are
reIeased and these get mixed up with the chyme. The biIe saIts Iower the surIace tension oI the Iat
dropIets in the chyme and emuIsiIy them to IaciIitate their digestion. The Iat or trigIyceride particIes
in the emuIsion have a diameter oI 0.5 to 1.0 m. The emuIsiIication oI trigIyceride exposes it to the
action oI pancreatic lipase which hydroIyzes trigIycerides to Iorm a mixture oI Iree Iatty acids (FFA)
and monogIycerides and digIycerides (Fig. 7.1). The pancreatic Iipase reacts most readiIy with
trigIycerides having Iong Iatty acid chains, and Ior this the required optimum pH Iies between 7 and 9.
In artiodactyIs the hydroIysis oI Iats is done by the action oI bacteria present in the rumen, and the
gIyceroI is converted to propionic acid.
The Iatty acid esteriIied in position-2 is not Iit Ior the IipoIytic attack, hence the Iatty acid residue
is transIerred to 1-position. As a resuIt oI hydroIysis the principaI products, Iree Iatty acids and
monogIycerides aIong with biIe saIts and phosphoIipids are dispersed into Iine particIes known as
micelles. The miceIIes contain smaII amounts oI di-and trigIycerides. The Iats in the Iorm oI miceIIes
enter the mucosaI ceIIs and get surrounded by endopIasmic reticuIum. During their entry through the
mucosaI ceIIs, the products oI Iipase action are resynthesized into trigIycerides.
Resynthesis oI trigIycerides may take pIace either by reacyIation oI 2-monogIycerides or by the
acyIation oI 3-gIycerophosphates. Free gIyceroI is not used Ior resynthesis. The short-chain Iatty acids
are absorbed into the portaI bIood, whiIe the majority oI Iong-chain Iatty acids escape esteriIication
and become bound to pIasma proteins. A Iayer oI protein and phosphoIipids is Iormed around the
resynthesized trigIycerides beIore they pass through the mucosaI ceIIs. The protein coated dropIets oI
Iats are known as chylomicrons having a diameter oI about 0.5 m.
Animal Physiology !
Digestion of NucIeic Acids
The enzymes hydroIyzing nucIeic acids are present in the pancreatic tissue and can be divided into
endonucIeases and exonucIeases. EndonucIeases carry on the hydroIysis oI poIynucIeotide chain in
the middIe, and the exonucIeases remove the terminaI nucIeotides. DeoxyribonucIease I, an
endonucIease, hydroIyzes between aII pyrimidine-purine pairs in a DNA chain, whereas ribonucIease
hydroIyzes RNA chains into nucIeotides. Phosphodiesterase hydroIyzes nucIeotides successiveIy Irom
the 3`end oI both DNA and RNA oIigonucIeotides. NucIeosidases are quite speciIic in nature. There
is a type which attacks onIy the purine containing nucIeosides, whiIe another type breaks the
pyrimidine nucIeosides Iiberating uraciI, cytosine and thymine.
7.4 DlGESTlDN lN MAMMALS
There are certain variations in the mechanism oI digestion among vertebrates, but the digestive
process in man and the mammaIs, which is generaIIy studied in the Iaboratory, is typicaI oI aII such
processes. The digestive process in mammaIs IaIIs under three distinct divisions:
(i) digestion in the mouth;
(ii) digestion in the stomach; and
(iii) intestinaI digestion.
FIg. 7.1 Schematic diagram showing the digestion and absorption of fats in the intestinal lumen.
Digestion and Absorption !!
Digestion in the Mouth
The Iood materiaI captured has to be passed through the mouth which in the vertebrates is heIped by
a pair oI apposed movabIe jaws. These jaws are used in a variety oI ways to coIIect and hoId Iood or
in certain vertebrates to reduce the Iood to smaII particIes.
Three pairs oI saIivary gIands are present opening into the mouth by way oI ducts and their
secretory products are coIIectiveIy caIIed saIiva. These gIands, according to their position, are termed
as the parotids, the submaxiIIaries, and the subIinguaIs. Besides, the mouth aIso has a number oI so-
caIIed buccaI gIands pouring their secretions into the mouth. The chieI product oI these gIands is the
mucus. The Iood taken into the mouth is cut and ground by the teeth. By this process the Iood not
onIy is broken to pieces but aIso mixed with saIiva. The saIiva dissoIves the Iood to give a sense oI
taste to the taste buds. The enzyme ptyaIin initiates the digestion oI carbohydrates, and starch in
particuIar. The mixing oI saIiva with Iood eases the swaIIowing process.
Digestive ControI Mechanisms
Digestion is a coordinated process wherein proper amounts oI digestive juices must be secreted to
reach the Iood at desired times. This naturaIIy invoIves some kind oI controI mechanism to coordinate
various components oI the process. Numerous studies have reveaIed that both nervous and hormonaI
controIs are invoIved in the process. However, a secretogoguaI mechanism (presence oI Iood in the
aIimentary canaI aIso acts as a stimuIant) to stimuIate secretions has aIso been demonstrated to be
operative in the mouth and stomach. Nervous mechanisms dominate in the anterior part oI the
digestive tract and as nervous controIs decIine, hormonaI controIs take over to assume greater
importance.
SALIVARY CONTROL: The secretion oI saIiva is generaIIy coordinated with the intake oI Iood, but
oIIactory and gustatory stimuIi normaIIy initiate the nervous reIIex resuIting in the stimuIation oI
saIivary secretion. Conditioned reIIexes resuIting in the IIow oI saIiva are due to oIIactory stimuIation.
SaIivary gIands receive both sympathetic and parasympathetic nerve Iibres, hence either oI the
systems or both may exert controI over normaI secretion oI saIiva.
GASTRIC CONTROL: In many cases the presence oI Iood in the stomach has a stimuIatory eIIect on
the gastric secretion (secretogoguaI). Besides this, a nervous stimuIation is aIso necessary which is
IoIIowed by a hormonaI phase. A nervous stimuIus is necessary to produce the hormone gastrin Irom
the pyIoric end oI the stomach which is Iiberated in the bIoodstream and reaches back to the stomach
via circuIation. Gastric stimuIates the secretion oI hydrochIoric acid and probabIy heIps in the
secretion oI biIe and pancreatic juice.
CONTROL OF PANCREATIC SECRETION: The digestive enzymes oI the intestine mainIy originate
Irom the pancreas which are entireIy secreted under hormonaI stimuIus. The presence oI chyme in the
duodenum aIso initiates secretion oI pancreatic juice mediated through the hormones. The presence oI
hydrochIoric acid and partiaIIy digested IoodstuIIs stimuIate the duodenaI mucosaI ceIIs to secrete
hormones which are carried to the pancreas, Iiver and gaII bIadder through generaI bIood circuIation.
Animal Physiology !"
BayIiss and StarIing in the year 1902 suggested that the hormone responsibIe to stimuIate the
pancreatic tissue originates Irom the duodenum and they named it secretin. Recent work, however,
has shown that secretin contains Iive Iactors: (1) secretin which stimuIates a bicarbonate rich
pancreatic secretion and poor in enzymes; (2) pancreozymin which stimuIates pancreatic acinar ceIIs
to produce viscous IIuid Iow in bicarbonates and rich in enzymes; (3) hepatocrinin which stimuIates
Iiver to secrete a saIt-poor biIe; (4) cholecystokinin that causes evacuation oI gaII bIadder; and (5)
enterocrinin which stimuIates the IIow oI intestinaI juices (succus entericus).
CONTROL OF SECRETION: Excitation oI saIivary gIands is dependent upon the nerve impuIses. The
gIands receive the impuIses Irom the autonomic nervous system. There are three types oI stimuIi
which arouse reIIex secretion oI saIiva. These are: (1) tasting and smeIIing oI Iood (excitation oI
chemoreceptors); (2) chewing, or the presence oI soIid substances in the mouth (excitation oI pressure
receptors); and (3) seeing or even thinking oI good Iood (psychic reIIex).
Digestion in the Stomach
The Iood entering the stomach pushes the aIready existing Iood towards the sides and itseII remains
away Irom the gastric waIIs. This prevents the gastric secretions Irom mixing with immediateIy. The
newIy entered Iood, thereIore, continues to react with ptyaIin Ior some time tiII the gastric juices
penetrate into the Iood and stop the ptyaIin action. The stomach produces hydrochIoric acid, and
certain enzymes, viz. pepsin, rennin, and gastric Iipase The stomach acts as a reservoir Ior mixing the
Iood with its enzymes and Irom here the Iood is sIowIy passed into the intestine.
CHEMISTRY OF GASTRIC DIGESTION: The enzyme pepsin as such is not secreted directIy. The ceIIs
oI the gastric gIands produce a proenzyme, pepsinogen, which requires an acid pH Ior its desired
action. This is accompIished by the hydrochIoric acid secreted into the stomach by the, parietaI ceIIs
oI the Iundic gIands (Fig. 7.2). HydrochIoric acid removes the inhibitory poIypeptide Irom
pepsinogen converting it into active pepsin. SmaII amounts oI pepsin aIso covert pepsinogen into
pepsin and this process is auto-cataIytic. Pepsin is a proteinase and hydroIyzes proteins (proteocIastic)
to acid metaproteins, proteoses, and peptones. II pepsin is aIIowed to continue its action Ior Iong time,
the proteins wouId get hydroIyzed into traces oI amino acids. The pepsin attacks the peptide bonds
which are Iormed Irom the =-carboxyI oI an L-dicarboxyIic acid and the =-amino group oI an L-
aromatic amino acid, and a Iew others. ConsequentIy, the chieI amino acids, viz. L-tyrosine and L-
aIanine are Iiberated. Pepsin attacks the ceII waIIs and breaks them Iiberating the contents.
In man, caII, and pig, pepsin is produced Irom two regions in the stomach. One produced near the
Iundus has pH optima between 2.0 and 3.6; another produced near the pyIorus has pH optima
between 1.5 and 3.2. Peptic digestion wouId cease at pH 5, because at this pH the inhibitory
poIypeptides recombine with pepsin and inactivate it.
Rennin is an important enzyme in the digestive system oI some young mammaIs. The enzyme is
secreted by ceIIs in the Iundus as zymogen prorennin. Prorennin as such is inactive and requires acid
Ior its activation. The hydrochIoric acid transIorms prorennin into an active rennin. Rennin acts
rapidIy upon caseinogen, the chieI protein oI miIk. In miIk caseinogen is present in a soIubIe Iorm.
The nature oI action oI rennin on caseinogen is not deIiniteIy known, but it is beIieved that it miIdIy
Digestion and Absorption !#
hydroIyzes caseinogen. As a resuIt oI the action oI rennin on caseinogen, casein is produced. The
caIcium ions present in miIk combine with casein which is precipitated in the Iorm oI caIcium
caseinate. Rennin thus prepares miIk suitabIe Ior gastric digestion. The curdIed miIk is retained in the
stomach where caIcium caseinate wouId be attacked by pepsin. The optimum pH Ior its action is 4.
The Iat spIitting enzyme Iipase present in the stomach is inactive at the normaI acidity oI gastric
contents. But, highIy homogenizd Iats such as those oI miIk, and egg-yoIk wouId, however, undergo
partiaI hydroIysis. There is disagreement over the secretion oI this enzyme in the stomach. Some
account its presence due to regurgitation oI intestinaI contents into the stomach. But, the miIk IipoIytic
activity observed in extracts oI gastric mucosa suggests that the gastric gIands do secret traces oI
Iipase.
GASTRIC MOVEMENTS: The stomach is chieIIy composed oI smooth muscIes. The movements oI
the stomach are controIIed by the autonomic nervous system which are increased by parasympathetic
FIg. 7.2 Secretory activity of the stomach and the intestine and its associated structures.
Animal Physiology !$
stimuIation, and inhibited by sympathetic activity: The gastric movements are oI three main types:
they are hunger contractions, IiIIing, and emptying. OI these IiIIing and emptying are important in
view oI digestion.
(a) Filling: The muscIe oI the stomach waII progressiveIy reIaxes as more and more Iood enters it
and as a resuIt the stomach gets expanded. When Iood is present, the stomach muscIes bring
about vigorous movements IaciIitating thorough mixing oI Iood with digestive juices.
(b) Emptying: The peristaItic waves in the stomach propeI the Iood towards the pyIoric sphincter.
However, the emptying oI materiaI across the pyIorus depends upon the reIative pressure in the
stomach and duodenum, the opening oI the pyIoric sphincter, and the IIuidity oI the gastric
contents.
PASSAGE OF CHYME THROUGH PYLORUS: The stomach contents are passed through the pyIorus
into duodenum. By opening at brieI periods, the pyIoric sphincter aIIows materiaIs Irom the stomach
to pass into the intestine at a sIow pace and this process prevents overcrowding oI the intestine. This
materiaI has a thick soup-Iike consistency and is caIIed the chyme. It is acidic in nature. PyIoric
sphincter needs chemicaI stimuIus Ior the requisite reIaxation and contraction. Acidity oI chyme may
Iead to the opening oI the pyIoric sphincter. When the acid chyme comes in contact with mucosa oI
the pyIorus, the sphincter gets contracted. As a resuIt, peristaItic waves are set in that carry Iorward
the acidiIied gastric contents towards the sphincter which then aIIows chyme to pass bit by bit into the
duodenum. Duodenum aIso pIays a roIe in the evacuation oI stomach contents through pyIorus. It
Iunctions in two ways, i.e. by physicaI and by chemicaI means.
In the Iirst case, the motiIity oI stomach is at its optimum when the duodenum is empty, and as a
resuIt the chyme is pushed Irom stomach to duodenum. Entry oI chyme increases pressure in the
duodenum arid this prevents gastric contractions. Once again, motiIity oI stomach wouId be resumed
as and when the duodenaI contents are emptied.
In the second case it is by chemicaI means. Enterogastrone, Iiberated into the bIood by the
duodenaI ceIIs under the inIIuence oI Iipids or high concentration oI sugars, prevents gastric motiIity.
The gastric motiIity wouId be resumed once the duodenum is empty and secretion oI enterogastrone is
prevented.
Digestion in the lntestine
As the chyme enters the duodenum, its HCI content excites the mucosaI ceIIs oI that region to activeIy
secrete a hormone, secretin. This hormone is a poIypeptide and being reIativeIy simpIe in structure it
easiIy diIIuses into the bIood. It is then carried through the bIood to the pancreas where it excites the
active secretion oI pancreatic juice.
The pancreatic juice contains a series oI enzymes which progressiveIy hydroIyze proteins to
poIypeptides, dipeptides, and amino acids. These enzymes are coIIectiveIy known as pancreatic
proteases. Two such enzymes are trypsin and chymotrypsin. The Iormer acts more rapidIy than the
Iatter and both are present as zymogens (inactive Iorms) in the pancreas, i.e. in the Iorm oI
trypsinogen and chymotrypsinogen. The chymotrypsinogen is activated by trypsin. The trypsinogen is
prevented Irom being active by an inhibitor protein. When trypsinogen is extracted Irom the pancreas,
the inhibitor aIso accompanies it. In such a case the inhibitor wouId be sIowIy destroyed iI IeIt Ior
Digestion and Absorption !%
some time. It can aIso be destroyed rapidIy in acid soIution (pH1). Trypsinogen, Iree Irom inhibitor,
can be activated rapidIy by traces oI trypsin. It thus undergoes an autocataIytic reaction. But during
the intestinaI digestion trypsinogen is normaIIy activated to trypsin by enterokinase.
When proteins reach the intestine they are aIready in a partIy hydroIyzed state due to the action oI
pepsin oI the stomach. On such proteins the pancreatic proteases act bringing out compIete
proteoIysis. Trypsin activity is optimum in aIkaIine medium between pH 8 and 9. The pH is brought
about in the intestinaI contents by the aIkaIine saIts oI the pancreatic juice and the biIe. These saIts
neutraIize the acidity oI the chyme and bring the required aIkaIinity. Trypsin attacks on partIy
hydroIyzed proteins and causes them to pass through severaI intermediate products, viz. aIkaIi
metaproteins, proteoses and peptones. Thus trypsin acts upon proteins arriving in the intestine and
spIits them into poIypeptides. Another enzyme known as erepsin, Iound in the intestinaI mucosa,
spIits proteoses, peptones and peptides. It is now known that this spIitting is not by a singIe enzyme
erepsin, but is done by a group oI enzymes caIIed peptidases. One oI these enzymes, viz.
carboxypeptidase is Irom the pancreatic juice. This enzyme disrupts the peptides by attacking at the
end oI the amino acid chain where the Iree COOH group is pIaced.
The action oI pancreatic enzymes on Iood is dependent upon the emuIsiIying action oI biIe. This
action oI biIe is due to biIe saIts. When biIe is not secreted into the intestinaI Iumen, as it happens in
case oI jaundice patients, the Iat Irom the Iood Iorms a coating over proteins and carbohydrates oI the
chyme and prevents them Irom being digested by pancreatic enzymes. This is because the water
soIubIe pancreatic enzyme cannot penetrate the Iatty, coating over the nutrient materiaIs in the chyme.
The presence oI biIe aIso hIeps in the absorption oI products oI digestion. The Iatty acids and the
insoIubIe caIcium soaps are dissoIved in biIe and in this state they are easiIy absorbed by the mucosaI
ceIIs oI the smaII intestine. The aIkaIinity oI biIe heIps to neutraIize the acidity oI chyme.
Composition of bile: The biIe, soon aIter secretion, contains as much as 97 per cent oI water and
is usuaIIy transparent. The biIe is then conveyed to the gaII bIadder Ior storage. The waIIs oI gaII
bIadder absorb water Irom the biIe. The secretory ceIIs oI gaII bIadder add some oI the constituents
into the biIe. The biIe is reIeased by the gaII bIadder onIy upon receiving the proper stimuIus. When
reIeased, biIe consists onIy about 80 per cent oI water and abundant suspended matter. It contains
chieIIy proteins, biIe saIts, choIesteroI, biIe pigment, inorganic saIts, Iecithin and other Iipoid
substances.
BiIe SaIts
About 1 g oI choIesteroI is eIiminated Irom the body per day through the Iaeces either in the Iorm oI
choIesteroI or biIe acids (biIe saIts). BiIe acids are synthesized in the Iiver Irom choIesteroI, and the
principaI constituents incIude choIic acid and chenodeoxychoIic acid. Other physioIogicaIIy important
biIe saIts are the sodium saIts oI gIychoIic and taurochoIic acids. These saIts are soIubIe in water and
aIcohoI and they are perIectIy aIkaIine. The biIe saIts have remarkabIe power oI Iowering the surIace
tension and emuIsiIy Iats. EmuIsiIication is aIso partIy due to the power oI biIe saIt soIutions to
dissoIve Iatty acids and the water-insoIubIe soaps. The soIvents power oI biIe is Iurther augmented in
the presence oI choIesteroI. Both choIesteroI and Iecithins are Iipoid compounds, oI which choIesteroI
is present in greater amounts in biIe than in any other body IIuid.
Animal Physiology !&
In the intestine, the biIe acids Iurther undergo modiIication to Iorm secondary biIe acids such as
deoxychoIic and IithochoIic acids by the activity oI intestinaI bacteria. ChoIesteroI is procured by the
animaIs through the pIant or animaI Iood, or synthesized in the Iiver Irom its precursor, that is acetyI-
CoA. ChoIesteroI is the precursor oI aII steroid hormones in the body and pIays an important roIe in
the membranes. Excess oI choIesteroI is excreted in the biIe. EIevated IeveIs oI choIesteroI is present
in VLDL (very Iow density Iipoproteins) or LDL (Iow density Iipoproteins) and is associated with the
disease atheroscIerosis.
BiIe Pigments
The biIe has two chieI pigments which are bilirubin and biliverdin. BiIirubin is yeIIowish whereas
biIiverdin is green in coIour and this variation is due to the presence oI diIIerent pigments. BiIirubin,
a breakdown product oI haemogIobin, is the predominant pigment in the biIe. It is estimated that in an
aduIt human being, 1-2 10
8
erythrocytes are destroyed per hour, making a turnover oI about 6 g oI
haemogIobin. Conversion oI haeme to biIirubin takes pIace by reticuIoendotheIiaI ceIIs and then
transported to the Iiver by pIasma aIbumin. Further metaboIism oI biIirubin takes pIace in the Iiver
(Fig. 7.3).
FIg. 7.3 Bilirubin metabolism schematic.
Haeme catabolism in
reticuloendothelial system
Bilirubin-albumin complex
Uptake, conjugation, and
excretion of bilirubin (liver)
Conjugated bilirubin in bile
Conversion to urobilinogen
by gut bacteria
Free bilirubin
Excretion of urobilinogen
in faeces
Renal excretion of
urobilinogen
Immature erythroid
cells 15%
RBCs 85%
Bilirubin produced from
enzymes in liver
Bone marrow
Enterohepatic circulation
of urobilinogen
Digestion and Absorption !'
BiIirubin is sIightIy soIubIe in water, but when bound to aIbumin it becomes water-soIubIe.
However, binding with aIbumin increases the soIubiIity oI biIirubin in the pIasma. TotaI biIirubin
content oI the serum incIude conjugated and unconjugated amounts oI biIirubin. Conjugation oI
biIirubin with gIucuronic acid renders it water-soIubIe by an enzyme gIucoronosyItransIerase residing
in the endopIasmic reticuIum. Unconjugated biIirubin is not IiItered by the gIomeruIus, traveIs to the
Iiver, where it is separated Irom aIbumin, conjugated biIirubin with gIucuronic acid (digIucuronide) is
activeIy secreted into the biIe, which is IiItered by the gIomeruIus (Fig. 7.3). Increases in the serum
aIbumin resuIts in jaundice and haemoIytic anaemias.
Conjugated biIirubin is secreted into the biIe through active transport mechanism. When it
reaches the Iarge intestine, the gIucuronides are removed by the enzymes secreted by intestinaI
bacteria and broken down to urobilinogens, a portion oI which is reabsorbed and resecreted through
the Iiver. NormaIIy, the urobiIinogens are coIourIess.
CONTROL OF BILE SECRETION: The secretion oI biIe Irom the Iiver ceIIs is controIIed by nervous
and chemicaI stimuIi. The nervous stimuIus on biIe secretion is indirect, in that it Iirst stimuIates the
IIow oI more bIood into the Iiver which in turn activates the Iiver ceIIs. The continuous secretion oI
the biIe is due to the presence oI chemicaI stimuIants. The presence oI biIe saIts and acid in the
intestine stimuIates the secretory activity oI the Iiver ceIIs. The biIe saIts coming into the intestine are
absorbed through the waIIs oI the intestine and traveI to the Iiver via portaI circuIation.
The acid Irom the stomach, upon reaching the intestine, stimuIates the mucosaI Iining to secrete
something in addition to pancreatic secretin, which wouId aid the secretory activity oI the Iiver ceIIs
(Fig. 7.3). Protein diet inIIuences biIe secretion. In the stomach protein increases the secretion oI HCL
which in eIIect stimuIates the duodenaI mucosa to produce secretin. This eIIect oI acid in stimuIating
secretin production has been expIained to stimuIate Iiver activity.
Flov of bile: The biIe IIuid, aIthough continuousIy produced by the Iiver wouId not be aIIowed to
IIow into the intestine. Its IIow is prevented by the contraction oI a smaII sphincter present at the point
where the common biIe duct opens into the intestine. It thereIore Iinds its way into the gaII bIadder.
The waII oI the gaII bIadder has thin Iayer oI nonstriated muscIe Iibres. These muscIes when excited
contract to Iorce the contents into the intestine. The excitation Ior this contraction oI bIadder muscIes
and the simuItaneous reIaxation oI the sphincter are provided either by the nervous stimuIus or by the
presence oI acids or Iats in the intestine. The presence oI the Iatter in the intestine is beIieved to
stimuIate the production oI a hormone, cholecystokinin, in addition to secretin. ChoIecystokinin when
carried to the gaII bIadder stimuIates it to contract and Iorces the biIe into the intestine.
INTESTINAL MOVEMENTS: In the intestine the chyme is mixed with the intestinaI juices and passed
posteriad. Two types oI intestinaI movements IaciIitate this process. The mixing is IaciIitated by the
segmenting or dividing movements and propuIsion oI the chyme is carried out by peristalsis. Dividing
motions aIong the Iength oI the intestine are perIormed by repeated aIternate constrictions and
reIaxations oI the circuIar muscIes. At equidistant regions, contractions appear dividing the intestine
into a number oI sac-Iike compartments (Fig. 7.4). In the next step the circuIar muscIes at the
constrictions reIax but those at the adjacent sac-Iike compartments constrict. Such aIternate
movements are repeated rhythmicaIIy and the number oI repetitions may range between 20 and 30 per
Animal Physiology "
minute. The changing pressure oI the intestinaI contents against the waIIs, perhaps, stimuIates the
nerve net present in the intestine. This nerve net is beIieved to reguIate the rhythmic movements.
Peristalsis: The dividing movements oI intestine are Irom time to time interrupted by peristaItic
waves. This wave is caIIed diastalsis. The wave proceeds towards the posterior end oI the intestine
graduaIIy Iorcing the Iood in that direction. The dividng motion is resumed, once the peristaItic wave
dies out. DiastaIsis is carried out by the myenteric reIIex action.
Anastalsis: The movement oI Iarge intestine, especiaIIy that oI the descending coIon, consists oI a
wave oI contraction which moves upward preventing the contents oI coIon Irom reaching the rectum.
Such a movement oI the Iarge intestine is caIIed anastaIsis or antiperistaIsis.
MUCOSAL STRUCTURE: To IaciIitate absorption oI the digested Iood, the surIace area oI the
epitheIiaI Iining oI the smaII intestine is enormousIy increased by villi and microvilli (Fig. 7.5). The
viIIi are Iinger-Iike projections extending into the intestinaI Iumen. AII the epitheIiaI ceIIs on their Iree
surIace are covered over by microviIIi. The microviIIi are presumed to be the excrescences oI the
pIasma membrane occurring on the Iree surIace oI each epitheIiaI ceII. These microviIIi Iorm the
brush border over the epitheIiaI ceIIs (mucosaI ceIIs). It is estimated that each epitheIiaI ceII has 2,000-
4,000 microviIIi. The epitheIiaI ceIIs oI the viIIi have a short IiIe-span oI about 3 days. The oIder ceIIs
are repIaced by new ceIIs which are Iormed at the proIiIerative zones Iying at the bases oI the viIIi.
These zones are caIIed crypts oI Lieberkuhn. The viIIi are suppIied with capiIIary network and a
IacteaI.
FIg. 7.4 Dividing movements of the intestine. The constricted portions seen in the first phase (a) are due to the
contractions of circular muscles. The portions between the constrictions appear as sacs. In the second phase
(b), the constricted muscles relax and the muscles at the sacs constrict. Such alternate contractions and
relaxations of the muscles are repeated several times and this brings about the mixing of food.
(a)
(b)
(c)
(d)
Digestion and Absorption "
MUCOSAL FUNCTION: Intestinal fuice or succus entericus incIudes a number oI enzymes secreted
into the intestine by the various gIands oI the intestinaI mucosa. IntestinaI mucosa has gIands and their
secretions aid in the digestive process. Brunners glands present in the submucosa at the upper end oI
duodenum secrete mucus which protects the intestinaI waII Irom the acid as weII as Irom the digestive
enzymes. The secretion oI these gIands is aIkaIine. One oI the important constituents oI the intestinaI
juiceI is enterokinase, and it is secreted by crypts of Lieberkuhn. In the intestine enterokinase
cataIyzes the transIormation oI pancreatic trypsinogen to trypsin. Enzymes Iike peptidases, sucrase,
maItase, Iactase and Iipase are present within the mucosaI ceIIs oI the intestine and they are not
secreted into the intestine. The action oI these enzymes on the Iood is interIocked with the absorptive
mechanism. The action oI the peptidases in the mucosaI ceIIs was attributed to that oI a singIe enzyme
erepsin. But now erepsin is known to contain a group oI peptidases. The carboxypeptidase and
aminopeptidase beIong to this group.
The activation oI parasympathetic Iibres greatIy increases secretion oI intestinaI juice. The
presence oI chym in the intestine stimuIates the mucosa to secrete a hormone enterocrinin, which
stimuIates the intestinaI gIands to secrete the intestinaI juice.
Carbohydrates, proteins, and Iats are beIieved to be compIeteIy digested in the intestinaI Iumen to
Iorm their constituent units. But the presence oI disaccharidases, dipeptidases, aminopeptidase,
aIkaIine phosphatase, Iipase, and esterase in the mucosaI membrane indicated that the Iast oI the
digestive reactions occur in the membrane and not in the intestinaI Iumen. The uItimate hydroIysis on
or in the brush borders oI the mucosaI ceIIs ensures abosorption oI the products the moment they are
Iormed. It is presumed that the nutrients enter the ceII via membrane transport, pinocytosis, or through
membrane pores directIy into the endopIasmic reticuIum.
A Iarge number oI transport systems and mechanisms have been expIained as responsibIe Ior the
transport oI muItipIicity oI nutrietnts across the membrane oI the mucosaI ceII Iacing the Iumen.
These have been expIained under the section ABSORPTION. AIter entering the mucosaI ceII, the
nutrients are transported to the various organs to satisIy their metaboIic needs. To achieve this, the
nutrients Iirst traveI through the mucosaI ceII, then Ieave through the serosaI membrane, they next
enter the interstitiaI IIuid, then squeeze through their waIIs oI the Iymphatic and vascuIar capiIIaries,
and IinaIIy reach the sites where they are required Ior metaboIism.
MOVEMENT OF SUBSTANCES THROUGH ILEOCECAL VALVE: By the time the intestinaI content
reaches the iIeocecaI vaIve, most oI the digested proteins, carbohydrates, Iats, vitamins, and mineraIs
are absorbed in the intestinaI mucosa. At this stage the residue containing unabsorbed nutrients enters
the Iarge intestine through the iIeocecaI vaIve.
SECRETIONS FROM THE LARGE INTESTINE: The Iarge intestine does not secrete digestive enzymes
and the secretion is mostIy mucin. This secretion is aIkaIine and has a pH oI about 1.8. It is rich in
bicarbonate and potassium. The secretory activity oI the Iarge intestine is under parasympathetic
controI, but there is no evidence oI hormonaI reguIation. The appendix spontaneousIy secretes a Iarge
quantity oI IIuid which is poured into the Iarge intestine.
COLONIC MOVEMENTS: The coIon perIorms aII those movements discussed under intestinaI
movements. As a resuIt oI segmenting, and peristaItic movements, the semisoIid materiaI that has
Animal Physiology "
FIg. 7.5 The absorptive surface of the intestinal lumen is greatly increased due to the presence of finger-like pro]ections
of the intestinal mucosa (a) villi and (b) microvilli of the plasma membrane of the epithelial cells.
Central
lacteal
Heberkuhn
follicle
Lymphatic
plexus
Auerbach s
plexus
¢
Serous coat
Longitudinal muscle
Circular muscle
Muscles of the mucosa
Submucosa
Meissner s plexus ¢
Nerve net
Artery
Vein
(a)
Surface coat
Microvilli
(b)
Digestion and Absorption "!
entered the coIon gets mixed with the secretions and the micro-organisms oI the Iarge intestine. The
antiperistaItic movements oI the Iarge intestine prevent the residue Irom reaching the rectum.
Most oI the micro-organisms swaIIowed aIong with the Iood, are kiIIed in the stomach and in the
upper part oI the intestine. However, a Iew yeasts, some acid producing bacteria, and some bacteriaI
spores remain aIive. There is a graduaI increase oI these micro-organisms towards the posterior end oI
the intestine. These acid producing bacteria impart acidity to the undigested or partIy digested Iood
and subject it to acid Iermentation as it passes Iarther and Iarther aIong the intestine. The intestines oI
animaIs have various types oI micro-organisms which are speciIic to the species they Iive in.
In the coIon the Iood stays Ior a considerabIy Iong time oI 3 to 4 hours, and this IaciIitates the
micro-organisms to Iurther carry out Iermentative and putreIactive eIIects. As a resuIt oI fermentation
compIex substances such as poIysaccharides and Iats are converted to simpIer substances. The
conversion oI proteins by bacteria into simpIer substances is known as putrefaction and this term is
speciIic Ior proteins.
Enzymic hydroIysis oI organic substances is compensated in the Iarge intestine by the bacteria.
The bacteria spIit the poIysaccharides, Iats and proteins to yieId partiaI or compIete hydroIysis
products. The ceIIuIose consumed by herbivores is broken down due to Iermentation by the intestinaI
bacteria and as such none oI the higher animaIs has enzymes capabIe oI hydroIyzing it. In such
animaIs the cecum can retain Iood Ior a Iong time to compIete the Iermentative process.
The bacteria in the Iarge intestine produce enough quantity oI vitamin K and some components oI
the vitamin B compIex. These vitamins are absorbed to meet the body requirements. GeneraIIy,
adequate amounts oI these vitamins reach the intestine through the ingested Iood and as such the body
does not suIIer Irom their deIiciency.
WhiIe some oI the products oI Iermentation are harmIess, there are substances such as indoIe,
skatoI, phenoI, and hydrogen suIphide that have a pungent odour and toxic nature. OI the toxic gases,
CO
2
and methane are produced chieIIy Irom carbohydrate Iermentation, whereas H
2
S and N
2
are
produced Irom protein putreIaction. The toxic products are absorbed into the portaI bIood and are
taken to the Iiver Ior Iurther oxidation or transIormation to reIativeIy harmIess substances.
Faeces: AIter Iermentation and putreIaction the materiaI in the Iarge intestine contains
indigestibIe matter as weII as undigested Ioods. A Iarge proportion oI the Iaeces, however, constitutes
bacteria and intestinaI epitheIiaI ceIIs. The biIirubin, present, in the Iaeces, is converted to
urobilinogen which is then oxidized to pigment urobilin. The coIour oI the Iaeces is due to pigment.
In addition, the Iaeces contain inorganic constituents that entered through Iood and remained
unabsorbed. About 75 per cent oI the Iaeces is water. This percentage is maintained in the Iaeces
because oI the secretory and absorptive abiIity oI the coIon. The quantity oI the Iaeces Iormed is
mainIy dependent upon the quaIity and quantity oI ingested Iood.
Defecation: The accumuIation oI Iaeces distends the rectum and stimuIates the proprioceptors.
The impuIses Irom the proprioceptors are propagated to the sacraI portion oI the spinaI cord. ImpuIses
strong enough to stimuIate the motor nerves innervating the smooth muscIes oI the rectum are created
onIy when the pressure in the rectum reaches the required IeveI. In humans, the required pressure
IeveI is about 40 mm Hg. This deIecation reIIex, coordinated at the sacraI IeveI, may be inhibited or
enahanced by higher controI centres. The deIecation reIIex may be inhibited by the voIuntary
Animal Physiology ""
contraction oI anaI sphincter. The enhancement oI deIecation reIIex is caused by contracting the
abdominaI muscIes and increasing the pressure in the abdomen. AbdominaI pressure may be Iurther
increased by increasing the intrapIeuraI pressure and by Iorcing the diaphragm to descend. The
pressure resuIting Irom the combined activty oI diaphragm and the abdominaI muscIes is suIIicient to
squeeze the rectum and push the Iaeces through the anaI sphincter.
7.5 DlGESTlDN lN DTHER VERTEBRATES
SaIivary digestion in generaI is wanting among the vertebrates, but the saIiva oI Irogs and toads, and
oI the IowI contains the enzyme amyIase. The enzymes such as amyIase and disaccharidases are aIso
present in the intestine oI vertebrates. In bony Iishes both amyIase and maItase are secreted by the
pancreas. EnzymoIogicaI studies on a goId Iish, a Iizard and certain birds have reveaIed the presence
oI chitinase in the saIiva.
Stomach is absent in prochordates and consequentIy there is no production oI pepsin. In other
vertebrates, except hoIocephaIi, dipnoi and many teIeosts, a stomach is present and serves both
storage and digestive Iunctions. The stomach in these groups secretes pepsin-Iike enzyme acting in
acid medium. In amphibia, pepsin is secreted more in the oesophagus than in the stomach. In Iishes,
amphibians, reptiIes and mammaIs, individuaI proteases are simiIar, iI not identicaI. The acidity oI the
stomach contents in vertebrates is generaIIy Iower than that oI man and dog. The pH vaIues range
between 2.5 and 4.5 in Iishes, amphibia, and birds. However, in some rays and bony Iish, the stomach
content is aIkaIine in spite oI the presence oI pepsin. In contrast to this, the sharks have an acidity
twice that oI man.
A smaII amount oI gastric Iipase is secreted in the stomach oI some birds and Iishes. In their
intestine the proteases are generaIIy distributed as in mammaIs. Secretion oI Iipase and the presence
oI biIe saIts in the intestine is a generaI Ieature oI aII vertebrates. Honey-guides are a kind oI birds that
Ieed on bees-wax but do not produce esterases required Ior its digestion and are dependent on their
microIIora. AutoIytic and bacteriaI digestion has been observed in the crop oI IowI.
There are scattered reIerences on hormonaI and nervous controI oI digestion among vertebrates.
In some animaIs (seIachians) neither nervous nor hormonaI controI was evident. Studies on controI oI
pepsinogen secretion reveaIed that the nervous (vagus) stimuIation was not needed in Rana, whereas
in the toad Bufo, some nervous controI is required. There is an indication oI the presence a hormone
gastrin in amphibia. In some (saImon, dog-Iish, Irog, tortoise, etc.) secretin is present but its activity is
not estabIished.
The probIem oI intraceIIuIar digestion has been soIved by the presence oI Iood vacuoIe. The
vacuoIe encIosing the Iood is sphericaI and consists oI IIuid and a surrounding membrane. The Iood
in the vacuoIe graduaIIy breaks down and disappears, which is due to the secretion oI appropriate
enzymes into the vacuoIe Irom the surrounding cytopIasm. The Iood constituents diIIuse into the
cytopIasm and get assimiIated. The Ieucocytes oI higher animaIs, which enguII Ioreign particIes
(phagocytosis), aIso have simiIar intraceIIuIar digestive mechanism. The Iood vacuoIe in these is
anaIogous to the gastrointestinaI tract oI higher animaIs and Ior this reason, it is appropriateIy known
as gastric vacuole.
Digestion and Absorption "#
7.8 DlGESTlDN lN lNVERTEBRATES
Our knowIedge oI the digestive processes among invertebrates is based on the morphoIogicaI and
anatomicaI Ieatures oI their digestive organs and enzymes present in them. The aIimentary canaI oI
invertebrates is reIativeIy simpIe and aII the enzymes are oIten secreted by a singIe gIand. Further,
these enzymes nearIy aIways digest the Iood in one part oI the aIimentary canaI which is anatomicaIIy
simpIe and undiIIerentiated into IunctionaI zones.
In generaI, aII animaIs possess enzymes necessary Ior spIitting starch, gIycogen, proteins and Iats.
Some oI the enzymes in uniceIIuIar organisms are present in the Iysosomes, whiIe others are Iound
attached to the ceII membrane.
In many echinoderms and IameIIibranchs intraceIIuIar digestion is perIormed by wandering ceIIs.
In IameIIibranchs, these ceIIs may even enter the mantIe cavity and ingest Iood particIes. The
wandering ceIIs can spIit aII three cIasses oI Iood, viz. carbohydrates, proteins and Iats.
In most animaIs, extraceIIuIar digestion takes pIace compIeteIy within the digestive tract. There
are some animaIs which partIy digest certain types oI Iood outside the body. Such an externaI
digestion has been observed in some species oI rhabdocoeIidae and in bIowIIy maggots. The Iatter
excrete proteases through the Iaeces in order to IiqueIy the meat in which they Iive. Their IiqueIied
meat is then ingested.
The power oI digestion oI Iood is very much Iimited among certain parasites since they have
weakIy deveIoped digestive tract. The Fasciola hepatica, Ieeding on bIood, has a proteinase, but most
oI the other nutrients are absorbed through the body surIace. Ascaris, however, does not absorb
nutrients through its body surIace but ingests both digested and undigested Ioods and in its digestive
tract they are attacked by a group oI enzymes, viz. amyIase, maItase, protease, peptidase, and Iipase.
Parasite Iike 1aenia has no digestive tract and it sustains itseII on predigested Iood Irom the host.
Among invertebrates, the carbohydrases have not received as much attention as proteases. The
amyIase Irom a number oI groups is very simiIar to vertebrate amyIase. It can attack starch to spIit it
to maItose, but it IaiIs to spIit pure starch grains, and usuaIIy has a pH optimum sIightIy on the acid
side oI neutraIity. Many invertebrates can hydroIyze the three common disaccharides maItose,
sucrose and Iactose. In some animaIs, snaiI in particuIar, the disaccharidases can hydroIyze at Ieast
seventeen sugars and reIated substances. The snaiI produces enzyme inuIase to digest the inuIin oI the
compositae into Iructose. The snaiI can aIso digest ceIIuIose and chitin with the heIp oI symbiotic
bacteria. The occurrence oI cellulase has been reported among a Iew protozoans, earthworms, some
wood boring beetIes, and the wood boring bivaIve 1eredo, etc. Chitinase has been Iound in soiI
amoebae, in coeIenterates, nematodes, earthworms, and in aII animaIs consuming arthropods as Iood.
The proteinase oI Maia, Iike vertebrates, requires an activator and in Iact, it is secreted aIong with
it. The gut oI a crab (Maia), and a marine snaiI (Murex) has been Iound to contain Iour proteases
proteinase, carboxypeptidase, aminopeptidase, and dipeptidase. AII these proteases resembIe those
present in vertebrates. The pH optima Ior these enzymes are oI the same orders those Ior vertebrate
enzymes. The enterokinase which activates the proteinase in the vertebrates can aIso activate the
puriIied proteinase Irom Maia, suggesting its resembIance with that oI vertebrates. In severaI insects
the protease is known to be consisting oI a tryptic proteinase, a carboxypeptidase, an aminopeptidase
Animal Physiology "$
and a dipeptidase. The proteinase and its activator Irom caecum oI Sepia have simiIarities with those
oI trypsin and its activator enterokinase oI vertebrates. Thus in generaI the protein digesting enzymes
oI invertebrates are activated by the same series oI enzymes that activate in vertebrates. The proteases
oI Pheretima and Iarvae oI Calliphora and other meat-eating IIies react in a sIightIy acid medium and
are comparabIe to pepsin.
The Iipases among invertebrates IargeIy diIIer Irom those oI vertebrates. Many invertebrate
Iipases hydroIyze esters oI Iower Iatty acids more easiIy than oiIs and Iats, and Ior this reason, they
are more aptIy caIIed esterases than Iipases. Bees-wax consumed by wax-moth is partIy digested by
bacteriaI action and partIy by enzymes.
B. ABSDRPTlDN
The process oI absorption takes pIace chieIIy in the smaII intestine. To a Iimited extent, absorption oI
ordinary Ioods aIso takes pIace in the stomach. NontypicaI Ioods such as pepper, mustard,
condiments, and aIcohoIic drinks seem to be absorbed in the stomach.
SmaII intestine is most suitabIe Ior absorption. For this purpose, the epitheIiaI Iining oI the smaII
intestine is weII adapted. The smaII intestine has an extensive absorbing surIace Iormed due to the
enormous number oI smaII papiIIiIorm viIIi. The intestinaI contractions as weII as the contractions oI
the viIIi constantIy expose the entire surIace oI the smaII intestine to the Iiquid materiaI Ior maximum
absorption.
The digested materiaI Irom the intestine is absorbed either into the bIood capiIIaries or into the
Iymphatics, both oI which are present in the viIIi. The materiaI absorbed into the capiIIaries is then
carried to the mesenteric veins and the portaI vein. From the Iatter, it gets into the Iiver beIore being
sent to the generaI circuIation oI the body. In another pathway the absorbed materiaI wouId reach the
bIood indirectIy. In this case the materiaI is absorbed into the Iymph spaces oI the viIIi and the Iymph
vesseIs oI the intestine. It is then transported into the Iarge IacteaI vesseIs and the thoracic duct. The
materiaI transported through the IacteaIs is termed chyle. The thoracic duct empties the chyIe into the
venous system near the heart.
7.7 CARBDHYDRATE ABSDRPTlDN
Carbohydrates are chieIIy absorbed by the smaII intestine, in the Iorm oI monosaccharides. The
absorbed sugars are utiIized Ior the metaboIic needs. The monosaccharides Ior the most part are
absorbed by active transport mechanism. IntestinaI membrane has seIectivity in absorbing simpIe
sugars. Cori, in 1925, observed that the sugars administered into the stomach oI rats disappeared Irom
the intestine at diIIerent rates. The pentoses have smaIIer moIecuIes and thereIore diIIused more
rapidIy than hexoses. OI the hexoses, gaIactose and gIucose are more rapidIy absorbed than Iructose.
This rapid intake is due to their active absorption against the concentration gradients. It has been
suggested that Ior active transport the sugars must contain six carbon atoms in the Iorm oI a D-
pyranose ring with an intactOH at the 2-carbon position as iIIustrated in Fig. 7.6. Fructose does not
conIorm with this minimaI required structure and Ior this reason it does not enjoy active transport.
Digestion and Absorption "%
StiII, its rate oI absorption is Iaster than mannose, xyIose, and arabinose. This is so because oI its
conversion in the epitheIiaI ceII to Iactic acid (WiIson and Wiseman, 1954) in rat and hamster, and to
gIucose (Hers and Kusaka, 1953) in guinea pig and hamster. In rat and human intestinaI ceIIs, the
gIucose-6-phosphatase, required Ior the conversion oI Iructose into gIucose, is absent.
The precise mechanism Ior the transport oI sugars is not known. However, aII sugars transported
activeIy are beIieved to be attached to the common carrier on the IumenaI border oI the epitheIiaI ceII
membrane. Since they aII have a common carrier, some oI the sugars having greater attraction to the
carrier compete with others to gain attachment Ior their transport into the ceII. Because oI this
competition, the rate oI intake oI some sugars is higher than the others. Though the IoIIowing
hypothesis is with reIerence to the absorption oI gIucose. the same is beIieved to hoId good Ior other
sugars aIso.
GIucose transport invoIves two systems (Fig. 7.7). The Iirst system consists oI a carrier or
transIocase with two binding sites; one Ior attachment with gIucose and the other Ior Na
¹
. The carrier
with both Na
¹
and gIucose attached moves to the membrane surIace Iacing cytopIasm. In this process,
the carrier is subjected to the Iorces oI two gradients, an outward gIucose gradient and an inward Na
¹
gradient. The Na
¹
gradient exerts greater Iorce on the carrier compIex than the gIucose gradient, and
resuIts in the inward movement oI the carrier compIex. On reaching the inside surIace, gIucose and
Na
¹
dissociate Irom the carrier and enter the cytopIasm. Thus the Iirst transport system brings gIucose
and Na
¹
ions Irom the Iumen into the cytopIasm. II this continues, Na
¹
ion concentration in the ceII
increases and the gradient diminishes. However, this does not occur. The second transport system
removes Na
¹
brought in by the Iirst transport system and thus maintains the inward Na
¹
gradienta
high concentration outside and Iow concentration inside the ceII. Since the second transport system is
invoIved in the pumping oI Na
¹
against the gradient, it requires energy. The energy Ior this process,
comes Irom the hydroIysis oI ATP.
FIg. 7.6 D-pyranose ring with an intact-OH at the 2-carbon position can be readily absorbed by active transport.
OH
O
D-pyranose ring
O
Animal Physiology "&
7.8 PRDTElN ABSDRPTlDN
The proteins enter the bIood onIy in the Iorm oI amino acids. The inward movement oI amino acids
across the membrane is simiIar to that oI gIucose absorption. The transport system contains a compIex
oI carrier its speciIic amino acids, and Na
¹
.
There are Iour types oI systems each oI which is speciIic Ior a group oI cIoseIy reIated amino
acids. Amino acids such as gIycine, aIanine, and Ieucine are transported by a speciIic type oI transport
system. SimiIarIy there is a transport system speciIic Ior acidic amino acids Iike gIutamic acid and
aspartic acid. StiII other types oI transport systems are speciIic Ior basic amino acids. ProIine and
hydroxyproIine have a common transport system. One oI the signiIicant and common properties oI
these transport systems is the requirement oI the presence oI high concentration oI Na
¹
in the Iumen
oI the intestine.
The absorption oI amino acids is thus a seIective process rather than simpIe diIIusion. Their
absorption is rapid and active. AIter studying the rates oI absorption, Gibson and Wisemen (1951)
observed that in case oI 13 amino acids the intestinaI waII preIerred the L-Iorm (naturaI Iorm) to its
D-Iorm (opticaI isomers). The amino acids thus absorbed enter the bIood and are rapidIy removed
Irom there to the Iiver. In the transport oI amino acids, the IacteaI system oI the intestinaI waII pIays
no signiIicant roIe.
The neutraI amino acids appear to share a common earIier Ior their transport across the membrane
oI the mucosaI ceII (Fig. 7.8). For active transport oI these amino acids the transport systems must
possess the required opticaI speciIicity (the L-stereoisomer), an intact carboxyI group (COOH), an =-
amino group, an =-hydrogen, pyridoxaI phosphate, and the Iat soIubIe side chain (R).
The carrier system which transports cystine aIso transports the basic amino acids, viz. Iysine,
arginine and ornithine. The existence oI this common transport system came to Iight during
FIg. 7.7 The mechanism of glucose absorption.
Hydrolases
F.G.
Na
+
X

H O
2
G + Na
+
Na
+
~ P
G+Na
Mobile carrier
systems
Fructose
Glucose
Cytoplasm
Brush border
region
Medium
Digestive
surface
Apparent
diffusion
barrier
Digestion and Absorption "'
investigations on cystinurea. Cystinurea (existence oI cystine in urine) is a disease caused by a genetic
deIect. Due to this deIect, the carrier responsibIe Ior the absorption oI cystine does not IunctionaIIy
exist, and in such cases the absorption oI not onIy cystine but aIso that oI Iysine and ornithine is
prevented Irom the intestine. It is beIieved that a simiIar carrier exists in both the kidneys and the
intestine Ior these amino acids.
Amino acids proIine and hydroxyproIine have a common (betaine) transport system, and the
existence oI this system eIiminates these amino acids Irom competing with the neutraI amino acid
transport system. OnIy smaII quantities oI gIutamic and aspartic acids are recoverabIe in the portaI
bIood aIter their absorption Irom the intestine and this has been expIained to be due to transamination
during absorption.
7.8 ABSDRPTlDN DF FAT
The digestion oI Iat is never so compIete to Iorm onIy gIyceroI and Iatty acids. The digested Iat is a
mixture oI trigIycerides, digIycerides, monogIycerides, and Iree Iatty acids aIong with gIyceroI. AII
these can be absorbed by the intestinaI ceIIs. However, monogIycerides, Iatty acids, and gIyceroI Iorm
a signiIicant part oI the materiaI absorbed by the intestine. The biIe saIts act as detergents and bring
the Iatty acids, choIesteroI and monogIycerides in contact with the microviIIi. The biIe saIts are
dissociated Irom the digested Iats as they are absorbed and become avaiIabIe once again to bring the
digested Iats in contact with the microviIIi. Some suggested that dissociation is taking pIace in the
Iumen (Lack and Weiner, 1963). In such a case, the biIe saIts wouId have the mucosaI ceII and come
back into the Iumen.
The gIyceroI is water soIubIe, and being a smaII moIecuIe, it is speediIy absorbed by the intestine.
The Iatty acids and gIycerides are said to be taken into the ceII by pinocytosis (PaIay and KarIin,
1959). But biochemicaI and eIectron microscopic studies did not reveaI any signiIicant increase oI
FIg. 7.S Transport of neutral ammo acid across the membrane of mucosal cell.
COO

C
H
NH
3
+
P
y
r
i
d
o
x
a
l
p
h
o
s
p
h
a
t
e
R
Lipid
Animal Physiology #
pinocytic incIusions between Ied and Iasted rats. Whatever might be the process, these Iatty acids
enter the mucosaI ceIIs, and are transIormed to trigIycerides within the endopIasmic reticuIum.
Two pathways exist Ior the transport oI Iats Irom the mucosaI ceIIs. The trigIycerides Iormed by
Iong chain (about, or more than 12 carbon atoms) Iatty acids are coated with a protein to Iorm
chilomicrons. These are then secreted by the mucosaI ceIIs into the Iymph spaces. The chiIomicrons
are Iipoproteins, about I in diameter, and impart a miIky coIour to the Iymph spaces and Iymph
yesseIs, which Ior this appearance are caIIed lacteals. The chiIomicrons are then carried aIong with
the Iymph Irom the Iymphatics into the venous bIood via thoracic duct.
In the other pathway, the short chain Iatty acids are directIy absorbed into the bIood capiIIaries oI
the intestinaI viIIi. They then enter the portaI bIoodstream, Irom where they are quickIy removed by
the Iiver and Ior this reason pIasma wouId not appear miIky.
OI the choIesteroI present in the Iumen oI the intestine, about haII is derived Irom the biIe. The
choIesteroI is said to pass into the ceII through soIution Irom the Iipid portion oI membrane. The Iatty
acids, especiaIIy oIeic acid, as weII as the pancreatic juice, stimuIate and enhance the absorption oI
choIesteroI into the mucosaI ceIIs. From the mucosaI ceII they are passed into the Iymph. The
IoIIowing postuIation expIains the process. The choIesteroI enters the chiIomicrons aIong with
trigIycerides. The biIe heIps in esteriIication and the chiIomicron Iormation. These chiIomicrons are
then secreted into the Iymph Ior transport (WiIson, 1962).
7.30 ABSDRPTlDN DF DTHER SUBSTANCES
Absorption of NucIeic Acids
As a resuIt oI the hydroIysis oI nucIeic acids by ribonucIease and deoxyribonucIease, the nucIeotides
and nucIeosides are Iormed. These products are then absorbed by the mucosaI ceIIs inside the mucosaI
ceIIs the nucIeotides are spIit to nucIeosides to enabIe them to diIIuse through the serosaI side into the
intestine.
Absorption of Water SoIubIe Vitamins
The reIativeIy Iow moIecuIar weight oI the water soIubIe vitamins wouId enabIe them to enter the
mucosaI ceIIs oI the intestine by simpIe diIIusion. The vitamin B
12
moIecuIe is, however, the Iargest
oI aII the B group oI vitamins. To be absorbed it requires a gastric intrinsic Iactor (IF), which is aIso
a Iarge moIecuIe. It is secreted by the stomach. Due to the presence oI acid medium in the stomach,
the vitamin B
12
is reIeased Irom the ingested animaI protein. The IF then gets attached to the vitamin
B
12
(Fig. 7.9) and traveIs down through the digestive tract and is absorbed in the iIeum. The ceIIs in
the iIeum have speciIic capacity to absorb vitamin B
12
. The IF-B
12
compIex in the presence oI Ca
¹¹
gets attached to the receptor sites on the surIace oI mucosaI ceIIs oI the iIeum. For adequate
absorption oI vitamin B
12
, there shouId be enough IF and it shouId Iorm the compIex (IF- B
12
) beIore
it gets attached to the receptor site. In suIIicient or excIusive quantities oI IF wouId Iead to inadequate
absorption oI vitamin B
12.
AIter this attachment, it is not cIear how the vitamin enters the ceII. One view is that the entire IF-
B
12
compIex enters the ceII by pinocytotic process. According to another view the B
12
is spIit Irom the
Digestion and Absorption #
compIex by a reIeasing Iactor and is then taken into the ceII. Whether vitamin B
12
enters the ceII aIone
in association with IF, it must get dissociated Irom the IF and bind to a protein within the mucosaI
ceII. This protein moIecuIe is smaII enough to pass though the capiIIary waII into the bIood-stream.
The vitamin B
12
protein compIex in the pIasma is caIIed transcorrin and it is an = 1-gIobuIin. In this
Iorm, the vitamin B
12
is transported.
Absorption of Fat SoIubIe Vitamins
The biIe is essentiaI Ior the absorption oI these vitamins which are Iound in association with Iipids
(e.g. as esters) in the diet. The vitamin A ester (retiny Iester) is Iirst hydroIyzed in the intestinaI Iumen
to Iorm retinoI (a Iree vitamin aIcohoI). The retinoI then enters the mucosaI ceII and gets re-esteriIied
with paImitic acid (Mahadevan and GanguIi, 1961) to Iorm retinyI paImitate, and this Iorm it enters
into the chiIomicrons. These chiIomicrons are then secreted into the Iymph and transIerred to Iiver via
bIood. In the Iiver, it is stored as paImitate ester. SimiIarIy some oI the >-carotene (a provitamin) is
converted to retinyI ester on its entry into the mucosaI ceII and it is transported to the Iiver as retinyI
pamitate.
Inadequacy oI protein in diet has adverse eIIect on the absorption oI vitamin A and carotene.
What precise roIe do the proteins pIay in preventing the vitamin A and carotene absorption is not
known.
Water and EIectroIyte Absorption
Water and eIectroIytes reach the intestinaI Iumen Irom two sources, i.e. through the ingested diet and
water through the intestinaI juices. The quantity oI Irom water source is greater than Irom the Iormer.
Most oI the water is absorbed throughout the Iength oI the intestine and passed into the bIood. This
process oI movement oI water in the intestine has been reIerred to as gastrointestinal circulation. The
transIer oI water and saIts through the mucosaI waII is partiaIIy dependent on the active metaboIism oI
FIg. 7.9 Absorption of vitamin B
l2
.
Ca
IF
B
12
Intrinsic
factor
Vitamin B
12
Calcium molecule
Receptor site
(a) (b) (c)
Animal Physiology #
the mucosaI ceIIs. GeneraIIy, the rate oI absorption oI divaIent ions is sIower than that oI monovaIent
ions. The absorption oI Ca
¹¹
is 50 times sIower than that oI Na
¹¹
.
CaIcium Absorption
CaIcium is very much needed Ior young animaIs to meet the requirements Ior bone growth and Ior
this reason caIcium is eIIicientIy absorbed Irom the intestine. The caIcium absorption has IittIe to do
with age and in young and oId its absorption is need based. When the body needs more caIcium,
active transport system adjusts to this need and enters the mucosaI ceII more eIIicientIy. The caIcium
absorbed by the mucosaI ceIIs is derived Irom the ingested Iood and the gastrointestinaI secretions.
Since the quantity oI caIcium reIeased aIong with the secretions is diIIicuIt to ascertain, the quantity
oI caIcium absorbed by the intestinaI mucosa is not possibIe to determine accurateIy. However, the
diIIerence in the quantity oI caIcium between ingested Iood and excreted matter is taken as the
quantity oI caIcium absorbed. The caIcium absorption is greater in the duodenum and jejunum than in
the distaI portions oI the smaII intestine. The studies to cIariIy mechanism oI caIcium absorption were
initiated with the avaiIabiIity oI Ca
¹¹
. In these studies, the caIcium is observed passing into the
mucosaI ceIIs against the concentration gradient, thus indicating active transport across the
membrane.
Lactose is beIieved to act directIy on caIcium so as to maintain it in a Iorm suitabIe Ior transport
across the membrane oI the mucosaI ceII. Vitamin D aIso pIays an important roIe in the increased
absorption oI caIcium. However, its action is not directIy upon caIcium but upon the intestinaI
mucosa. The precise action oI vitamin D is not yet deIiniteIy known. There is some evidence that
vitamin D heIps in the synthesis oI a protein which is necessary Ior the membrane transport oI
caIcium, but is not weII received. The Iact that inhibition oI oxidative phosphoryIation does not
prevent vitamin D inIIuenced caIcium transport suggests that this transport system does not require
energy.
Another view is that the parathyroid hormone aIong with vitamin D reguIates the totaI amount
and the ratio oI caIcium and phosphate ions in the internaI environment. However, the exact
mechanisms oI this combined eIIort are not satisIactoriIy expIained.
Absorption of lron
It is weII estabIished that the excess iron, which may enter the body either by injection, or by the
disruption oI the normaI reguIation oI iron absorptive process, is not excreted through Iaeces or urine.
The Iact that the intestinaI mucosa absorbs iron but does not excrete suggests that its movement is
unidirectionaI. Excess oI iron in the body accumuIates in the ceIIs as iron-containing hemosiderin.
There are Iour important views regarding the mechanism oI reguIation oI iron absorption.
MUCOSAL BLOCK THEORY OF GRANICK: According to this theory, the quantity oI iron absorption
is determined by the Ierritin content within the mucosaI ceIIs oI duodenum and upper jejunum. II the
body has aIready absorbed adequate iron, high IeveIs oI Ierritin are Iormed in mucosaI ceIIs. High
Ierritin content in the mucosaI ceIIs wouId bIock Iurther iron absorption; and Iow Ierritin content
permits iron absorption and its combination with the protein apoferritin in the ceII to Iorm Ierritin.
Iron is absorbed more readiIy its divaIent Iorm and thereIore Granick proposes Iirst the transIormation
Digestion and Absorption #!
oI Ierric ion (Fe
¹¹¹
) to Ierrous Iorm (Fe
¹¹
) in the intestinaI Iumen and then its absorption into the
mucosaI ceII (Fig. 7.10). Once in the mucosaI ceII, the Ierrous iron is oxidized to Ierric Iorm which
combines with apoIerritin to Iorm Ierritin. II the body needs iron, Ierritin in the mucosaI ceII is spIit to
Iorm apoIerritin and Ierric iron. The Ierric iron is reduced to Ierrous Iorm, which then passes through
the serosaI membrane into the bIood. Upon entering the bIood, the iron is reoxidized and attached to
the protein transferrin which is an iron-binding 1-gIobuIin.
CHELATION AND EQUILIBRIUM BINDING THEORY: CharIey et aI. (1963) suggested that in the Iumen
the Ierrous ion combines with a Iigand such as sorbitoI or Iructose to Iorm a soIubIe uncharged
compIex. This compIex enters the ceII and the iron combines with other Iigands oI Iow moIecuIar
weight as weII as apoIerritin. The passage oI iron across the serosaI membrane into circuIation
depends upon the avaiIabiIity oI unbound transIerrin.
MANIS AND SCHACHTER`S IRON ABSORPTION THEORY: According to Manis and Schachter (1962)
both the mucosaI ceII iron and its serosaI transIer are energy dependent. The Iormer action is rapid
and proportionateIy increases with the concentration oI iron in the Iumen. The serosaI transIer oI iron
is maintained constant and maximaI and requires the energy derived Irom oxidative metaboIism
within the ceII. According to these authors, both Ierric and Ierrous ions pass through the mucosaI
membrane Iacing the Iumen, whereas Ior its transIer through the serosaI membrane onIy the Ierrous
Iorm is preIerred.
'MESSENGER IRON` ABSORPTION THEORY: Conard, Weintraub and Crosby (1964) suggested that
the iron administered oraIIy was incorporated in the mucosaI ceIIs oI the smaII intestine as messenger
iron. II mucosaI ceIIs contain Iarge quantities oI messenger iron, this wouId mean more nutritive iron
in the body and consequentIy they reject iron absorption. II the body is deIicient in iron, messenger
iron content in mucosaI ceIIs is very IittIe or totaIIy absent, and such mucosaI ceIIs wouId IreeIy
absorb iron.
FIg. 7.1û Diagram illustrating Cranick´s hypothesis for iron absorption.
}
Lumen Epithelial Plasma
Fe
+++
Fe
++
Fe
++
Fe
+++
Fe
++
Ferritin
Apoferritin Apoferritin
Transferrin
Fe
+++
Fe
++
Fe
++
Fe
+++
Ligand
Fe –Complex Fe –Complex
Low molecular
Weight ligands
Macromolecules
Fe –chelate
Transferrin
LiIe began in a medium, the physicaI Iorces and chemicaI Iactors oI which were quite congeniaI to
permit its muItipIicity and continuity. Such Iactors existed in seawater. The Iirst organisms which
arose in this medium contained in themseIves a IIuid whose concentration is simiIar to seawater. But
the IIuid in the organism has to be something diIIerent Irom seawater in order to carry out IiIe
activities. For this the organisms contain a baIanced IIuid oI organic and inorganic substances. In this
biochemicaI processes take pIace, and to IaciIitate these processes the composition oI the internaI
IIuid must be meticuIousIy maintained at the required IeveI. For this a barrier exists between the IiIe
sustaining internaI IIuid and the IiIe giving externaI medium (seawater). Such a barrier is in the Iorm
oI a semipermeabIe membrane. The importance oI the membrane barrier is deaIt under Section 8.1.
Many oI the Iiving organisms moved Irom the seawater to other habitats in the course oI
evoIution. A great many organisms even IeIt the aquatic habitats and chose extremeIy dry terrestriaI
habitats. These habitats tend to bring changes in the water and saIt content oI the organisms. Water
continues to be an essentiaI requirement Ior aII organisms and is the universaI bioIogicaI soIvent,
hence is the most suitabIe medium to suppIy the necessary substances to carry out the biochemicaI
reactions.
In the very primitive and the simpIest oI the Iiving marine organisms the procurement oI Iood,
oxygen, and the eIimination oI wastes are carried out directIy between the intraceIIuIar IIuid and the
seawater. The more compIex muIticeIIuIar animaIs have deveIoped tissues which are not accessibIe
Ior direct contact with seawater. In these animaIs the tissues are directIy bathed in the extraceIIuIar
IIuid which is in osmotic equiIibrium with the surrounding seawater. These body IIuids suppIy the
tissues with nutrients and oxygen, and the tissues in turn eIiminate waste products into them. Since
the body IIuids subserve the Iunction oI sea, as medium around the tissues, it is said that they, act as
internal sea. The voIume oI these body IIuids is usuaIIy smaIIer than that oI ceIIs and hence the
composition oI the IIuids is maintained constant to meet the needs oI the ceIIuIar requirements oI the
tissues. The depIeted IeveIs oI oxygen and nutrients in the body IIuids are soon repIenished by
respiration and digestion.
Woter ReIotions ond
lonic ReguIotions
+ 0 ) 2 6 - 4
&
Water Felations and Ionic Fegulations ##
The voIume oI water and the composition oI soIutes in the body IIuids are controIIed by the
excretory organs which either remove or conserve substances aIready present in the body IIuids.
However, at the other two sites, i.e. gut Iining and body surIace in aquatic animaIs, the saIts and water
are transported in either direction. The deveIopment oI an internaI medium, i.e. the body IIuids,
heIped the maintenance oI ceIIuIar composition oI not onIy the compIex marine animaIs but aIso that
oI Ireshwater and terrestriaI animaIs. AII these animaIs reguIate their body IIuid concentrations at
IeveIs speciIic to the various groups. In Ireshwater animaIs the voIume oI water and the composition
oI saIts in the internaI medium is maintained remarkabIy at the required IeveI in spite oI the disturbing
eIIects oI diIIusion and osmosis. In terrestriaI animaIs the internaI medium Ioses water and saIts
through the body surIace and kidneys. Water is Iost by evaporation mainIy through the Iungs. They
deveIoped mechanisms Ior conserving water and saIts. These animaIs stiII Iose certain amounts oI
water and saIts in spite oI conserving mechanisms. Such a Ioss is compensated onIy by absorbing
them Irom the Iood and water ingested Irom outside into the digestive system.
8.3 RDLE DF MEMBRANES lN DSMDTlC AND lDNlC
REGULATlDNS
The unit membrane, besides encIosing the cytopIasm and oIIering some sort oI protection Irom minor
coIIisions, serves Ior the transport oI seIected substances across it.
A number oI muIticeIIuIar and a ceIIuIar organisms Iive in an environment that is diIIerent in
some respects Irom their internaI environment. Even iI the ceIIs are bathed in a medium that has an
osmotic concentration simiIar to seawater, a diIIerence in the ionic composition between the internaI
and externaI environments oI the ceIIs is aIways maintained. Within the ceIIs there is sort oI baIance
in the amount oI water, saIts and organic substances. The entry oI substances into the cytopIasm and
expuIsion into the externaI medium is meticuIousIy reguIated.
The ceII membrane is permeabIe to many substances in either direction. For this the membrane
possesses a structure, the chemicaI composition oI which is suitabIe Ior transport oI seIected
substances. The exact chemicaI composition is stiII under investigation. However, based on important
observations certain hypotheses regarding membrane structure have been made and these were
discussed in Chapter 1.
For convenience, the mechanisms invoIved in the transport oI substances across the membrane
can be treated under eight types. OI these, Iour are physicaI mechanisms in which the Iorces that drive
substances across the membrane are suppIied Irom the environment oI the ceII. The transport by these
mechanisms is oIten termed as passive transport which does not invoIve chemicaI covaIent bond
breaking and bond making reactions. These physicaI mechanisms are diffusion, osmosis, events
Ieadings to Donnan distribution and solubilization. The remaining Iour mechanisms comprise
compIex enzymatic reactions and incIude processes such as pinocytosis or phagocytosis, facilitated
diffusion active transport and cellular secretions. These Iour mechanisms make use oI the energy
produced by the ceII`s own metaboIism.
Animal Physiology #$
Passive Transport
DIFFUSION: In a soIution the major component is termed soIvent and the substances dissoIved in
the soIvent are termed soIutes. InitiaIIy, iI a soIute in a soIution is in unequaI distribution, in time due
to random movements oI the soIute particIes they get distributed uniIormIy and produce a
homogenous soIution. When a concentrated soIution oI a substance is separated Irom the same
quantity oI a diIute soIution oI the same substance by means oI a membrane permeabIe to soIute
moIecuIes, the soIute moIecuIes wouId then move Irom the concentrated soIution towards the diIute
one untiI an equiIibrium is reached. The movement oI soIute particIes down the concentration
gradient is a physicaI phenomenon and does not depend on ceIIuIar energy. In this case the soIute
particIes diIIuse down the concentration gradient (see Chapter 1, Section 1.2).
DIFFUSION DOWN THE ELECTRICAL GRADIENT: In soIution the moIecuIes oI the soIute are usuaIIy
dissociated into ions that carry an eIectric charge. The IIuid media inside and outside the ceIIs have
charged particIes and the ceII membranes have the abiIity to maintain potentiaI diIIerence between
inside and outside. The potentiaI diIIerence oI the membrane is measured with microeIectrodes and it
has been Iound to range Irom 50 mV to 100 mV. The existence oI such a potentiaI diIIerence is due to
the asymmetricaI distribution ions between the inside and outside oI the membrane.
The ions invoIved in the Iormation oI potentiaI gradient are potassium and chIoride. The
intraceIIuIar concentration oI potassium ions in most ceIIs oI higher animaIs is higher than its
concentration in the extraceIIuIar medium. Likewise, the concentration oI sodium ions is higher in the
extraceIIuIar medium. These K
¹
and Na
¹
ions tend to move down their concentration gradients across
the pores in the membrane and iI these movements continue uninterrupted the potentiaI diIIerence
wouId coIIapse. But the ceIIuIar membranes maintain the potentiaI gradient by transIerring the Na
¹
and K
¹
ions against their concentration gradients. The movement oI the charged materiaIs is
inIIuenced by the eIectricaI charge existing on either side oI the membrane hence the materiaIs diIIuse
against their concentration gradients.
OSMOSIS: When two aqueous soIutions oI diIIerent concentrations are separated by a membrane
permeabIe to water but impermeabIe to soIute moIecuIes, water diIIuses through the membrane Irom
the soIution oI Iow soIute concentration to that oI high soIute concentration untiI the moIaI
concentrations on either side are the same (Fig. 8.1)
This process oI soIvent movement is caIIed osmosis. In an artiIiciaI system the movement oI
water by osmosis increases the hydrostatic pressure oI the high concentration soIution to a IeveI at
which no Iurther movement oI water in that direction is aIIowed. The hydrostatic pressure required to
prevent the movement oI water Irom pure water to the soIution side oI the semipermeabIe membrane
is known as the osmotic pressure oI the soIution. In symboIs, the osmotic pressure oI a soIution can be
expressed as
P ÷ R1C
where R is 0.0825 Iitre-atm/moIes-degree, 1 is absoIute temperature, and C is the moIaI concentration
oI the soIute.
WhiIe this equation hoIds good, the direct determination oI osmotic pressure oI soIutions is
technicaIIy a diIIicuIt process because it requires a reIativeIy Iarge voIume oI soIution to estimate the
Water Felations and Ionic Fegulations #%
number oI soIute particIes. However, since the osmotic pressure oI soIution is dependent on properties
such as the depression oI the vapour pressure, eIevation oI the boiIing point and depression oI the
Ireezing point, which are aII directIy proportionaI to one another, it wouId be easier to determine the
osmotic concentration oI a soIution by taking one oI these coIIigative properties into account. OI
these, the depression oI the Ireezing point is the property that is oIten utiIized to express the osmotic
concentration oI the soIution concerned. With this process the osmotic concentration oI even minute
quantities oI soIutions can be measured. A depression in Ireezing point by 1.858°C wouId indicate
one moIaI soIution oI an ideaI noneIectroIyte. Most oI the investigators in this IieId preIer to express
osmotic concentrations in the Iorm oI freezing point depressions rather than the moIaI concentrations
oI soIutions. For convenience, the term Ireezing point depression is abbreviated as ,.
The reIation between depression oI the Ireezing point and concentration can be expIained in the
IoIIowing equation:
,t
f
÷ K
f
C
where ,t
f
is the change in Ireezing point Ior a given soIvent, K
f
is a cryoscopic constant, and C is the
moIaI concentration. The K
f
equaIs to 1.858°C per moIe oI ions oI neutraI compounds in 1,000 gm oI
water. The vaIue oI K
f
wouId change with the type oI soIvent. II the soIvent is cycIohexanoI the K
f
vaIue wouId be 41.8. The vaIue oI K
f
Ior a given soIvent is determined as the sIope oI pIot oI Ireezing
point versus moIaI concentration oI a soIubIe soIute.
Body IIuids contain both strong eIectroIytes and weak eIectroIytes such as phosphates or
magnesium saIts and due to their compIete and incompIete dissociation their osmotic coeIIicients
diIIer. Such a diIIerence is partIy the resuIt oI incompIete dissociation and partIy due to the departure
oI the particIes Irom ideaI behaviour. Due to this reason, it is diIIicuIt to make an accurate estimation
oI osmotic pressure oI body IIuids Irom its chemicaI composition. The accurate method oI
FIg. S.1 Osmosis
P
w
- vapour pressure of pure water, P
0
- vapour pressure of the solution, P
H
- osmotic pressure. The osmotic
pressure is calculated by the formula, P
H
- PTC, where C is molal concentration, P is 0.0825 l-atm. per
degree, T is absolute temperature.
Po Pw
Po
P
RTC
H
Pw
B
Animal Physiology #&
determining osmotic pressure oI bioIogicaI soIution oI unknown concentration wouId be by
measurement oI the Ireezing point depression or one oI the other coIIigative properties.
The vaIue oI t
f
is determined by measuring the Ireezing point oI pure water. Then the vaIue oI t
f
is divided by K
f
to get the osmolality oI the soIution. The osmotic pressure oI bioIogicaI soIutions is
expressed in terms oI osmoles. A soIution is said to contain one osmoIe iI the amount oI soIute in one
Iitre oI water exerts the same osmotic pressure as does one moIaI soIution oI ideaI noneIectroIyte.
A soIution oI one-gram moIecuIar weight oI gIucose in one Iitre oI water is equaI to one osmoIe
(1 osmoIe/Iitre). On the other hand a soIution oI one gram moIecuIar weight oI sodium chIoride in one
Iitre oI water is approximateIy equaI to two osmoIes.
EXCHANGE DIFFUSION: There are some membranes which are impermeabIe to ions, but contain
carrier units Ior ion exchange materiaI. When soIutions are separated by such membranes the ions IaiI
to diIIuse IreeIy across the membrane. However, the membranes have within themseIves carrier unit
materiaIs which have high aIIinity to ions in the two soIutions. These ions carrying units traveI within
the membrane Irom one surIace to the other and due to their aIIinity they are aIways saturated (Figure
8.2).
Ion carrying units saturated with the ions oI the soIution-1 traveI to the surIace oI the membrane
Iacing soIution-2 to have 1:1 exchange oI ions with the soIution-2. The ions carrying units, now
saturated with the ions Irom the soIution-2 wouId move to the surIace oI the membrane Iacing
scIution-1 to have a 1:1 exchange with the ions oI soIution-1. Thus in exchange diIIusion process, a
1:1 exchange oI ions wouId take pIace on either side oI the membrane, so that the totaI IIux in both
the directions remains same and hence the concentrations oI the two soIutions wouId remain
unchanged.
The exchange diIIusion is carried out onIy iI a signiIicant concentration exists on either side oI
the membrane. II the soIution-1 is repIaced by a pure soIvent, obviousIy there wouId be no IIux oI
ions by way oI exchange diIIusion and wouId occur Irom soIution-1 to soIution-2, and thereIore the
FIg S.2 Exchange diffusion: The carrier in the membrane forms complexes with the ions. When the carrier with the ion
of solution-l reaches the membrane surface facing the solution-2. a l:l exchange of ions lakes place between
the carrier-ion complex of that solution. Similar l:l exchange of ions would take place if the carrier carrying ion
of solution-2 reaches the membrane surface facing solution-l.
1
Membrane Solution-2 Solution-1
2
2
1
1
1
1
2
1
2
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
Water Felations and Ionic Fegulations #'
IIux oI ions Irom soIution-2 to soIution-I aIso wouId cease. This is the case in exchange diIIusion, and
it diIIers Irom the simpIe diIIusion, in which the IIux wouId be Irom the soIution to the pure soIvent.
Active Transport of lons
AII diIIusibIe substances enter or Ieave the ceII down their concentration gradients, and iI aIIowed
uninterrupted the organization in the Iiving system wouId be jeopardized. The ceII membrane oI aII
Iiving ceIIs has the capacity to transport some substances against the gradient and such a transport is
caIIed the active transport.
The active transport can be distinguished Irom the passive transport by an important criterion, i.e.
as a resuIt oI the active transport oI soIute the entropy decreases and the Iree energy oI the system
increases, whereas in passive transport the Iree energy in the system wouId decrease. But the second
Iaw oI thermodynamics says that in the universe no spontaneous process occurs that wouId resuIt in a
decrease oI entropy or a net increase in Iree energy oI the system. ThereIore, in the active transport
Iree energy cannot increase by itseII.
The increase is due to the production oI Iree energy by a process that is coupIed with the active
transport. A change in the Iree energy oI a system does occur aIter transport which may be active or
passive. There are equations to caIcuIate the change in Iree energy oI the system. II the Iree energy
change is positive the process is an active transport. On the other hand, iI the change is negative the
process is passive transport. The equation to caIcuIate the change oI Iree energy when 1.0 moIe oI an
uncharged soIute is transported Irom one compartment to another is:
G
o
÷ 2.3 R1 Iog
10

C
C
2
1
C
1
and C
2
are the concentrations oI the Iree soIute at the beginning and end oI the transport process,
R is the gas constant, and 1 is the absoIute temperature.
Let us assume that one gram moIecuIar weight oI gIucose is to be transported Irom a
compartment in which its concentration is 0.001 M to a compartment in which its concentration is
0.1 M, i.e. up aIong the concentration gradient. Then the change in Iree energy can be caIcuIated with
the above equation.
G ÷ 2.3 1.98 298 Iog
10

0100
0 001
.
.
÷ 2.3 1.98 298 2.00 ÷ 2680 caI; G ÷ 2.68 kcaI
The Iree energy change is 2.68 kcaI. Since it is positive in sign it indicates increase in Iree energy.
II the movement oI gIucose is Irom a compartment in which its concentration is 0.1 M, to a
compartment in which its concentration is 0.001 M, i.e. down the concentration gradient oI 100 1,
the Iree energy change wiII be oI the same magnitude but in negative sign i.e. 2.68 kcaI.
The above cited IormuIas hoId good to uncharged soIute moIecuIes.
For the active transport oI Na
¹
, which is a charged moIecuIe, it is required to move against two
gradients. These gradients are: (a) the concentration gradient; and (b) the eIectricaI gradient. Since
there are two gradients, more work is required to move such a charged ion up.
Animal Physiology $
IMPORTANT FEATURES OF ACTIVE TRANSPORT SYSTEM: Active transport systems have the
IoIIowing characteristics; (a) these systems are dependent on the metaboIic processes yieIding ATP;
(b) these are soIute speciIic; (c) their activity depends on the concentration oI the substances being
transported; (d) these are direction speciIic; (e) these transport systems may be seIectiveIy poisoned;
(f) as a resuIt oI the integrated action oI active transport mechanisms the internaI soIute and ion
composition oI the ceIIs is maintained at a remarkabIy constant IeveI, despite IIuctuations in the
externaI composition.
(a) The active transport is dependent on the source oI metaboIic energy. This phenomenon has
been expIained with reIerence to the transport oI K
¹
and Na
¹
between the RBC and the
pIasma.
The RBC has high K
¹
and reIativeIy IittIe Na
¹
. The pIasma surrounding the RBC has very IittIe
K
¹
and high Na
¹
. Since the RBC membranes is permeabIe to both Na
¹
and K
¹
, they tend to
move down their concentration gradients. But the Na
¹
and the K
¹
diIIusing, down their
concentration gradient, are pumped back. Since the pumping in both the cases is against the
concentration gradient, energy is required. For this active transport, the energy comes Irom the
gIycoIytic pathway.
II gIycoIysis is stopped there wouId be no production oI ATP and the intraceIIuIar
concentration oI K
¹
wiII graduaIIy IaII and that oI Na
¹
wiII rise untiI both K
¹
and Na
¹
concentrations are equaIized on both sides oI the RBC membrane. This indicates that the
transport oI Na
¹
and K
¹
across the membrane oI RBC is energy dependent. In other kinds oI
ceIIs such as Iiver or kidney ceIIs, energy requirement is met Irom the oxidative phospho-
ryIation.
(b) There are many transport systems pumping substances against the gradients. Each system has a
speciIic substance or substances which it can pump. The active transport oI onIy certain
speciIic substances across the membrane oI some ceIIs suggests that they contain transport
system speciIic to those substances. For exampIe, the RBC oI some mammaIs transport
D-gIucose inward rapidIy, whereas they transport D-Iructose onIy very sIowIy.
Some other ceIIs have a pump speciIic Ior neutraI amino acids Iike gIycine and aIanine which
have uncharged R groups, but these ceIIs IaiI to transport gIutamic acid or Iysine since R
groups oI these have an eIectricaI charge.
(c) The movement oI gIucose into the ceIIs is carried out by active transport. The rate oI this
process depends on the externaI concentration oI gIucose. The rate oI gIucose inIIux increases
with the rise oI its externaI concentration untiI a peak is reached when no Iurther increase is
possibIe. This can be interpreted as due to compIete saturation oI its active transport system.
Such a property has aIso been Iound in case oI enzyme activity.
(d) The active transport has a speciIic direction. For exampIe, the K
¹
in most ceIIs is activeIy
pumped onIy in the inward direction. SimiIarIy, gIucose and amino acids are pumped in the
inward direction by respective systems. On the other hand, there are active transport systems
which are directed outward. The system responsibIe Ior pumping Na
¹
aIways transports Na
¹
in
the outward direction.
Water Felations and Ionic Fegulations $
(e) The active transport speciIic to various substances can be prevented by seIective poisoning.
For exampIe the active transport oI gIucose in the kidney can be poisoned by Phlorizin which
is a gIucoside obtained Irom the bark oI pear tree. In another exampIe the active transport oI
Na
¹
can be inhibited by gIucoside ouabain.
(I) Integrated actions oI the active transport mechanisms maintain the intraceIIuIar soIute and ion
composition remarkabIy constant even when their composition in the externaI medium
IIuctuates wideIy. In this respect the yeast and bacteria can be taken as exampIes having
remarkabIe abiIity to adjust their internaI soIute composition compatibIe with ceIIuIar Iunction
under variabIe pH.
Active transport oI ceII membranes resembIes enzymes in that (a) they show substrate speciIicity;
(b) they can be inhibited; and (c) they can be saturated by their substrates. These characters suggest
that the active transport system contains two major components. The Iirst is a carrier or porter
moIecuIe with a binding site speciIic to the substance to be transported and it is a protein. The second
component is a protein or group oI proteins which transIers energy to the Iirst component in order to
transport the substrate against the concentration gradient.
ACTIVE TRANSPORT OF K
+
AND Na
+
: The active transport systems IaII under two generaI types. OI
these, one type maintains a baIance oI K
¹
, Na
¹
, and water in the ceII. The other type pertains to the
transport oI organic nutrients such as gIucose and amino acids into the ceII and this we have incIuded
in Chapter 3. The Iirst type, i.e. the active transport oI K
¹
and Na
¹
is described here.
In most oI the vertebrate ceIIs the K
¹
concentration is reIativeIy high and constant and it ranges
between 100 and 150 mM. The Na
¹
concentration in the ceIIs is quite Iow. K
¹
concentration in the
ceIIs is high because oI its roIe in carrying out vitaI enzymatic reactions at a Iast rate. Such high and
Iow concentrations oI K
¹
and Na
¹
in the ceIIs oI higher animaIs are made possibIe because oI the
presence oI an active transport system (Figure 8.3) that can pump K
¹
into the ceII and Na
¹
out oI the
ceII. The carrier component oI the active transport system, responsibIe Ior the transport oI K
¹
and
Na
¹
, is an enzyme caIIed ATPase which is present in the ceII membrane. It has a Iarge particIe weight
and consists, oI two or, more component protein moIecuIes. This enzyme hydroIyzes ATP to Iorm
ADP and phosphate when activated by Na
¹
¹ K
¹
and Ior this reason it is caIIed Na
¹
K
¹
dependent
ATPase. Na
¹
K
¹
dependent ATPase system is Iixed in the membrane in such a way that it aIways
transIers Na
¹
ions out oI the ceII and K
¹
ions into the ceII, both moving again their concentration
gradients. It has been Iound that Ior each moIecuIe oI ATP hydroIyzed, three Na
¹
ions are removed
Irom the ceII and nearIy an equaI number oI K
¹
ions are brought inward. The hydroIysis brings about
two events; it decreases the Iree-energy causing a conIigurationaI change, or possibIy a rotation oI the
carrier (ATPase) so that the attached Na
¹
ion is brought in contact with the surIace oI the membrane
Iacing outside and that K
¹
is brought to the inside surIace. The second event causes a transIer oI
terminaI phosphate Irom ATP to IunctionaI group to the carrier. Since the IunctionaI group receives
this phosphate it is said to have undergone phosphoryIation and this process wouId take pIace beIore
the enzyme compIetes the transport oI Na
¹
and K
¹
.
Most oI the ATP produced in the ceIIs is used by the ATPase present in the ceII membrane. The
epitheIiaI ceIIs oI the kidney and nerve ceIIs in the brain consume most oI the ceIIs ATP.
Animal Physiology $
WATER BALANCE BY ATPASE: The Na
¹
K
¹
stimuIated ATPase in the membrane is aIso
responsibIe Ior the maintenance oI water baIance in the ceII. II K
¹
is constantIy pumped into the ceII
without the Ioss oI cation Irom the ceII. Water wouId enter the ceII aIong with the K
¹
ions as a resuIt
oI which the ceII sweIIs. This event is prevented by the simuItaneous pumping oI Na
¹
aIong with an
equaI amount oI water. Thus the ceII maintains internaI K
¹
and water baIance.
8.E SDME DEFlNlTlDNS
BeIore a discussion oI the osmotic and ionic reguIations in animaIs is made it wouId be necessary to
deIine certain technicaI terms oIten used in connection with osmoreguIation. In osmoreguIatory
studies our interest is mostIy centred on the concentrations oI IIuids, inside and outside the ceIIs and
even outside the organism. The concentrations oI these IIuids are expressed either in terms oI the
quantity per unit weight oI soIvent, i.e. water.
The quantity oI soIute can be measured either in terms oI grams (g), miIIigrams (mg ÷ 10
3
g), and
micrograms (g ÷ 10
6
g), or in terms oI moIes (M), i.e. gram-moIecuIes, miIIimoIes (mM ÷ 10
3
M), or
micromoIes (M ÷ 10
6
M).
In body IIuids the quantity oI a soIute may usuaIIy be expressed in moIes or miIIimoIes because in
this way the number oI particIes present in a Iitre oI soIution or in a Kg oI water is perceived.
A moIar soIution is one in which the moIecuIar weight oI a substance in grams (moIe) is
dissoIved and made up to one Iitre with water.
A one-moIar soIution contains the moIecuIar weight oI a substance in grams (moIe) dissoIved in
1,000 gm oI water.
In IairIy diIute soIutions Iike water in nature and the body IIuids oI many animaIs there is IittIe
diIIerence between concentrations expressed by moIarity or moIaIity. This Iack oI signiIicant
FIg S.3 Active transport system for K
+
and Na
+
.
ATP
2 – 3k
+
ADP + Pi
3Na
+
Na – k ATPase
molecule
+ +
Cell membrane
Water Felations and Ionic Fegulations $!
diIIerence is due to the absence oI substances with high moIecuIar weight in these IIuids. In more
concentrated soIutions Iike body IIuids and the bIood oI higher animaIs, and the protopIasm oI most
ceIIs, substances oI high moIecuIar weights are present and thereIore a signiIicant diIIerence exists
between moIaI and moIar concentrations.
For this reason the concentrations oI these IIuids are expressed in moIaIities. The concentration oI
body IIuids is oI the IeveI oI miIiimoIes and hence they are convenientIy expressed in miIIimoIes
rather than in moIes.
Dsmotic Pressure
One oI the very important physicaI properties oI soIutions in which we are mainIy concerned at this
juncture is the osmotic pressure. The osmotic pressure oI a soIution is reIated more directIy to the
moIaI than to the moIar concentration. Besides, osmotic pressure, the other coIIigative properties oI
soIutions are the depression oI the vapour pressure, the eIevation oI the boiIing point, and the
depression oI the Ireezing point. The coIIigative properties are directIy proportionaI to one another.
The direct measurement oI osmotic pressure oI soIutions, whether artiIiciaI or obtained Irom
organisms, is technicaIIy diIIicuIt and requires Iarge voIumes oI IIuid. For this reason, the osmotic
pressure is caIcuIated indirectIy Irom one oI the coIIigative properties, i.e. the depression oI the
Ireezing point. Though the determination oI Ireezing point depression in bioIogicaI IIuids is beset
with severaI diIIicuIties, it is the most convenient method because it requires onIy minute quantities oI
IIuid.
Pure water has a Ireezing point oI 0C. Freshwater and the seawater have soIute particIes and
hence their Ireezing temperature IaIIs beIow that oI pure water. Such a Ireezing point depression is
directIy proportionaI to the moIaI concentration oI the soIution. Freezing point depressions are used
very IrequentIy to determine the concentrations, and the depression is usuaIIy denoted by the Greek
capitaI ,. The greater the depression in Ireezing point, the higher is the soIute concentration. Seawater
with its high concentration oI soIute particIes has a Ireezing point depression oI 2.2C (2.2,C).
The Ireshwater has Iar Iess soIute particIes and has Ireezing point depression between 0.03 and
0.05C (0.03, and 0.5,C). A one-moIar soIution Ireezes at 1.86C (1.86,C).
Tonacity and Dsmoticity
A soIution is said to be isoosmotic with another iI it exerts the same osmotic pressure. SoIutions oI
simiIar osmotic pressure have the same vapour pressures, Ireezing points and boiIing points.
An isotonic solution is one which neither sweIIs nor shrinks the ceII that is not immersed in it. An
isotonic soIution is generaIIy aIso isoosmotic, but this need not necessariIy be so. A sIight diIIerence
in the osmotic pressures oI the medium and the ceIIuIar IIuid does not bring about change in the
voIume oI the ceII because oI the rigidity oI the ceII waII. This shouId not Iead to the inIerence that
the two soIutions are isoosmotic. Since this soIution did not bring about change in voIume oI the ceII
it is said to be an isotonic soIution.
A soIution which is more diIute than another is termed hypoosmotic and the one which is stronger
is hyperosmotic. AnimaIs which have isoosmotic and hypoosmotic body. FIuids exist in marine
habitat, whereas those with hyperosmotic body IIuids Iive in Ireshwaters. In TabIe 8.1 the Ireezing
point depression oI the body IIuids oI diIIerent groups oI animaIs in reIation to their habitats is given.
Animal Physiology $"
Marine invertebrates and hagIish are the true saItwater animaIs and descended Irom marine
ancestors and their body IIuids are isoosmotic with the seawater. They have the same Ireezing point
depression as that oI seawater. There are aIso other animaIs such as Iampreys and teIeost Iishes, which
invaded sea Irom Ireshwater. Their body IIuids are hypoosmotic with the seawater. In hypoosmotic
Iorms, the water Irom the body IIuids ends to move into the hyperosmotic medium.
The Ireezing point depression oI the body IIuids oI aII Ireshwater animaIs given in TabIe 8.1
suggests that they are hyperosmotic in reIation to the Ireshwater and thereIore they tend to gain water.
The Ireezing point depression oI terrestriaI animaIs is very near to that oI Ireshwater animaIs
suggesting their origin Irom Ireshwater animaIs. The probIems that are posed by the terrestriaI
environment are quite diIIerent Irom those oI aquatic environment. The Iand animaIs tend to Iose
water through evaporation.
8.3 A0UATlC AND TERRESTRlAL HABlTATS
The animaIs which migrated to diIIerent environments during the course oI evoIution deveIoped
suitabIe physioIogicaI adaptations. What probIems did these environments impose on other
inhabitants and how eIIectiveIy the species Iiving there had made physioIogicaI adjustments to
IIourish there can best be understood iI we Iirst know the ideaI reIationship between the true marine
Iorms and their environment, i.e. the sea. In Iact, there aIways exists a constant interaction between
the organisms and their environments due to certain physicaI Iorces and chemicaI Iactors acting upon
them.
SEAWATER: The physicaI and chemicaI Iactors oI these water such as mineraI concentration,
temperature, density, and acidity remain IairIy constant except Ior Iimited variations during aII seasons
oI the year. Even these sIight variations tend to appear sIowIy giving adequate time Ior the animaIs
Iiving there to bring about necessary physioIogicaI adjustments.
TabIe S.1 The Relationship between the Osmotic Pressures of Body Fluids of Animals and Their Habitats
Søa (2.2,ºC) FrøsnwaIør (0.03,ºC) TørrøsIr¡aI ønv¡rønmønI
INvERTEBRATES
Blood roughly isoosmotic Most freshwater invertebrates: Insects
with medium 0.+, to 0.8, 0.6, to 0.8,
Molluscs: 0.2,
vERTEBRATES
Teleosts: 0.8, to l.l, Teleosts: 0.5, to 0.7,
0.8, Eel 0.6,
(migratory)
Amphibia: 0.+, to 0.5,
Turtles: 0.6, Reptiles: about 0.5, 0.6,
Birds: 0.6,
Whale: 0.7, Mammals: 0.5, to 0.6,
Adapted from Pr¡n¿¡pIøs ø/ An¡maI Pn)s¡øIøg) by D. W. Wood: with slight modifications
Water Felations and Ionic Fegulations $#
BRACKISH WATERS: Brackish waters are mixohaIine having their saIinity between 30 per cent and
0.5 per cent as per Venice system. Open seas such as Arctic ocean, have saIinities as Iow as 30 per
cent. The partiaIIy encIosed seas such as BaItic or Bay oI BengaI have signiIicantIy Iow saIinities, i.e.
beIow 30 per cent. The Iower Iimit oI brackish water saIinity is not so cIearIy deIined and it is above
0.5 per cent, which is the saIt content oI Ireshwater Iakes and rivers. The brackish water is the
physioIogicaI bridge between sea and Ireshwaters. It has a gentIe saIinity gradient through which
marine animaIs, in course oI evoIution, migrated to Ireshwaters. The saIinity gradient at the estuaries
provided an opportunity Ior the graduaI adaptation oI marine animaIs to Iower saIinity oI brackish
waters during their migration to Ireshwater.
FRESHWATER: The physicaI and chemicaI Iactors are very much variabIe. The concentration oI
mineraIs is much Iower than that oI the seawater and varies considerabIy. Even the ionic composition
oI Ireshwater varies Irom pIace to pIace and season to season. The cIimatic Iactors such as rain and
temperature bring about quick changes in mineraI concentration, density, acidity and temperature oI
the Ireshwater. The swiIt IIowing waters oI the rivers contain more oxygen than the sea. The oxygen
content in stagnant waters is very Iess.
TerrestriaI Environment
This environment is IiIIed with air which is a mixture oI gases. The temperature and humidity oI this
environment IIuctuate very oIten. The terrestriaI environment has a Iess dense atmosphere compared
to the aquatic one. The radiation Irom the sun vaporizes the water Irom the seas and ponds, and the
vapour remains in the air. The amount oI water vapour in the air increases with temperature. Not onIy
the water oI the seas and ponds but aIso that present within the terrestriaI organisms is subjected to
evaporation. However, since the organisms are covered by nonaqueous materiaI evaporation is very
much reduced. The cIimate oI the terrestriaI environment varies Irom pIace to pIace and time to time.
The temperature and humidity near the seashores are diIIerent Irom that oI the desert. The cIimate at
high aItitudes is diIIerent Irom that oI the sea IeveI. SimiIarIy the cIimate at the equator is not the same
as the one prevaiIing at the poIar regions.
8.4 PRDBABLE MDVEMENTS DF ANlMALS BETWEEN
DlFFERENT ENVlRDNMENTS
We have mentioned earIier in this chapter that the animaIs moved Irom the sea to other habitats. Such
a movement did not occur directIy Irom sea to Ireshwater. The body IIuids oI the marine animaIs are
isoosmotic to sea medium, but compared to Ireshwater, they are hyperosmotic. The true marine
animaIs when transIerred to Ireshwater wouId die because they have no mechanisms to pump out
water that enters into their body by osmosis. ThereIore any movement oI marine animaIs into
Ireshwater wouId have been accompanied by the graduaI deveIopment oI suitabIe physioIogicaI
mechanisms to remove the inIIuxed water. Such a movement is a step by step process and occurred
through the brackish water that exists near the estuaries.
To suit the conditions in Ireshwater, true marine animaIs in course oI evoIution deveIoped such
drastic changes in their nature oI IiIe, that their return to sea seemed inconceivabIe. However, during
Animal Physiology $$
evoIution, many vertebrates moved Irom the Ireshwater back to the sea. A schematic presentation oI
probabIe movement oI vertebrates into diIIerent media is given in Fig. 8.4.
In the earIy history oI the vertebrates, the ancestraI agnatha (jawIess Iishes) deveIoped capacity to
Iive in Ireshwater. From these agnatha the jawed Iishes evoIved in Ireshwater. EIasmobranchs and
bony Iishes evoIved Irom the earIy jawed Iishes. The Iorms giving rise to eIasmobranchs migrated to
the sea. Some oI the marine eIasmobranchs Iike Pristis reinvaded Ireshwaters. Three oIIshoots arose
Irom the bony Iishes. One oIIshoot consists oI Iishes which invaded the sea to Iorm the ancestors oI
the modern marine teIeosts. These marine teIeosts aIso beIieved to have migrated back to Ireshwater
Ieading to the evoIution oI a number oI Ireshwater teIeosts oI today incIuding some pipeIishes.
FIg S.4 Schematic presentation of the probable movement of the vertebrate groups into different media during
evolution.
FRESHWATER
–0.03°C
SEA
–2.2°C
LAND
Ancestral
agnatha
Rise of early fish
Bony fish
AMPHIBIA
Frogs,
Lizards
tortoises
snakes, etc.
REPTILIA
Pipa
necturus
Modern freshwater
bony fish
Some pipefish
Turtles
crocodiles, etc.
Ducks and
waders, etc.
others
water rats etc.
In
v
a
s
io
n
o
f
th
e
s
e
a
Marine teleosts
Invasion of the sea
prisis
E
l
a
s
m
o
b
r
a
n
c
h
s
R
e
i
n
v
a
s
i
o
n
o
f
b
r
a
c
k
i
s
h
A
n
d
f
r
e
s
h
w
a
t
e
r
R
e
in
v
a
s
io
n
o
f
b
r
a
c
k
is
h
A
n
d
f
r
e
s
h
w
a
t
e
r
Elasmobranchs
Marine lizard
turtles
crocodile
sea sn kes a
Hagfish
A
q
u
a
t
i
c
s
e
m
i
-
t
e
r
r
e
s
t
r
i
n
Toads
AVES
Most birds
MAMMALIA
Most mammals
Penguins
ducks
gulls, etc.
Whales
seals
dugong, etc.
Water Felations and Ionic Fegulations $%
Another oIIshoot oI bony Iishes continued in Ireshwater. The third oIIshoot invaded Iand resuIting in
the origin oI amphibians. The higher vertebrates, i.e. amphibia, reptiIia, aves and mammaIia evoIved
Irom non-marine Iorms, and aII but amphibian incIude some species which are associated with
seawater. Marine turtIes, sea snakes Irom among reptiIes, penguins and guIIs, etc., among birds, and
whaIes, seaIs, dugong, etc., Irom mammaIs are the IamiIiar exampIes that migrated to the sea.
The invertebrates too migrated Irom sea to Ireshwater and Iand. The terrestriaI invertebrates, Iike
vertebrates, evoIved mostIy and directIy Irom Ireshwater ancestors. However, a Iew terrestriaI
invertebrates such as Iand crabs, wood-Iice and some moIIuscs have invaded the Iand directIy Irom the
sea. SeveraI groups oI invertebrates directIy coIonized the Ireshwater at diIIerent times during
evoIution. The puImonate moIIuscs and aquatic insects beIong to the group that migrated Irom Iand to
Ireshwater.
Such an invasion Irom one environment to another is possibIe onIy when the animaIs acquired
adaptive mechanisms to maintain the composition oI their body IIuids at a IeveI required by the ceIIs
to carry out their normaI physioIogicaI activities. In the absence oI such adaptive mechanisms, the
ceIIuIar Iunctions wouId succumb to the dominating physicaI Iorces oI the new habitats. The ceIIs
wouId thereIore shrink iI transIerred to a habitat containing highIy concentrated medium, and wouId
sweII iI kept in Iow concentration. In either case the ceIIs cannot carry out their physioIogicaI
activities and wouId reach a perIect equiIibrium state with the medium, i.e. they become inanimate.
In order to perIorm normaI physioIogicaI activities, the ceIIs require IoIIowing conditions:
(a) The ceIIs shouId be surrounded by a water medium.
(b) The ceIIs shouId excrete water as quickIy as it enters.
(c) The ceIIs shouId be abIe to adjust their internaI concentration to match the variations that
might occur in the externaI medium.
In higher invertebrates and vertebrates the ceIIs are surrounded by body IIuids. The concentration
and composition oI the body IIuids bathing the ceIIs are dependent on the Iorces imposed by the
environment. The bIood concentration oI sea invertebrates is simiIar to that oI seawater and hence sea
poses no threat to the concentration oI bIood. The Ireshwater medium has ion concentration much Iess
than that oI seawater. BIood concentration oI the Ireshwater animaIs is above that oI Ireshwater and it
must be maintained against the Iorces Irom the environment in order to provide ideaI bathing medium
Ior the ceIIs. Because bIood is in higher concentration than that oI the environment, water tends to
enter inside by osmosis. II this movement continues, bIood gets diIuted and consequentIy the ceII
voIume and the composition oI the ceIIuIar IIuid change abnormaIIy impairing the normaI
physioIogicaI Iunctions oI the ceIIs and the organism as a whoIe. The air breathing aquatic Iorms have
a body surIace which is aImost impermeabIe to water and ions. But in case oI animaIs with aquatic
respiration the body surIace is permeabIe to oxygen as weII as water and inorganic ions. ThereIore, in
these aquatic animaIs the water entering by osmosis is removed as urine, and the inorganic ions
escaping into the water medium are activeIy transported back to the bIood.
The brackish water is an environment that very oIten varies in concentration. Further, the
concentration IIuctuations are very high. Under such variations the true marine Iorms cannot survive.
In order to Iive successIuIIy in such an environment, the animaIs must be equipped with speciaI
adaptations. UnIike the true marine Iorms, the brackish water animaIs have deveIoped toIerance to the
Animal Physiology $&
concentration IIuctuations in their body IIuids. These animaIs aIIow IIuctuations in the concentration
oI their body IIuids to suit the change oI concentrations in brackish waters. Besides this toIerance, the
animaIs, Iike aII other organisms, have the capacity to increase or decrease the rate oI active transport
oI speciIic eIectroIytes in reIation to the concentration oI the medium. At the same time a change in
the bIood concentration oI these brackish water dweIIers brings about a suitabIe aIteration in the
soIute concentration oI the ceIIs. However, in the absence oI such a modiIication the body ceIIs wouId
either shrink or sweII jeopardizing their physioIogicaI activities.
AnimaIs Iiving in water have direct access to the saIts and the dissoIved gases in addition to
water. The terrestriaI environment Iacks water and saIts, but has onIy the gases. This poses probIems.
FirstIy, these animaIs do not directIy receive water and saIts Irom this environment, and secondIy, the
heat and the dryness oI the environment causes desiccation. Such probIems were overcome to a
Iimited extent by Iand animaIs through modiIications oI many oI the mechanisms aIready acquired by
their aquatic ancestors and by evoIving a Iew new ones oI their own.
The mechanisms IaIIing under the Iirst category are: (a) tightening up oI water permeabIe
coverings, (b) drinking oI water, (c) extrarenaI excretion oI saIts, (d) reduction oI gIomeruIar
IiItration, and (e) the abiIity oI protopIasm to carry out ceIIuIar activities with aItered amounts oI
eIectroIytes and water. Under the second category the new mechanisms deveIoped by these animaIs
are: (a) the abiIity to recover Iarge amounts oI water Irom urine (hypertonic urine), (b) the capacity to
absorb signiIicant amounts oI water at the surIaces, (c) the abiIity to depend IargeIy upon the
metaboIic water, and (d) the behaviouraI responses oI avoiding desiccating microhabitats, and Iiving
not Iar Irom the water source.
8.5 RDLE DF BDDY FLUlDS
There are two major types oI body IIuidsintraceIIuIar and extraceIIuar IIuids. The singIe ceIIed
organisms have onIy the intraceIIuIar IIuid and these organisms osmoreguIate directIy with the
externaI medium in which they Iive.
Higher metazoa have extraceIIuIar body IIuids with which the ceIIs oI the interior tissues perIorm
osmotic and ionic reguIations. These extraceIIuIar body IIuids are simiIar in concentration to that oI
seawater. ThereIore, the body IIuids, bathing the tissue ceIIs, can be described as being surrounded by,
what we may caII, an internaI sea. The extraceIIuIar IIuids in higher metazoa are separated into two
compartments, viz. a primary body cavity or haemocoele, and a secondary body cavity or coelome.
The IIuids oI the primary body cavity are bIood and Iymph and they are constantIy circuIated
throughout the body. There are other speciaIized body IIuids such as cerebrospinal fluid in the centraI
nervous system, occular fluids in the eye, endolymph and perilymph in the ear, etc.
The coeIome usuaIIy receives the genitaI and excretory products and Iorms gonoducts or
excretory ducts. There exists a reciprocaI reIationship between the size oI the coeIome and that oI
haemocoeIe. In echinoderms, vertebrates, anneIids and cephaIopods the coeIome Iorms Iarge
perivisceraI spaces, whereas it is very much reduced to pericardium, gonoducts and excretory system
in the arthropods, and in gastropod and IameIIibranch moIIuscs it is Iarge.
Water Felations and Ionic Fegulations $'
The bIood drawn Irom the bIood vesseIs is caIIed vhole blood and it contains bIood ceIIs
surrounded by the IIuid. FIuids Iike plasma and serum can be separated Irom the whoIe bIood. PIasma
is separated Irom the bIood ceII and other soIid particIes by centriIuging the whoIe bIood. Serum can
be obtained by aIIowing the whoIe bIood to cIot. The serum, however, has simiIar eIectroIyte
composition to that oI pIasma.
Invertebrates Iacking a circuIatory system possess tissue IIuids or Iymph. This IIuid Iorms minute
Iakes which surround the ceIIs. It contains substances required by the ceIIs Ior their nutrition and
osmoreguIation, and carries away the wastes Irom the ceIIs. The Iymph has bIood ceIIs which are
phagocytic in nature. The Iymph in higher vertebrates occurs in a speciaI system oI channeIs caIIed
Iymphatics. These wouId commence bIindIy in the tissues and join the veins to empty the Iymph into
them. Thus, in these animaIs with cIosed circuIatory system, the bIood capiIIaries and the Iymphatics
have IIuids distinctIy separated Irom the tissue IIuids. The tissue IIuids are Iormed as a resuIt oI the
IiItration through the waIIs oI capiIIaries into the tissue spaces. The Iymph is derived Irom the tissue
IIuids and it enters the Iymphatics either by diIIusion or by IIowing through the terminaI openings oI
the Iymphatics.
In animaIs with open circuIatory system the bIood, the Iymph and the tissue IIuids do not exist as
separate entities. The IIuid oI the open circuIatory system is caIIed hemoIymph because it moves
through vascuIar channeIs and the tissue spaces.
8.8 ADAPTATlDN TD MARlNE HABlTAT
AnaIysis oI the body IIuids Irom a number oI marine animaIs has resuIted in the IoIIowing
generaIizations:
(a) The body IIuid concentrations are simiIar to that oI seawater.
(b) They diIIer Irom seawater in reIation to the ionic composition.
(c) ConsiderabIe variation exists in the ionic reguIation by various groups oI animaIs.
(d) In reIated animaIs the ionic reguIation does show simiIarities. The body IIuids oI most marine
invertebrates and the hagIishes are in osmotic equiIibrium (isoosmotic) with seawater. In some
groups oI animaIs, i.e. coeIenterates and echinoderms, the degree oI reguIation oI ions is not
great. Their individuaI ionic concentrations do not vary signiIicantIy Irom that oI the seawater,
which has the IoIIowing standard concentrations oI common ions (mM/kg).
Sodium Potassium Calcium Magnesium Chloride Sulphate
mMfkg +78.3 l0.l3 0.+8 5+.5 558.+ 28.77
However, majority oI the marine members oI other invertebrate groups, viz, crustaceans,
moIIuscs, etc., maintain high concentration oI potassium and caIcium; and oIten Iow concentrations oI
suIphate and magnesium, in their bIood as compared to seawater. Thus they diIIer in ionic
composition Irom that oI seawater. From the above observations it is evident that whiIe coeIenterates
and echinoderms maintain roughIy simiIar ionic composition to that oI seawater, the crustaceans and
moIIuscs maintains an ionic composition that is diIIerent Irom that oI seawater.
Animal Physiology %
ReguIatory Mechanisms
The maintenance oI diIIerences in ionic composition between the animaI and its environment is vitaI
and depends on the passive and active Iactors. The passive Iactors are: (1) the permeabiIity oI the
body waII that is in contact with the medium; (2) the presence oI protein in the body IIuids which
wouId produce Donnan eIIects, and bind some oI the ions, particuIarIy caIcium in indiIIusibIe
compIexes. The active Iactors in ionic reguIation are: (i) the excretion oI saIts and water, and (2) the
active absorption oI saIts and water.
PERMEABILITY OF THE BODY WALL: The body waII oI marine invertebrates is permeabIe to saIt
and water and it is because oI this that these animaIs are isoosmotic with seawater. The soIt marine
invertebrates when pIaced in a diIIerent saIinity oI seawater, become isoosmotic with this new
medium. Acquisition oI this new equiIibrium is partIy due to the osmotic movement oI water and
partIy due to the movement oI saIt.
DISTRIBUTIONS OF IONS DUE TO PROTEIN IN BODY FLUIDS: Protein in the body IIuids aIIects the
distribution oI ions between the body IIuids and the outside medium in the IoIIowing ways; that is, (1)
by Iorming indiIIusibIe compIexes with some oI the ions, particuIarIy caIcium; (2) by inducing a
Donnan equiIibrium aIIecting the distribution oI aII the ions.
EXCRETION AND IONIC REGULATION: Excretory organs pIay an important roIe in reducing the
concentrations oI some ions in the bIood. In the invertebrates, the excretion oI saIts is perIormed by
renaI or antennary gIands. The bIood oI decapods is poor in magnesium and suIphate, but rich in
potassium and caIcium. That is because the renaI organs tend to remove magnesium and suIphate and
conserve potassium and caIcium. By this conservation process the concentration oI potassium and
caIcium ions is maintained at a IeveI not above that oI seawater. But as stated above, decapods have
potassium and caIcium in higher concentration than in seawater, and such concentrations are due to
active uptake oI these ions Irom seawater.
UPTAKE OF SALTS AND WATER: The diIIerentiaI permeabiIity, the eIIects oI the presence oI protein
in the body IIuids, and the excretion may account Ior some degree oI ionic reguIation. But higher
concentrations oI ions in body IIuids than in the seawater are possibIe onIy iI they are activeIy
transported. In addition to active uptake oI ions, marine invertebrates need water to compensate its
Ioss in the production oI urine. For this, the water is absorbed through the gut. Active uptake oI ions
at the body surIace produces very IocaIized concentration diIIerence and this prompts water uptake at
that region.
HagIishes, oI which Myxine is an exampIe, are the onIy group oI vertebrates which remained
marine throughout their evoIution (Fig. 8.1). The body IIuids oI these hagIishes are isoosmotic with
seawater and the major part oI the osmotic pressure is accounted Ior by the inorganic ions. As in
many crustaceans, concentrations oI magnesium and suIphate ions oI the Myxine bIood are Iess than
that oI the seawater. Potassium and caIcium concentrations are aIso Iower, yet the osmotic pressure oI
its bIood is maintained by the strongIy concentrated sodium. The osmotic reguIation in these
hagIishes is not very diIIerent Irom that oI marine invertebrates.
In marine teIeosts and Iampreys, concentration oI bIood is a IittIe higher than that oI Ireshwater
Iorms. Since these Iorms are hypoosmotic to the seawater, they tend to show dehydration as a resuIt oI
Water Felations and Ionic Fegulations %
the osmotic Ioss oI water through the epitheIiaI Iining oI the mouth, pharynx and giIIs. Loss oI water
through the generaI body surIace is greatIy reduced due to the adaptive changes such as thickening oI
the dermis, presence oI mucous gIands on the body surIace and the growth oI scaIes. The osmotic
water Ioss Irom these hypoosmotic Iorms can be repIaced by drinking, and in Iact this is one
mechanism adapted by teIeosts. In the gut, water is absorbed by osmosis, provided that a major part oI
ions is aIso absorbed Irom the seawater.
The Iish may drink seawater as much as 50-200 mI/kg day. Drinking seawater creates a new
probIem. The saIts go on accumuIating and the NaCI in particuIar increases in the bIood iI not
continuousIy removed. ThereIore, saIt shouId be eIiminated without Iosing water. SaIt eIimination
takes pIace through the giIIs and this was demonstrated by heart-giII preparation. The experiment has
reveaIed that the saIt composition oI bIood returning Irom the giIIs and that oI the medium bathing the
giIIs had undergone deIinite changes. This, as weII as recent experiments using isotopes demonstrated
that the giIIs oI the teIeost Iish wouId secrete saIts into the medium against the concentration gradient.
The active extrusion oI sodium and chIoride seems to have been perIormed by aII the ceIIs in the giII
epitheIium.
In these marine teIeosts considerabIe amount oI saIts is aIso Iost by way oI urine. The kidney oI
these Iishes cannot produce urine that is hyperosmotic to the bIood but it is sIightIy hypoosmotic to
the bIood. Increased amounts oI saIts cannot be eIiminated by the kidneys, as this wouId require the
Iormation oI more urine. Marine teIeosts cannot aIIord to Iose more water, and thereIore they reduce
the production oI urine to the bare minimum. The urine produced in these teIeosts contains
magnesium, caIcium and suIphate that Iorce their entry into the bIood. Thus the kidney pIays an
important roIe in the maintenance oI the ionic composition oI the bIood.
8.7 ADAPTATlDNS TD BRACKlSH WATER HABlTAT
Brackish water is deIined as diIute seawater with concentration anywhere between 1.5 per cent and 90
per cent oI that oI pure seawater. Marine Iauna cannot survive in diIutions beIow the upper Iimit oI
brackish water concentrations. Brackish waters exist in restricted coastaI regions, such as estuaries or
saIt marshes where the Ireshwater Irom the rivers mixes with the seawater. The IandIocked seas such
as BaItic, the Caspian and the AraI Sea are aIso brackish water.
Marine animaIs Iiving in shaIIow water near the shores and particuIarIy those near the estuaries
are constantIy subjected to changing concentrations. The marine animaIs that cannot toIerate
concentration variations must bring about suitabIe modiIications in their biochemistry, physioIogy and
behaviour to Iive under these varying concentrations. The gentIe saIinity gradient existing Irom sea to
Ireshwater provides an opportunity Ior the graduaI adaptation oI marine animaIs to Iower saIinities.
The Iauna Iiving between the saIinity ranges oI the brackish water are oI three types: (a) marine
animaIs with toIerance to Iow saIinities existing at the upper end oI brackish water saIinity range; (b)
Ireshwater animaIs with toIerance to moderate saIinities existing at the Iower end oI the brackish
water saIinity range; and (c) true brackish water animaIs which are not Iound in either seawater or
Ireshwater aIthough they are abIe to survive in them.
Animal Physiology %
Marine animaIs are isoosmotic at 100 per cent seawater and most oI them cannot maintain their
normaI vigour at Iower saIinities oI the brackish water and Ior this reason, the number oI marine
species decIines with saIinity Carcinus maenas (a shore crab) and Mytilus edulis (a musseI) are
characteristic marine animaIs Iiving in brackish water. A considerabIe number oI these animaIs can
penetrate down to about 15 per cent oI seawater.
Palaeomonetes varians and Nereis diversicolar are the true brackish water animaIs which can
toIerate seawater, but do not Iive there. Variations in the body IIuid concentrations oI a Iew species
dweIIing in brackish water are given in Figure 8.5 which indicates that they conIorm to the IairIy wide
IIuctuations in the medium. The concentrations oI body IIuids are expressed in this diagram in terms
oI depression in Ireezing point. This change in the concentration oI the body IIuid oI each animaI
under experimentation is measured Ior every change in the concentration oI the medium and pIotted.
The animaIs respond to the change in the externaI medium by suitabIy aItering the concentrations oI
their body IIuids. A graph is obtained Ior each animaI that indicates the abiIity or otherwise oI the
animaI to reguIate its saIt and water content in media oI changing concentrations. The graph so
obtained is a straight Iine, which iI extrapoIated passes through zero. The bIood concentration oI the
animaI concerned varies directIy with the change in that medium. In such a case the animaI is
FIg S.5 Brackish water animals have tolerance to the changing concentrations of the medium. The blood concentration
of these animals varies directly with the changes in the concentration of the medium.
Water Felations and Ionic Fegulations %!
incapabIe oI any degree oI reguIation. II the curve obtained deviates Irom the Iine representing
isotonicity (i.e. Iine passing through zero), the animaI concerned has the abiIity to reguIate to changes
in the concentration oI externaI medium. The greater the degree oI deviation oI the curve, the greater
is the animaI`s abiIity to reguIate its bIood concentration against the osmotic eIIects oI the diIute
medium.
The Iinear curves obtained in case oI Arenicola (AnneIida) and Mytilus (LameIIibranchiata)
suggest that they are isoosmotic species with no abiIity to reguIate their bIood concentrations against
changes in the concentrations oI the medium. However, a IaII in bIood concentration in tune with that
oI externaI concentration poses reguIatory probIem between the bIood and the body ceIIs in generaI.
In these animaIs the bIood is hypoosmotic to that oI ceIIs. Hence the osmotic and ionic reguIations are
conIined between the ceIIs and the bIood.
Brackish water animaIs such as Nereis diversicolar (AnneIida). Palaemonetes varians, and
Carcinus (Decapoda) have the abiIity to reguIate their bIood concentration in order to maintain it at
hyperosmotic IeveI despite wide changes in the brackish water concentration. In spite oI these
reguIations, the bIood concentration oI these animaIs IaIIs beIow that oI true marine Iorms. In Fig. 8.5,
the graphs Ior two crabs, Carcinus and Maia suggest the reIation between the concentration variations
oI the medium and the body IIuids. The Iormer, which is commonIy Iound in estuaries, can
osmoreguIate and the Iatter, the bIood oI which is isoosmotic with its marine medium, cannot
osmoreguIate iI wide variations occur in medium concentration. The bIood concentration oI Carcinus
corresponds to about 60 per cent seawater when it is Iiving in 15 per cent seawater. In Nereis the
abiIity to reguIate is Iess than Carcinus but the animaI is capabIe oI Iiving even in 5 per cent seawater
because it can toIerate osmotic eIIects oI Iow saIinity by suitabIy reducing bIood concentration to a
IeveI equivaIent to 30 per cent seawater. The bIood concentration oI the brackish water prawn, viz.
Palaeomonetes is rather diIIerent Irom those oI marine animaIs Iiving in brackish waters.
Palaeomonetes maintains its bIood concentration corresponding to 50-70 per cent seawater even
when the concentrations oI the medium range anywhere between 5 and 110 per cent seawater. It
appears that it can aIso survive in concentrations beIow 5 per cent seawater, but beIow 0.5 per cent
seawater it dies. The graphs oI Carcinus, Mytilus, Arenicola, and to some extent that oI Nereis
indicate that these animaIs tend to act in Iine with the IaII in the contraction oI the medium by
reducing their concentration to the extent possibIe, thereby reducing active work required to maintain
ionic and osmotic reguIation. This is the generaI Ieature Ior aII saIt water animaIs that penetrate into
Ireshwater; and, in Iact, aII Ireshwater species do have bIood concentrations Iower than their nearest
marine reIatives.
Mechanisms of Dsmotic ReguIation
Most oI the brackish water arthropods maintain their bIood concentrations, greater than that oI the
medium and hence water tends to enter by osmosis and ions tend to escape by diIIusion. To maintain
hyperosmotic condition oI bIood, the water entered is returned to those medium and the ions escaped
are activeIy transported back into the bIood. The water is removed partIy as urine and partIy as
extrarenaI Water. The active uptake oI soIutes invoIves expenditure oI energy, which shouId be
minimized.
Animal Physiology %"
The Carcinus is much Iess permeabIe to both saIts and water than strictIy marine reIatives Iike
Cancer and Hyas. The urine produced by Carcinus is approximateIy isoosmotic to the bIood but
hyperosmotic to medium. This suggests that the saIts are Iost aIong with the eIimination oI water.
Tracer studies have reveaIed that Ioss oI saIts aIso takes pIace aIong with the extrarenaI excretion oI
water. The antennary organ oI crustaceans is now thought to be primariIy an organ Ior ionic reguIation
rather than osmotic reguIation. The IIuid produced by the antennary organ is high in magnesium as
compared with the medium. This is then excreted through the excretory pore. However, the saIt Ioss is
compensated by the active transport oI saIts through the giIIs.
8.8 ADAPTATlDN TD FRESHWATER HABlTAT
Freshwater animaIs have body IIuids hyperosmotic to their medium. They have osmotic probIems
simiIar to those Iacing the brackish water animaIs, but more extreme in their nature. Freshwater
animaIs meet these osmotic probIems by improving upon some oI the osmotic and ionic reguIatory
mechanisms oI the type existing in brackish water animaIs. The permeabiIity oI the body surIace oI
these animaIs is Iar Iess than that oI brackish water animaIs. But Ireshwater moIIuscs have more
permeabIe body surIace, a Ieature IavourabIe Ior the inIIux oI water. However, the inIIux oI water is
greatIy reduced because the bIood concentration oI these moIIuscs is Iar Iower than that oI other
Ireshwater animaIs.
The entry oI water inside wouId reduce bIood concentration. In order to stabiIize the bIood
concentration, either the water or the saIts are to be removed Irom bIood. Freshwater animaIs
conserve saIts by producing urine which is generaIIy Iess concentrated than bIood. In a Iew animaIs
the urine may be isoosmotic to the bIood. Even though saIt Ioss through urine is minimized, it
continues to be the main avenue through which signiIicant amount oI saIts is Iost. The Iormation oI
very diIute urine is the way by which the body gets rid oI excess oI water. In 24 hours the crayIish,
Astacus, produces urine which may be as much as 4 per cent oI the body weight. The production oI
urine is thus essentiaI Ior the osmotic and ionic reguIation and such a Iunction is perIormed by the
antennary gIands. These gIands have a coeIomic sac, a Iabyrinth, a nephridiaI canaI and a urinary
bIadder (Fig. 8.6). The urine is Iormed by IiItration in the coeIomic sac.
Studies on the antennary gIands oI Ireshwater Astacus and that oI the marine Homarus reveaIed
an important morphoIogicaI diIIerence. Astacus has a Iong nephridiaI canaI with ampIe increase in
surIace area. The bIood suppIy to antennary organ is greater in Ireshwater Iorm than in the marine
Iorm. In the Ireshwater, Iorm the number oI the bIood vesseIs and the Iacunae suppIying the antennary
organ is much greater than in the marine Iorm. The Ionger nephridiaI canaI absorbs the chIorides and
secretes water. The Ireshwater crayIish compensates the amount oI water and saIt Ioss, by a
continuous uptake oI the substances through the giIIs even iI their concentration in the externaI
medium is very Iow. It is beIieved that apart oI the Ioss oI water and saIts is aIso compensated easiIy
through the Iood.
We have aIready Iearnt that the Ireshwater animaIs have bIood concentrations Iess than brackish
water Iorms. The smaII diIIerence in the gradient between bIood and Ireshwater medium requires
minimum work to be done Ior active transport oI substances and hence expends Iess energy.
Water Felations and Ionic Fegulations %#
In case oI aquatic insect Iarvae, the osmotic and ionic reguIations are perIormed by the gut. To
IaciIitate this certain areas oI the gut are speciaIized Ior this purpose. In Aedes aegypti the anaI-
papiIIae and the rectaI waII are responsibIe Ior the conservation oI the saIts.
FRESHWATER TELEOST AND LAMPREYS: The Ireshwater Iishes and the Ireshwater invertebrates
have simiIar osmotic conditions and reguIatory mechanisms. Both Lampreys and teIeosts have
hyperosmotic bIood. The concentration oI bIood in the Ireshwater species is maintained at a IairIy
constant IeveI. Due to hyperosmotic nature oI these Iorms, water tends to enter their body via generaI
body surIace, giII and mouth epitheIia. The permeabiIity oI skin in Iampreys is greater than that oI the
teIeosts. The Iampreys have skin which is naked whereas the skin oI teIeosts is covered by scaIes. The
scaIes greatIy reduce the rate oI water diIIusion. Lampreys Iiving in Ireshwater take up water through
the skin but in teIeosts, the water uptake is mainIy through the giIIs. This way in 24 hours the teIeosts
may take water equivaIent to about 30 per cent oI their body weight and this is secreted copiousIy in
the Iorm oI urine. Most oI the saIts in the urine is reabsorbed and concentration oI urine is about
0.04°C which is hypoosmotic to bIood. Though the kidney conserves saIts by reabsorbing them, stiII
the amount Iost through urine is considerabIe. The saIt uptake in the Iood is Iar Iess than the saIt Ioss
Irom the body. The saIt Ioss is, however, compensated by the active uptake oI them through the giIIs.
There is aIso some evidence suggesting the uptake oI ions Irom the Ireshwater medium directIy by the
body surIace. The Ireshwater Iishes do not normaIIy drink their medium to compensate water and saIt
Ioss.
8.8 ADAPTATlDNS TD TERRESTRlAL HABlTAT
Various animaI groups have invaded Iand at diIIerent times. Insects, terrestriaI arachnids and
tetrapods, Ior exampIe, are Iound Iirst in the Devonian period. At a Iater time animaI groups such as
the opercuIate gastropods, the opisthobranchiates, the isopods and crabs have coIonized the Iand.
SimiIarIy a Iew other groups such as earthworms, onychophorans, tricIads, etc., aIso took to terrestriaI
FIg S.6 The antennary glands of (a) freshwater crayfish, AsIa¿us and (b) marine crayfish, Hømarus.
Labyrinth
Coelomic sac
Urinary bladder
(b) (a)
Labyrinth
Coelomic sac
Nephridial canal
Urinary bladder
Animal Physiology %$
IiIe though they Iive in damp habitats. Many oI the animaIs that migrated to terrestriaI environment
continue to Iive in damp areas or nearer to water source. However, there are other animaIs which Iater
migrated to semiarid and arid environments. These environments are hazardous, as they couId
desiccate the animaI and cause quick death. The deveIopment oI air breathing system has heIped in
procuring oxygen directIy Irom the air. But breathing dry air has increased the danger oI desiccation.
The water, which is essentiaI to maintain ceII voIume and to act as a medium in which ceIIuIar
activities proceed uninterruptedIy, gets evaporated through the breathing organs as weII as through the
generaI body surIace. Besides these, water is aIso Iost by way oI urine and Iaeces. However, during
the transition Irom aquatic to the terrestriaI IiIe the animaIs have evoIved suitabIe adaptations to
withstand the Iuries oI the terrestriaI environment. The animaIs have brought about morphoIogicaI,
physioIogicaI, and behaviouraI adaptations to continue their vitaI activities on Iand. AII these
adaptations heIp in reducing the Ioss oI water and saIts. The skin oI mammaIs is Iess keratinized than
that oI reptiIes. Yet the Ioss oI water through the skin oI mammaIs is as Iow as in the reptiIes. Despite
reduced water Ioss through the skin, the overaII Ioss Irom the mammaIs such as rats is much higher as
compared to reptiIes oI comparabIe size. This increase in Ioss is mainIy due to the removaI oI more
water in the respired air. Two Iactors inIIuence this Ioss and they are high metaboIic rate and higher
body temperature.
1. High metaboIic rate raises water Ioss. The metaboIic rate is higher in homeotherms than in
reptiIes. Such a high metaboIic rate necessitates rapid rate oI breathing and hence increased Ioss oI
water. The metaboIic rate per unit mass is reIated to the body size oI the animaIs. In smaIIer animaIs
the metaboIic rate per unit mass is higher than in Iarger animaIs. AccordingIy the water Ioss Irom
smaII animaIs such as rates is higher than man.
2. The mammaIs Ioose water by way oI respiration even iI they inhaIe air saturated at the ambient
temperature. This is possibIe iI the body temperature oI the mammaIs is higher than the ambient
temperature. The exhaIed aim oI such mammaIs wouId have a temperature higher than ambient
temperature. At higher temperature, the air hoIds more moisture. MammaIs are IiabIe to suIIer Irom
heat stroke iI they are exposed to higher temperatures. When the body temperature oI these animaIs is
increased 4-5
o
C above normaI, the body sweats which then evaporates making the body cooI. Though
cooIing is essentiaI to bring down temperature, water Ioss in this process brings about an undesirabIe
viscosity oI the bIood. Increased viscosity oI bIood reduces the speed oI bIood circuIation. Due to
reduced speed the bIood cannot remove aII the heat Irom the body. ThereIore, the body heat increased
and when the animaI Ioses about 10 per cent oI its body water it dies. The hot and dry cIimate oI
deserts is not ideaI Ior comIortabIe Iiving and wouId cause heat stroke. But certain animaIs such as
kangaroo rat, cameI and donkey have coIonized deserts by deveIoping suitabIe physioIogicaI and
behaviouraI adaptations to desert cIimate.
The kangaroo rat (Dipodomys), which is weII adapted to desert IiIe, has deveIoped noveI
mechanisms to conserve water. The water Ioss is considerabIy reduced due to the IoIIowing Iactors:
(a) Reduction oI evaporative Ioss through skin and Iungs.
(b) Production oI concentrated urine.
(c) Production oI dry Iaeces.
Water Felations and Ionic Fegulations %%
Absence oI sweat gIands is another Iactor in reducing the Ioss oI water through the skin. Because
oI the absence oI sweat, gIands, the cooIing mechanism is ineIIicient but the animaI deveIoped
toIerance to temperatures upto 41°C, i.e. 6°C above its normaI temperature. However, higher day
temperatures are avoided by the kangaroo rat by deve1oping behaviouraI habits such as Iiving in
reIativeIy cooI and humid burrows during the day, and Ioraging during nights (nocturnaI) when the
ambient temperature IaIIs down to a comIortabIe IeveI.
Much oI the evaporative Ioss oI water in kangaroo rat is by way oI respired air. In dry air, the
evaporative Ioss in kangaroo rat is estimated to be more than 70 per cent oI the totaI Ioss. But in the
reIative humidity oI 80 per cent existing in the burrows, the water Iost is onIy 40 per cent oI the totaI
water Ioss. At 10 per cent humidity, the water Ioss by way oI respiration is compensated by the
metaboIic water produced. At aII reIative humidities above 10 per cent the animaI maintains the water
baIance by Iosing Iesser amount oI water; and excessive water that is taken in through the hygroscopic
Iood as weII as the excess oI metaboIic water is excreted in the Iorm oI more urine.
WhiIe a greater part oI conservation is responsibIe Ior the existence oI humidities in the burrows,
the success in reducing evaporative Ioss through Iung is aIso partIy due to the cooIing eIIect oI the
nose. From the nose a smaII quantity oI water evaporates and as a resuIt the nasaI passages are cooIed
to a temperature oI onIy 24°C. Moisture Irom the expired air condenses on the mucosa oI nasaI
passages. Thus, the water that is escaping is recovered.
The mammaIs incIuding kangaroo rat produce hyperosmotic urine. The kangaroo rat`s urine is a
20 per sent soIution whiIe that oI man is onIy 8 per cent soIution. ThereIore the kangaroo rat can
excrete more nitrogen without much Ioss oI water.
In kangaroo rat, the water Irom the Iaeces is absorbed at the posterior end oI the gut and the
remaining is voided as dry Iaeces. The amount oI water that is Iost by this way is very Iess and
accounts Ior one third the dry weight oI Iaeces.
As a resuIt oI such meticuIous conservation oI water by kangaroo rat, the water content oI the
bIood is maintained at a constant IeveI.
CameI can go without water Ior Iong periods. The oId taIes that they store water in the reservoirs
in stomach or hump are no Ionger true. CameI Ioses water by evaporation through the skin and the
Iungs. Water is aIso Iost through the Iaeces and urine, Irom digestive tract and the kidney respectiveIy.
However, it has evoIved mechanisms to minimize water Ioss through these organs. UnIike the desert
rat, cameI is Iarge and hence cannot burrow and is exposed to hot and dry cIimate oI the deserts. For
this reason, the methods oI conservation in cameI are diIIerent Irom those oI kangaroo rats which aIso
Iive in deserts.
During winter months cameI meets its water needs by browsing on bushes and succuIent pIants.
ThereIore it goes without drinking water Ior periods Ionger than two months and stiII shows no signs
oI dehydration. However a cameI Ied on compIeteIy dry Iodder couId go without drinking Ior severaI
weeks, but it Ioses water steadiIy through Iungs and skin and through the Iormation oI urine and
Iaeces and consequentIy the animaI Ioses weight that is equaI to the weight oI water Iost. When
accessibIe to water, the cameI drinks enough oI it within minutes and regains the weight Iost. In 10
minutes the cameI gains its normaI appearance. One might wonder how the cameI Ied on dry Iodder
can go without water Ior severaI weeks. The Iirst expIanation is that cameI obtains metaboIic water by
Animal Physiology %&
the oxidation oI IoodstuIIs and the reserve Iat stores. The metaboIic water produced by the oxidation
oI IoodstuIIs is Iess than even the water Iost through the expired air. FoodstuIIs contribute diIIerent
amounts oI water and the amount oI water produced by way oI oxidation depends upon their
hydrogen content. One gram oI Iat yieIds 1.07 gm oI water; 1 gm oI carbohydrate, 0.60 gm oI water;
and 1 gm oI protein, 0.3 gm oI water.
CameI obtains water aIso Irom the oxidation oI Iat stored in the hump. The cameI with 100
pounds oI Iat can obtain 110 pounds oI water, i.e. more than 13 gaIIons. However, water obtained by
oxidation is Iess than the amount oI water the cameI Ioses by evaporation Irom the Iungs.
The second expIanation is that these animaIs have deveIoped water conserving mechanisms.
These, however, diIIer Irom those oI kangaroo rat. In spite oI these water conserving mechanisms,
cameI stiII suIIers water Ioss. But it can go without water Ior proIonged periods.
During summer in desert the temperature soars to 65°C or more. Such an ambient temperature
tends to raise the body temperature oI higher animaIs. Since they cannot toIerate change in their body
temperature, they sweat in order to cooI their body. In this process, they Iose the precious water which
is scarce in the desert. They then die oI heat stroke. But cameI has remarkabIe powers to withstand
dehydration and rise in body temperature. Though it toIerates dehydration better than man, the
process oI dehydration is very much sIow. Such a sIow process is due to (a) the excretion oI smaII
quantity oI urine which may be as Iow as a quart a day during summer; and (b) the reduction oI
sweating.
Further, the water Ioss in cameI does not bring about a signiIicant reduction in its bIood voIume.
II 50 Iitres oI water is Iost Irom cameI, its bIood voIume decreases onIy by 1 Iitre.
CameI`s kidney is highIy eIIicient. When it is Ied on dry Iood, the urine IIow is considerabIy
reduced; it may be around 500 mI/day. II the dry Iood oI cameI is rich in proteins one might expect a
high urea content in its urine as in desert rat. But in cameIs the urea output is greatIy reduced. The
exact mechanism oI the kidney in this reduction process is not known. Further the maximum
concentration oI urea in cameI is not known with certainty but it appears that it is a IittIe over haII that
oI kangaroo rat.
In cameIs water Ioss by sweating is greatIy reduced in spite oI the prevaiIing high temperatures in
deserts. They have the abiIity to raise their body temperature Irom a minimum oI 52°C to a maximum
oI 58°C, a diIIerence oI 6°C, without sweating. During the hot day, cameI absorbs heat Irom the rising
temperature oI the environment. But onIy when its body temperature rises above 58°C does the
sweating initiate to cooI Irom Iurther rise. The body, however, attains this maximum temperature onIy
aIter much oI the hot day is over. Thus the need to cooI the body by sweating is restricted Ior a short
period and this abiIity oI cameI conserves signiIicant amount oI precious water.
8.30 RETURN TD THE SEA
The terrestriaI animaIs which return to sea or depend on sea Ior their Iood, receive high doses oI saIts
either by drinking seawater or by eating isoosmotic sea-animaIs. The terrestriaI air-breathing animaIs
though Iive on marine Iorms cannot toIerate high concentrations oI saIts. The saIt concentration in
their body IIuids shouId be Iimited to about one per cent, i.e. Iess than one third oI the saIt
Water Felations and Ionic Fegulations %'
concentration oI seawater and this is possibIe iI the excess saIt is removed by some means. The
reptiIes, birds and mammaIs that returned to marine IiIe did possess eIIicient way oI removing saIts. II
man drinks saIt water, it wouId cause diarrhoea and consequentIy the tissues suIIer dehydration. The
marine reptiIes and sea birds do drink seawater; their kidneys are Iess eIIicient than those oI man and
yet they suIIer no iII eIIects. This is because the sea birds have a speciaI organ, viz. the saIt gIand
which is much more eIIicient in eIiminating saIts than the kidney. It appears that the marine reptiIes
aIso possess such a saIt eIiminating gIand.
When sea guII is given seawater equaI to a tenth oI its body weight, nearIy aII the saIt content oI
it has been excreted within three hours. The saIt gIands are responsibIe Ior the removaI oI 90 per cent
oI the saIt with Iess Ioss oI water. The remaining 10 percent oI the saIts is removed by kidney with
greater amount oI water Ioss. ObviousIy, this wouId mean that the nasaI IIuid is more concentrated
and the urine Iess concentrated.
The nasaI IIuid is Iive times as saIty as the bird`s bIood and other body IIuids. In order to
understand how the saIt gIand produced such a concentrated soIution, it is necessary to understand the
anatomy oI the gIand. A cross section oI the gIand reveaIs that it consists oI a number oI paraIIeI
cyIindricaI Iobes (Fig. 8.7), each Iobe consisting oI severaI thousand branching tubuIes which radiate
Irom a centraI duct. Thus each Iobe oI the gIand appears Iike that oI a bottIe brush. The tubuIes
secrete saIty IIuid. Each Iobe is suppIied with a network oI capiIIaries which run paraIIeI to the Iength
oI the tubuIes (Fig. 8.8). The bIood IIow in these capiIIaries is opposite to the direction oI the IIow oI
FIg S.7 Salt gland (A) showing location of the salt gland, (B) cross section of salt gland showing lobes, (C) cross section
of the lobe showing tubules.
B
Lobe
, ,
Salt
gland
C
Tubule
A
Animal Physiology &
saIt soIution in the tubuIes. Such a counter current IIow ampIiIies the transIer oI saIt Irom the bIood in
the capiIIaries to the IIuid in the tubuIes. A simiIar arrangement existing in mammaIian kidneys is
responsibIe Ior their eIIiciency in producing concentrated urine. The reptiIian kidney has no such
counter current system, but in the birds it is onIy sIightIy deveIoped. Besides counter current IIow,
there is another Iactor which is invoIved in saIt concentration and it is an increase in the area oI
secretion oI the tubuIe by Iorming IoIds.
The ceIIs oI the tubuIe have some physioIogicaI mechanisms to pump sodium and chIoride ions
Irom the diIute saIt soIution oI the bIood to the more concentrated soIution in the Iumen. The
mitochondria oI the ceIIs oI the tubuIe appear to have invoIved in the transport oI sodium and chIoride
ions.
Despite certain simiIarities, the saIt gIand diIIers Irom mammaIian kidney in some important
Ieatures. They are: (a) The saIt gIand is a simpIer organ. (b) Compositionwise the secretions oI the saIt
FIg S.S Enlargement of a single tubule surrounded by capillaries. (Redrawn from Sci. Amer., l959, vol. 200, No. l, pp.
l09-ll6).
Artery
Vein
Interlobular
connective tissue
Secretary
tubules
Central
connective
tissue
Central canal
Water Felations and Ionic Fegulations &
gIand contain onIy sodium, chIoride and water except Ior traces oI potassium. This is the soIe Iunction
oI the saIt gIand. In contrast to this the kidney perIorms a variety oI conservative and eIiminative
tasks. It produces a compIex IIuid which varies in composition based on the physioIogicaI activities.
Some oI the substances Irom this compIex IIuid are reabsorbed to conserve them at that particuIar
time. (c) The saIt gIand`s abiIity to remove saIt is greater and in one minute, it can produce saIt
soIution equivaIent to its own weight. The human kidney can produce onIy about twentieth oI its
weight oI urine in one minute. (d) WhiIe the saIt gIand Iunctions intermittentIy whenever needed to
eIiminate saIt, the kidney Iunctions continuousIy and secretes at varying rates.
The Iunctioning oI saIt gIand depends on saIt concentration in bIood. When the concentration oI
saIt in bIoodstream increases, some centre perhaps in the brain responds and sends impuIses through
centraI nervous system.
SaIt gIands are aIso present in marine reptiIes. In marine turtIes, the gIands are positioned behind
the eyebaII and pour out secretions through a duct that opens into the eye. When these turtIes come to
the shore, the secretion can be cIearIy seen pouring out Irom the eye. This Ied peopIe to beIieve that
the marine turtIes weep. No one untiI recentIy knew that the marine turtIes 'weep¨ to eIiminate saIt
Irom their body. In composition, the tears oI sea turtIes are very much Iike the secretions Irom the saIt
gIands oI marine birds. AnatomicaI studies oI marine crocodiIes and sea snakes have reveaIed the
presence oI Iarge gIands in their heads. The Iunction oI these gIands seems to be simiIar to that oI the
saIt gIand.
Marine mammaIs such as seaIs satisIy their water needs with the IIuids oI the Iish on which they
Ieed. Since these IIuids aIso contain saIts, the seaIs eIiminate them through the kidneys. The whaIes
Ieeding on pIankton, squid, etc., are required to eIiminate Iarge quantities oI excess saIt. For this, the
whaIes seem to possess more powerIuI kidneys than those present in human beings.
BioIogicaI membranes, aIso caIIed pIasma membranes, surround aII individuaI ceIIs and Iorm cIosed
compartments. The membrane is asymmetric, highIy viscous and dynamic in nature to provide
seIective permeabiIity owing to the presence oI ion-channeIs and ion pumps. In pIants, it Iies internaI
to the ceII waII and encIoses the ctytopIasm oI the ceII. Besides transport oI ceIIuIar materiaIs, ions,
water and macromoIecuIes, the membranes aIso Iunction in transmembrane signaIing and ceII-to-ceII
interactions. DeIiciencies in ceII membrane resuIt in a variety oI diseases, which wiII be deaIt within
chapter 23 on physioIogicaI disorders.
8.3 CHEMlCAL CDMPDSlTlDN DF MEMBRANES
Membranes are Iound to consists oI mainIy Iipids, proteins, some carbohydrates, and water. The
protein to Iipid ratio varies greatIy. For exampIe, the inner mitochondriaI membrane has 76° protein,
whiIe the myeIin membrane oI neurons possess onIy 18° protein. The diIIerence in protein-Iipid ratio
accounts Ior the speciIic Iunctions the organeIIes have to perIorm.
Nature of Membrane Lipids
Lipids in the membrane are a compIex mixture oI choIesteroI and Iatty acids, mainIy in the Iorm oI
gIycerides and phosphoIipids. ChoIesteroI is wideIy distributed in the membrane, though
phosphoIipids predominate. Because oI its high phosphoIipid content, the myeIin oI the nerve ceIIs
can eIectricaIIy insuIate the ceII Irom its enviornment. The Iipid composition varies among diIIerent
membranes.
Five types of PhosphoIipids Found in Membranes
Five important types oI phosphoIipids incIude phosphatidic acid, Iecithin, phosphatidyI inositoI,
phosphatidyI serine, and phosphatidyI ethanoIamine (Fig. 9.1). Though aII membranes contain a
Membrone FhysioIogy
+ 0 ) 2 6 - 4
'
Membrane Physiology &!
substantiaI proportion oI phosphoIipids, predominant being phosphogIycerides having a gIyceroI
backbone. AII membrane phosphoIipids are amphipathic, having both hydrophiIic and hydrophobic
portions (Fig. 9.2). Other Iipids incIude choIesteroI, gIycoIipids, phosphatidyIchoIine and
sphingomyeIin. SphingomyeIin Iacks a gIyceroI backbone, but quite common in pIasma membranes.
Instead oI a gIyceroI backbone it contains sphingosine, an amino aIcohoI with a Iong unsaturated
hydrocarbon chain. A Iatty acyI side chain is Iinked to the amino group oI sphingosine by an amide
bond to a ceramide. The terminaI hydroxyI group oI sphingosine is esteriIied to phosphochoIine,
making the hydrophobic head oI sphingomyeIin simiIar to that oI phosphatidyIchoIine.
A major diIIerence among phosphoIipids concerns the charge carried by the poIar head groups at
neutraI pH. Some phosphogIycerides (phosphatidyIchoIine, phosphatidyI ethanoIamine) have no net
eIectric charge; others (cardioIipin, phosphatidyIserine) have a net negative charge. A Iew rare Iipids
carry a net positive charge at neutraI pH. NonetheIess, the poIar head groups in aII phosphoIipids can
pack together into the characteristic biIayer structure. SphingomyeIin and gIycoIipids are simiIar in
shape and can Iorm biIayer with them.
ChoIesteroI an lmportant Constituent of Membrane Lipids
ChoIesteroI an its derivatives constitute another important cIass oI membrane Iipids, the steroids. The
basic structure oI the steroids is the Iour-ring hydrocarbon (Fig. 9.3). ChoIesteroI is the major
FIg. 9.1 Amphipathic nature of phospholipids: showing hydrophilic and hydrophobic regions.
CH OCOR
2
1
R COO
2
C H
CH
2
O P O
OH
3 sn-Phosphatidic acid
OH
CH OCOR
2
1
R COO
2
CH
CH
2
O P OCH CH N(CH )
2 2 3 3
O
O

+
Phosphatidyl choline
CH OCOR
2
1
R COO
2
CH
CH
2
O P O
O
OH
OH H
OH H
H
OH OH
H
H
OH
Phosphatidyl inositol
Phosphatidyl aminoethanol
CH OCOR
2
1
R COO
2
CH
CH
2
O P OCH CH NH
2 2 33
O
O

+
CH OCOR
2
1
R COO
2
CH
CH
2
O P OCH CH N(CH )
2 2 3 3
O
OH
+
Phosphatidyl serine (Cephalin)
COO

Animal Physiology &"
FIg. 9.2 Structure of phospholipids present in the plasma membrans.
FIg. 9.3 Structure of cholesterol whose derivatives are present in the membrane.
constituent (a steroid) oI animaI tissues; other steroids pIay important roIes in pIants. AIthough
choIesteroI is entireIy a hydrocarbon in composition, it is amphipathic because it contains a hydroxyI
group that interacts with water. ChoIesteroI is especiaIIy abundant in pIasma membrane oI mammaIian
ceIIs, but Iound to absent Irom most prokaryotic ceIIs.
CH –N (CH )
2 3 2
CH
2
O
P O
O
O
CH –CH– CH
2 2
O O
C O C O
CH
2
CH
2
CH
2
CH
2
CH
2
CH
CH
2
CH
CH
2
CH
2
CH
2
CH
2
CH
2
CH
2
CH
3
CH
3
Hydrophobic Tail
Hydrophilic Head
Special region
Phosphate
Fatty acid tail
CH
2
CH
2
CH C
C
CH
2
HO
CH
CH
2
CH
CH
3
CH
CH
2
CH
2
C
CH
CH
2
CH
2
CH
CH
3
CH
CH
2
CH
2
CH
2
CH
3
CH
CH
3
CH
3
Cholesterol (full structure)
Membrane Physiology &#
Proteins are aIso found in Membranes
Proteins Iorm the buIk oI ceII membrane, existing as integral or peripheral proteins.
lntegraI Membrane Proteins
Many oI the proteins associated with the pIasma membrane are tightIy bound to it, whiIe some are
attached to Iipids in the biIayer. In others-the transmembrane proteins, the poIypeptide chain actuaIIy
traverses the Iipid biIayer. AII G-protein coupIed receptors (e.g. receptors oI peptide hormones, and
odours), each span the pIasma membrane seven times (Fig. 9.4). In aII these cases, the protein with the
Iipid biIayer consists primariIy oI hydrophobic amino acids. These are usuaIIy arranged in an aIpha
heIix so that the poIar C ÷ O and NH groups at the peptide bonds can interact with each other
rather than with their hydrophobic surroundings. Those portions oI the poIypeptide that project out
Irom the biIayer tend to have a high percentage oI hydrophiIic amino acids. Furthermore, those that
project into the aqueous surroundings oI the ceII are usuaIIy gIycoproteins, with many hydrophiIic
sugar residues attached to the part oI the poIypeptide exposed at the surIace oI the ceII. Some
transmembrane proteins that span the biIayer severaI times Iorm a hydrophiIic channeI through which
certain ions and moIecuIes can enter or Ieave the ceII (Fig. 9.5).
FIg. 9.4 A C protein-coupled receptor. It consists of seven transmembrane proteins with N-terminal pro]ecting to the
exterior.
PeripheraI Membrane Proteins
PeripheraI membrane proteins are those that adhere onIy IooseIy to the membrane with which they are
associated. These moIecuIes do not span the Iipid biIayer core oI the membrane, but attach indirectIy,
typicaIIy by binding to integraI membrane proteins. ThereIore, the so caIIed reguIatory protein
subunits oI many ion channeIs and transmembrane receptors, Ior exampIe, may be deIined as
peripheraI membrane proteins. These proteins, in contrast to integraI membrane proteins, tend to
I
a
IV
III
II
V
VI
VII
TT
b
LIGAND
NH
2
Plasma membrane
Cytoplasm
COOH
GDP
Animal Physiology &$
coIIect in the water-soIubIe Iraction during protein puriIication. These are more IooseIy associated
with the membrane. They are usuaIIy attached noncovaIentIy to the protruding portions oI integraI
membrane proteins. Membrane proteins are oIten restricted in their movements (Fig. 9.5).
Carbohydrates are AIso Present in the Membrane
Carbohydrates in the pIasma membrane are present in the Iorm oI covaIentIy-Iinked moIecuIes with
proteins and Iipids. There two types: glycoproteins and glycolipids. The common sugars associated
with the proteins are D-gIaaucose, D-gactose, D-mannose etc., which are oIigosaccharide compIexes.
Besides simpIe sugars, sugar derivatives such as N-acetyI-D-gIucosamine and N-acetyI-neuraminic
acid (siaIic acid) are aIso present. AImost aII proteins present on the outer surIace oI the membrane
have not got carbohydrate component, as wiII be seen Irom the TabIe 9.1.
TabIe 9.1 variation in Protein, Lipid and Carbohydrate Composition of Some Nembranes
MømDranø PrøIø¡n ² L¡p¡ø ² CarDøn)øraIø ²
Nyelin l8 79 3
Human erythrocyte +9 +3 8
Nitochondrial inner membrane 79 2+ 0
AmøøDa plasma membrane 5+ +2 +
8.E MEMBRANE ARCHlTECTURE
Membrane has a dynamic structure. AIthough there are Iarge variations in the composition oI
membrane, the basic structuraI unit oI virtuaIIy aII bioIogicaI membranes is the phospholipid bilayer.
This biIayer is a sheet-Iike structure composed oI two Iayers oI phosphoIipid moIecuIes whose poIar
head groups Iace the surrounding water and their Iatty acid chains Iorm a continuous hydrophobic
interior and 3 nm thick.
FIg. 9.5 Topographical arrangement of proteins in the plasma membrane.
Phospholipid
bilayer
Integral
membrane protein
Peripheral
membrane protein
Peripheral
membrane
protein
Transmembrane
protein
Membrane Physiology &%
Each phosphoIipid Iayer in this IameIIar structure is caIIed a leaflet (Fig. 9.6). The major driving
Iorce Ior the Iormation oI phosphoIipid biIayers is the hydrophobic interaction between the Iatty acyI
chains oI gIycoIipid and phosphoIipid moIecuIes. Van der waaIs interactions among the hydrocarbon
chains Iavour cIose packing oI these hydrophobic taiIs. Hydrogen bonding and eIectrostatic
interactions between the poIar head groups and water moIecuIes aIso stabiIize the biIayer. MiceIIes are
generaIIy not Iormed by phosphoIipids in aqueous soIutions, since the Iatty acyI chains in
sphingomyeIins, gIycoIipids, and aII phosphoIgycerides are too Iarge to Iit into the interior oI a
miceIIe (Fig. 9.7).
FIg. 9.6 Bileaflet medel of the membrane showing arrangement of proteins and their sugar components.
FIg. 9.7 Amphipathic phospholipid molecules in the aqueous phase: (a) formation of micelles in which polar heads are
directed towards water, (b) formation of bilipid layer.
Exterior
Intergal
protein
Oligosaccharide Glycoprotein Glycolipid
Peripheral protein
Cytosol
Hydrophilic
Protein
Integral protein
Peripheral proteins
Hydrophilic polar
head
Fatty acyl
tails
P
h
o
s
p
h
o
l
i
p
i
d
P
h
o
s
p
h
o
l
i
p
i
d
b
i
l
a
y
e
r
Leaflets
H
y
d
r
o
p
h
o
b
i
c
c
o
r
e
(a) (b)
Water Water
Animal Physiology &&
FIuid-mosaic ModeI of PIasma Membrane
The fluid-mosaic model oI the pIasma membrane is the universaIIy accepted modeI, which was
proposed by Singer and NicoIson in 1972. The modeI suggests that the Iipids Iorm a viscous, two-
dimesionaI IIuid matrix into which proteins are inserted and integrated more or Iess deepIy. The
peripheraI proteins are superIiciaIIy Iocated and many oI them Iunction as enzymes, whiIe the integraI
proteins are associated with Iipids and penetrate into the interior oI the membrane aIong with Iatty
acid side chains (9.8). They are tightIy bound to the Iipids and constitute IunctionaI proteins that are
not easiIy separabIe. AII membrane-bound enzymes and carriers are incIuded in this category.
PeripheraI proteins have a Ioose aIIinity and can be easiIy dispIaced. Such a membrane is more
dynamic and expIains the intricate semi-permeabIe phenomenon.
FIg. 9.S Fluid-mosaic model of Singer.
Drientation of Proteins in the Membrane
Orientation oI the proteins is important in the Iunctioning oI the membranes. The N-terminus is
aIways at the side that is turned away Irom the cytosoI. UsuaIIy the hydrocarbon residues get attached
to the N-terminus. TypicaI membrane proteins can thereIore be counted among the gIycoproteins. The
C-terminus oI proteins can either Iie at the outside, within the Iipid Iayer or protrude into the cytosoI,
i.e. the site oI protein synthesis (Fig. 9.9).
Lipid layer Integral protein
Glycolipid
Peripheral protein
Membrane Physiology &'
lntegraI Proteins Bind AsymmetricaIIy to the Lipid BiIayer
Every integraI membrane protein has a singIe, speciIic orientation with respect to the cytosoIic and
exopIasmic Iaces oI the membrane. MoIecuIes oI integraI membrane protein, such as glycophorin, Iie
in the same direction, providing asymmetry to the two membrane Iaces. In contrast to phosphoIipids,
proteins have never been observed to IIip-IIop across a membrane, because such movement wouId be
energeticaIIy unIavourabIe and wouId require a transient movement oI hydrophiIic amino acids and
sugar residues through the hydrophobic interior oI the membrane. The asymmetry oI membrane
proteins is estabIished during their biosynthesis and maintained throughout proteins` IiIetime.
Membrane asymmetry is most obvious in the case oI membrane gIycoproteins. In the pIasma
membrane, aII the O-and N-Iinked oIigosaccharides oI gIycoproteins and oIigosaccharides in
gIycoIipids are on the exopIasmic surIace. In the endopIasmic reticuIum, they are Iound on the interior
or IumenaI membrane surIace.
Lipid Composition of Different Membrane LeafIets
AII the pIasma membranes have diIIerent Iipid composition in the two IeaIIets. In the human
erythrocyte, aII the gIycoIipids and aImost aII oI sphingomyeIin and phosphatidyI choIine are Iound in
the exopIasmic IeaIIet. In contrast, the cytosoIic IeaIIet contains Iipids with neutraI or negative poIar
head groups, such as phosphatidyIethanoIamine and phosphatidyIserine. The reIative abundance oI a
particuIar phosphoIipid in the two IeaIIets oI a membrane can be determined on the basis oI its
susceptibiIity to hydroIysis by phosphoIipases when added to the ceII exterior, because phosphoIipases
are unabIe to penetrate the cytosoIic Iace (Fig. 9.10).
Movement of MoIecuIes is Two-dimensionaI
In both naturaI membranes and pure phosphoIipid biIayers, thermaI motion permits phosphoIipid and
gIycoIipid moIecuIes to rotate IreeIy around their Iong axis and to diIIuse IateraIIy within the
membrane IeaIIet. Sine these movements are IateraI or rotationaI, the Iatty acyI chains remain in the
hydrophobic interior oI the membrane (Fig. 9.11).
FIg. 9.9 Integral membrane proteins showing two membrane-spanning regions, i.e. glycophorins.
+
+ +
COO–
+
+
+ +
Lipid
bilayer
+
+
+
NH
3
O-linked
oligosaccharides
Extracellular
domain
Central
hydrophobic
alpha helix
Cytosolic
hydrophilic
domain
Animal Physiology '
FIg. 9.1û Schematic showing lipid composition in erythrocyte membrane. The relative abundance of phospholipids in
each leaflet accounts for their specific functions.
(a)
(b)
FIg. 9.11 Nembrane lipids are constantly mobile: (a) rotational movement, (b) lateral movement.
The phosphoIipids in pure Iipid biIayers do not IIip-IIop or migrate Irom one IeaIIet to the other.
However, in some naturaI membranes, occasionaI movement is observed owing to cataIysis by
membrane proteins. EnergeticaIIy, such movements are extremeIy unIavourabIe, because the poIar
head oI phosphoIipid must be transported through the hydrophobic interior oI the membrane.
ArtificiaI Membranes can be Formed by MechanicaI Dispersion of
PhosphoIipids
Two systems oI pure phosphoIipid biIayer are liposomes and pIanar biIayers. Liposomes are sphericaI
vesicIes upto I in diameter consisting oI a phosphoIipid biIayer that encIoses a centraI aqueous
compartment, Iormed by mechanicaIIy dispersing phosphoIipids in water. PIanar biIayers are Iormed
across a hoIe in a partition that separates two aqueous soIutions. When a suspension oI Iiposomes or
a pIanar biIayer composed oI a singIe type oI phosphoIipid is heated, it undergoes an abrupt change in
physicaI properties over a narrow temperature range. This phase transition is due to increased motion
about the C-C bonds oI the Iatty acyI chains, which pass Irom a highIy ordered, geI-Iike state to a
more mobiIe IIuid state. During geI-to-IIuid transition, a reIativeIy Iarge amount oI heat is absorbed
over a narrow temperature range that is the meIting temperature oI the biIayer. Lipids with short chain
or unsaturated Iatty acyI chains undergo phase transition at Iower temperatures than Iipids with Iong
or saturated chains.
Exoplasmic
Cytoplasmic leaflet
% of
total
phospholipid
Sphingomyelin
Phosphatidyl choline
Phosphatidyl ethanol amine
Phosphatidyl serine
50
40
30
20
10
0
20
30
20
10
Total phospholipids
10
Membrane Physiology '
8.3 MEMBRANE TRANSPDRT FUNCTlDNS
The pIasma membrane Iunctions as a barrier between the ceII and its extraceIIuIar environment but
ensures transport oI essentiaI moIecuIes, such as gIucose, amino acids, Iipids, and ions etc., into the
ceII and aIIows wastes to Ieave the ceII.
Membrane is SeIectiveIy PermeabIe
SeIective permeabiIity oI the pIasma membrane aIIows the ceII to maintain a constant environment in
the interior. SimiIarIy, organeIIes within the ceII oIten have a diIIerent internaI environment Irom that
oI the surrounding cytosoI, a diIIerent maintained by the organeIIer membranes. For exampIe, the
Iysosomes within an animaI ceII are invoIved in the digestive and scavenging roIes, where the
concentration oI protons is 100-1000 times that oI the cytosoI. This proton gradient is maintained by
proteins in the organeIIe membrane.
PermeabiIity of ArtificiaI Membranes
An artiIiciaI membrane composed oI pure phosphoIipid or oI phosphoIipid and choIesteroI is
permeabIe to gases, such as CO
2
and O
2
and smaII moIecuIes, such as ethanoI. These moIecuIes can
cross ceII membranes unaided by transport proteins. AbsoIuteIy no metaboIic energy is expended
because movement is Irom high to Iow concentration oI the moIecuIes, down the concentration
gradient.
In contrast, a pure phosphoIipid membrane is onIy sIightIy permeabIe to water and is essentiaIIy
impermeabIe to most water soIubIe moIecuIes, such as hydrogen, sodium, caIcium and potassium.
Proteins pIay important roIe in the transport oI such moIecuIes and ions across aII ceIIuIar membranes
because diIIerent ceII types require diIIerent composition oI these Iow moIecuIar weight compounds,
since the pIasma membrane oI each ceII type contains a speciIic set oI transport porteins that negotiate
onIy certain ions or moIecuIes to cross, as does the membrane surrounding each type oI organeIIe
(Fig. 9.12).
Some Transport Proteins Function as lon-channeIs
Some membrane-Iocated proteins Iunction as ion-channeIs to transport water or speciIic types oI ions
down the concentration gradient. They Iorm a protein-Iined passageway across the membrane through
which muItipIe water moIecuIes or ions move simuItaneousIy in a singIe IiIe at a very rapid rate (10
8
/
second). For exampIe, the pIasma membrane oI aII animaI ceIIs is rich in K
¹
and its movement
downhiII through aIways-open channeIs generates an eIectricaI potentiaI across the membrane. Many
other types oI channeI proteins are usuaIIy cIosed, and open onIy in response to speciIic signaIs (Fig.
9.13).
Another cIass oI membrane proteins, caIIed transporters, move a wide variety oI ions and
moIecuIes across the membrane. These transporters bind onIy one or a Iew substrate moIecuIes at a
time, undergo a conIormationaI change to transport moIecuIes across the membrane. ConIormationaI
change oI proteins requires energy Ior movement, hence their movement is sIow, about 10
2
10
4
moIecuIes per second.
Animal Physiology '
Three types oI transporter moIecuIes have been identiIied, which incIude uniporters, antiporters,
and symporters. Uniporters transport one moIecuIe at a time down the cocentration gradient (e.g.
gIucose and amino acids). The antiporters and symporters cataIyze movement oI one type oI ion or
moIecuIe against the concentration gradient, coupIed to the movement oI diIIerent ion or moIecuIe
(Fig. 9.14). These are oIten reIerred to as active transporters but without hydroIysis oI ATP.
Gases
CO , N
2 2
O
2
Urea
ethanol
H O
2
Glucose
K , Mg
+ 2+
Ca , HCO
2+
3
HPO
4
Amino acids
ATP
Glucose–P
FIg. 9.12 Na]or types of transport proteins. One type couples ATP hydrolysis for up-hill movement of ions, the other two
types, which are not ATPases, transport ions down-hill.
FIg. 9.13 Transport proteins can be classified into various types, channel proteins transport water or specific ions down
the concentration gradients or electrical gradients down-hill. Ions or water molecules move single file at a
rapid rate.
Outside
Channel
Ion
channel
Open
ADP+Pi
Closed
ATP
ATP pump
Cystosol
C
l
o
s
e
d
Membrane Physiology '!
8.4 MECHANlSMS FDR TRANSPDRT DF
MATERlALS ACRDSS MEMBRANES
SeveraI transport mechanism have been proposed.
Passive Diffusion
Passive diIIusion is movement oI a moIecuIe Irom the aqueous soIution into the hydrophobic interior
oI the phosphoIipid biIayer. The hydrophobicity oI a substance is measured by the partition coefficient
K, the equiIibrium constant Ior its partition between oiI and water. Since the composition oI the
interior oI the phosphoIipid biIayer resembIes that oI oiI, the partition coeIIicent oI a substance
moving across a biIayer equaIs the ratio oI its concentration just inside the hydrophobic core oI the
biIayer C
m
to its concentration in the aqueous soIution C
aq
:
K ÷ C
m
/C
aq
The partition coeIIicient is a measure oI the reIative aIIinity oI a substance Ior Iipid versus water.
Once a moIecuIe moves into the hydrophobic interior oI a biIayer, it diIIuses across it; IinaIIy, the
moIecuIe moves Irom the biIayer into the aqueous medium on the other side oI the membrane. The
hydrophobic core oI a typicaI ceII membrane is 100-1000 times more viscous than water, hence the
diIIusion rate oI aII substances across phosphoIipid membrane is much sIower than the diIIusion rate
oI the same moIecuIe in water. Thus, movement across the hydrophobic portion oI a membrane is the
rate-Iimiting step in diIIusion.
GIucose Transport is Uniporter-CataIyzed
Very Iew moIecuIes enter or Ieave ceIIs, or cross organeIIe membranes without the aid oI proteins.
Transport proteins IrequentIy acceIerate transport oI moIecuIes such as water, and urea that can IreeIy
diIIuse through phosphoIipid biIayers. It is essentiaI to understand the properties oI various kinds oI
membrane proteins and their roIes in organismic physioIogy. This has been possibIe with the heIp oI
Iiposomes (artiIiciaI membrane). Liposomes having a singIe type oI transport protein can be used to
examine properties oI transport protein (Fig. 9.15). A non-ionic detergent, such as octygIucoside,
soIubiIizes the integraI proteins oI an erythorocyte membrane. The transport protein, a uniporter, can
be puriIied and then incorporated into Iiposomes made oI pure phosphoIipids.
Uniporter Symporter Antiporter
FIg. 9.14 Transport proteins are either symporter, uniporter or antiporter type, named according to the directional
movement of molecules.
Animal Physiology '"
Uniporters cataIyze movement oI one gIucose moIecuIe at a time down a concentration gradient.
SimiIar to enzymes, uniporters acceIerate a reaction that is thermodynamicaIIy Iavoured, and the
movement oI a substance across the membrane down the concentration gradient wiII have a
negative ,G. This type oI movement is reIerred to as facilitated diffusion.
Important properties oI uniporter-cataIyzed transport:
1. The rate oI uniport transport is quite high.
2. Uniport transport is speciIic.
3. Uniport transport occurs via a Iimited number oI transporter proteins, rather then throughout
phosphoIipid biIayer. ConsequentIy, there is a maximum transport rate, which is achieved onIy
when the concentration gradient across the membrane is very Iarge.
Two ModeIs for Transport
The Iirst modeI is the carrier model, in which the transporter protein binds the moIecuIes to move at
one Iace, moves through the membrane, and reIeases the moIecuIe at the other Iace (Fig. 9.16).
The second modeI envisages use oI too much energy. For exampIe, the antibiotic vaIinomycin
increases the transport oI K
¹
ions across bioIogicaI membranes by Iorming a sphere around each K
¹
ion (Fig. 9.17). The hydrophobic amino acid side chains oI the antibiotic Iie on the outer surIace, and
six or eight oxygen atoms on the inside coordinateIy bound to the K
¹
. The hydrophobic exterior
FIg. 9.15 Uniporter catalyzed transport of glucose. Liposomes help to examine the functional properties of membrane
proteins. The figure shows a liposome containing a single type of transport protein. A nonionic detergent
solubilizes the integral proteins of erythrocyte membrane. A uniporter type of glucose transport protein can be
incorporated into the liposome made of pure phospholipids.
Glucose transport
protein
Transport protein
with detergent
molecules
ATP
ADP
Glucose
Phospholipid
Disrupt
membrane
Liposome
Membrane Physiology '#
FIg. 9.16 Carrier-mediated transport of sugar molecules.
Outer surface
hydrophobic
amino acids
K
+
O
2
Four O
interacting
with K
2
+
Valinomycin
FIg. 9.17 Antibiotic valinomycin-facilitated transport of K
+
ions.
makes the K
¹
carrier compIex soIubIe in the Iipid interior oI the membranes. It is beIeved that
membrane transporters undergo conIormationaI changes that permit bound ions or moIecuIes to pass
through the membrane.
Transport of GIucose
The gIucose transporter aIternates between two conIormationaI states:
(a) GIucose-binding site Iaces the outside oI the membrane.
(b) In the other gIucose Iace the inside oI the ceII.
UnidirectionaI transport oI gIucose Irom outside to inside occurs when the transporter with
gIucose Irom outside undergoes a conIormationaI change so that the outward Iacing site is inactivated
and the bound gIucose moves through the protein and becomes attached to the newIy-Iormed inward
Iacing site. The gIucose is reIeased into the ceII interior, the transporter undergoes the reverse
conIormationaI change, inactivating the inward-Iacing gIucose binding site and retreating the
outward-Iacing gIucose binding site (Fig. 9.18).
Exterior
Sugar
molecules
Interior
Unloading
of sugar
Carrier
returned
Membrane
Animal Physiology '$
Passage Through lon-channeIs
The movement oI ions across the pIasma membrane and organeIIer membranes is aIso mediated by
transporter proteins; symporter and certain antiporter co-transport ions together with speciIic smaII
moIecuIes. Ion-channeIs, ion pumps and some antiporters transport onIy ions, but the rate and extent
oI ion transport is inIIuenced by the ion concentrations on the two sides oI the membrane as weII as
by an eIectric potentiaI that exists across the membrane.
lonic Gradients Maintain the EIectric PotentiaI
Ionic composition oI the cytosoI diIIers Irom that oI the surrounding IIuid in aImost aII types oI ceIIs.
The cytosoIic pH is near neutraI (pH 7.0) and the cytosIoic K
¹
ion concentration is aIways higher that
the Na
¹
ions. In both invertebrates and vertebrates, K
¹
ion concentration is 2040 times higher in the
ceII than in the bIood, whiIe Na
¹
ion concentration is aIways Iower. However, the concentration oI
Iree Ca
¹¹
ions in the cytosoI is generaIIy Iess than 1 micromoIar, about a 1,000 times Iower than the
bIood.
The pIasma membrane is provided with channeI proteins that aIIow the principaI ions (Na
¹
, K
¹
,
Ca
¹¹
and CI

) to move through at rates determined by their concentration gradients. The seIective
movements oI these ion through the channeIs create a diIIerence in eIectric potentiaI between the
inside and outside oI ceII. The magnitude oI this potentiaI is 70 mV with respect to inside. The
pIasma membrane is an eIectricaI device caIIed capacitor. The ionic gradients and eIectric potentiaI
are responsibIe to drive many bioIogicaI processes, hence opening and cIosing oI ion channeIs are
essentiaI to conduction oI eIectricaI impuIses.
K
+
ChanneIs Generate EIectric PotentiaI
The distribution oI K
¹
, Na
¹
and CI

ions is aImost simiIar in animaI ceII and its environment and iI the
membrane is impermeabIe to aII ions, no ions wiII IIow across the membrane and there wiII be no
potentiaI diIIerence. As noted above, the membrane potentiaI across the pIasma membrane is about
70 mV due to negative charge on the cytosoIic Iace. The membrane contains many open K
¹
channeIs, but very Iew open Na
¹
and Ca
¹¹
channeIs, resuIting in major ionic movement oI K
¹
Irom
the inside to outward, Ieaving an excess oI negative charge on the inside and positive charge on the
outside.
Glucose
Binding
site
Exterior Inward
binding site
Glucose
Cytosol
Plasma
membrane
FIg. 9.1S Clucose transporter protein alternates between two alternative states.
Membrane Physiology '%
The Na
¹
K
¹
ATPase ion pump moves K
¹
ions into the cytosoI Irom the extraceIIuIar medium,
generating K
¹
concentration gradient. Movement oI K
¹
ions through potassium channeIs Irom the
cytosoI down the concentration gradient generates the inside negative membrane potentiaI. The
potassium channeIs have now been cIoned and sequenced.
Active Transport Machanisms
The active transport oI moIecuIes and ions requires an input oI metaboIic energy, which can be
derived either Irom direct coupIing to the hydroIysis oI ATP or by coupIing to the movement oI an ion
down its concentration gradient.
Active lon Transport
ATP-powered pumps transport ions against their concentration gradients. For instance, the Na
¹
K
¹
ATPase pumps K
¹
into the ceII and Na
¹
outwards, estabIishing a high cytosoIic concentration oI K
¹
that is essentiaI Ior generation oI negative potentiaI across the pIasma membrane. The Ca
¹¹
ATPase
pumps Ca
¹¹
out oI the cytosoI into the extraceIIuIar medium or into the intraceIIuIar organeIIes in
order to maintain concentration oI Ca
¹¹
into the cytosoI much Iower than in the extraceIIuIar medium.
The pump derives its energy Irom the hydroIysis oI ATP (Fig. 9.19).
FIg. 9.19 ATP-powered pumps transport ions against concentration gradients. Na
+
-K
+
-ATPase pumps out K
+
and Na
+
into the cell. The Ca
2+
- ATPase pumps out Ca
2+
of the cytosol. The pumps can be inhibited by 2, +-dinitrophenol.
Existence oI these pumps came Irom studies in which aerobic production oI ATP in ceII was
inhibited by 2, 4-dinitrophenoI. The ion concentration inside the ceII graduaIIy approached that oI the
externaI environment as the ions moved through the membrane channeIs down the concentration
gradient, uItimateIy Ieading to the ceII death because K
¹
requirement oI the ceII couId not be met.
Three CIasses of lon Pumps
Three cIasses oI ATP-powered pumps have been recognized, caIIed P, V, and F. CIass P pumps are
simpIest and composed oI Iour transmembrane subunits, such as two aIpha and two beta poIypeptides
(Fig. 9.20). The Iarger aIpha subunit is phosphoryIated during transport oI ions. Na
¹
K
¹
ATPase and
Ca
¹¹
ATPase pumps are incIuded in this category.
ATP
ADP + Pi
K
+
ATPase
pump
Inhibited by
2, 4 – diitrophenol
Ca
2+
Na
Ca
2+
Membrane
Cell
+
Animal Physiology '&
The V and F types oI pumps, though unreIated to cIass P pumps, transport onIy protons. F-cIass
pump contain three types oI transmembrane proteins and V-cIass pumps contain atIeast two kinds oI
proteins. V-cIass pumps are ATP powered pumps that maintain Iow pH oI pIant vacuoIes and oI
Iysosomes and other vesicIes in animaI ceIIs by using energy Irom ATP hydroIysis to pump protons
Irom the cytosoI to the exopIasmic Iace oI the membrane. F-cIass pumps are Iound in mitochondria,
chIoropIasts and in the pIasma membrane oI bacteria.
GIucose Transport lnto lntestinaI CeIIs is ATP-Driven
The IumenaI ceII oI the intestine have two domains, diIIerentiated on the basis oI Iipid and protein
composition oI the membrane. The membrane with ceIIs having brush border Iace the Iumen carrying
microviIIi, and the basoIateraI surIace is in contact with neighbouring ceIIs and bIood capiIIaries. The
microviIIi heIp in increasing the ceII surIace Ior absorption oI nutrients.
GIucose, other sugars as weII as amino acids are transported across the membrane Irom Iow
concentration in the Iumen oI the intestine to a higher concentration in the cytosoI oI the epitheIiaI
ceIIs by a symporter protein, which is ion-driven active transport process. The energy comes Irom the
movement oI Na
¹
down its concentration gradient. The basoIateraI side oI the epitheIiaI ceIIs, in
contact with the bIood capiIIaries, maintain a concentration gradient oI gIucose across this membrane
to aIIow gIucose to move out oI the ceII by IaciIitated diIIusion through a transporter. The Iow
concentration oI Na
¹
inside the epitheIiaI ceIIs is maintained by Na
¹
K
¹
ATPase pump on the
basoIateraI membrane (Fig. 9.21).
8.5 BULK TRANSPDRT SYSTEMS
CeIIs have aIso deveIoped mechanisms to transport Iarge moIecuIes across the pIasma membrane,
which otherwise cannot diIIuse through the membrane barrier. Such moIecuIes incIude proteins,
FIg. 9.2û Three classes of pumps have been recognized. v-class pumps are found in plant vacuoles and lysosomes,
while F and v-class pumps are found in mitochondria and bacterial plasma membranes.
b
Exterior
a
a c c c
T T
A A
ATP-binding
regions
ABC superfamily F- and V-class pump
P-Class pump
ATP-binding
site
Cytosol
ATP-binding
region
b
a
g
d
Membrane Physiology ''
poIysaccharides, poIypeptides and poIynucIeotides etc. This is done by a process caIIed endocytosis.
SimiIarIy particuIate matter, secretory moIecuIes Iikes hormones, and proteins can be transported out
oI the ceII by a process caIIed exocytosis. Both the processes invoIve the Iormation oI vesicIes.
Endocytosis
Endocytosis is essentiaIIy an energy dependent process and occurs in aImost aII eukaryotic ceIIs.
ExtraceIIuIar macromoIecuIes are enguIIed and transported to the ceII interior where it is
progressiveIy encIosed in a smaII portion oI the pIasma membrane. Three distinct types oI endocytotic
processes have been observed, which incIude phagocytosis, pinocytosis and receptor-mediated
endocytosis.
Phagocytosis
Phagocytosis is a major mechanism where particuIate matter is enguIIed without IIuid, such as
viruses, bacteria, and macromoIecuIes. The process is particuIarIy observed in protozoans, and in
muIticeIIuIar organisms it is carried out by speciIic ceIIs such as macrophages, poIymorphs,
Iymphocytes and neutrophiIs, where it is a Iorm oI Ieeding process. The particIe to be ingested is
enguIIed in a Iarge endocytic vesicIe caIIed phagosome (Fig. 9.22). The particIe then binds to the
surIace oI the phagocyte aided by a surIace receptor and the vesicIe encIosing the particIe is enguIIed
with its pIasma membrane. The phagosome then Iuses with a Iysosome so that ingested particIe is
broken down and digested in the cytosoI, whiIe undigested materiaI is Iound in the Iorm oI residuaI
bodies to be transported out oI the ceII.
Pinocytosis is the Process of FIuid-intake
Pinocytosis or ceII-drinking is a constitutive process, occurring continuousIy in aImost aII kinds oI
ceIIs. A ceII sipping away at the ertraceIIuIar IIuid by pinocytosis acquires a representative sampIe oI
FIg. 9.21 Nechanism of glucose transport in intestinal epithelial cells.
Epithelial cell
ATP
Na
+ Na
+
K
+
ADP + Pi
Na K – ATPase
+ +
H O
2
H O
2
Carrier
Glucose
Glucose
Transporter
of glucose
Gut
lumen
High Na
+
Blood
Glucose
Low Na
High K
+
+
Animal Physiology
moIecuIes and ions dissoIved in the extraceIIuIar IIuid. SmaII areas oI the pIasma membrane are
ingested in the Iorm oI vesicIes which are returned to the ceII surIace. These are pinocytic vesicIes
which encIose a smaII amount oI extraceIIuIar IIuid. This is a non-speciIic endocytosis, but provides a
much more eIegant method Ior ceIIs to pick up criticaI components oI the extraceIIuIar IIuid that may
be in scant suppIy.
Receptor-mediated Endocytosis
Some integraI membrane proteins dispIayed at the membrane surIace Iunction as receptors Ior
extraceIIuIar IIuid components. For instance, iron in the bIood is transported compIexed with a protein
caIIed transferrin whose speciIic receptor is Iocated on the surIace. When a receptor encounters
transIerrin, binding takes pIace and the receptor with the transIerrin is endocytosed, reIeasing iron in
the cytosoI whiIe the receptor is returned to the surIace Ior recycIing (Fig. 9.23). ChoIesteroI is aIso
taken up by the ceIIs by receptor-mediated endocytosis. The most abundant choIesteroI carriess in
humans are the Iow-density Iipoproteins or LDLs. PeopIe who inherit deIective genes Ior LDL
receptor have poorIy Iunctioning receptors, which create excessiveIy high IeveIs oI LDL in their
bIood, predisposing them to atheroscIerosis and heart attacks. This is a IamiIiaI disease caIIed
hypercholesterolemia.
Exocytosis
Exocytosis is reverse oI endocytosis in which membrane-bound vesicIes move to the ceII surIace
where they Iuse with the pIasma membrane. Exocytic vesicIes are Iormed in various ways. Some
vesicIes are simpIy endosomes traversing the ceIIs, whiIe some are either pinched oII Irom endosomes
beIore they Iuse with the Iysosomes. Some vesicIes may be Iormed Irom the endopIasmic reticuIum
FIg. 9.22 Two modes of endocytosis: phagocytosis and pinocytosis.
Material
Endocytosis
Endosome
Lysosome
Pinocytosis
Plasma membrane
Extracellular
fluid
Pinocyte
Vesicle
Membrane Physiology
FIg. 9.23 Receptor-mediated endocytosis.
FIg. 9.24 Elimination of substances (wastes) through exocytosis.
Phospholipid
Cholesterol
Plasma membrane
Receptors
recycled
Cholesterol
Cytosol
LDL receptor
Clathrin
coat
Lysosome
LDLs digested
Rough endoplasmic
reticulue
Lysosome
Transport vesicle
Plasma membrane
Extracellular space Exocytosis
Secretory
vesicle
Clathrin
Golgi
Animal Physiology
and the GoIgi to take their products to the ceII surIace. Formation oI exocytic vesicIes is shown in Fig.
9.24. Exocytosis is essentiaI to restore the normaI amount oI pIasma membrane, and ensures dispIay
oI its characteristic ceII-surIace proteins. It aIso heIps in the secretion oI various components oI the
extraceIIuIar matrix. The exocytosis oI Iysosomes suppIies the membrane much needed materiaI to
repair the wounds in the pIasma membrane.
DiIIerent Iorms oI energy maniIested in the Iiving matter are a resuIt oI biochemicaI reactions. AII
biochemicaI reactions come under the IieId oI metaboIism which constitute degradative as weII as
synthetic reactions. Synthetic processes require energy which is made avaiIabIe to the system
through oxidations. AII the energy reIeased during the oxidative process is not utiIized; however, some
oI it is dissipated out oI the body in the Iorm oI heat. Thus metaboIism and heat production are
intimateIy reIated. Many biochemicaI reactions are extremeIy temperature sensitive. A 10°C rise in
temperature acceIerates the rate oI reactions twoIoId, whereas Iow temperatures have an opposite
eIIect. Since IiIe oI organisms is dependent on chemicaI reactions, it IoIIows that aII bioIogicaI
processes may be proIoundIy inIIuenced by temperature IIuctuations.
BioIogicaI systems have predominance oI carbon compounds which are stabIe within a
temperature range oI 40-45°C. The Iower Iimit oI the temperature range is cIose to the Ireezing point
oI water which is 1°C and the upper Iimit Iies cIose to the 45-50°C range beyond which proteins get
denatured. A Iew aIgae have been known to thrive at 70°C. AIthough the environmentaI temperatures
have a wide range, the bioIogicaI activity exists in onIy a smaII part oI the totaI range Iying cIose to the
Iower Iimit.
30.3 HABlTATS DF ANlMALS
The habitats oI animaIs can be divided into three categories, nameIy, terrestriaI, aquatic and aeriaI.
AnimaIs Iiving in terrestriaI environment have an acute probIem oI temperature. Because oI the radiant
heat oI the sun, environmentaI temperature may reach an upper IethaI Iimit. Air has a Iow speciIic
heat and so it gains or Ioses heat rapidIy. AIter sunset considerabIe heat gained by the environment
gets Iost so that Iower IethaI Iimit is reached. TerrestriaI animaIs have acquired greater adaptabiIity
since they have to Iive under wide range oI temperatures. In deserts, the temperatures exceed the
bioIogicaI Iimits and sandy tracts attain temperatures as high as 70°C, whiIe the air temperature may
Temperoture ReguIotion
+ 0 ) 2 6 - 4

Animal Physiology "
be around 50
o
C. In the tropics and subtropics, sometimes the temperature reaches beIow Ireezing
point (65°C to 50°C).
AnimaIs Iiving in aquatic habitats do not Iace acute thermaI probIems as Iaced by terrestriaI ones.
Water has a high speciIic heat and it gains or Ioses heat sIowIy, thus making IittIe changes in
temperature. ThermaI adjustments are not a probIem with aquatic animaIs. AeriaI animaIs Iike birds
have a higher Iimit oI thermaI toIerance (35-42°C) due to higher rate oI metaboIism (Fig. 10.1).
FIg. 1û.1 Temperature ranges of various animals.
Temperature adjustments are reIated to physioIogicaI adjustments. Aquatic animaIs have a Iow
rate oI metaboIism and cannot adjust to extremes oI temperature. NevertheIess, terrestriaI animaIs
have the capacity to step up or step down their metaboIic rates in accordance with the thermaI
changes.
30.E NDMENCLATURE DF THERMDREGULATlDN
On the basis oI body temperatures animaIs are cIassiIied as varm-blooded or cold-blooded. These
terms are rather vague and have been repIaced by more appropriate terms such as homeothermic and
poikilothermic. AnimaIs which are capabIe oI maintaining a reIativeIy constant body temperature in
spite oI great variations oI externaI temperature are said to be homeothermic, whereas animaIs in
which the body temperature varies with that oI the environment are caIIed poikiIothermic.
PoikiIotherms incIude invertebrates and aquatic animaIs Iike Iishes and amphibians. Some animaIs
°C
100°
50° upper limit of desert animals
45° limit of turtle and camel
39-44° temperature of birds
35-40° core body temperature of most mammals
25° limit of shore invertebrates
D
i
u
r
n
a
l
v
a
r
i
a
t
i
o
n
s
o
f
d
e
s
e
r
t
a
n
i
m
a
l
s

Temperature Fegulation #
have a high rate oI thermaI conductance and Iow rate oI heat production. Such animaIs acquire heat
Irom the environment and reguIate their body temperatures quite independent oI the heat produced in
the body. These animaIs are known as ectothermic and incIude vast majority oI animaIs species. In
contrast to this, a Iew animaIs produce suIIicient heat due to their own oxidative metaboIism and
maintain body temperature at a constant IeveI. Such animaIs are caIIed endothermic which incIude
homeotherms Iike birds and mammaIs.
There is yet another category oI animaIs which do not maintain constant body temperature Iike
prototheria, but during activity they show endothermic reguIation. These are caIIed heterothermic
animaIs. They are aIso caIIed IacuItative endotherms since they are capabIe oI reguIating physioIogicaI
temperature at certain times onIy.
30.3 ENERGY RELATlDNSHlPS DF ANlMALS
The temperature reIations between the organisms and the environment are dependent upon the water
contents oI the individuaIs. TerrestriaI animaIs have a compIex environment, hence it is diIIicuIt to
make an accurate measurement oI their thermaI environment. However, thermaI reIationships oI
aquatic animaIs are easier to determine. Water has a Iow heat conductivity and it gets heated up
sIowIy. ThereIore, aquatic animaIs maintain their body temperature cIose to the ambient temperature.
TerrestriaI animaIs, on the other hand, are Iaced with much greater probIem oI thermaI reguIation.
Most oI the heat produced by the body is Iost to the environment through conduction, convection,
radiation or evaporation. MammaIs have eIIicient thermoreguIatory physioIogicaI devices to maintain
their body temperature. When the ambient temperature exceeds the body temperature, the body
temperature is not aIIowed to rise by evaporation oI water through body surIace. Evaporation Iowers
the temperature oI the body. The skin and the respiratory system oI animaIs have tremendous
thermoreguIatory signiIicance.
3
l0
law
The outside temperature aIIects the metaboIism in the same way as it does Ior bioIogicaI
reactions. The heat production oI an individuaI is directIy reIated to the body metaboIism. The
biochemicaI reactions are extremeIy sensitive to temperature; an increase in temperature acceIerates
the rate oI reactions. This Iact was expIained by van`t HoII who stated that the biochemicaI reactions
are approximateIy doubIed by 10°C rise in temperature. This generalization was known as 3
l0
law
and can be quantitatively expressed as:
Q
I0
÷
10
t
t
k
k
Where k
t
is the veIocity constant at temperature t and k
t
¹ 10 the veIocity constant at 10°C
higher, and the vaIue is caIcuIated by the IormuIa
Q
I0
÷
k
k
t t
1
2
10
1 2
F
H
G
I
K
J
( )
or Iog Q
I0
÷
10
1 2
1 2
Iog Iog k k
t t

b g
Animal Physiology $
Where k
1
and k
2
are veIocity constants corresponding to temperatures t
1
and t
2
respectiveIy. The
reIationship is not a Iinear one, but Iogarithmic. In case oI chemicaI reactions, Q
10
is IairIy constant
and Iies between 2 and 3, but at higher and Iower temperatures this reIationship is not IoIIowed.
Homeotherms do not IoIIow this Iaw since they can adapt to the heat production when the heat is
Iost. Enzyme cataIyzed chemicaI reactions are not Iinear in Iunction, hence Q
10
Iaw is not appIicabIe.
InIIuences oI temperature on bioIogicaI reactions were expIained by Arrhenius equation:
K ÷ A
c
E
a
/R1
where K is veIocity constant, A
c
is a constant reIating to moIecuIar coIIision Irequency, E
a
is
activation energy, and R and 1 are gas constant and absoIute temperature respectiveIy. However,
because oI extreme thermaI IIuctuations a straightIorward Iaw an animaIs cannot be IormuIated.
30.4 LDW TEMPERATURE EFFECTS
Majority oI Iiving organisms Iace environments where temperature IIuctuates both diurnaIIy and
seasonaIIy. OnIy birds and mammaIs are abIe to reguIate their internaI temperature, whiIe other Iiving
organisms conIorm to prevaiIing externaI temperatures. ProtopIasm can exist in Iiving state between
0°C and 45°C, and very Iew organisms can withstand such a wide range temperatures.
AnimaIs respond to coId in severaI ways. Many try to avoid coId by migrating to warmer regions.
Migration in birds Irom coIder regions to warmer regions is quite a IamiIiar phenomenon which is,
however, seasonaI. Such animaIs deveIop coId toIerance and adapt to changed environments by
resorting to hibernation, spending their periods oI inactivity in burrows.
GeneraIIy, Iow temperatures have an adverse eIIect on the IiIe processes oI animaIs. II an animaI
is sIowIy subjected to Iow temperature, metaboIic rates become IeebIer and IeebIer and uItimateIy
death ensues. The protopIasm oI the ceIIs is an aqueous soIution and Ireezes a Iew degrees beIow
zero. SIow Ireezing causes Iormation oI ice crystaIs which cause IethaI eIIects. On the other hand,
Iast cooIing does not aIIow the Iormation oI ice crystaIs and the tissues are preserved in a chill
comma stage. This is caIIed supercooling.
Vinegar nematodes and certain species oI protozoa survive temperatures as Iow as 197°C when
pIaced in Iiquid air. Protozoa in the encysted stage and aIso some insects can withstand proIonged
sub-zero temperatures. This is due to the eIIect oI supercooIing. Winterhardy species oI insects can
survive supercooIing since they can toIerate temperatures 23°C to 30
o
C. SIow Ireezing has
obviousIy some disadvantages:
(a) Freezing causes Iormation oI ice crystaIs in the ceII and disturbs the ceII organization.
(b) MetaboIism is greatIy Iowered and as such the rate oI oxygen consumption is aIso very Iow.
This is because the diIIusion oI O
2
and CO
2
through the ice is very sIow.
(c) The enzymes become inactive.
PoikiIotherms have their body temperature generaIIy Iower than the surroundings, but severe coId
induces a Iactor oI accIimatization. The IethaI eIIects oI coId or Iow temperature may be avoided by
aItering the Ireezing points. The Ireezing point oI any soIution is Iower than that oI the pure soIvent.
Temperature Fegulation %
Any increase in the osmotic content oI the body IIuids wiII Iower the Ireezing point and protect the
organisms Irom being Irozen. Hence, poikiIotherms avoid coId by acquiring an antifreeze
phenomenon or may avoid coId by supercooIing. Insects sometimes Iace temperatures Iower than the
Ireezing point oI the body IIuids. A parasitic hymenopteran, Bracon cephi, can withstand
supercooIing at 47°C. It has been Iound that in such insects the haemoIymph normaIIy contains
gIyceroI which Iowers the Ireezing point and oIIers protection to the Irozen tissues Irom damage.
Vertebrates do not have toIerance to Ireezing or supercooIing as compared to invertebrates.
Fishes in the Arctic are not abIe to survive when Irozen compIeteIy. The temperature which kiIIs a
poikiIotherm is not Iixed and depends upon its previous thermaI history. AccIimatization can,
however, aIter the IethaI Iimits to a smaII extent. It is generaIIy beIieved that accIimatization invoIves
either the synthesis oI new Iorms oI enzymes which are abIe to operate under new temperature zone
or quantitative changes in the amounts oI existing enzymes.
30.5 TEMPERATURE RELATlDNS lN PDlKlLDTHERMS
The activity oI poikiIotherms depends on the prevaiIing ambient temperature, and in doing so they do
not expend any energy on thermoreguIation since their metaboIism is at a Iower IeveI with IittIe or no
heat production. It has been discussed aIready that the rates oI bioIogicaI processes approximateIy
doubIe Ior each 10°C increase untiI a IethaI Iimit is reached. However, when comparing the rates oI
metaboIic processes during summer and winter, one may Iind Q
10
Iess than 2. Thus, Iiving organisms
have the abiIity to compensate Ior environmentaI temperature changes by aItering their metaboIic rate.
In coId conditions their body temperature is Iow and in hot weather the body temperature rises. The
body gains heat Irom the environment and the metaboIic rate is acceIerated. Thus there is no Iixed
metaboIic rate in poikiIotherms and it varies with the ambient temperature. PoikiIotherms, however,
reguIate their temperature by physicaI mechanisms onIy:
(a) Poor insuIation aIIows greater heat Ioss and prevents conservation oI heat.
(b) Core body temperature (measured through the rectaI region) is Iower than the ambient
temperature.
(c) In hot environments body heat is removed through evaporation.
(d) In Iow ambient temperatures, there is no reguIated way oI heat production since chemicaI
reguIation is wanting.
Aquatic PoikiIotherms
ThermaI reguIation in aquatic poikiIotherms is a simpIe phenomenon. Heat exchanges in aquatic
animaIs are IargeIy by conduction and convection. ThermaI environment oI aquatic animaIs is
reIativeIy stabIe, stiII seasonaI variations do occur in the surIace Iayers oI the sea and Iakes. For
aquatic animaIs which do not possess coId-hardiness, even the temperature above the Ireezing point
may prove IethaI. On the other hand, some poikiIotherms cannot toIerate high temperatures. In such
cases, death may occur even beIow temperatures at which proteins are usuaIIy denatured.
AQUATIC INVERTEBRATES: Aquatic invertebrates can toIerate wide ranges oI temperature
IIuctuations as compared to poikiIothermic vertebrates. Chironomid Iarvae in hot springs can toIerate
Animal Physiology &
temperatures as high as 50°C, whereas in some overwintering species oI insects survivaI at sub-zero
temperatures Ior proIonged periods is possibIe. Such adaptations are, however, species speciIic
having a temperature range oI their own.
AQUATIC VERTEBRATES: Fishes are giII-breathing aquatic poikiIotherms whose body temperature
is maintained cIose to that oI water. Their metaboIic rate is very Iow; hence their rate oI heat
exchange is aIso Iow. A Iish whiIe swimming may produce some heat due to muscuIar activity which
may increase the body temperature temporariIy, yet there is no appreciabIe diIIerence between its
body temperature and surrounding water. This is because the heat produced due to muscuIar activity
is immediateIy transIerred to the bIood eventuaIIy reaching the giIIs which are in immediate contact
with water. GiIIs are extremeIy eIIicient organs Ior respiratory exchanges and aIso heIp in
equiIibrating temperature oI the bIood and the surrounding water. PhysicaI Iactors Iike Iarge surIace
areas oI the Iish, counter-current mechanisms and thin-waIIed bIood vesseIs IaciIitate exchange oI
heat between water and the Iish so that the body temperature remains equaI to that oI water. There is,
however, one notabIe exception to this generaIization. In case oI a Iarge and Iast swimming Iish tuna,
the temperature oI the axiaI muscIes is about I2
o
C higher than the surrounding water. The heat
produced due to muscIe activity is reguIated by the counter-current mechanism to a Iimited extent
and the dissipation oI heat is reduced.
It has been Iound that the matching between body temperature and water temperature wiII be
cIoser in smaIIer species than in Iarge ones. Under conditions oI sustained activity, Iarge Iorms wiII
show transient increases in body temperature. Fishes are generaIIy more susceptibIe to drastic
changes in environmentaI temperature. Fishes Iiving in shaIIow waters or in the surIace Iayers oI the
sea experience drastic temperature IIuctuations seasonaIIy. These Iishes are reIativeIy independent oI
temperature in their physioIogicaI adjustments. On the other hand, Iishes Iiving in tropics or in deep
waters at any Iatitude do not Iace temperature IIuctuations, hence are extremeIy sensitive to changes
in environmentaI temperatures. Fishes that normaIIy experience seasonaI changes in temperature are
known to have evoIved biochemicaI adjustments to maintain normaI Iunctions despite changes in
body temperature.
TerrestriaI PoikiIotherms
TerrestriaI poikiIotherms maintain their body temperature aImost equaI to that oI environment.
However, terrestriaI animaIs Iace greater temperature IIuctuations. The heat baIance oI such animaIs
is more reIated to their water baIance as compared to aquatic animaIs.
The probIems oI terrestriaI poikiIotherms are varied. Desert animaIs are subjected to daiIy
temperature variations. The days are warm and the nights are cooI, showing a temperature range
between 10
o
C and 45
o
C. In hot summer days, the temperature may exceed even 50
o
C. In arctic
region aIso the temperature varies Irom 20 to 60
o
C.
Owing to Iow speciIic heat air exchanges heat quickIy. On Iand, animaIs absorb the radiant heat
with readiIy and give up heat with the same rapidity. This is because air is a poor conductor oI heat.
PoikiIotherms Iose heat readiIy by evaporation oI water Irom the body surIace.
TERRESTRIAL INVERTEBRATES: Invertebrates are perhaps the most important group oI animaIs
which have acquired maximum adaptabiIity to their environment. Their habitats are varied and so aIso
Temperature Fegulation '
their thermaI requirements. In this context, our description wiII be restricted to the arthropods and
insects in particuIar since they are Iound to be active in extreme thermaI environments. The body
temperature oI insects may vary Irom that oI the air due to three reasons: (a) heat Ioss by evaporation
oI water Irom the body surIace, (b) absorption oI heat by radiation; and (c) heat production by
metaboIic activity oI the body.
(a) Heat loss by evaporation: Many insects are abIe to maintain their body temperature 3-5
o
C
Iower than the air. This is possibIe by Ioss oI heat Irom the body by evaporation. Water is
generaIIy Iost Irom the tracheaI system through spiracuIar openings. In dry air, excessive
water Ioss Irom the body poses the risk oI death due to desiccation. The cuticIe oI insects is
impermeabIe to water because oI the presence oI a waxy Iayer in it. However, iI temperature
oI the body exceeds 40°C, the waxy coat meIts rendering the cuticIe permeabIe to water
causing dehydration oI the body.
(b) Absorption of the radiant heat: Insects absorb radiant heat oI the sun and raise their body
temperature. The amount oI heat absorbed by an insect depends on the pigmentation, surIace
area oI the body, and orientation oI the body in respect to the sun. Dark coIoured insects
absorb more heat as compared to Iight coIoured insects. Orientation oI the body in respect to
the sun`s rays is an important parameter, Schistocerca, a desert Iocust, is active at 17-20°C
and orients itseII perpendicuIar to the sun`s rays to get maximum heat.
(c) Heat production due to metabolism: Heat production in insects increases during IIight activity.
At Iow temperature the IIight muscIes remain inactive and sustained IIights may not be
possibIe at aII. Many insects warm up by Ianning their wings beIore commencing actuaI
IIights. Warming up period is Ionger at Iow temperatures. Observation on Janessa indicates
that it takes about 6 minutes at 11
o
C, 1
1
2
mintues at 23°C, 18 seconds at 34
o
C and none at
37
o
C to warm up. In sociaI insects Iike honeybee and termites, metaboIic heat is useIuI Ior
temperature reguIation in the coIonies. IdeaI temperature Ior brood deveIopment in honeybees
is 34.5-35°C. Excessive heat oI summers creates uneasy situation Ior the brood which is
overcome by transporting and spreading water in the hive by workers. On the other hand, Iow
temperatures during winter Iorce the honey bees to cIuster together to increase the
temperature oI the hive a IittIe above the air temperature.
TERRESTRIAL VERTERBRATES: Amphibians are a unique group oI animaIs which show a
remarkabIe exampIe oI temperature adjustment in reIation to the environment. The skin oI
amphibians, aIthough ineIIective Ior physioIogicaI reguIation, oIIers a good protection in extreme
situations. In dry and warm surroundings, water is Iost Irom the skin by evaporation. When on Iand,
the wet skin Iunctions Iike a wet-buIb thermometer and the constant evaporation oI water Irom the
skin keeps the body temperature beIow that oI the environment. GeneraIIy the amphibians are very
sensitive to high temperatures and in this respect they have a poor adaptabiIity as compared to
reptiIes, birds and mammaIs. Amphibians cannot withstand high temperatures on Iand owing to,
inadequte physioIogicaI mechanisms. However, they reguIate their body temperature through
behaviouraI adjustments and thermaI accIimatization (see Sections 10.9 and 10.10).
Animal Physiology
30.8 TEMPERATURE RELATlDNS DF HDMEDTHERMS
AIthough reptiIes have some environmentaI constraints, they are the Iirst group oI terrestriaI
vertebrates which mark the beginning oI homeothermy by exhibiting thermoreguIatory mechanisms at
the primary IeveI. Birds and mammaIs maintain their body temperature independent oI the
environment and have evoIved eIIicient thermoreguIatory devices. Heat is produced and conserved in
coId environments, whiIe heat is Iost in hot environments. Heat exchanges between the body and the
environment are reguIated by thermoreguIatory centres Iocated in the hypothaIamus which Iunctions
Iike a thermostat. ReguIation oI the body temperature is brought about in the IoIIowing ways:
(a) Heat production and heat Ioss are rapidIy adjusted in reIation to body and environmentaI
temperatures. This is physicaI heat reguIation.
(b) Heat production is reguIated by chemicaI heat reguIation. This is done by acceIerating
metaboIic rate when heat requirements oI the body are high.
PhysicaI Heat ReguIation
Homeotherms maintain a constant body temperature. In order to do so, it is necessary that the heat
production must be equaI to heat Ioss. When the ambient temperature is Iower than the body, the
body Ioses heat to the environment (Fig. 10.2). In order to compensate this heat Ioss, homeotherms
are capabIe oI producing heat by stepping up their metaboIic rate.
According to Newton`s Iaw oI cooIing, the change oI heat in a body per unit time is proportionaI
to the diIIerence between its temperature and the ambient temperature. The reIationship can be
expressed thus:
dH
dt
÷ C (1
B
1
A
)
where C is thermaI conductance, 1
B
is body temperature and 1
A
is ambient temperature. Since heat
Ioss ÷ heat gain ÷ heat production ÷ metaboIic rate, heat Ioss ÷ C(1
B
1
A
). ThereIore, C ÷ metaboIic
rate/(1
B
1
A
).
Heat loss: Heat is Iost Irom the body by skin, Iungs and excretions. Skin Iorms by Iar the most
important source oI heat Ioss. Homeotherms dissipate heat by conduction, convection, radiation and
evaporation. ThermaI conductance oI the body is oI utmost importance since accumuIation oI heat in
the animaI may produce death due to overheating. The probIem oI overheating has been observed in
Iur seaIs, Callorhinus ursinus, which Iive in the arctic region. Fur seaIs Iive in water and dissipate
heat to the environment, the diIIerence between core body temperature and that oI the environment
being about 30°C. This is overcome by a heavy and waterprooI insuIation and a subcutaneous Iayer
oI Iat. When Iur seaIs are in water, Iarge quantity oI heat is generated due to swimming which is Iost
to the water through Iarge and richIy vascuIarized IIippers. WhiIe on Iand, the IIippers do not aIIow
heat Ioss as eIIicientIy since air has a Iow speciIic heat. This creates a probIem Ior Iur seaIs when air
temperature rises above 12°C. Heat Ioss is not IaciIitated, hence death may IoIIow.
The externaI Iactors that determine the amount oI heat Ioss are temperature, humidity oI the air,
veIocity oI air currents, and temperature oI surrounding objects. GeneraIIy homeotherms maintain
Temperature Fegulation
their core temperature higher than that oI the ambient temperature aIIowing heat Ioss through skin to
cooI the body. This estabIishes a temperature gradient Irom the core to the skin surIace. II thermaI
conductivity oI the subcutaneous Iat is changed by aItering the bIood IIow, the direction oI
temperature gradient is aIso reversed.
Heat Iost Irom the skin is Iinked with two probIems, i.e. the bIood IIow in the skin, and the
externaI insuIation.
Blood flov in the skin: BIood IIow in the skin is responsibIe Ior the reguIation oI heat Ioss.
During conditions oI hypothermia (Iow core temperature) the IIow oI bIood to the surIace oI the
body is restricted minimizing the heat Ioss. ConsequentIy, the temperature oI the skin surIace IaIIs.
On the other hand, during hyperthermia (high core temperature) the bIood IIow through the skin is
augmented so that there is a greater Ioss oI heat through the skin. In such circumstances the
diIIerence between the core body temperature and the skin surIace is minimized.
BIood IIow in the skin is controIIed by the sympathetic nervous system. In conditions oI
hyperthermia diIation oI the bIood vesseIs takes pIace to increase the bIood IIow. This is brought
about by:
(i) ReIaxation oI the activity oI the nerves which cause vasoconstriction:
(ii) Increase in the activity oI sympathetic vasodiIator Iibres; and
(iii) ReIease oI chemicaI substance, bradykinin Irom the sweat gIands having a vasodiIatory action.
External insulation: In homeotherms the skin is provided with structures Iike Ieathers, Iur, hair,
etc., which Iunction as insuIators. The eIIectiveness oI these insuIating structures is enhanced by the
sympathetic nervous system. Air, which is a bad conductor oI heat, is trapped between the Ieathers
or Iurs oI the skin and acts as a barrier Ior the Ioss oI heat.
FIg. 1û.2 Relationship between body temperature and the ambient temperature for certain animals.
40
30
20
0
0 10 20 30 40
Cat
Opossum
Ornithorhynchus
Echidna
L
i
z
a
r
d
B
o
d
y
t
e
m
p
e
r
a
t
u
r
e
°
C
10
External temperature °C
Animal Physiology
ChemicaI Heat ReguIation
PracticaIIy aII the heat in homeotherms is derived Irom the oxidation oI IoodstuIIs. AIthough every
tissue contributes to heat production by oxidative mechanisms, the skeIetaI muscIes contribute the
Iargest amount. Heat production mechanisms invoIve two processes.
HEAT PRODUCTION DUE TO MUSCULAR ACTIVITY: In poikiIotherms the chemicaI action varies
directIy with the temperature oI the reacting agents. The heat production is correspondingIy reduced
IoIIowed by a IaII in the temperature. In coId environments, the rate oI metaboIism graduaIIy decIines
in coId bIooded animaIs. In coId environments, homeotherms show muscuIar activity to increase heat
production. CoId produces 'shivering¨ which may increase heat production between 2 and 5 times
the basaI IeveI. This invoIves the somatic nervous system. On the other hand, exercise is abIe to
remove shivering by producing more heat and increasing the rate oI heat Ioss. However, additionaI
heat produced as a resuIt oI exercise does not have a thermoreguIatory signiIicance.
NONSHIVERING THERMOGENESIS: In many mammaIs production oI heat is stepped up without
invoIving muscuIar exercise. In resting or Iasting state aIso, heat is produced at a steady IeveI.
Nonshivering thermogenesis heIps in accIimatization oI mammaIs to Iow temperatures. Exercise has
no eIIect on nonshivering thermogenesis.
Heat production during nonshivering thermogenesis invoIves some change in the intermediary
metaboIism which may be brought about by caIorigenic action oI hormones or brown Iat.
Calorigenic action of hormones: CoId accIimated rats are abIe to utiIize and synthesize more
gIucose which is a consequence oI hormonaI reguIation. Injection oI norepinephrine in coId
accIimated rats shows a caIorigenic action by enhancing body temperature and oxygen consumption.
Thyroxine aIso augments oxygen consumption increasing the heat output by acceIerating the
metaboIic rate.
Brovn fat: In the young oI many mammaIian species (especiaIIy primates and rodents), brown
Iat tissue occurs which is highIy vascuIar and muItiIocuIar. It is weII deveIoped in hibernating
mammaIs and is an important site oI nonshivering thermogenesis. The brown Iat deposits are Iocated
around the neck, thorax and major bIood vesseIs. During proIonged Iow temperature exposures oI the
body, brown Iat deposits are increased. The brown Iat has a rich bIood suppIy and owing to this the
average oxygen consumption oI it is higher than the rest oI the tissues. The heat produced in the
brown Iat is transported to the brain and head through bIood circuIation.
30.7 TEMPERATURE RELATlDNS DF HETERDTHERMS
Certain mammaIs beIonging to the cIass Prototheria and Metatheria (e.g Echidna, Ornithorhynchus,
ArmadiIIos, Opposums, three-toed sIoths, etc.) have Iow body temperatures in reIation to their
environments and show a wide range oI temperature and metaboIic IIuctuations. Such animaIs are
caIIed heterotherms. Some parts oI the body Iike Iegs, taiI, ears, etc., have poor insuIation as
compared to other parts and as such the temperature oI these parts is Iower than the core
temperature. Echidna has its body temperature at 34°C in reIation to its environmentaI temperature
which is 35°C. In contrast to homeotherms, iI the externaI temperature IaIIs, the body temperature oI
Temperature Fegulation !
Echidna aIso IaIIs considerabIy. Some endotherms show diurnaI variations in their body temperature.
SmaII mammaIs and birds come under this category. In herring guIIs, the core temperature ranges
Irom 38°C to 41°C, but temperature oI some peripheraI parts ranges between 6 and 13°C. The guIIs
can waIk on ice at temperature 30°C, but iI the guIIs are accIimatized to warm Iaboratory conditions
and then aIIowed to waIk on ice, their Ieet are Irozen. In some birds the diurnaI variations are
correIated with the activity during day as compared to the activity at night.
30.8 THERMDREGULATDRY CDNTRDL CENTRE
Endotherms maintain a stabIe core body temperature and in order to achieve this a thermoreguIatory
controI centre becomes operative to baIance heat production with heat Ioss. This is controIIed by the
nervous system. VoIuntary muscuIar activities or shivering enhance heat production and both these
activities are eIIected through motor nerves. Heat Ioss can be aItered by varying the amount oI bIood
IIowing through the skin or it can be increased by sweating. These activities are under the controI oI
sympathetic nervous system. BIood IIow through the skin is abIe to maintain smaII adjustments in the
body temperature; however, Iarger adjustments are possibIe through shivering or sweating.
In homeotherms thermoreguIatory controI centres are Iocated in the hypothaIamus which
integrates the incoming sensory inIormation through temperature receptors. There are two kinds oI
thermoreceptors, viz. the peripheraI thermoreceptors, and the centraI thermoreceptors. PeripheraI
thermoreceptors are distributed aII over the body surIace and in certain portions oI the aIimentary
canaI. CentraI thermoreceptors are situated in the body core.
The HypothaIamus
The hypothaIamus is a smaII part oI the brain situated beIow the thaIamus. It Iorms the IIoor and part
oI the Iower centraI waIIs oI the third ventricIe. It is important in the internaI reguIation and contains
temperature sensitive ceIIs constituting the thermostat oI birds and mammaIs. It aIso contains
osmoreguIatory receptors. HypothaIamus aIso exerts controI on the endocrine activity oI the body by
inIIuencing the pituitary Iunction. Thus it is obvious that the hypothaIamus controIs the autonomic
and endocrine Iunctions oI the body. Food and water intake, sexuaI behaviour, sIeep and emotionaI
responses are aIso under the controI oI hypothaIamus.
STIMULATION OF THE HYPOTHALAMUS: HypothaIamus contains thermoreguIatory centres which
can be stimuIated by eIectricaI or thermaI stimuIus. Techniques have been evoIved by pIacing Iine
eIectrodes in the hypothaIamic areas to IocaIize temperature sensitive centres. It has been
demonstrated that there are two centres in the hypothaIamus concerned with temperature reguIation.
These are an anterior 'heat Ioss¨ centre and a posterior 'heat production¨ centre.
The anterior part oI the hypothaIamus behaves as a thermotaxic centre. It receives aIIerent
impuIses Irom temperature-sensitive receptors in the skin and probabIy in the muscIe in response to
which it is abIe to controI Ioss oI heat by sweating. EIectricaI stimuIation oI the anterior heat Ioss
centre causes vasodiIation in the skin, vigorous panting and cessation oI shivering. StimuIation oI the
posterior 'heat production¨ centre causes vasoconstriction oI bIood vesseIs in the skin, enhances
shivering and inhibits panting.
Animal Physiology "
The two regions oI the hypothaIamus concerned with the responses to hyperthermia and
hypothermia are anatomicaIIy interconnected. Hyperthermia activates the heat Ioss centre whereas
hypothermia activates heat production centre. ThermoreguIatory centres in the brain can be activated
by thermaI receptors in the skin or by changes in the temperature oI the bIood.
A study oI the eIectricaI recordings oI the hypothaIamus has shown that there are at Ieast three
types oI ceIIs which show thermaI sensitivity. These are:
(a) Heat receptorsceIIs which increase their activity when the hypothaIamic temperature
increases, but skin temperature does not aIIect them.
(b) Cold receptorsceIIs which increase their discharge when hypothaIamic temperature is
Iowered and remains unaIIected by changes in the skin temperature.
(c) Mixed receptorsceIIs which respond to increase in skin temperature, but Iurther increase
their discharge when the hypothaIamus aIso gets heated.
1hermal receptors in skin: Skin contains heat and coId receptors. Heat receptors are situated
deeper in the skin whiIe the coId receptors are superIiciaI in Iocation and generaIIy more abundant.
Many oI these receptors are in the Iorm oI naked nerve endings. By increasing environmentaI
temperatures, the skin temperature is aIso raised causing increased discharge Irom the heat receptors
momentariIy (about 2-3 seconds) and then settIes down to the Irequency corresponding to the
temperature. Upon withdrawaI oI the heat stimuIus, the heat receptors reduce their Irequency oI
discharge. SimiIarIy coId receptors can be made to discharge at a higher Irequency by Iowering the
temperature untiI they acquire adjustment to aItered temperature. When the coId stimuIus is
withdrawn, the coId receptors are temporariIy withdrawn.
30.8 TEMPERATURE REGULATlDN lN ENDDTHERMS
BIRDS: GeneraIIy birds have a higher core temperature than the mammaIs. This is advantageous to
birds in hot weather, especiaIIy Ior those Iiving in arid cIimate. However, the temperature range oI
desert and non-desert species IaIIs within the same range. The upper IethaI Iimits Ior desert as weII as
non-desert birds show marked diurnaI cycIes in body temperature with a narrow variation oI 2-3°C.
MuscuIar activity increases body temperature temporariIy.
In hot surroundings birds Iose more water through respiration. In certain cases (American
CardinaI) at higher ambient temperature increased respiratory activity resuIts in water Ioss at Ieast
Iour times between 34°C and 40°C. This is evaporative cooling.
Heat transfer in birds: Besides evaporative cooIing, there are severaI devices which IaciIitate heat
transIer to the environment. Such devices incIude hoIding the wings away Irom the body to expose
body parts, compression oI pIumage, increased bIood IIow to the Iegs and to the combs which
increase thermaI conductance. In addition to this there are certain behaviouraI aspects invoIved in
temperature reguIation. Many birds move into the shady area during day and reduce heat gain.
Soaring birds ascend to high aItitudes to escape the heat oI Iower aItitudes. DiurnaI birds keep their
activities at a bare minimum in hot summer days to reduce metaboIic heat production.
MAMMALS: The core body temperatures oI most oI the mammaIs IaII between 35°C and 40°C,
which is generaIIy higher than the prevaiIing ambient temperature. ThereIore, temperature reguIation
Temperature Fegulation #
in mammaIs mainIy concerns with ecoIogicaI and morphoIogicaI adaptations. MammaIs continuousIy
Iose heat to the environment by heat transIer mechanisms. The thermoreguIatory process concerns
with (1) controI oI rate oI heat Ioss to the environment and, (2) increasing heat production.
MammaIs Iiving in coId regions maintain a uniIormIy high temperature by controIIing heat Ioss
and increasing metaboIic heat production. The greatest contrast between poikiIotherms and
homeotherms is in the heat production in reIation to externaI temperatures (Fig. 10.3). During intense
coId the body temperature oI mammaIs is maintained IairIy constant. This is made possibIe by (a)
eIIicient body insuIation consisting oI hair, Iur, subcutaneous Iat, etc, (b) eIIective vasomotor controI
and counter-current heat exchanges in the vascuIar system, and (c) decreasing coId sensitivity oI
peripheraI regions.
In desert mammaIs, the probIem oI temperature is rather acute since the ambient temperature
exceeds body temperature. Under such circumstances heat moves Irom the environment to the body.
Since heat transIer takes pIace in a reverse direction, cooIing oI the body is brought about by
evaporation.
FIg. 1û.3 Pattern of heat production in respect of variations in body temperatures of homeotherms in relation to
variable external temperatures. The dashed line P shows the heat production in poikilotherms (Adapted from
Hoar, l966).
Homeothermy
Metabolic heat
production
Hyper–
thermy
Core temperature
P
C
o
r
e
t
e
m
p
e
r
a
t
u
r
e
M
e
t
a
b
o
l
i
c
h
e
a
t
p
r
o
d
u
c
t
i
o
n
C
o
l
d
d
e
a
t
h
t
1
L
e
t
h
a
l
t
e
m
p
t
2
t
3
t
4
t
5
t
6
C
r
i
t
i
c
a
l
t
e
m
p
N
e
u
t
r
a
l
z
o
n
e
L
e
t
h
a
l
t
e
m
p
H
e
a
t
d
e
a
t
h
External temperature
H
y
p
e
r
t
h
e
r
m
y
Animal Physiology $
Adaptations to High Temperatures
ThermoreguIation is a probIem Ior endotherms especiaIIy in desert regions where animaIs are Iaced
with intense heat. The ambient temperature exceeds the core body temperature and under such
circumstance heat moves Irom the environment to the body. Two physioIogicaI mechanisms are said
to be Iunctioning:
1. ControI oI the rate oI heat Ioss.
2. TransIer oI endogenous heat against the thermaI gradient Irom the body to the hot
environment by evaporation to keep the body cooI. In deserts, water is in short suppIy, hence
animaIs cannot aIIord to Iose water. The physioIogicaI soIutions to meet this handicap are,
however, not yet avaiIabIe. Deserts abound in herbivorous mammaIs which support many
carnivorous birds, reptiIes and mammaIs.
Adjustments oI animaIs to intense heat oI the desert is a probIem oI adaptation. Deserts are
usuaIIy Iocated Iar away Irom the equator and experience marked seasonaI changes in temperature.
Besides, the animaIs Iace a diurnaI temperature cycIe, that is during the day the temperatures are high,
aIter sunset quite Iow. Nights are coId. Thus the animaIs do not Iace continuous stress oI heat.
ThereIore, vertebrate animaIs Iiving in the tropicaI deserts adjust to the extreme cIimatic conditions by
behaviouraI means according to their physioIogicaI capabiIities aided by the compIex nervous system.
ThermoreguIatory probIems oI desert animaIs IaII under three categories:
(a) ReIaxation oI thermaI Iimits during which homeostatic controI is maintained.
(b) BehaviouraI adjustments predominate thermoreguIatory devices.
(c) SpeciaI structuraI and IunctionaI adaptations deveIop.
These aspects wiII be considered here in respect oI desert mammaIs and birds.
The kangaroo rat (Dipodomys) is a smaII nocturnaI desert mammaI. This rat cannot withstand
high temperatures oI the day, hence spends the hot day time underground retreating in the burrows
where humid conditions prevaiI. AIter sunset when the temperature comes down, the rat comes out
oI the burrow. In this way, this smaII animaI avoids evaporative cooIing. This adjustment in the
kangaroo rat is oI utmost importance since it cannot obtain its water requirement by drinking due to
non-avaiIabiIity oI water. Water requirements, however, are partiaIIy met with Irom dry seeds and
pIants on which it Ieeds, or Irom the metaboIic water by oxidation oI Ioods.
CameI is yet another exampIe exhibiting desert adaptations and physioIogicaI mechanisms which
enabIe it to survive most successIuIIy in high temperatures oI desert. CameI is Iamous Ior traveIIing
Iong distances without drinking any water Ior days together. Schmidt-NieIson has expIained certain
physioIogicaI mechanisms existing in the cameI. According to him, and contrary to the popuIar beIieI,
cameI does not have any storage space Ior water in its body.
CameI can toIerate very high environmentaI temperatures. This is because it has an unusuaIIy high
core temperature. When cameI has no access to drinking water, the core temperature during the day
time may exceed 40°C, and when it has access to water the core temperature may be around 34°C.
Variation in core temperature is a means to conserve water by storing heat during the day. It has been
estimated that in a cameI weighing about 500 kg, a rise oI 6°C in core temperature wouId heIp in
storing about 2500 kcaI. Besides this thermoreguIatory mechanism, cameI`s Iur aIso acts as an
Temperature Fegulation %
eIIective barrier to heat transIer. It heIps conserve water and retards heating up oI the body. As
stated earIier, the cameI does not have any storage capacity oI water and avoids evaporation oI water
by diurnaI variations in the core temperature. NevertheIess, it does Iose some water by way oI
urination and respiration. It can withstand dehydration up to 25-30 per cent during Iong journeys
across the desert and avoids heat stress. When water is avaiIabIe cameI can recover Irom dehydration
by drinking Iarge quantities within a short time (see Chapter 8 aIso).
Birds have exceIIed themseIves Irom the mammaIs in matters oI adaptation to high temperatures
and high rate oI heat production. They are more prone to meet the chaIIenges oI the environmentaI
temperatures. Birds have a temperature range oI 39-45°C and thereIore can sustain in areas oI intense
heat. In certain cases when the ambient temperature is higher than the body temperature, birds can
Iose heat by physicaI processes Iike conduction, convection and radiation. AIthough birds have a high
body temperature, they neither Iose heat nor resort to sweating. However, evaporative cooIing, as it
occurs in vertebrates, is IaciIitated. The thick covering oI Ieathers acts as an insuIator and aIIords
minimum water Ioss. NevertheIess, water is Iost Irom the body Irom the buccaI cavity and the
respiratory system whiIe the bird pants. Panting increases breathing movements. In tropics and
temperate zones during summer, humidity is high owing to which birds Iose about haII oI their body
heat by evaporation. In moderateIy high humid environments the body temperature oI birds rises
resuIting in hyperthermia, IaciIitating passive heat Ioss Irom the body. In avian hyperthermia there is
heat Ioss, whereas in the cameI hyperthermia is caused by heat storage. In extremeIy Iow humid
environments, the body temperature oI some birds is maintained beIow the ambient temperature. This
resuIts in panting, and in order to sustain this some birds have evoIved a noveI method oI gular flutter
requiring Iess expenditure oI energy.
Effect of CooIing
CoId receptors upon stimuIation evoke reIIex responses to conserve heat. As a resuIt oI stimuIation oI
coId receptors, constriction oI bIood vesseIs suppIying to the skin takes pIace reducing heat Ioss
considerabIy. CoId may bring about erection oI hairs, Ieathers and increased muscuIar activity. The
bIood temperature is Iowered consequent upon which heat reguIating centres become operative
IoIIowed by shivering.
Shivering steps up metaboIic rate to produce more heat. It is beIieved that the adrenaI cortex is
stimuIated by exposure to coId which Iiberates noradrenaIine. Increased metaboIic response is due to
the combined caIorigenic action oI adrenaIine and the thyroid gIand.
Adaptation to CoId Environments
In order to cope up with energy requirements, endotherms consume more Iood in coId cIimate.
However, a rich Iood suppIy cannot be aIways ensured, hence certain adaptive patterns have been
evoIved by smaII mammaIs and such patterns are grouped under adaptive hypothermia.
HIBERNATION: Hibernation or winter dormancy is a phenomenon in which the body temperature
IaIIs to a Iow IeveI in accordance with the ambient temperature during coId periods. It is a pattern oI
adaptive hypothermia usuaIIy Iound in smaII mammaIs Iike rodents, insectivores and bats. In these
animaIs, the cIimatic stress and Iood shortage poses a probIem oI survivaI and as such the animaIs
Animal Physiology &
behave as poikiIothermic during coId weather. The hibernants show a number oI physioIogicaI
attributes which are as IoIIows:
(a) The core body temperature IaIIs 1-2°C beIow the environmentaI temperature.
(b) Oxygen consumption is reduced to as Iow as 5 per cent oI the basaI metaboIic rate.
(c) Breathing rates are considerabIy reduced, sometimes proIonged suspension oI respiration takes
pIace.
(d) Heart rate oI the animaI is markedIy reduced, as Iow as 5-6 beats per minute. However, the
bIood pressure remains adequate.
(e) A condition oI torpor or proIound sIeep occurs during hibernation.
(I) Spontaneous arousaI Irom torpor is possibIe in re-estabIishing high body temperatures oI the
endotherms by stepping up heat production.
The adaptive responses described above are Iound in various types oI hypothermia which have
been evoIved independentIy in diIIerent orders under the inIIuence oI ecoIogicaI and physioIogicaI
stresses. We can take the case oI smaII birds and mammaIs which maintain normaIIy high body
temperatures whiIe active. During periods oI inactivity, body temperature and oxygen consumption
drop to a Iow IeveI. These animaIs have restricted Ieeding habits and as such undergo daiIy periods oI
torpidity (birds Ieed during the day time and remain inactive during night). In regions oI Iow
temperatures smaII mammaIs undergo proIonged periods oI hypothermia (dormancy) in contrast to
mammaIs having daiIy torpor. Hibernation is an adaptive chaIIenge requiring a previous preparation
beIore entering hibernation. BeIore winter dormancy starts, the animaIs store Iarge amounts oI Iats
and experience periods oI Iethargy IoIIowed by Iong periods oI dormancy.
Arousal from hibernation: It is a compIex process. The hibernants arouse Irom their winter sIeep
severaI times and the period oI arousaI may Iast Irom a Iew hours to severaI days. This period is
utiIized Ior eIimination oI metaboIic wastes and sometimes to consume Iood previousIy stored in the
hibernating site. The cause oI arousaI has been attributed to shivering and nonshivering thermogenesis
resuIting in spurts oI heat production and oxygen consumption.
In contrast to hibernation, many animaIs respond to periods oI drought or high temperature and
aestivate to avoid hot cIimatic stress. Ground squirreIs oI the genus Citellus, which have a
cosmopoIitan distribution, hibernate during winter and aestivate when serious drought prevaiIs. Many
endotherms such as rodents, insectivores, marsupiaIs, etc., aestivate.
30.30 ACCLlMATlZATlDN
Acclimatization is the term oIten used to denote adjustments to temperatures in the IieId in naturaI
environment, whereas acclimation is the term used Ior adjustment in Iaboratory conditions. Changes
in the cIimate are aIways associated with the changes in the metaboIic rate oI the animaI. An animaI`s
IiIe can be studied in reIation to its environment incIuding temperature, oxygen suppIy, avaiIabiIity oI
Iood and water, etc. II an animaI is kept in a new environment other than its own, it may show
adjustments Ior its survivaI, IaiIing which the animaI may die. Some poikiIotherms show an abrupt
increase in their metaboIic rate when externaI temperature is raised and on cooIing show a sudden
decIine. These changes in the metaboIic rates are described as compensation which are a
Temperature Fegulation '
consequence oI accIimation. When the animaI is returned to its normaI temperature, the rate oI
reactions does not return to the originaI IeveI, but may be higher or Iower as the case may be
depending on the direction oI accIimation.
ThermaI AccIimatization
The probIem oI thermaI accIimatization has a compensatory inIIuence oI temperature on the
metaboIic rate. Amphibians can toIerate high temperature which is in essence a consequence oI
accIimatization.
REPTILES: ReptiIes enjoy a transitory position in the animaI worId. They are beIieved to have
given rise to birds and mammaIs. With the exception oI a Iew aquatic reptiIes (crocodiIes and turtIes),
they are undoubtedIy terrestriaI in habits and show beginnings oI some physioIogicaI
thermoreguIatory mechanisms. AIthough thermaI reguIation oI reptiIes resembIes that oI amphibians,
they are capabIe oI varying their temperature by habitat seIection. They show many behaviouraI
adaptations and evoIution oI physioIogicaI capabiIities anticipating thermoreguIatory mechanisms oI
birds and mammaIs.
Lizards kept in Iaboratory under constant conditions acquire body temperature equaI to that oI the
environment and thus behave as poikiIotherms. However, iI the Iizard is kept in its naturaI habitat it
may behave diIIerentIy by empIoying a thermoreguIatory behaviour. Many snakes and Iizards move
into the sun iI the air temperature is Iower than the body and gain heat. When the body temperature
rises above the preIerred temperature, they again move in the shade and Iose heat. Thus they maintain
their body temperature within a narrow Iimit by aItering their behaviour. In desert reptiIes
thermoreguIatory behaviour is more eIIicient to suit various preIerred temperatures. The American
desert iguana, Disosaurus, can adjust to temperature as high as 48°C which is more than birds and
mammaIs.
PhysioIogicaI mechanisms invoIved in temperature reguIation oI reptiIes are stiII at inIancy stage.
Poor insuIation oI the skin aIIows a quick heat Ioss or heat gain. The heating and cooIing rates are
under cardiovascuIar controI. During eating, the heart rate is Iaster than at cooIing. NevertheIess, the
rate oI heat exchange between the Iizard and the environment depends on the bIood voIume IIowing
per unit time between core and the surIace. ObviousIy, the circuIation is Iaster during heating and
sIower during cooIing. The GaIapagos marine iguana (Amblyrhynchus cristatus) maintains its body
temperature at about 37°C by behaviouraI reguIation.
About 70-90 per cent oI the totaI body weight oI organisms consists oI body IIuids which circuIate in
the body. The IIuid remains in a state oI motion and IIows through a network oI vesseIs (open or
cIosed) so as to reach every part oI the body. Motion oI the body IIuid remains in a state oI dynamic
equiIibrium so Iong the animaI is aIive. The composition as weII as the voIume oI these body IIuids is
aIso maintained in a steady state. In aquatic animaIs, which are Iiving constantIy under water, voIume
oI the internaI IIuids remains constant irrespective oI changes in the pressure oI air or water.
ThereIore the internaI pressure and the voIume oI the IIuids inside the body remain constant.
33.3 MAJDR TYPES DF BDDY FLUlDS
Within the body oI animaIs, body IIuids occur either as intracellular fluids or extracellular fluids. The
intraceIIuIar IIuids are present within the ceII which are responsibIe Ior metaboIic reactions.
ExtraceIIuIar IIuids, which appear outside ceIIs and within tissues, provide nourishment to the ceIIs
and aIso serve to eIiminate waste products. In protozoa, onIy intraceIIuIar IIuid is present which is
responsibIe Ior aII the exchange mechanisms. However, the metazoans possess extraceIIuIar IIuids
because oI their increasing compIexity in structure. In metazoans, extraceIIuIar spaces occur
prominentIy in the Iorm oI Iumen and cavities and the IIuid circuIating in these spaces is
compartmentaIized. In acoeIomate animaIs, the spaces appear as interstitiaI channeIs, whereas in
coeIomates additionaI circuIatory system is present.
The extraceIIuIar IIuid can be cIassiIied into severaI types.
In many pseudocoeIomates Iike nematodes, entoprocta and rotiIers, the extraceIIuIar IIuid is
known as coelomic fluid. It is a watery IIuid which suppIies nourishment to diIIerent parts oI the body.
It is aIso responsibIe Ior removing the wastes, but has no roIe in respiration.
In arthropods and moIIuscs (except CephaIopods), the extraceIIuIar IIuid is caIIed the
haemolymph which circuIates in open channeIs. AIthough watery in consistency, it possesses some
*@O .KE@I
+ 0 ) 2 6 - 4

Body Iluids
pigments aIso. Owing to the presence oI these pigments, this IIuid serves Ior nutrition as weII as Ior
respiration. It is rich in proteins.
Lymph is a coIourIess IIuid which is Iound in aII vertebrates except cycIostomes and
eIasmobranchs. It circuIates in a weII deveIoped network oI Iymph channeIs which are extremeIy thin-
waIIed with a true endotheIiaI Iining. The channeIs originate in connective tissue spaces.
The Iymph is simiIar to the pIasma oI bIood in composition and contains Iymphocytes and
granuIocytes. The Iymphatic system is an open system consisting oI anastomosing channeIs and
Iymph sinuses occurring beneath the skin, in the muscIes, in the waIIs oI the digestive system and
around the nervous system. Lymph IIuid Irom the sinuses IIows into the Iymph vesseIs and Irom there
enters the bIood veins. At the junctions where the Iymph vesseI joins the vein there are smaII
contractiIe lymph hearts which ensure a continuous IIow oI Iymph into the bIood vascuIar system.
Lymph hearts are present in Iower vertebrates, such as Iishes, amphibians and reptiIes. They are
absent in birds and mammaIs.
In mammaIs, Iymph nodes or lymph glands are present which are soIid bodies made up oI
connective tissue and pIaced in the way oI Iymph vesseIs. These nodes contain aggregations oI
Iymphocytes which are Iormed inside them, and as the Iymph IIows past these nodes they are carried
away into the Iymph circuIation. Lymphocytes are a type oI white bIood corpuscIes. Lymph nodes aIso
act as 'IiIter¨ organs which prevent harmIuI substances Irom reaching the bIood vascuIar system.
The IIow oI Iymph is reguIated by vaIves which aIIow it to go Irom smaIIer to Iarger vesseIs.
Movements oI muscIes, viscera, etc., pressing upon the deIicate waIIs oI the Iymphatics, squeeze the
Iymph.
Lymphatic system has many Iunctions. One oI the important Iunctions oI Iymph is to convey
proteins to the bIood pIasma. The Iymphocytes produced in the Iymph nodes are responsibIe Ior the
destruction oI Ioreign bodies and harmIuI bacteria. They aIso produce antibodies. Another Iunction oI
Iymph is to convey Iipids Irom the intestine to bIoodstream.
TransceIIuIar FIuids
These are certain speciaIized cavities or spaces in the body which contain IIuids diIIering Irom each
other in their composition. Such cavities are distinguished as pIeuraI, pericardiaI or cerebrospinaI
cavities containing transceIIuIar IIuids. These IIuids Iubricate the organs contained in the cavities and
provide protection against shocks and injury.
33.E BLDDD
BIood is a Iiquid tissue which IIows through a network oI cIosed circuIating channeIs. The chieI
Iiquid component is the bIood pIasma containing bIood ceIIs. Because oI its physioIogicaI
signiIicance, bIood oI humans wiII be deaIt with in somewhat greater detaiIs.
Functions of BIood
Since the bIood is a circuIating IIuid and aImost every organ receives a bIood suppIy, it perIorms a
number oI vitaI Iunctions in the body which are as IoIIows:
Animal Physiology
(1) Respiration: Transportation oI oxygen and carbon dioxide is the IundamentaI Iunction oI the
bIood. Transport oI oxygen Irom the Iungs to diIIerent tissues, and the transport oI carbon
dioxide Irom the tissues to Iungs is mainIy eIIected by the bIood.
(2) 1ransport of food materials: BIood is the onIy medium by means oI which the absorbed Iood
materiaIs are transported to various parts oI the body.
(3) Excretion: MetaboIic wastes Iike urea, uric acid, creatine, water, carbon dioxide, etc., are
transported by bIood, to kidneys, Iungs, skin and intestine Ior removaI.
(4) Regulation of body temperature: The bIood has an important roIe in the reguIation oI body
temperature by distributing heat throughout the body. This heat is generated in the muscIes by
the oxidation oI carbohydrates and Iats.
(5) Maintenance of acid-base balance: The bIood has buIIering capacity and maintains normaI
acid-base baIance in the body.
(6) Regulation of vater balance: BIood serves to maintain water baIance in the body by
exchanging water between the bIood and the tissue IIuid.
(7) Defense: BIood aIIords protection to the body against inIections and the antibodies.
(8) 1ransport of hormones: BIood is the onIy medium which serves to distribute hormones to
diIIerent parts oI the body.
(9) Clotting: Loss oI bIood Irom the body through injury is prevented by the action oI
thrombocytes oI the bIood.
(10) 1ransport of metabolites: BIood is responsibIe Ior the suppIy oI chemicaIs and essentiaI
metaboIites.
33.3 GENERAL PRDPERTlES DF BLDDD
COLOUR: CoIour oI the bIood is generaIIy red which depends on the nature oI the haemogIobin, a
red pigment within red corpuscIes. The venous bIood has Iess redness and more bIueness as compared
to the arteriaI bIood which is oxygenated.
BIood is a Iiquid tissue mainIy consisting oI the plasma and the bIood corpuscIes IIoating in it.
NormaIIy in a heaIthy person totaI bIood voIume varies Irom 6 to 8 per cent oI the body weight.
About two-thirds oI the totaI bIood is pIasma and one-third is the corpuscIes. The voIume oI bIood in
human body is about 8 per cent oI the body weight. Thus, iI a man weighs 80 kg, his body wouId
normaIIy contain about 6.4 kg oI bIood.
SPECIFIC GRAVITY: SpeciIic gravity oI the bIood IargeIy depends upon the number oI red ceIIs.
The speciIic gravity oI normaI bIood is 1.06, but may vary Irom 1.05 to 1.06.
OSMOTIC PRESSURE: Osmotic pressure oI the bIood is about 28 mm oI mercury. This osmotic
pressure is due to the presence oI various saIts, waste substances, proteins, and sugars dissoIved in the
pIasma.
THE PH: The pH oI the bIood is about 7.35, that is, it is a weak aIkaIine soIution. BIood has a
seII-buIIering capacity and the pH is maintained weII within Iimits. A pH oI 8 or much beIow 7 wouId
be IataI Ior an individuaI.
Body Iluids !
33.4 CDMPDSlTlDN DF BLDDD
Oxygenated bIood is about 3-4 times more viscous than water. II the bIood is centriIuged, two distinct
Iractions can be removed: (a) the plasma and (b) bIood ceIIs caIIed the Iormed eIements.
The PIasma
The pIasma is a homogeneous IIuid, paIe yeIIow in coIour and aIkaIine in reaction. Under normaI
conditions, in man pIasma Iorms 55-60 percent oI the totaI voIume oI bIood. It is composed oI about
91 per cent water and 9 per cent oI soIid materiaIs, out oI which about 7 per cent are proteins onIy.
The composition oI the bIood in man has been thoroughIy worked out, hence the description
presented here wouId reIate to human bIood onIy.
PLASMA PROTEINS: The totaI protein concentration in the pIasma is about 7gms/100 mI. AII
proteins may be separated by precipitation by diIIerent saIt concentrations and the reIative amounts oI
diIIerent proteins may be accounted Ior by paper eIectrophoresis. Four major categories oI pIasma
proteins are known: aIbumins, gIobuIins, Iibrinogen and haptogIobins. Various Iractions oI these
proteins are shown in TabIe 11.1.
TabIe 11.1 Composition of Plasma Proteins in GNSf100 NL of Fresh Blood
PIasma prøIø¡ns NørmaI vaIuøs gms,JUU mI
Total proteins 6.3-7.8
Albumins 3.2-5.1
Globulins 2.5
=
1
- Globulins 0.06-0.39
=
2
- Globulins 0.28-0.7+
>- Globulins 0.69-1.25
C- Globulins (Immunoglobulins) 0.8-2.0
IgA 0.15-0.35
IgG 0.8-1.8
IgN 0.08-0.18
IgD 0.003 approximately
Fibrinogen 0.2-0.+
Nucoprotein 0.135 approximately
Haptoglobins 0.03-0.19
The concentration oI pIasma proteins remains constant even during dietary variations and
abnormaI conditions. ProIonged maInutrition, however, aIIects the protein concentration. AII types oI
pIasma proteins can be isoIated and quantitativeIy determined by paper eIectrophoresis. This method
commonIy empIoyed in cIinicaI work is known as immunoeIectrophoresis. This is a semiquantitative
method, but zone eIectrophoresis in starch or poIyacryIamide geI gives a better and accurate
separation.
Animal Physiology "
Albumins: These have the Iowest moIecuIar weight (69000), and are synthesized mainIy in the
Iiver. AIbumins have a haII-IiIe oI 17-20 days and about 10-12 gms oI these are produced every day in
a heaIthy person. In certain abnormaI conditions the aIbumin content oI the pIasma is Iowered;
concentrations beIow 2 gms/100 mI are aIways associated with oedema.
Globulins: The moIecuIar weight oI gIobuIins varies between 90,000 and 100,000. They are
separabIe into a number oI sub-Iractions (TabIe 11.1). =-and >-gIobuIins carry the Iipid Iraction oI
proteins, whiIe gamma gIobuIins contain antibodies Ior generating immune responses. Variation in
various Iractions oI gIobuIins is oI diagonostic importance. GIobuIins are synthesized in the
reticuIoendotheIiaI system, in macrophages and in the Iymphocytes.
Fibrinogen: This is essentiaIIy a type oI gIobuIin oI a high moIecuIar weight, 400,000. It is a
precursor oI Iibrin in the bIood coaguIation process. Fibrinogen is excIusiveIy Iormed in the Iiver, but
its increased concentration in the pIasma is associated with a rapid erythrocyte sedimentation rate.
Haptoglobins: Four types oI haptogIobins are known so Iar that are present in varying
combinations. They have the property oI binding smaII amounts oI haemogIobin, about 1.35 mg/100
mI oI haemogIobin can be bound in this way.
PIasma proteins have severaI important roIes. FirstIy, they heIp in maintaining coIIoid osmotic
pressure oI the pIasma. The osmotic pressure oI the bIood is about 28 mm oI mercury under normaI
circumstances. SecondIy, pIasma proteins are essentiaI in immune reactions oI the body. ThirdIy,
protein deIiciency oI Iood is made good by utiIizing the pIasma proteins. And, above aII, pIasma
Iibrinogen is essentiaI in cIotting oI bIood.
Plasma carbohydrates and fats: There are smaII amounts oI gIucose and Iats dissoIved in the
bIood pIasma. GIucose concentration in pIasma varies considerabIy due to metaboIic disorders. There
are, however, severaI devices which maintain the gIucose concentration in bIood within normaI Iimits.
The Iats are in the Iorm oI neutraI Iats.
Inorganic ions: Inorganic saIts oI iron, caIcium, potassium, magnesium and sodium in the Iorm oI
chIorides, suIphates carbonates and phosphates are present in concentrations which, under normaI
circumstances, do not vary much and behave as eIectroIytes.
Plasma Nitrogen: PIasma nitrogen is present in the Iorm oI urea, uric acid and other non-protein
compounds. Besides these, IairIy good amount oI nitrogen is present in pIasma proteins.
Other substances: Gases Iike oxygen, carbondioxide are Iound in the pIasma. Certain hormones
are aIso present in the pIasma which incIude adrenaIine, nonadrenaIine, androgens, oestrogens,
insuIin, adrenocorticotrophic hormone, thyroxine and pituitary hormones. A very Iarge number oI
enzymes are Iound in the pIasma. Some important enzymes are: aIkaIine phosphatase, aIdoIase,
dehydrogenase, gIucose-6-phosphatase, Iipase, maItase etc. AII the vitamins are aIso present in the
pIasma.
Non-protein constituents oI the whoIe bIood and the pIasma are given in TabIe 11.2.
BLOOD ELECTROLYTES: BIood is rich in anions and cations which Iunction as eIectroIytes. The
average concentrations oI these in the pIasma and ceIIs are given in TabIe 11.3. The pIasma shouId be
eIectricaIIy neutraI, that is, the number oI anionic charges must be equaI to the number oI cationic
charges. Besides, the ionic concentration shouId be independent oI strong eIectroIytes, that is to say,
the presence oI Na
¹
, CI

and HCO
3

ions shouId be independent oI sodium chIoride and sodium
Body Iluids #
TabIe 11.2 Non-protein Organic and Inorganic Constituents of Whole Blood and Plasma values
in mg,100 ml
CønsI¡IuønIs ½nøIø DIøøø PIasma ør Sørum
Nøn-prøIø¡n n¡Irøgøn
Total - N 28 - 39 22 - 29
Urea - N 8.9 - 15.2 9.6 - 17.6
Amino acid - N +.6 - 6.8 +.3 - 7.7
Creatine - N 1.0 - 1.6 0.3 - 0.+
Creatinine - N 0.+ - 0.6 0.+ - 0.5
Uric acid - N 0.3 - 1.3 0.3 - 1.3
Nucleotide - N +.+ - 7.+ 0.2 - 0.+
Ammonia - N 0.01 - 0.02 0.01- 0.02
Bilirubin (total) - 0.26 - 1.+
Bilirubin (direct) - 0.1- 0.5
CarDøn)øraIøs
Glucose 60 - 90 120 (maximum)
Glycogen 1.6 - 16.2 -
Hexosamine - 83.+
Pentoses - 1.80 - 3.29
Hexuronic acids +.1 - 9.3 0.+ - 1.+
Neuraminic acid - 60
L¡p¡øs
Total, ether soluble 397 - 722 +00 - 700
Neutral fats 85 - 237 0 - +50
Fatty acids 290 - +20 200 - +50
Non-esterified fatty acids - 10 - 17
Cholesterol total 129 - 228 120 - 250
Free cholesterol 80 - 110 30 - 60
Bile acids 2.5 - 6.0 0.2 - 3.0
Bile salts - 5 - 12
Phospholipids total - 150 - 250
MøIaDøI¡¿ prøøu¿Is
Acetone bodies 0.5 0.3 - 0.9
Pyruvic acid 0.+1- 1.11 0.5 - 1.0
Lactic acid +.7 - 15.1 6.1 - 16.9
Citric acid 1.3 - 2.3 1.6 - 3.2
Nalic acid 0.2+ - 0.75 0.01 - 0.9
1nørgan¡¿ maIør¡aIs 0.8 0.9
bicarbonate. In the bIood sodium ions are mainIy extraceIIuIar and potassium ions intraceIIuIar, the
distribution oI which are maintained by active transport. The kidney is aIso responsibIe in controIIing
the cations in the bIood through acid base baIance and hormonaI inIIuence.
Animal Physiology $
TabIe 11.3 Principal Blood Electrolytes in One Litre of Whole Blood (1 Litre of whole Blood = 550 ml
Plasma Plus +50 ml Cells).
PIasma ¿ønsI¡IuønIs CøII ¿ønsI¡IuønIs TøIaI
mEq,JPIasma mEq,J mEq,J ¿øIIs mEq,J mEq,q
wnøIø wnøIø wnøIø
DIøøø DIøøø DIøøø
CaI¡øns
Na
+
135 - 155 79.8 16 - 25 9.5 89.3
K
+
3.1 - 5.5 2.3 92 - 100 +2.8 +5.1
Ca
+
2.1 - 2.7 1.+ - - 1.+
Ng
+
1.3 - 1.8 0.9 2.5 1.1 2.0
Total 153.3 8+.3 118.5 53.3 137.6
An¡øns
CI
-
100 - 107 56.7 58.9 26.5 83.2
HCO
3
-
27.0 1+.9 16.7 7.5 22.+
Phosphate 2 1.1 1.5 0.7 1.8
Sulphate 1 0.6 - - 0.6
Plasma proteins 15.6 8.6 - - 8.6
X
-
+.7 2.+ +.7 2.1 +.5
Haemoglobin - - 36.7 16.5 16.5
Total 153.3 8+.3 118.5 53.+ 137.6
There are two types oI anions in the bIood: These are anions oI mineraI acids Iike CI

and SO
4
2
which do not combine with hydrogen at the bIood pH. Other anions pertain to organic acids which
incIude Iactate and pyruvate. The second type oI anions comprise oI the pIasma proteins,
haemogIobin, oxyhaemogIobin, HCO
3

and PO
4
2
(phosphate). These act as bIood buIIers. PIasma
proteins carry negative charges, hence caIIed anions. SimiIarIy, haemogIobin and oxyhaemogIobin
aIso act as anions since their isoeIectric point is Iower than the bIood pH.
33.5 FDRMED ELEMENTS DF BLDDD
The Iormed eIements or the structuraI components oI the bIood incIude the erythrocytes (red bIood
ceIIs), the leucocytes (white bIood corpuscIes) and the thrombocytes (bIood pIateIets) which are
suspended in the pIasma.
HaematoIogic Parameters of Red BIood CeIIs
A. Red Blood Cells. In mammaIs and the humans, erythrocytes are circuIar and biconcave,
without a nucIeus. Their size averages about 7.6 in thickness and about 8.8 in diameter. The
stroma oI red ceIIs is permeated with haemogIobin, estimated to be about 90° oI the weight oI the
ceIIs. The red bIood ceII (RBC) count gives the number oI RBCs Iound in a cubic miIIimeter (mm
3
) oI
whoIe bIood and provides an indirect estimate oI the bIood`s haemogIobin content. NormaI vaIues are
4.5 to 6.0 miIIion/mm
3
oI bIood Ior maIes: 4.0 to 5.5 miIIion/mm
3
Ior IemaIes.
Body Iluids %
B. Haematocrit (Hct) or packed cell volume (PCV). It measures the percentage by voIume oI
packed RBCs in a whoIe bIood sampIe aIter centriIugation. It is determined by putting uncoaguIated
whoIe bIood in a Wintrobe tube which is caIibrated (Fig. 11.1). The tube is centriIuged Ior 30 minutes
at a speed producing 1500 g and the percentage is caIcuIated Ior the voIume oI red ceIIs. The Hct
vaIue is usuaIIy three times the haemogIobin vaIue and is given as percent. A Iow Hct indicates such
conditions as anaemia or overhydration; a high Hct denotes such conditions as poIycythemia or
dehydration.
FIg. 11.1 Determination of Haematocrit. Whole blood is centrifuged in a tube and allowed to settle. The haematocrit, that
is, the volume of red cells per 100 ml of whole blood, is obtained by multiplying the number at the top of the
red cell fraction by 10.
C. Haemoglobin (Hb). HaemogIobin, a compIex oI protein (gIobin) and iron, is produced in the
red ceIIs and synthesised Irom acetic acid and gIycine. The product is caIIed a porphyrin, which
combines with iron to produce a haeme moIecuIe. Four haeme moIecuIes then combine with one
moIecuIe oI gIobin to Iorm haemogIobin (Fig. 11.2). The moIecuIar weight oI haemogIobin is about
64,500. The haemogIobin content can be measured in a haemogIobinometer which measures the
grams oI haemogIobin contained in a 100 mI oI whoIe bIood and provides an estimate oI the oxygen-
carrying capacity oI the RBCs. NormaI vaIues range Irom 14 to 18 g/100 mI Ior maIes and Irom 12 to
16 g/I00 mI Ior IemaIes. The high vaIue depends on the number oI RBCs and the amount oI
haemogIobin in each RBC. A Iow Hb vaIue indicates anaemia.
D. Wintrobe Indices or RBC indices. They provide important inIormation regarding RBC size, Hb
concentration and Hb weight. They are primariIy used to categorise anaemias.
Plasma
Cells
Red cells
Blood white
10
9
8
7
6
5
4
3
2
1
0
Animal Physiology &
(a) Mean corpuscular volume (MCV) is the ratio oI the Hct to the RBC count:
Hct (°) 10
RBC count (in miIIions)

÷ MCV
The MCV vaIue essentiaIIy evaIuates average RBC size and reIIects any variation in RBC size.
A Iow MCV indicates microcytic (undersized) RBCs, as occurs in iron deIiciency. A high
MCV indicates macrocytic (oversized) RBCs, as occurs in vitamin B
12
or IoIic acid deIiciency.
The normaI vaIue oI MCV is 90 10.
(b) Mean corpuscular haemoglobin concentration (MCHC) represents the average concentration
oI Hb in an average RBC, deIined as:
Hb 100
Hct

÷ MCHC
The normaI vaIue Ior MCHC is 34 2. A Iow MCHC indicates hypochromia, resuIting Irom
decreased Hb content.
FIg. 11.2 Chemical structure of haemoglobin. (a) pyrrole ring, (b) haemoglobin molecule-the carbon atoms of the
pyrrole rings carry groups which are either methyl (CH
3
-), vinyl (CH
2
= CH-), or propionic acid
(HOOCCH
2
-CH
2
) groupings.
HC
N
HC
CH
CH
H
Pyrr le
(a)
o
CH
2
CH
C
N
H
C
N
CH
C
C C—CH = CH
2
O
2
H C
3
HC
N N
Fe
H C —C
3
C—CH
3
CH
2
CH
2
CH
2
CH
2
COOH COOH
Globin
haemoglobin
(b)
CH
3
C
H
Body Iluids '
(c) Mean corpuscular haemoglobin (MCH) represents the amount oI Hb in an average RBC and
is deIined as:
Hb 10
RBC count (in miIIions)

÷ MCH
The normaI range oI MCH is 30 4.
E. Reticulocyte Count. It is a measure oI immature RBCs (reticuIocytes), which contain remnants
oI nucIear materiaI. They circuIate in the bIood Ior about 1 to 2 days in this Iorm hence, this provides
an index oI bone marrow production oI mature RBCs. ReticuIocytes normaIIy comprise 0.5° to 1.5°
oI the totaI RBC count, or 25,000 to 75,000/mm
3
. An increased count occurs during haemoIytic
anaemia, acute bIood Ioss and iron deIiciency. ApIastic anaemia occurs due to a decreased count.
F. Erythrocyte Sedimentation. Sedimentation eIIect resuIts Irom aIterations in pIasma proteins.
Sedimentation rate can be Iound out Irom the RBC settIing Irom whoIe, uncoaguIated bIood over
time. NormaI rates range Irom 0 to 15 mm/hr Ior maIes and Irom 0 to 20 m/hr Ior IemaIes.
Erythrocyte sedimentation rate (ESR) increases in acute or chronic inIections, rheumatoid etc. ESR is
useIuI in demonstrating the presence oI occuIt organic disease.
White BIood CeIIs IWBC¡
The WBC are caIIed leucocytes, which are sIightIy Iarger than the red ceIIs. They are coIourIess or
transparent and can be easiIy counted under microscope aIter proper staining. They are nucIeated
possessing one, two or more nucIei, and move about with pseudopodia. There are Iive main cIasses oI
WBC (Fig. 11.4). The normaI range oI WBCs is 5,000 to 10,000/mm
3
. An increased WBC count
signaIs inIection, and a decreased count indicates bone marrow depression, resuIting Irom viraI
inIection or toxic reactions to chemicaI agents (TabIe 11.4).
FIg. 11.3 Types of leucocytes.
The WBC diIIerentiaI evaIuates the distribution and morphoIogy oI Iive major types oI WBCs
the neutrophiIs, basophiIs and eosinophiIs (granulocytes) and the Iymphocytes and monocytes
(nongranulocytes).
A. Neutrophils incIude poIymorphonucIear Ieucocytes, aIso known as PMNs, and immature
bands. NeutrophiIs stain with neutraI dyes and phagocytize and degrade many types oI particIes. They
serve as the body`s Iirst Iine oI deIense when tissue is damaged or Ioreign materiaIs gain entry. They
congregate at the sites oI inIection in response to a speciIic stimuIus through a chemotactic action.
Certain bacteriaI, viraI and IungaI inIections cause an increase in their number resuIting in
neutrophilic leucocytosis. A decrease in the number oI neutrophiIs may cause neutropenia.
Neutrophil Eosinophil Basophil Monocyte Lymphocytes
Animal Physiology !
TabIe 11.4 Percentage values of WBC Cell Differential Count Under Normal and Infection Conditions
½n¡Iø DIøøø ¿øII ¿øunI
CøII I)pø NørmaI ½¡In ¡n/ø¿I¡øn
pør¿ønIagø vaIuø
Total white blood cells 8,000 (100¾) 15,5000(100¾)
Neutrophils
Polymorphonuclear leucocytes 50-70¾ 82¾
Segmented bands (immature) 3-5¾ 6¾
Lymphocytes 20-+0¾ 10¾
Nonocytes 0-7¾ 1¾
Eosinophils 0-5¾ 1¾
Basophils 0-1¾ 0¾
B. Basophils. They stain deepIy with bIue basic dyes and are Iew in number (1°). They are smaII
and contain Iarge granuIes; in tissues they are reIerred to as mast cells. An increased number oI
basophiIs (basophilia) may occur with chronic myeIogenous Ieukemia.
C. Eosinophils. They stain deep red with acid dyes and are associated with immune reactions.
They contain a biIobed nucIeus and show phagocytic behaviour. An increase in the number oI
eosinophiIs, known as eosinophilia, occurs during acute aIIergic reactions (asthama, drug aIIergy etc.)
and parasitic inIestations.
D. Lymphocytes. They have a Iarge bean-shaped nucIeus with dominant roIe in immunoIogic
activity. They produce antibodies. Two main cIasses are B Iymphocytes and T Iymphocytes; T
Iymphocytes are Iurther subdivided into heIper (Th) and suppresor (T
s
) ceIIs. An increased number oI
Iymphocytes, caIIed lymphocytosis, usuaIIy accompanies a normaI or decreased totaI WBC count,
caused by viraI inIections. A decrease in number, lymphopenia, may occur due to severe iIIness,
immunodeIiciency or the AIDS virus.
E. Monocytes. These are Iargest oI aII white bIood ceIIs, ranging Irom 16 to 22 in diameter, and
characterised by the presence oI a Iarge, indented or horseshoe shape nucIeus. They are phagocytic
and destroy or devovour inIectious agents. Monocytosis, i.e. increase in number oI monocytes occurs
during acute inIections.
Thrombocytes or PIateIets
The pIateIets, smaIIest Iormed eIements oI the bIood (about 2 to 3 in diameter), are very IragiIe,
irreguIarIy shaped, containing distinct granuIes but no nucIeus. They are invoIved in bIood cIotting
and are vitaI to the Iormation oI a haemostatic pIug aIter vascuIar injury. The normaI range oI pIateIet
count is 150,000 to 300,000/mm
3
. However, their number may vary Irom time to time, usuaIIy
increasing aIter exercise and haemorrhage. The pIateIets, Iormed inside the bone marrow, are derived
from megakaryocytes by budding whiIe passing through the waIIs oI sinusoids. The IiIe oI pIateIets is
about 10 days in the circuIating bIood, and in case oI transIusion into a patient having no or Iow
pIatetIets, their IiIe-span is reduced to one or two days. A decrease in pIateIet count causes
Body Iluids !
thrombocytopenia, which can occur in conditions, such as idiopathic thrombocytopenic purpura,
dengue fever (haemorrhagic Iever caused by Aedis aegypti), or occasionaIIy Irom drugs Iike quinidine
and suIIonamides.
Besides their participation in cIotting, pIateIets are aIso beIieved to possess the property oI
adhesion owing to which they are abIe to stick to Ioreign surIaces and pIug up hoIes in
capiIIaries. The pIateIets contain a thrombopIastin precursor and quantities oI histamine and
5-hydroxytryptamine, which are reIeased during coaguIation. AnticoaguIants reduce the adhesion
property oI pIateIets.
Drigin of Formed EIements
The process by which aII types oI bIood ceIIs are Iormed is caIIed haemopoiesis and the organs where
these are Iormed are caIIed haemopoietic organs.
Erythropoiesis. The Iormation oI erythrocytes or red ceIIs is known as erythropoiesis. In the
embryonic IiIe, red ceIIs are produced by Iiver, spIeen and thymus and aIter birth they cease to
produce them and the Iunction is taken over by the red marrow oI bones, ribs, vertebrae, and to some
extent, with the exception oI chiIdren, in the ends oI the Iimb bones. The red ceIIs pass through
severaI stages oI deveIopment beIore they enter the peripheraI circuIation. The RBCs originate Irom
megaIobIasts which are devoid oI haemogIobin in earIy stages, but possess a nucIeus. At a Iater stage,
it acquires haemogIobin and undergoes reduction in size, a stage caIIed proerythrobIast, IoIIowed by
normobIast stage (Fig. 11.4). NormobIast stiII has a nucIeus which is graduaIIy expeIIed in course oI
maturation. The ceIIs, now caIIed reticuIocytes, are discharged in the bIoodstream, and within Iew
hours, Iose their reticuIated pattern and transIorm into mature erythrocytes.
FIg. 11.4 Formed elements of the blood derived from the stem cells of bone marrow. Nature cells are found in the
peripheral blood circulation.
Proerythroblasts Reticulocytes Erythrocytes
Megakaryoblasts Megakaryocytes Thrombocytes
(platelets)
Monoblasts Promonocytes Monocytes
Myeloblasts Myelocytes
Segmented
granulocytes
(bands)
Neutrophils
Basophils
Eosinophils
Lymphoblasts Polymorphocytes
T lymphocyte
B lymphocyte
Plasma cell
Pluripotent
stem cells
(Bone
marrow)
Pool of
Committed
Stem cells
Precursor cells Mature cells
Animal Physiology !
Erythropoiesis or red ceII production is controIIed by a kidney-produced humoraI Iactor caIIed
erythropoietin, whose primary action is considered to be the stimuIation oI ceIIs in the marrow,
producing increased number oI erythroid eIements. However, the kidney is not the onIy source oI
erythropoietin, since very smaII amounts oI the hormone with the same marrow stimuIating eIIect
have been detected in the pIasma oI nephrectomised patients.
Erythrocytes have a short IiIe-span, about 110 days, aIter which they are destroyed in the Iiver.
Upon destruction, haemogIobin is Iiberated and undergoes changes to Iorm bilirubin, that is IinaIIy
excreted in the Iaeces. The iron component is set Iree and a good part oI it is reused in the Iormation
oI new haemogIobin. ApproximateIy 2.5 miIIion ceIIs are destroyed per second and aImost equaI
number is produced each second. This mass destruction oI erythrocytes produces about 250 mg biIe
saIts per day.
Production of Leucocytes. The three varieties oI granuIocytes are Iormed in the bone marrow,
whereas smaII Iymphocytes are produced in the Iymph nodes and Iymphoid tissue, generaIIy
throughout the body. ReticuIocytes are eIements oI reticuloendothelial system, consisting oI primitive
ceIIs normaIIy present in the generaI connective tissue, Iung, spIeen, Iiver, Iymph nodes, bone marrow
etc. There are many varieties oI these, some oI which are motiIe and possess phagocytic properties.
Monocytes are aIso derived Irom reticuIoendotheIiaI system.
The reticuIoendotheIiaI ceIIs in the bIood sinuses in the Iiver are known as Kupffer cells. These as
weII as those oI the bone marrow and connective tissues possess the abiIity to convert haemogIobin
into biIe that is Iiberated Irom erythrocyte disintegration. SpIeen aIso contains macrophages, aIso
caIIed neutrophiIs, which are phagocytic. In embryonic IiIe granuIocytes are aIso Iormed in the
spIeen, but its abiIity ceases just beIore birth.
33.8 BLDDD GRDUPS AND TRANSFUSlDNS
The transIusion oI whoIe bIood into persons who have Iost a great deaI oI bIood due to haemorrhage
or accidents brings up the probIem oI bIood grouping or bIood typing. BIood cannot be transIused
indiscriminateIy and the donor`s bIood has to be matched with that oI the recipient needing a
transIusion. This is caIIed compatibility of blood. II the whoIe bIood oI a wrong type is given, the red
ceIIs stick together or agglutinate causing pIugging up oI bIood capiIIaries resuIting in death oI the
recipient. Such a bIood is incompatibIe.
The most outstanding Iand mark in the history oI bIood transIusion was the discovery oI
isoaggIutination and A-B-O bIood groups in human beings by KarI Landsteiner in 1900. His
sensationaI discovery won him a NobeI prize. SubsequentIy, in 1902 DecasteIIo and SturIi discovered
the Iourth and the rare bIood group AB.
In 1927 Landsteiner and Levine discovered the M and N bIood groups by injecting human red
ceIIs into rabbits. This produced antibodies M and N, resuIting in the identiIication oI M, N and MN
types oI human popuIations. In the same year, another bIood group P was reported. In 1937
Landsteiner and Wiener discovered a bIood group Iactor by injecting the red ceIIs oI Rhesus monkey
into rabbits and designated it as Rh-factor. SubsequentIy, about a hundred oI diIIerent bIood Iactors
beIonging to about 12 bIood group systems were described oI which onIy a Iew are cIinicaIIy
important.
Body Iluids !!
lnheritance of BIood Groups
BIood group Iactors are highIy speciIic and IoIIow a typicaI MendeIian inheritance pattern. In the A-
B-O bIood groups, suppose the three aIIeIes A, B and O occur in one Iocus oI a chromosome. The
occurrence oI the aIIeIes is in such a way that onIy two aIIeIes can combine in one individuaI. The
possibIe gene combinations that may arise are: A A, B B, O O (homozygous) and A O, B O, and A B
(heterozygous), assuming A and B are dominant and O recessive. The gene O is caIIed an amorph
since it does not produce any recognizabIe aIIects. The possibIe genotypes and phenotypes in the
A-B-O system are shown in TabIe 11.5.
TabIe 11.5 Blood Groups-A-B-O and Possible Genotypes and Phenotypes
BIøøø grøups GønøI)pøs PnønøI)pøs
A AA or AO A
B BB or BO B
AB AB AB
O OO O
TabIe 11.6 gives the possibIe genotypes oI the chiIdren arising Irom matching in diIIerent bIood
groups.
TabIe 11.6 Blood Groups of the Offspring in A-B-O Natgsing
BIøøø grøup ø/ parønIs BIøøø grøup ø/ ¿n¡Iørøn BIøøø grøups InaI ¿annøI Dø
O O O A,B, AB
O A O, A AB, B
O B O, B A, AB
O AB A, B O, AB
A A A, O B, AB
A B A, B, AB, O None
A AB A, B, AB O
B B B, O A, AB
B AB A, B, AB O
AB AB A, B, AB O
Antigen-antibody Reactions
It has been Iound that the bIood proteins are species speciIic which behave as Ioreign substances
when introduced into the body oI a diIIerent species. Such diIIerences between proteins oI diIIerent
animaI species can be detected by means oI precipitin test. Introduction oI a serum protein into the
body oI an animaI to whom it is Ioreign has been studied in reIation to immunoIogicaI reactions. For
exampIe, iI the bIood oI a patient suIIering Irom pneumonia containing Pneumococcus is given to a
heaIthy person, the normaI reaction oI the tissues is to produce antibodies which are speciIic to the
Animal Physiology !"
proteins oI the inIecting organisms. II the heaIthy person survives the disease, he is said to be immune
Irom the inIection. His bIood contains antitoxins which neutraIize the toxins produced by the invading
baciIIus.
There are two types oI substances in the bIood known as antigens (aggIutinogens) and antibodies
(aggIutinins). The antigens are compIex chemicaI substances which are present in the red bIood ceIIs.
ChemicaIIy, the antigens are a combination oI a protein component caIIed hapten which cannot
produce antibodies but can combine with them. The red ceII antigens are present on the surIace.
An antibody is a protein present in the serum gIobuIin that is Iormed in response to an antigenic
stimuIus. Human serum gIobuIins contain many antibodies oI diIIerent types.
AImost aII proteins act as antigens which react with antibodies iI injected into an animaI who
does not possess speciIic proteins in its tissues. The reaction between a given antigen and its
corresponding antibody is known as antigen-antibody reaction. Both antigen and antibody cannot be
present in the same bIood, Ior the red ceIIs oI a donor do not aggIutinate by the serum oI the recipient.
There are two types oI red ceII antibodies present in the human sera: (1) NaturaIIy occurring
antibodies Iike anti-A and anti-B isoaggIutinins (isoaggIutinin is a aggIutinin which reacts with the
aggIutinogen Iound in members oI the same species) and, (2) Immune antibodies which are produced
as a resuIt oI antigenic stimuIus. The process oI antibody Iormation is known as immunization.
II the antigen is derived Irom a member oI the same species, it is known as iso-immunization, and
on the other hand, iI antigen is derived Irom a member oI another species, the process is caIIed
hetero-immunization.
AggIutination
The red ceII antigens when mixed with their corresponding antibodies on a sIide cause cIumping
(aggIutination) or haemoIysis oI the red ceIIs. The antibody causing aggIutination is caIIed agglutinin
and the antigen producing it is reIerred as agglutinogen. When the red ceIIs burst open, haemoIysis
resuIts and the antibody causing it is caIIed haemolysin, and the antigen as haemolysinogen.
The A-B-D BIood Group System
Under this system, there are Iour bIood groups designated as A, B, AB and O. In this system the
serum oI a heaIthy individuaI is tested with the red ceIIs oI other heaIthy individuaIs. These tests
depend upon the presence oI two antigens caIIed A and B present in the human red ceIIs and their
corresponding antibodies anti-A and anti-B present in the serum (TabIe 11.7).
TabIe 11.7 Blood Groups, Their Antigens and Antibodies in Human Blood
BIøøø grøup AnI¡gøn AnI¡Døø) Frøquøn¿) ¡n 1nø¡an
(aggIuI¡nøgøn} (aggIuI¡n¡n} pøpuIaI¡øn
¡n røø ¿øIIs ¡n sørum
A A Anti-B 22¾
B B Anti-A 33¾
AB A & B None 5¾
O None Anti-A and
Anti-B +0¾
Body Iluids !#
The tabIe indicates that the bIood group oI an individuaI is named aIter the presence or absence oI
one or both antigens A and B in the red ceIIs. In a person oI group B or group O, antigen A is absent,
but naturaIIy occurring antibody anti-A is present. In persons with group A or group O, antigen B is
Iacking whiIe the serum contains anti-B. The serum oI group AB contains antigens A and B, but none
oI the antibodies. The bIood group AB is rare and was discovered in 1902 by decasteIIo and SturIi.
Wiener suggested that the bIood group O serum contains an isoaggIutinin anti-C in addition to anti-A
and anti-B.
In active bIood transIusions, iI the red ceIIs oI the transIused bIood aggIutinate by the recipient`s
serum, the transIusion cannot be made and the bIood is said to be incompatibIe. In order to determine
compatibiIity oI bIood, a smaII amount oI the bIood is diIuted with the normaI saIine and then a drop
oI this mixture is added to the test sera beIonging to group A and B separateIy. ThereaIter the bIood is
examined under a microscope to observe iI aggIutination has taken pIace or not. II aggIutination does
not occur, the bIood is said to be matching. IndividuaIs beIonging to group O are caIIed `universal
donors¨ because their red ceIIs Iack antigens A and B and are not aggIutinabIe by the sera oI other
bIood groups. IndividuaIs oI group AB are said to be universal recipients since their sera Iack
antibodies anti-A and anti-B. Persons oI this group can receive bIood Irom aII other groups
(TabIe 11.8).
TabIe 11.S Determination of Blood Groups
Pø¿¡p¡ønI
Dønør Grøup O Grøup A Grøup B Grøup AB
Pøø CøIIs O; Pøø ¿øIIs A; Pøø ¿øIIs B; Pøø ¿øIIs AB;
pIasma AB pIasma B pIasma A pIasma O
Group O - - - -
Group A + - + -
Group B + + - -
Group AB + + + -
Note: - denotes absence of agglutination
+ denotes agglutination
The Rh System
It has been observed that an individuaI oI bIood group A can donate his bIood to individuaIs oI group
AB. This is possibIe since AB is a universaI recipient group. Sometimes it was observed that
aggIutination occurred in such cases which must have been due to some unknown Iactor. This was
discovered by Landsteiner and Wiener in 1937 and was named Rh factor or Rhesus factor. The Iactor
was named aIter the rhesus monkey, Macacus rhesus in which it was discovered Iirst. Landsteiner and
Wiener injected rhesus monkey`s bIood (red ceIIs) into a rabbit to produce an immune serum or anti-
rhesus serum. This anti-serum aggIutinated red ceIIs in 85° human popuIation and rhesus monkey red
ceIIs as weII. This suggested the presence oI a new antigen in human erythrocytes caIIed Rh` in the
antiserum that produces anti-Rh antibody. The human, popuIation possessing Rh antigen are caIIed
Rh positives, and those Iacking it are Rh negatives. The distribution oI Rh antigen in man is
Animal Physiology !$
independent oI the bIood groups and the Rh antibody appears in the serum oI an individuaI aIter
immunization onIy. The Rh-negative individuaIs can be immunized against the Rh Iactor in the
IoIIowing ways:
1. By transIusing Rh-positive bIood,
2. By intramuscuIar injection oI Rh-positive bIood, and
3. By pregnancy with a Rh-positive Ioetus.
The incidence oI Rh-positive and Rh-negative individuaIs in diIIerent raciaI popuIations is given
in TabIe 11.9.
TabIe 11.9 Percentage of Rh-negative and Rh-positive Population in Different Races
Pa¿øs Pn-nøgaI¡vø Pn-pøs¡I¡vø
Whites 85.0 15.0
Negroes 95.5 +.5
Indians 93.0 7.0
Japanese 99.+ 0.6
Chinese 98.5 1.5
WhiIe studying speciIic cases it was observed that transIusion oI Rh-positive bIood to Rh-
negative individuaIs resuIts in the Iormation oI anti-Rh bodies (antibodies) without any apparent iII
eIIects. II the individuaI is subsequentIy transIused with Rh-positive bIood even aIter a Iapse oI
severaI years, a haemoIytic reaction IoIIows that oIten proves IataI.
A simiIar situation arises iI an Rh-negative woman conceives a Rh-positive Ioetus. II the baby`s
Rh-positive ceIIs get into mother`s circuIation at the time oI deIivery, these ceIIs cause the mother to
produce Rh-antibody, aIthough no harm is done to the mother since she does not possess Rh ceIIs.
First baby wiII be unharmed. However, iI the mother becomes pregnant second time with an Rh-
positive Ioetus, the antibodies Irom maternaI circuIation enter the IoetaI circuIation through the
pIacenta and buiId up a high concentration destroying the red ceIIs. II by chance, the mother is given
a second transIusion oI Rh-positive red ceIIs, the Rh antibodies wiII be Iormed and aggIutination wiII
occur causing haemoIysis oI Rh-positive ceIIs proving IataI. Hence, Rh-negative girIs and women oI
chiId-bearing age must never be injected with Rh-positive bIood.
Dther BIood Groups
Besides A-B-O and Rh systems, there are other bIood groups oI IittIe cIinicaI importance which are
inherited independentIy oI A-B-O groups according to MendeIian Iaws. Some oI these weII known
groups are Iisted beIow aIong with the names oI their discoverers:
M-N-S Landsteiner and Levine (1927)
P Landsteiner and Levine (1927)
Rh-Hr Landsteiner and Wiener (1937)
KeII Coombs, Mourant and Race (1946)
Lutheran CaIIender and Race (1946)
Body Iluids !%
Lewis Mourant (1946)
DuIIy Catbush, MoIIison and Parkin (1950)
Kidd AIIen, Diamond and NeidzeiIa (1951)
I-i Wiener and Unger (1956)
HaemoIytic Disease
The study oI bIood groups is important in the IieId oI haemoIytic disease oI the newborn. Sometimes
the newborn babies with bIood Groups A and B born oI mothers oI Group O, start showing cIinicaI
symptoms oI jaundice. The symptom occurs soon on the Iirst or the second day aIter the birth. This is
caused due to erythrobIastosis. The cause is yet not IuIIy known. It has been shown that the pIacenta
is permeabIe to certain antibodies present in the maternaI bIood which cross over to the IoetaI
circuIation. These antibodies are caIIed 'immune¨ antibodies and cause haemoIysis oI IoetaI red ceIIs.
AIthough most chiIdren possess bIood group antigens which are inherited Irom the Iather (mothers
usuaIIy Iacking them), mothers generaIIy do not produce immune antibodies. However, in rare cases
when immunization oI mothers occurs, the Ioetus is aIIected and deveIops haemoIytic disease. The
most important antibody which may cause haemoIytic disease oI the newborn is that oI Rh antigen D.
33.7 CDAGULATlDN DF BLDDD
When a sampIe oI bIood is drawn Irom the bIood vesseIs, it turns into a jeIIy-Iike mass within 3 to 10
minutes. This process is caIIed clotting or coagulation AIter some time the cIot shrinks and a IIuid
caIIed serum is expeIIed Irom it. Upon microscopic examination, the cIot is Iound to consist oI
corpuscIes oI bIood enmeshed in a network oI thread-Iike substance caIIed fibrin. Fibrin is a geI
which is not present as such in the circuIating bIood, but is Iormed Irom Iibrinogen which remains
dissoIved in the pIasma. The conversion oI Iibrinogen into Iibrin is cataIyzed by an enzyme thrombin
which is produced Irom it precursor prothrombin. The conversion oI prothrombin to thrombin takes
pIace with the heIp oI thromboplastin in the presence oI caIcium. ThrombopIastin is reIeased Irom
damaged tissues (bIood vesseIs) and the bIood pIateIets. The reason that bIood does not cIot whiIe in
circuIation is that this enzyme is absent Irom circuIating bIood and is reIeased onIy when the bIood
vesseIs get cut or injured. CaIcium ions are normaIIy present in the pIasma. This process has been
summarized in the IoIIowing scheme:
Blood
Plasma Leucocytes Erythrocytes
Thromboplastin
Platelets
Tissues
Prothrombin
Fibrinogen + Thrombin
Fibrin + Corpuscles
Clot
+ Ca +
++
Animal Physiology !&
The thrombopIastic activity originates Irom two sources, the extrinsic and intrinsic systems. The
extrinsic Iactors are present in the tissues and the intrinsic Iactors in the pIasma itseII (TabIe 11.10).
Tissue thrombopIastin is present in the tissue extracts oI Iung, brain, pIacenta and testis which is
Iiberated due to injury.
TabIe 11.1û Clotting Factors and Their Synonyms
Fa¿Iør Namø S)nøn)m
I Fibrinogen
II Prothrombin
III Thromboplastin
Iv Calcium
v Labile factor Proaccelerin, accelerator globulin
(Ac-globulin)
vII Proconvertin Stable factor, Serum prothrombin
conversion accelerator (SPCA),
Cothromboplastin, autoprothrombin
vIII Antihaemophilic factor (AHF) Antihaemophilic globulin (AHG)
IX Christmas factor Plasma thromboplastin component (PTC)
X Stuart-Power factor
XI Plasma thromboplastin anticedent (PTA)
XII Hageman factor
XIII Fibrin-stabilizing factor (PSF) Laki-Lorand factor (LLF), Fibrinase
ThrombopIastin IStage l¡
ThrombopIastin cataIyzes the conversion oI prothrombin to thrombin. Substances Ior thrombopIastin
activity are reIeased Irom the pIasma, pIateIets and the tissues. The Iactors which contribute to the
thrombopIastic activity incIude AntihaemophiIic gIobuIin (AGH-Iactor VIII), pIasma thrombopIastin
anticedent (PTA-Iactor XI, Christmas IactorIactor IX), Hageman Iactor (Iactor XII), Stuart-power
Iactor (Iactor X), and IabiIe Iactor (Iactor V). ThrombopIastic precursors are aIso contributed by the
tissues as weII as Irom the pIateIets.
Prothrombin IStage ll¡
Prothrombin is a gIobuIin and an inactive precursor oI thrombin which keeps on circuIating in the
pIasma. Prothrombin is Iormed in the Iiver and reIeased into the bIoodstream. The conversion oI
prothrombin to thrombin requires interaction oI thrombopIastic Iactors which incIude Iactors VII, IX
and X. This process requires suIIicient quantities oI vitamin K since caIcium is necessary in cIotting.
Lack oI any oI these Iactors wouId inhibit the conversion oI thrombin Irom prothrombin.
Fibrinogen IStage lll¡
Fibrinogen is another protein which is essentiaI in the process oI coaguIation. Fibrinogen is aIso
Iormed in the Iiver which Iunctions under the inIIuence oI thrombin. The conversion oI Iibrinogen to
Iibrin requires Iactor II.
Body Iluids !'
33.8 THEDRlES DF CDAGULATlDN
BIood coaguIation is a compIex chemica1 process. SeveraI theories have been advanced to expIain the
mechanism; however, no singIe theory is compIete in itseII. Some oI the theories proposed by various
workers are given beIow.
HoweII's Theory
HoweII studied the bIood cIotting mechanism in Limulus. He extended his observations to the cIotting
mechanism in the mammaIian bIood which were Iater modiIied by Ferguson. According to HoweII`s
theory, thrombopIastin is reIeased by the dying ceIIs and the pIateIets, aIthough smaII quantity oI
thrombopIastin is aIso present in the bIood pIasma. In the next step, this thrombopIastin reacts with a
prothrombin-antiprothrombin compIex to reIease prothrombin. Prothrombin is then converted into
thrombin in the presence oI caIcium ions. Thrombin now reacts with Iibrinogen to Iorm Iibrin. It was
suggested that an enzyme tryptase is responsibIe to convert prothrombin to thrombin. The theory is,
however, incompIete in the sense that it does not expIain the exact nature oI thrombopIastic
substances. The exact roIe oI tryptase in the cIotting process and the chemicaI reaction invoIving
Iibrinogen to Iibrin have not been expIained satisIactoriIy. The process can be summarized as shown
beIow.
FuId and Spiro Theory
The theory put Iorward by FuId and Spiro diIIers Irom that oI HoweII in one important respect. They
showed the presence oI an enzyme thrombokinase which is produced by the bIood pIateIets. This
enzyme activates prothrombin to thrombin in the presence oI caIcium ions. Thrombin then reacts with
Iibrinogen to produce Iibrin.
Theory by 0uick and Coworkers
Quick and his coworkers proposed a theory which is quite diIIerent Irom HoweII`s theory. According
to this theory, the bIood pIateIets reIease an enzyme 1hromboplastinogen. A IabeIIizing inIIuence is
aIso exerted on the pIateIets so that the cIotting process is hastened. The scheme can be summarized
as IoIIows:
Blood
Plasma Corpuscles
Prothrombin—Antithrombin Thromboplastin (Cephalin)
Prothrombin + Ca
++
Thrombin Fibrin
Fibrinogen
Animal Physiology "
33.8 HAEMDLYSlS
Disintegration oI red bIood corpuscIes and subsequent reIease oI haemogIobin Irom them is known as
haemolysis. The chieI cause oI haemoIysis is the changes in the osmotic pressure inside the red ceIIs.
The osmotic pressure inside the red ceIIs is equaI to the osmotic pressure oI the pIasma. II the
corpuscIes are pIaced in hypotonic saIt soIutions, sweIIing up oI the corpuscIes takes pIace which
Ieads to their bursting and consequent reIease oI haemogIobin. HaemoIysis can aIso occur iI the
corpuscIes are kept in distiIIed water. Certain chemicaI agents can aIso cause haemoIysis. DiIute acids
and aIkaIies and biIe saIts can cause haemoIysis. MechanicaI shaking oI bIood with ether and
chIoroIorm destroys the corpuscIes by dissoIving the Iipids oI the stroma. Snake venoms have a
haemoIyzing inIIuence which is due to speciIic substances caIIed haemolysins. When Ioreign bIood is
injected into the body oI an animaI, haemoIysis occurs. BacteriaI inIections produce speciIic
haemoIysins in the bIood (e.g.. streptococci, Bacillus tetanus, etc.) causing haemoIysis. HaemoIysis is
aIso brought about by whipping the bIood, by Ireezing or thawing. HaemoIyzed bIood becomes
transparent and acquires a deep red coIour due to the reIease oI haemogIobin.
CIot Retraction
During the cIot Iormation the Iibrin threads are Iormed. The cIot then undergoes contraction which
brings the Iibrin threads cIoser due to shortening. The texture oI the cIot becomes hard and it adheres
to the vesseI in which the bIood is contained. This phenomenon oI cIot contraction is termed as cIot
retraction. During cIot retraction serum is squeezed out. BIood pIateIets are necessary Ior cIot
retraction.
AnticoaguIants
IntravascuIar cIotting is prevented by certain substances present in bIood which act as naturaI
inhibitors oI coaguIation. Such substances are caIIed anticoaguIants. IntravascuIar coaguIation oI
bIood can take pIace due to injury oI bIood vesseIs, or presence oI Ioreign substances Iike bacteria. It
may aIso be induced by injecting Iarge amount oI tissue extracts. In the normaI course, anticoaguIants
present in the bIood wouId retard the coaguIation process. There are at Ieast three inhibitors present in
the bIood, which are heparin, anticephaIin and antithrombin.
CoaguIation may be inhibited by removing Iree caIcium ions by adding neutraI saIts Iike sodium
suIphate (Na
2
SO
4
) or magnesium suIphate (MgSO
4
). Vigorous strirring oI bIood aIso prevents


Lebellizing
influence
Thrombin + Fibrinogen
Fibrin
Thromboplastin + Prothrombin + Ca
++
Plasma Platelets
Thromboplastinogen
(Enzyme)
Stage I
Stage II
Stage III
Body Iluids "
coaguIation. In this process Iibrin is deposited on the stirring rod which can be removed Irom the
bIood.
ReaI probIem oI preventing bIood coaguIation is Iaced in Iaboratory experiments whiIe doing
bIood anaIysis. For such experiments, chemicaI substances are used which act as anticoaguIants, such
as sodium citrate, sodium oxaIate and disodium ethyIenediamine tetraacetic acid (EDTA). Two
important anticoaguIants, heparin and coumarin are obtained Irom animaI and pIant sources. Heparin
is a normaI constituent oI bIood which is Iormed chieIIy in the Iiver, Iung and muscIes. Heparin
inhibits coaguIation at two points; the Iormation oI thrombin and reaction between thrombin and
Iibrinogen are interIered.
Another chemicaI, coumarin oI pIant origin, is an active anticoaguIant which interIeres with the
production oI prothrombin, Iactor VII and Iactor X in the Iiver. Coumarin, which is generaIIy known
as dicumarol, acts as a vitamin K antagonist and inhibits the reIease oI Iactor VII. Thus the action oI
coumarin can be reversed by administration oI vitamin K. Thus, coumarin and heparin appear to be oI
much vaIue in preventing intravascuIar cIotting.
Thrombosis
EarIier it has been seen that the IiIe-span oI bIood pIateIets is Ior Iour days onIy. It is thus cIear that
the pIateIets are constantIy undergoing destruction, and aIso new ones are being Iormed
simuItaneousIy. One wouId expect that due to destruction oI these pIateIets coaguIation process may
set up in the vesseIs. However, this does not happen since an anticoaguIant is present in the
circuIation. Yet there may be conditions when intravascuIar cIotting may take pIace. Due to some
injury or other reasons, a cIot may be Iormed intravascuIarIy which graduaIIy becomes hard. This cIot
may be detached Irom its position and may enter in circuIation, sometimes occIuding the bIood
vesseIs causing thrombosis. Intravenous cIotting is more common in veins due to sIuggish IIow oI
bIood. IntravascuIar cIotting is accompanied by proIonged rest in bed and varicosity oI the veins. In
certain cases, thrombosis may occur 8-12 days aIter surgicaI operations owing to increase in the
number oI pIateIets.
PuImonary thrombosis or embolism is another case oI thrombosis which usuaIIy occurs aIter
surgicaI operations. In spite oI the normaI wound heaIing, suddenIy the patient deveIops a serious
condition and expires. This is due to the bIood cIot cIogging the puImonary bIood vesseIs. UsuaIIy the
cIot is Iormed eIsewhere, but is carried away in the circuIation to the puImonary vesseIs. PuImonary
emboIism occurs due to overIoading oI bIood with thrombopIastin, exceeding the amount oI heparin.
Haemostasis
The cIotting oI bIood may cause a number oI diseases incIuding occIusion oI puImonary bIood vesseIs
Ieading to death. Disturbances in bIood coaguIation may Iead to bIeeding diseases. These processes
are responsibIe Ior haemostasis.
FaiIure oI bIood cIotting mechanism causes a disease haemophilia in which the bIood is
incoaguIabIe due to the absence oI Iibrinogen. The disease is a genetic one which is sex-Iinked. In this
disease the IemaIes act as the carriers whereas the maIes are aIways the suIIerers. Due to this genetic
deIIect, Iactor VIII, and probabIy some other Iactors are not produced in suIIicient quantities.
Animal Physiology "
There is another haemorrhagic disease, thrombocytopenia in which the pIateet count is very Iow.
Whenever there is a smaII wound the bIeeding occurs continuousIy Ior a Iong time. CoaguIation IaiIs
to occur owing to the IaiIure oI the smaII bIood vesseIs to contract. II at aII the cIots are Iormed, they
IaiI to retract. As a resuIt oI smaII haemorrhages in skin and mucous membranes, bIeeding occurs in
subcutaneous spaces giving the area a bIue or purpIe tinge. This disease is known as
thrombocytopenic purpura wherein the bIood Ioses its oxygen content.
33.30 HAEMATDLDGlCAL ABNDRMALlTlES
InterIerence oI drugs or chemicaIs resuIts in abnormaIities oI bIood ceII components or their numbers.
Some drugs aIIect the bone marrow, thereby disrupting aII Iormed eIements oI the bIood, whereas
others may interIere with onIy a particuIar type oI bIood component.
Anaemia
Anaemia is characterised by a decIine in the RBC count. There are severaI types oI anaemia attributed
to various causes.
(1) Aplastic anaemia deveIops when a drug suppresses or destroys bone marrow stem ceIIs,
causing deIiciencies oI aII Iormed eIements oI the bIood. Benzene derivatives, insecticides,
and chIoramphenicoI are some compounds that can cause apIastic anaemia.
(2) Megaloblastic anaemia stems Irom impaired synthesis oI DNA by RBCs, resuIting in sIow ceII
division and production oI Iarge, immature, dysIunctionaI RBCs.
(3) Pernicious anaemia is due to considerabIe reduction in the RBCs; ceIIs become nucIeated and
assume a Iarge size without appreciabIe Ioss oI haemogIobin.
(4) Disease related anaemia is caused by diseases such as maIaria, kaIaazar, sepsis,
ankyIostomiasis (hookworm disease) etc. These diseases cause Iarge scaIe destruction oI
RBCs.
(5) Anaemia due to nutritional deficiency resuIts when the rate oI Iormation oI RBCs is much
sIower than the rate oI destruction, or there may be a Iack oI haemopoietic Iactor.
(6) Secondary anaemia occurs due to the Ioss oI bIood by haemorrhages. BIeeding causes bIood
Ioss Iowering bIood pressure, and to restore the bIood voIume tissue IIuid migrates into it,
suppressing the bIood count signiIicantIy.
(7) Haemolytic anaemia, characterised by premature RBC destruction, may be induced by two
diIIerent drug-reIated mechanisms.
(a) Certain oxidant drugs such as antimaIariaIs and suIphonamides interIere with RBCs in
patients with gIucose-6-phosphate dehydrogenase deIiciency.
(b) A drug-induced immune haemolytic anaemia resuIts Irom certain antigen-antibody
reactions. For exampIe, with peniciIIin administration, IgG antibodies may react with the
RBC-penciIIin compIex, resuIting in haemoIysis.
(8) Sickle-cell anaemia, characterised by sickIe-shaped RBCs, generaIIy Iocked together
obstructing the IIow oI bIood in capiIIaries. This is a genetic abnormaIity prevaIent in Negro
Body Iluids "!
popuIations, oIten proves to be IataI, caused by substitution oI valine in pIace oI glutamic acid
in the protein chain oI haemogIobin.
Leucopenia
It is an abnormaIity in which white bIood corpuscIes (WBC) are considerabIy reduced.
(1) Agranulocytosis is a severe reduction in the number oI granuIocytes (basophiIs, eosinophiIs,
and neutrophiIs), caused by drug-induced hypersensitivity reactions or by bone marrow
suppression at the myIeobIast IeveI.
(2) Neutropenia is characterised by a decreased neutrophiI IeveI caused by oncoIogic drugs.
(3) Disease-related Ieucopenia is caused by Iever, sore throat, chiIIs, rash, and secondary
inIections.
Leucocytosis
Increased number oI Ieucocytes beyond the normaI range causes leucocytosis. InternaI inIections,
appendicitis and certain viraI inIections may Iead to abnormaIIy high number oI WBC (more than
10,000/mm
3
). During pregnancy and in the newborn aIso the number may increase. In contrast to this,
a decrease in number oI WBC resuIts in a condition known as leucopenia. Sometimes in the absence
oI any inIection, the WBC count becomes abnormaI, a situation arising Irom excessive proIiIeration
oI bone marrow myeIobIasts. This condition Ieads to bIood cancer or leukemia, which is associated
with Iow RBC count.
Thrombocytopenia
It is a condition characterised by abnormaI reduction in the pIateIet IeveI, may occur iI a drug or
disorder causes pIateIet destruction or decrease pIateIet production.
In the preceding chapter, we discussed the body IIuids and their Iunctions. OI aII the body IIuids,
bIood is the major transport medium in aII the vertebrates which circuIates in cIosed vesseIs. In order
to transport nutrients, gases, hormones and antibodies, the bIood IIows through a deIinite and
eIaborate circuIatory system. The bIood is propeIIed by a weII organized pumping organ into the
peripheraI parts oI the body through the arteries, veins and capiIIaries. The Iine capiIIary network
aIIows exchange oI water, eIectroIytes and nutritive materiaIs across their thin waIIs.
The eIIicient system oI bIood circuIation is responsibIe Ior the maintenance oI homeostatic
mechanisms in the body. It is essentiaI that the voIume and the composition oI the intraceIIuIar and
extraceIIuIar IIuids are maintained constant since the proper IIuid baIance wouId heIp the animaI
maintain its steady state. The voIume oI water and the concentration oI the eIectroIytes are reguIated
through the circuIatory system.
Lower groups oI animaIs have very simpIe structure and do not require an eIaborate circuIatory
system. In such animaIs, the metaboIic rate is Iow and the surIace area/body voIume ratio is very high.
In simpIe animaIs Iike CoeIenterates, the transport oI Iood particIes and dissoIved oxygen is achieved
by water currents created by sIow IIageIIar movements oI endoderm ceIIs. In smaII crustaceans bIood
is pushed through tissue sinuses by the movements oI Iegs and internaI organs. In Iarge crustaceans,
there is a dorsaI tubuIar heart which pumps bIood to diIIerent parts oI the body through arteriaI
vesseIs. The abdominaI vesseIs open into the cavities or sinuses which are IiIIed by the bIood. The
bIood comes in direct contact with the tissues. Such circuIatory systems are caIIed open systems.
Vertebrates, on the other hand, have a cIosed circuIatory system and the bIood does not come in
direct contact with the ceIIs and tissues; however, the diIIusion oI gases, water and other smaIIer
moIecuIes is possibIe through the waIIs oI the Iine capiIIary network.
CircuIotion of ßIood
+ 0 ) 2 6 - 4

Circulation oj Blood "#
3E.3 THE BLDDD VDLUME
The voIume oI bIood remains constant. In aduIt human beings, the totaI voIume oI bIood is about 5
Iitres. The average voIume oI bIood is caIcuIated on the weight basis, i.e. approximateIy 70 mI oI
bIood Ior each kiIogram body weight. The IIuid voIume oI bIood is not aIIected even when Iarge
voIume oI water is taken. The excess amount oI water is got rid oI by enhanced urine output.
SimiIarIy, during heamorrhage, considerabIe amount oI bIood is Iost which is soon restored to normaI
voIume. AIter haemorrhage, the IIuids Irom the tissues move into the bIood vesseIs to restore the
bIood voIume. At the same time the urine output is aIso Iowered considerabIy to make good the
Iosses. Apart Irom restoring the IIuid voIume oI bIood, the Ioss oI erythrocytes is aIso compensated by
their increased rate oI production in the spIeen and the bone marrow.
SeveraI methods are in use Ior determining the totaI bIood voIume in the body. The most reIiabIe
and eIIicient method is the radio isotope I
131
method. In this method, aIbumin is combined with I
131
.
AIbumin does not diIIuse through the capiIIaries, and I
131
can be determined easiIy. II the pIasma
voIume and the percentage oI the bIood corpuscIes are known, the totaI amount oI bIood can be
caIcuIated as IoIIows:
BIood voIume ÷
PIasma voIume 100
100 haematocrit

GeneraIIy, bIood voIume remains constant since the normaI bIood pressure has to be maintained
at aII times. However, under certain conditions the voIume may vary within narrow Iimits. The pIasma
voIume oI mammaIs decreases at high aItitudes; whereas the voIume oI the red bIood ceIIs increases.
Laws of CircuIation
Three major Iactors are invoIved in circuIation and maintenance oI pressures within circuIatory
channeIs:
1. Active state oI the animaI.
2. Cardiac output.
3. PeripheraI resistance.
In smaII and primitive animaIs, the generaI activity oI the animaI is IargeIy responsibIe Ior the
bIood IIow. In higher animaIs too, the bIood IIow in certain speciaIized areas depends on this Iactor
(Ior exampIe, in smaII veins oI birds and mammaIs). The cardiac output is IargeIy responsibIe Ior the
circuIation since the bIood voIume and the Iorce oI the heart vary considerabIy. PeripheraI resistance
is an important Iactor in the vertebrates and Iarger invertebrates with cIosed circuIation. The veIocity
and pressure oI bIood vary considerabIy within diIIerent areas governed by physicaI principIes.
3E.E THE CDMPDNENTS DF ClRCULATDRY SYSTEM
The bIood circuIation has two purposes: it serves to suppIy nutrients and oxygen to the tissues, and
removes wastes Iike carbon dioxide and others Irom the tissues. The essentiaI components oI the
circuIatory system are the heart, arteries, veins and the capiIIaries. Some inIormation about their
anatomy wouId be useIuI Ior the purpose oI a better understanding oI the circuIatory process.
Animal Physiology "$
ARTERIES: The arteries are thick-waIIed and muscuIar vesseIs that carry the bIood away Irom the
heart. StructuraIIy arteries are made up oI three Iayers: intima, media and externa. They may be Iarge,
medium and smaII. The medium sized arteries contain weII deveIoped muscuIature and are Iurther
divisibIe into smaII arteries or arterioIes. The waIIs oI the arterioIes aIso possess muscIe Iayers which
cause these vesseIs to constrict or diIate. This property oI Jasoconstriction oI arterioIes is responsibIe
Ior increasing the bIood pressure to enabIe it to IIow with a greater veIocity. ArterioIes are suppIied
with neurons which respond to sympathetic stimuIation. In response to sympathetic stimuIation,
chemicaI agents Iike norepinephrine are secreted which produce vasoconstriction. Other chemicaI
agents Iike epinephrine, serotonin and, angiotensin aIso produce the same eIIect. II the vasoconstrictor
neuron is severed, the arterioIe diIates. VasodiIation can aIso be caused by the action oI chemicaIs Iike
acetyIchoIine, bradykinin, histamin, etc.
VEINS: Veins are thin waIIed with Iewer eIastic Iibres. The three Iayers present in the arteries are
aIso present in the veins, but they are much thinner. SmaII veins are caIIed venuIes. The Iarger veins
oI the abdomen and Iower Iimbs possess vaIves which open in the direction in which the bIood is
IIowing, i.e. towards the heart.
CAPILLARIES: CapiIIaries are very Iine bIood vesseIs which are composed oI a thin waII made up
oI a singIe Iayer oI IIat endotheIiaI ceIIs. The ceIIs have a basement membrane which is continuous.
CapiIIary waII is so thin that it aIIows transIer oI gases or substances through it. Two types oI
capiIIaries can be distinguished:
1. True capiIIaries.
2. SinusoidaI capiIIaries.
True capiIIaries are present in most tissues and have a Iumen diameter ranging Irom 4 to 8 .
SinusoidaI capiIIaries are channeIs with irreguIar diameter ranging Irom 5 to 30 . Such capiIIaries
are generaIIy Iound in bIood Iorming tissues Iike thymus, Iymph nodes, bone marrow, Iiver, spIeen
and adrenaI cortex.
The capiIIary waIIs are permeabIe, but the permeabiIity is not the same the throughout the body.
The capiIIaries oI the Iiver are most permeabIe. In conditions oI trauma permeabiIity increases to the
extent that even ceIIuIar eIements can aIso pass through it. AIthough the capiIIary waIIs are very thin,
yet they are capabIe oI withstanding pressures as high as 90 mm Hg or even higher.
Heart
The heart is a muscuIar organ which propeIs bIood to various parts oI the body. It is responsibIe Ior
maintaining the direction oI the IIow with the heIp oI the vaIves present in it. The heart contracts
periodicaIIy to ensure continuous circuIation and its stoppage wouId mean the death oI the animaI. In
order to study the physioIogy oI the heart, it is necessary to consider the action and the controI
mechanism oI the heart.
3E.3 HEART DF lNVERTEBRATE
AcoeIomates do not possess bIood vesseIs and hearts (exception Nemertines). CoeIomic invertebrates
have hearts which can be cIassiIied into three types:
Circulation oj Blood "%
1. TubuIar hearts.
2. PuIsating hearts.
3. AmpuIIar hearts.
TubuIar Hearts
In arthropods, the systemic hearts consist oI Iong, tubuIar contractiIe structures. The heart may be
suspended in a Iarge pericardial chamber by means oI eIastic Iigaments or it may be Iree without any
support. The heart is bathed in the surrounding haemoIymph. In most arthropods (insects), the heart is
heId in position by speciaI alary muscIes and receives bIood by means oI IateraI paired openings
caIIed ostia. The ostia are guarded by vaIves. These ostia openings cIose when the aIary muscIes
contract, and the bIood is pushed through the artery. Consequent upon the contractions oI the heart, a
negative pressure is created within the pericardiaI chamber thereby Iorcing the Iresh suppIy oI bIood
Irom the haemocoeI into the heart through the ostia. The entire heart may show wave oI contraction.
In case oI crustaceans, the bIood passes Irom the heart into the arteries and arterioIes and Irom there
to the giIIs. The veins then bring back the bIood to the pericardiaI chamber. The heart oI tunicates is
a convoIuted tube situated in the pericardium. The heart pumps bIood in one direction Ior some time
and then the direction oI the IIow is reversed.
PuIsating Hearts
PuIsating hearts are characteristic oI anneIids which have a cIosed circuIatory system. These puIsatiIe
hearts contract in a peristaIic Iashion. In the earthworm, rhythmic puIsatiIe movements are observed
in the dorsaI tubuIar vesseI Irom the posterior to the anterior end. The IateraI vesseIs, commonIy
known as hearts, aIso beat rhythmicaIIy independent oI each other. In Hirudinaria, there are two
IateraI channeIs which show aIternate contractions.
AmpuIIar Hearts
In certain animaIs ampuIIar hearts or accessory booster hearts are present which Iunction as booster
pumps to Iorce the bIood with increased pressure. Such accessory hearts are commonIy Iound in
cephaIopods and insects. In cephaIopods, these hearts heIp in Iorcing the bIood into smaII peripheraI
vesseIs. In insects they are situated at the base oI antennae, wings and Iegs. In aphids, booster hearts
Iorce the extraceIIuIar IIuids into the Iegs.
3E.4 HEART DF VERTEBRATES
The hearts oI vertebrates are known as chambered hearts. Chambered hearts are aIso Iound in
moIIuscs where one or two auricIes and one ventricIe are present. In the vertebrate series, Iishes have
two chambers in the heart, the auricIe and the ventricIe. In addition, two antechambers, the sinus
venosus and the conus arteriosus are aIso present. The sinus venosus opens into the auricIe and the
conus arteriosus springs Irom the ventricIe. The venous bIood entering the sinus venosus is brought
into the auricIe Irom where the bIood comes into the ventricIe which distributes arteriaI bIood through
the conus arteriosus. The two chambered heart attained more speciaIization in its structure with the
evoIution oI Iand vertebrates. In reptiIes Ior the Iirst time the ventricIe became incompIeteIy divided
Animal Physiology "&
by an incompIete ventricuIar septum. This ventricuIar septum became compIete in birds and
mammaIs. Birds and mammaIs have Iour chambered hearts, having two auricIes and two ventricIes.
These hearts are highIy speciaIized in their structure and Iunction.
Structure of MammaIian Heart
The heart oI mammaIs has attained a high IunctionaI eIIiciency. In order to understand the physioIogy,
we can examine the human heart. In man, the heart is situated in the thoracic cavity sIightIy dispIaced
towards the IeIt side. The waII oI the heart is composed oI three Iayers, nameIy, the endocardium,
myocardium and the epicardium. The endocardium consists oI connective tissues Iined with a thin
Iayer oI endotheIium. The myocardium is the principaI muscIe Iayer which is thin in the auricIes and
thick in the ventricIe. The epicardium is made up oI epitheIiaI ceIIs and connective tissue. The heart is
encIosed in a pericardiaI membrane. The space between the pericardium and epicardium is known as
pericardiaI space which contains a IIuid. The pericardiaI IIuid Iubricates the heart.
The heart is Iour chambered. There are two auricIes and two ventricIes ensuring compIete
separation oI oxygenated and deoxygenated bIood (Fig. 12.1). The bIood enters the right auricIe Irom
systemic circuIation through the vena cavae. The IeIt auricIe receives bIood Irom the puImonary
circuIation. The bIood is then pushed into the two ventricIes. The right ventricIe receives
deoxygenated bIood Irom the right auricIe and pumps it into the puImonary circuIation. The IeIt
ventricIe receives oxygenated bIood Irom the IeIt auricIe and pumps it into the systemic circuIation
through the aorta.
The circuIation oI bIood through the heart is guided by Iour vaIves. The IeIt auricIe opens into the
ventricIe guarded by a mitral valve which is bicuspid, and the opening oI the right auricIe into the
ventricIe is guarded by a tricuspid valve (Fig. 12.1). There is an aortic vaIve between the IeIt ventricIe
and the aorta. The opening oI the puImonary artery into the right ventricIe is guarded by a puImonary
vaIve.
3E.5 PHYSlDLDGlCAL PRDPERTlES DF CARDlAC MUSCLES
The cardiac muscIes are syncytiaI in nature and show a number oI properties resembIing the skeIetaI
muscIes. The physioIogicaI properties oI the cardiac muscIes are discussed beIow.
ExcitabiIity and ContractiIity
Cardiac muscIes are excitabIe and respond to various stimuIi Iike thermaI, chemicaI, mechanicaI or
eIectricaI. In response to a speciIic stimuIus physicaI changes are caused in the heart muscIe. The
physicaI change is responsibIe to bring about contraction IoIIowed by a concomitant reIease oI energy
which is proportionaI to the Iength oI the Iibres. A stimuIus which causes contraction is caIIed the
threshold of the stimulus. WhiIe undergoing contraction the heart muscIe wiII not respond to any
stimuIus. This state oI the heart muscIe is caIIed reIractory state. When the phase oI contraction is
over, a subthreshoId stimuIus (IeebIe stimuIus) IaiIs to evoke an appreciabIe response; hence, a strong
stimuIus wouId be necessary to make the heart responsive. This period is known as reIative reIractory
period.
Circulation oj Blood "'
Automatic Rhythmicity
The heart beats are reguIar and occur in an orderIy manner. The Irog`s heart shows reguIar beats
starting Irom the sinus venosus IoIIowed by auricIes, ventricIe and the truncus arteriosus. The heart
has the inherent power to initiate its own heart beat without the heIp oI any externaI agency. II the
heart oI Irog is removed Irom the body and kept in Ringer`s* soIution, it continues to beat reguIarIy
Ior some time. The muscIe tissue beats Iaster than that oI the auricIes, and the auricuIar muscIes beat
Iaster than those oI the ventricIe. This has been shown concIusiveIy by appIying Stannius Iigatures. II
the Iigature is tied round the sinuatriaI junction, the sinus continues to beat, whiIe rest oI the heart
*Ringer`s soIution oI physioIogicaI saIine consists oI 0.6 gm oI sodium chIoride, 0.0075 gm oI potassium chIoride, 0.01 gm oI
caIcium chIoride, 0.01 gm oI sodium bicarbonate in 100 mI oI water.
FIg. 12.1 Internal structure of the mammalian heart.
External
carotid
Left common carotid
Innominate
Carotid body
Carotid sinus
Chemoreceptors
aortic arch
Pulmonary
artery
Pulmonary
veins
Left auricle
Bicuspid
valve
Left ventricle
Right ventricle
Tricuspid valve
Right auricle
Semilunar
valves
Aortic
sinus
Aorta
Animal Physiology #
stops and remains in a reIaxed condition Ior some time and Iater regains beating at a sIower rate. II a
second Iigature is appIied round the heart between the atria and the ventricIe, the ventricIe begins to
beat but at a sIower rate. It couId be concIuded Irom this experiment that the rate oI heart beats
diminishes in the descending order. The higher rhythmic activity oI the sinus venosus is due to the
sinu-auricular node consisting oI speciaI ceIIs that trigger the impuIse. This is caIIed the pacemaker,
Rhythmicity oI the heart does not depend on the centraI nervous system. AIthough the Irog`s heart is
governed by the vagus and sympathetic nerves.
In the Irog`s heart, sinus venosus sets the pace since it beats Iaster. This property has been studied
by giving eIectricaI stimuIi to the ventricIe to aIIow it to beat Iaster than the sinus. It has been
observed that in such a case the other chambers contract in a reverse order, i.e. the ventricIe, the
auricIes and then the sinus. II the sinus is warmed, it starts beating much Iaster, whereas the ventricIe
remains unaIIected.
Conductivity
The cardiac muscIes are syncytiaI in nature. Due to this remarkabIe property has been studied by
giving eIectricaI stimuIi to the ventricaI to aIIow it to beat Iaster than the sinus. It has been observed
that in such a case other any part oI the heart is stimuIated, the wave oI excitation spreads over aII
parts uninterrupted.
ALL-OR-NONE LAW: The muscIes oI the heart are aII interconnected. II an eIIective stimuIus is
appIied to the heart, it produces a maximum response. II the stimuIus is weak, it wiII not eIicit any
response. Thus, when an eIIective stimuIus is provided to the heart, it wiII produce a maximum
response making aII the Iibres contract. This is caIIed 'aII-or-none Iaw¨ (aIso reIer Chapter 12).
REFRACTORY PERIOD: In skeIetaI muscIe, the reIractory period is very short, Iess than the
contraction period. For this reason, repeated stimuIi can be given at short intervaIs producing
sustained contraction. In cardiac muscIe the reIractory period is quite Iong, aImost equaI to the
contraction period (Fig. 12.2). For this reason, the heart muscIe normaIIy does not show tetanic
contractions. In skeIetaI muscIe, the reIractory period Iasts Ior 0.0015 sec whereas in cardiac muscIe it
Iasts Ior about 0.4 sec. During the contraction phase oI the cardiac muscIe any stimuIus wiII prove
FIg. 12.2 Diagram showing the tracings of the heart beat.
d
e
g
f
c
a
b
2 sec
Circulation oj Blood #
ineIIective, hence this is caIIed absolute refractory period. AIter the phase oI contraction is over, the
muscIe undergoes reIaxation. In order to eIicit another contraction, a stimuIus greater than the usuaI is
necessary. This period is caIIed relative refractory period. In other words, the heart muscIe wiII not
show any response beIore reIaxation has taken pIace.
STAIRCASE PHENOMENON: II the stimuIi are appIied repetitiveIy at short intervaIs, graduaI increase
in the height oI Iour to Iive contractions is recorded (Fig. 12.3), aIter which the ampIitude oI
contractions remains constant. This phenomenon is caIIed the staircase phenomenon or treppe. This is
probabIy due to accumuIation oI products that are beneIiciaI. During contraction, Iactic acid is
produced as a resuIt oI which the pH and the temperature rise sIightIy.
FIg. 12.3 Staircase phenomenon.
EFFECTS OF INORGANIC IONS: II the excised heart oI a Irog is kept in Ringer`s soIution, it keeps on
beating in a normaI way Ior some hours. This is due to the Iact that the composition oI the Ringer`s
soIution is simiIar to the Irog`s pIasma. The sodium, caIcium and potassium ions are very essentiaI to
maintain the muscuIar responses oI the heart. Sodium ions contribute to the maintenance oI the
excitabIe properties oI the heart muscIe. WithdrawaI oI sodium ions Irom the Ringer`s soIution
weakens the contractions. PerIusion experiments with soIution containing sodium saIt onIy (caIcium
and potassium ions absent) brings about the weakening and uItimateIy IaiIure oI the heart beats; when
caIcium ions were added to the soIution, the heart beats restored rapidIy. Presence oI excess oI
caIcium ions is Iound to produce vigorous contractions. RemovaI oI potassium ions causes reIaxation
oI the heart to become IeebIe, uItimateIy stopping the systoIe. On the other hand, potassium-rich
soIution IaciIitates reIaxation.
CONDUCTION THROUGH THE HEART: The conduction system oI the heart initiates two eIectricaI
sequences that cause the heart chambers to IiII with bIood and contract. These are: (a) impulse
formation, the Iirst sequence, takes pIace when an eIectricaI impuIse is generated automaticaIIy, and
(b) impulse transmission, the second sequence, occurs once the impuIse has been generated,
signaIIing the heart to contract.
The conduction system consists oI Iour main structures composed oI tissue that can generate or
conduct eIectricaI impuIses.
(1) 1he sinuatrial or sinuauricular node (SA node), in the waII oI the right auricIe, contains ceIIs
that spontaneousIy initiate an action potentiaI. Serving as the heart`s main pacemaker, the SA
node initiates 60 to 100 beats per minute. ImpuIses generated by the SA node trigger auricuIar
Animal Physiology #
contraction. The impuIses traveI through internodaI tractsthe anterior tract, middIe tract,
posterior tract, and anterior interatriaI tract (Fig. 12.4).
(2) At the atrioventricular (A J) node, situated in the Iower inter-arteriaI septum, the impuIses are
deIayed brieIIy to permit compIetion oI auricuIar contraction beIore ventricuIar contraction
begins.
(3) At the bundle of His, the muscIe Iibres arising Irom the AV junction, impuIses traveI aIong the
IeIt and right bundIe branches, Iocated on either side oI the intraventricuIar septum.
(4) The impuIses reach the Purkinje Iibres, a diIIuse network extending Irom the bundIe branches
and ending in the ventricuIar endocardiaI surIaces. VentricuIar contraction then occurs.
The AV junction, bundIe oI His, and Purkinje Iibres are latent pacemakers, they contain ceIIs
capabIe oI generating impuIses. However, these regions are having a sIower Iiring rate than the SA
node. ConsequentIy, the SA node predominates except when it is depressed or injured.
BeIore cardiac contraction can take pIace, cardiac ceIIs must depoIarise and repoIarise, resuIting
Irom changes in the eIectricaI potentiaI across the ceII membrane, caused by the exchange oI sodium
and potassium ions. The action potential which reIIects this eIectricaI activity has Iive phases
(Fig. 12.5).
(1) Phase 0 (rapid depolarisation) takes pIace when sodium ions enter the ceII through Iast
channeIs; the ceII membrane`s eIectricaI charge changes Irom negative to positive.
(2) Phase 1 (early rapid repolarisation) occurs when Iast sodium channeIs cIose and potassium
ions Ieave the ceII. The ceII rapidIy repoIarises returning to resting potentiaI.
(3) Phase 2 (plateau) is reached when caIcium ions enter the ceII through sIow channeIs whiIe
potassium ions exit, stabiIises the membrane`s eIectricaI activity temporariIy.
FIg. 12.4 Conducting system of the mammalian heart.
Circulation oj Blood #!
(4) Phase 3 (final rapid repolarisation) takes pIace when potassium ions are pumped out oI the
ceII as the ceII rapidIy compIetes repoIarisation and resumes its initiaI negativity.
(5) Phase 4 (slov depolarisation). The ceII returns to its resting state, with potassium ions inside
the ceII and sodium and caIcium ions outside.
During depoIarisation/repoIarisation, a ceII`s abiIity to initiate an action potentiaI varies. The ceII
cannot respond to any stimuIus during the absolute refractory period (beginning during phase 1 and
ending at the start oI phase 3). A ceII`s abiIity to respond to stimuIi increases as repoIarisation
continues. During the relative refractory period, occurring at phase 3, the ceII can respond to a strong
stimuIus. When the ceII has been compIeteIy repoIarised, it can again respond to stimuIi. It has been
observed that ceIIs in diIIerent cardiac regions depoIarise at various speeds, depending on whether
Iast or sIow channeIs predominate. Sodium IIows through Iast channeIs, and caIcium through sIow
channeIs. In cardiac muscIe ceIIs where Iast channeIs dominate, depoIarisations occurs quickIy. SIow
channeIs dominate ceIIs oI the SA node and AV junction, consequentIy they show sIow
depoIarisation.
AbnormaI impuIse Iormation and conduction may give rise to arrhythmias. AbnormaI impuIse
Iormation may stem Irom depressed automaticity (escape beats and bradycardia) or increased
automaticity as in premature beats, tachycardia and extrasystoIe. ImpuIse conduction may become
abnormaI when there is a deIay or bIock in the conducting system, or unidirectionaI conduction.
Arrhythmias may decrease cardiac output, reduce bIood pressure, and disrupt perIusion oI vitaI
organs.
CONTROL OF THE HEART BEAT: The rhythmic activity oI the heart is an inherent property. As we
have discussed above, the pacemaker oI the heart is responsibIe Ior initiating and spreading the wave
oI heart beats. In some invertebrates, the wave oI heart beats starts at the posterior end and spreads
anteriorwards. In earthworm, the beating oI bIood vesseI starts Irom behind.
FIg. 12.5 Myocardial action potential curve. The curve represents ventricular depolarisationfrepolarisation. 0-phase 0
(rapid depolarisation), l-phase l (early rapid repolarisation), 2-phase 2 (plateau), 3-phase 3 (final rapid
repolarisation), +-phase + (slow depolarisation).
Animal Physiology #"
In certain insects aIso, the heart muscIes themseIves show the rhythmic contractions and no nerve
ceIIs or gangIia are associated as in Belostoma, Aeschna, etc.
In aII cases, the heart is a speciaIized muscuIar tissue which keeps on beating periodicaIIy.
However, the exact triggering mechanism has not yet been known. PhysioIogists have recognized two
types oI hearts.
Myogenic hearts: The myogenic hearts show their rhythmic activity due to the muscIes
themseIves. The vertebrate heart is myogenic type. The heart beat is initiated at the sinus venosus in
case oI Iishes and amphibians. In birds and mammaIs, heart beat starts Irom the sinuauricuIar node.
Some invertebrates aIso possess myogenic hearts in which the heart beats may originate Irom any
point.
Neurogenic hearts: In certain animaIs, the heart muscIes are innervated by nerves. In such cases
reguIation oI heart beats is dependent upon nervous reguIation. Majority oI arthropods and
invertebrates in generaI, possess neurogenic hearts. Among insects, especiaIIy the orthopteran species
have neurogenic hearts. The nerve endings, upon stimuIation, produce a chemicaI transmitter
substance caIIed acetyIchoIine which seems to acceIerate the heart beats.
The heart oI Limulus is suppIied with a gangIion ceII on the dorsaI surIace oI the heart. The
gangIion ceII is made up oI mutipoIar neurons having connection with the IateraI nerves. This median
gangIion is responsibIe Ior initiating heart beats. When the median gangIion is removed heart stops
beating. Among some anneIids too, such as Lumbricus and Arenicola, nerve ceIIs have been Iocated
in the hearts which act as pacemakers. AII neurogenic hearts are acceIerated by the action oI
acetyIchoIine.
THE CARDIAC CYCLE: Two phases can be recognized whiIe the heart is beating: (1) systolethe
contraction phase, and (2) diastolethe reIaxation phase. In mammaIs, the heart beats originate in the
sinuauricuIar node which Iunctions as pacemaker. The two auricIes simuItaneousIy contract and Iorce
their bIood into the ventricIes (auricuIar systoIe). AIter a sIight pause, the ventricIes contract
simuItaneousIy (ventricuIar systoIe) and Iorce their bIood into the puImonary artery and the aorta.
AIter each contraction phase the auricIes as weII as the ventricIes reIax Ior a whiIe. This reIaxation
period is caIIed the diastoIe. The sequence oI contractions and reIaxations oI the auricIes and the
ventricIes constitutes the cardiac cycIe oI the heart. The human heart normaIIy beats about 70 to 80
times per minute and each cycIe Iasts about 0.8 sec. The auricuIar systoIe Iasts about 0.1 sec. The time
taken by ventricuIar systoIe is 0.3 sec. and Ior the joint diastoIe, it is 0.4 sec (Fig. 12.6).
CARDIAC DYNAMICS: When bIood enters the right auricIe, the pressure oI bIood is aImost zero as
compared to the atmospheric pressure. The pressure oI bIood Ieaving the right ventricIe is at 25 mm
oI mercury, whereas the pressure oI bIood Ieaving the IeIt ventricIe is at 120 mm oI mercury.
Starlings lav: StarIing and his associates postuIated a Iaw oI the heart which states that the initiaI
Iength oI the cardiac muscIe Iibre determines the Iorce oI contraction. In other words, greater the
initiaI Iength oI the muscIes, greater wiII be the Iorce oI contraction. The Iaw oI the heart has been
summarized by StarIing as 'The energy oI the contraction is a Iunction oI the Iength oI the muscIe
Iibres¨. The initiaI Iength oI the heart muscIe depends upon the quantity oI bIood that IIows into the
ventricIe during diastoIe. The Iaw proves that the heart is governed by a seII-reguIatory mechanism
Circulation oj Blood ##
which permits the heart to adjust automaticaIIy to the changes in the voIume oI bIood during diastoIe
(Fig. 12.7).
CARDIAC OUTPUT: NormaIIy the voIume oI bIood expeIIed by each ventricIe is the same.
However, under exceptionaI circumstances bIood voIume expeIIed by both the ventricIes may diIIer
Ior a short time. Hence, we can deIine the cardiac output as the voIume oI bIood expeIIed by one side
oI the heart per minute. The quantity oI bIood expeIIed out oI the heart may depend on the IoIIowing
Iactors:
1. The Iorce oI contraction.
2. Amount oI bIood entering the ventricIes during diastoIe.
3. The heart rate.
FIg. 12.6 Diagram showing the cardiac cycle.
1
120
80
40
0
120
60
0
Systole Diastole
I II III
Heart
Sounds
Ventricular
volume
Artial
A-V valve
opens
Ventricular
pressure
Aortic
pressure
Aortic
valves
open
2 3 4 5 6 7 8
mm Hg
A-V valve
closers
Aortic valve
closes
Animal Physiology #$
The cardiac output in man is approximateIy 5.5 Iitres per minute which may increase during
vioIent exercise. The quantity oI bIood expeIIed out Irom one side oI the heart per beat is caIIed the
stroke volume. In man, the actuaI voIume at rest is about 80 mI. The stroke voIume as weII as the
cardiac output varies a great deaI with the amount oI muscuIar exercise.
SeveraI methods are used to determine the cardiac output in man. Some oI them can be brieIIy
mentioned here.
Ficks method: Fick`s principIe states that in a given time the totaI amount oI any gas gained or
Iost in the Iungs shouId be equaI to the diIIerence between the amounts oI the gas brought to the Iungs
in the arteriaI bIood and the amount Ieaving the Iungs in the venous bIood. II we measure (a) the
amount oI oxygen taken up by each mI oI bIood passing through the Iungs, (b) the amount oI oxygen
consumed per minute, and (c) the oxygen content oI the venous bIood, the cardiac output can be
caIcuIated as IoIIows:
Cardiac output
(mI min)
÷
Oxygen consumed per minute (mI min)
ArteriaI O content
(mI O /bIood)
Venous O content
(mI O /mI bIood)
2
2
2
2

On an average, at rest 250 mI oI oxygen are consumed per minute. The arteriaI oxygen content is
about 0.195 mI/mI and the venous oxygen content is about 0.150 mI/mI. By using Fick`s equation: .
Cardiac output ÷
250
0195
mI
mI/min 0.150 mI/mI
min
.
÷
250
0.045
÷ 5,556 mI/min
Radioisotope method: In this method, a known amount oI a radioisotope is injected into the arm
vein. UsuaIIy I
131
combined with protein is used. One mI oI standard isotope soIution is injected. Now
1 mI oI standard soIution is diIuted to a known voIume. AIter 10 minutes, a known voIume oI bIood
is drawn. Now 1 mI oI the diIuted standard is counted in a scintiIIation detector and simiIarIy 1 mI oI
bIood is aIso counted and the equiIibrium vaIue is determined.
FIg. 12.7 Relation between tension developed by a frog´s heart contracting isometrically and its initial contained volume.
60
40
20
0
0
0.02 0.04 0.06 0.08
5°C
15°C
P
r
e
s
s
u
r
e
(
m
m
H
g
)
Circulation oj Blood #%
Cardiac output ÷
C BIood voIume
C Time
eq
eq

where C
eq
÷ counts per minute at equiIibrium, and C
av
÷ average count per minute during Iirst
circuIation.
The bIood voIume is caIcuIated as:
BIood voIume ÷
Standard (c/min) 500
BIood (c/min)

where 500 is the diIution oI the standard soIution.
The cardiac output may vary under certain conditions. At rest, the cardiac output in man is about
5 Iitres per minute, whereas under abnormaI conditions it may increase or decrease.
3E.8 REGULATlDN DF THE HEART
From the preceding description, it is cIear that the heart possesses automatic rhythmicity and is
governed by a seII-reguIatory mechanism. The greater the eIasticity, the greater is the Iorce oI
contraction. However, the Iorce oI contraction depends upon nervous reguIation and a number oI
other Iactors such as temperature and hormones.
EIectricaI Activity of the MammaIian Heart
The Iunctioning oI the mammaIian heart (human) can be recorded in the Iorm oI eIectricaI activity
with the heIp oI eIectrocardiography. The recording instrument is provided with eIectrodes which are
pIaced on the surIace oI the body. In aII, there are Iour Ieads (eIectrodes) connected to the instrument
which are pIaced on the surIace oI the body in the IoIIowing manner:
(1) Lead I connected to the right and the IeIt arm
(2) Lead II connected to the right arm and the IeIt Ieg
(3) Lead III connected to the IeIt arm and the IeIt Ieg
(4) Lead IV is pIaced on the chest over the heart.
The eIectricaI activity oI the heart is recorded on the chart recorder with the heIp oI a moving
styIus. The typicaI eIectrocardiogram oI a cardiac cycIe (Fig. 12.8) consists oI a series oI waves
arbitrariIy designated by Einthoven as the P wave, the QRS compIex, the T wave and the U wave.
1he P Wave: The P wave represents depoIarization oI the arteiaI muscuIature which spreads
radiaIIy Irom the sinuauricuIar node to the auricuIo-ventricuIar node. It is ordinariIy upright in Iead I
and II (Fig. 12.8), but may be diphasic and inverted in Iead III depending upon the direction oI
depoIarization. Its duration is about 0.11 second and ampIitude about 2.5 mm.
1he PR Interval: The deIay in transmission oI impuIse at the AV-node on the eIectrocardiogram is
the PR segment oI about 0.2 second. This is measured Irom the beginning oI the P wave to the
beginning oI QRS compIex.
Animal Physiology #&
1he QRS Complex: The QRS compIex is measured Irom the beginning oI the Q wave to the S
wave and represents the wave oI depoIarization oI the ventricIe spreading through the auricuIo-
ventricuIar bundIe oI His and the ventricuIar Iibres. The normaI range oI QRS compIex in aduIts is
Irom 0.06 to 0.1 second. RareIy it is Iess than 0.06 and the duration greater than 0.1 sec is indicative
oI some cardiac disease.
The Q wave is about 3 mm in depth and is due to depoIarization oI the septum (about 0.03 sec
duration). The R wave is very high and varies between 4 and 22 mm in height with a duration oI
about 0.07 second. The S wave is about 6 mm in depth.
1he S1 Interval: The duration oI the ST intervaI is a measure oI the duration oI the depoIarized
state pIus that oI repoIarization. In most eIectrocardiograms, there is no true ST segment.
1he 1 Wave: The T wave represents the wave oI ventricuIar repoIarization. The deIIections above
the base Iine are positive waves and those beIow are negative. The T wave may be aItered due to
many physioIogic states other than those Iound in cardiac diseases. The physioIogic states that may
aIter the T wave are:
1. Drinking oI coId water prior to ECG recording.
2. Smoking
3. Extreme emotionaI upset
4. Variation in the position oI the heart
5. Under the medication oI digitaIis
A negative T wave is an indication oI some myocardiaI disease. NormaIIy the T wave (Lead 1) is
about 0.5 mm.
1he U vave: The U wave represents the positive aIter potentiaI and the period oI greater
excitabiIity oI the ventricIes. In most oI the eIectrocardiograms, it is not discernibIe, hence its
interpretation is diIIicuIt.
The wave Iorm oI the ECG is an indication oI the state oI heart and cardiac abnormaIities can be
detected by distortion and irreguIarities in the normaI wave Iorm. Some abnormaIities are discussed
here.
FIg. 12.S Electrocardiogram of the human heart showing the sequence of events during the cardiac cycle.
Circulation oj Blood #'
Atrioventricular block: This is caused by some disease aIIecting the auricuIo-ventricuIar bundIe
interIering with the bIood suppIy oI the heart. In such a case, the ECG wouId show two auricuIar
deIIections against one ventricuIar deIIection.
1achycardia: This is a disease in which the heart rate is rapidIy increased enhancing the bIood
IIow. The rate ranges Irom 150 to 250 per minute. In normaI heart the impuIses arise Irom the sinu-
auricuIar node, but in tachycardia they are generated eIsewhere (in the auricIes or auricuIo-ventricuIar
node or the ventricIe). The rapidIy occurring extra systoIes impose a Iimitation on the IiIIing time. The
drug atropine induces tachycardia.
Bradycardia: It is a disease causing the sIowing oI the heart beats.
Auricular fibrillation: This disorder is due to the deIect in the muscIe contraction oI the heart.
The waIIs contract more rapidIy, usuaIIy 400-600/minute and the auricIes are never emptied. The
normaI P waves are repIaced by smaII waves (F waves).
Nervous ReguIation
The Iorce oI contraction is governed by the nerves innervating the heart. In many invertebrates, such
as moIIuscs and arthropods, the heart beats are reguIated by certain nerve centres. These nerve centres
are Iocated in the centraIIy pIaced gangIia and may have acceIeratory or inhibitory eIIect.
In vertebrates too, the heart beat and the bIood IIow are controIIed by the nerves. The heart is
innervated by the autonomic nerves and the integration is achieved through meduIIa obIongata.
The Vagus Nerves
The heart oI mammaIs has a duaI controI. The vagus nerve (X CraniaI nerve) contains both
parasympathetic (motor) and sensory nerve Iibres. The heart receives outgoing branches oI the vagus
and sympathetic nerve Iibres Irom the upper thoracic region oI the spinaI cord coordinated through
the meduIIa where the control centres are Iocated. These controI centres are made up oI a number oI
ceII bodies which are oI two types: (a) cardioinhibitor centre, and (b) the cardioacceIerator centre. The
inhibitor centre gives rise to parasympathetic nerves that traveI to the heart and produce inhibitory
eIIect. The acceIerator centre gives rise to acceIerator nerves that traveI down the spinaI cord and have
an acceIerator eIIect on the heart. The cardiac activity is reguIated by these centres through vagaI and
acceIerator Iunctions. Both the centres aIso send short neurons to each other, so that the activity oI
inhibitory centres can depress the acceIerator centres and vice versa. The cardiac Iunctions are aIso
inIIuenced by other parts oI the brain such as thaIamus and hypothaIamus. These parts oI the brain
contain such centres which, upon stimuIation, aIIect the emotionaI states oI individuaIs and increase
rate oI heart beat, bIood pressure during sIeep and exercise.
The sinu-auricuIar and auricuIo-ventricuIar nodes are innervated by the parasympathetic neurons.
When the vagus neurons are stimuIated, the Iorce oI contraction is decreased showing sIow heart
beats. The heart may stop compIeteIy, iI stronger stimuIation is given. Continued stimuIation,
however, induces the ventricIes to region contractions. This phenomenon is caIIed vagus escape. In
other words, the ventricIes continue to beat independentIy without getting impuIses Irom the auricIes.
This shows that the vagus has no direct eIIect on the ventricuIar activity, since the ventricIes escape
Irom the inhibitory inIIuence oI the vagus. The vagus has an inhibitory inIIuence in suppressing the
Animal Physiology $
sinu-auricuIar and auricuIo-ventricuIar nodes which stops the ventricIe. But the continued beating oI
the ventricIe is due to the action oI the ventricuIar pacemaker.
The vagus nerves aIways send impuIses to the heart which have a retarding inIIuence on the rate
oI heart beat. This is caIIed the vagal tone. When the vagus nerves are cut, the heart rate is acceIerated
owing to the Ioss oI the inhibitory action oI the vagus.
The Sympathetic Nerves
The sympathetic nerves or accelerator nerves arise Irom the second, third and Iourth thoracic
segments oI the spinaI cord and reach the cervicaI sympathetic gangIia. From these gangIia
postgangIionic sympathetic nerve Iibres traveI to the heart and innervate the sinu-auricuIar, auricuIo-
ventricuIar nodes and the muscIe Iibres oI the heart. The sympathetic Iibres upon stimuIation,
acceIerate the heart rate and increase the Iorce oI contraction. II the sympathetic nerves are cut, there
is decrease in the heart rate, but iI the parasympathetic nerves are cut, the heart rate increases. The
two systems have an antagonistic Iunction.
BIood Pressure
BIood pressure is measured in terms oI systoIic reading which is 140 mm Hg and diastoIic reading oI
90 mm Hg. EIevation oI bIood pressure causes systemic hypertension in which systoIic reading is
greater than 140 mm Hg and a diastoIic reading greater than 90 mm Hg. BIood pressure is, thereIore,
equaI to (stroke voIume heart rate) totaI peripheraI resistance. AIteration oI any oI the Iactors on
the right side oI the equation wiII resuIt in a change in bIood pressure, as shown in Fig. 12.9.
FIg. 12.9 Blood pressure regulation.
There are various determinants oI bIood pressure associated with cardiac output and totaI
peripheraI resistance. Angiotensin, a vasopressor, not onIy increases totaI peripheraI resistance but, by
Cardiac
output
Blood
pressure
Total peripheral
resistance
Heart rate
Stroke
volume
Sympathetic
Adrenergic system
Kidney Renin
Angiotensin Plasma
volume
Venous
return
Aldosterone
= ´
Circulation oj Blood $
stimuIating aIdosterone reIease, Ieads to an increased pIasma voIume, venous return, stroke voIume,
and uItimateIy an increase in cardiac output. Factors that bring about the reguIation oI bIood pressure
are:
1. Sympathetic nervous system. In carotids and aortic arch pressure receptors, known as
baroreceptors, are Iocated which respond to changes in bIood pressure inIIuencing vasodiIation and
vasoconstriction. During vasoconstriction, the contractiIe Iorce strengthens, increasing the heart rate
and augmenting peripheraI resistance, thus increasing cardiac output. II pressure remains eIevated,
then baroreceptors reset at the higher IeveIs, sustaining hypertension.
2. Renal pressor system. Kidneys, besides excretory Iunctions, have a bIood pressure reguIating
Iunction. OccIusion oI the renaI artery and arterioIes by atheroscIerotic changes causes reduction in
the renaI suppIy. Decreased renaI perIusion pressure in aIIerent arterioIes stimuIates the
juxtagIomeruIar ceIIs (renaI cortex) to reIease an enzyme caIIed renin.
The renin reacts with a speciIic substrate, angiotensinogen, circuIating in the bIood to produce
angiotensin I which is a weak vasoconstrictor. Another enzyme in the bIood, a converting enzyme,
acts on angiotensin I to convert it to angiotensin II having a very powerIuI vasoconstrictor eIIect
about 200 times that oI noreptinephrine. The angiotensin increases the Iorce oI heart beat and
constricts the arterioIes, and this oIten resuIts in diminished renaI bIood IIow even though peripheraI
bIood IIow may remain unchanged. In addition to raising bIood pressure, angiotensin aIso causes the
constriction oI smooth muscIes. This vasopressor aIso stimuIates aIdosterone reIease, with a resuIting
increase in sodium reabsorption and IIuid voIume. NormaI kidneys contain an enzyme angiotensinase
capabIe oI destroying angiotensin. The reactions oI reninangiotensinaIdosterone system are shown
in Fig. 12.10.
FIg. 12.1û Reactions of the renal pressor system.
3. Fluid volume regulation. Increased IIuid voIume increases venous system distension and
venous return, aIIecting cardiac output and tissue perIusion. These changes Iead to aIterations
in vascuIar resistance, increasing the bIood pressure.
3E.7 CHEMlCAL REGULATlDN
The cardiac Iunctions are greatIy modiIied by chemicaI substances which are either administered, or
Iound in the bIood. They may be secreted by the nerves innervating the heart muscIes. These chemicaI
substances may be cIassiIied as IoIIows;
Converting
enzyme
Angiotensin I Angiotensin II
Aldosterone
Angiotensinase
(from kidney)
Angiotensinogen (a substrate
in blood released from liver)
Renin
(from renal cortex)
+
Animal Physiology $
(a) Neurotransmitters.
(b) Drugs acting on the heart.
Neurotransmitters
The parasympathetic nerve Iibres innervating the heart muscIes secrete acetyIchoIine; hence, they are
caIIed choIinergic nerves. AcetyIchoIine reduces the Irequency and Iorce oI contraction oI the heart.
When injected, acetyIchoIine brings about ventricuIar arrest, but the auricuIar contractions continue as
usuaI.
The sympathetic nerve Iibres upon stimuIation secrete noradrenaIine which serves to acceIerate
the rate oI heart beat and Iorce oI contraction. When injections oI noradrenaIine or adrenaIine are
given, they serve to increase the bIood pressure and reIIexIy sIow the heart. The smooth muscIes oI
coronary arterioIes in the viscera, muscIes and the skin are aIso innervated by the sympathetic Iibres.
Upon stimuIation by adrenaIine or noradrenaIine vasodiIation occurs in the coronary arterioIes, but in
the arterioIes oI the skin and muscIes vasoconstriction occurs.
In resting condition very IittIe amount oI adrenaIine is present in the bIood. AdditionaI amounts oI
adrenaIine are reIeased in the bIood when more energy is needed. Increased amounts oI adrenaIine
cause vigorous suppIy oI bIood to the heart and muscIes and eIevation oI bIood suger IeveI. More
bIood suppIy to the heart is owing to acceIerated heart rate and vasodiIation in the heart and the
muscIe. Enhanced adrenaIine secretions increase the breakdown oI gIycogen reserves; hence, increase
in bIood sugar is noticed.
Effect of Drugs on the Heart
1. Digitalis: It acts directIy on the heart muscIes and peripheraI circuIation. The drug has been in
use Ior Iong since it increases tonicity oI heart muscIes, contractiIity and irritabiIity. Hence the
drug serves as a powerIuI cardiac tonic in increasing the Iorce oI contraction.
2. Pilocarpine, Muscarine. etc: When administered, cause sIowing oI the heart by acting on the
heart muscIes or vagaI terminations. The eIIect oI the drugs can be removed by atropine.
3. Atropine causes acceIeration oI the heart beat.
4. Serotonin (5-hydroxytryptamine) inIIuences the bIood pressure. In dogs, it has a pressor
inIIuence whereas in cats, it acts as a depressant.
Effect of Temperature
The rate oI heart beat is proIoundIy inIIuenced by temperature. In most terrestriaI poikiIotherms,
increase in the rate oI heart beat is recorded with the increase in ambient temperature. This is owing
to Iarge amounts oI bIood needed Ior circuIation. In homeotherms, however, the temperature oI the
body is maintained constant irrespective oI change in the ambient temperature. The rate oI heart beat
remains constant, aIthough whiIe sweating and panting increased bIood IIow in the skin regions may
be caused.
AnimaI IiIe on earth is dependent upon its abiIity to utiIize oxygen and eIiminate carbon dioxide.
About 20 per cent oI oxygen is present in the atmospheric air, but the eIIiciency oI animaIs to utiIize
oxygen varies with their physioIogicaI state. The atmospheric oxygen must be transported to bIood
and reach every ceII oI the body so that the IoodstuIIs may be oxidized. The IoodstuIIs oI animaIs
comprise carbohydrates, Iats and proteins which contain the chemicaI Iorm oI energy. This energy can
be reIeased when the Ioods are burnt or oxidized. As described in Chapter 4, oxygen is essentiaI in the
bioIogicaI oxidations as the terminaI acceptor oI eIectrons and hydrogen ions during eIectron transport
system.
Oxygen reaches the ceIIs and carbon dioxide is given out in exchange through a compIicated
physioIogicaI process caIIed respiration. The oxygen requirements oI the ceIIs are aIso variabIe. Most
ceIIs oI the centraI nervous system, and the heart are extremeIy sensitive to Iow bIood IeveIs oI
oxygen. Lack oI oxygen renders most brain and heart ceIIs as dead within 3-5 minutes.
From the standpoint oI the physioIogist, respiration is accompIished in two major processes: one
invoIving breathing and the other associated with the reIease oI energy Irom the IoodstuIIs within the
ceIIs. The Iormer process is caIIed external respiration and the Iatter is caIIed internal or cellular
respiration. Besides obtaining suIIicient quantity oI oxygen and eIiminating carbon dioxide Iormed in
the body, respiration serves the IoIIowing purposes:
1. It heIps in keeping the Iunctions oI the bIood normaI by adjusting changes in the pH oI the
bIood.
2. It heIps in maintaining proper oxygen tension oI the bIood.
3. It heIps in maintaining normaI body temperature.
The oxygen suppIy and discharge oI wastes Iike carbon dioxide are eIIected through the
extraceIIuIar IIuids in which aII the tissues are bathed. The terrestriaI and aquatic vertebrates are Iaced
with wide range oI respiratory probIems. TerrestriaI vertebrates draw their oxygen requirements Irom
atmosphere through the process oI diIIusion and by a simiIar process carbon dioxide is discharged out
4AIFEH=JE
+ 0 ) 2 6 - 4
!
Animal Physiology $"
oI the body IIuids to the atmosphere. The oxygen content oI water is about 20 times Iess than air and
as such a huge voIume oI water must be passed over the respiratory surIaces to get the required
oxygen.
33.3 RESPlRATDRY DEVlCES
In majority oI organisms beIonging to the Iower phyIa, especiaIIy the aquatic ones, exchange oI gases
takes pIace through the body surIace. In Iarger animaIs such as vertebrates, respiration is a much more
eIaborate process since the body has attained high compIexity. There are speciaI organs to carry out
the exchange process. Gaseous exchange taking pIace between bIood and air (water in case oI aquatic
animaIs) is caIIed external respiration. In this case, no chemicaI process is invoIved. Gaseous
exchange between bIood and the active ceIIs oI the organism comprises internal respiration invoIving
chemicaI process.
There are a number oI organisms Iike protozoans, coeIenterates and IIatworms where speciaIized
respiratory organs are wanting and as such the gases enter and Ieave the body by a process oI sIow
diIIusion. SeveraI respiratory devices are Iound in higher organisms some oI which wiII be described
here.
lntegumentary Respiration
DiIIusion oI gases through the protopIasm is a very sIow process and as such it is unIikeIy that the
metaboIic demands oI animaIs are satisIied through diIIusion aIone. According to Krogh (1941), the
metaboIic demands oI animaIs Iarger than 1 mm in diameter may not be satisIied through this process.
Hence respiratory devices are so modiIied that they IaciIitate suIIicient exchange oI gases through the
body surIace. In a Iarge number oI aquatic animaIs, the integument is highIy vascuIar and readiIy
permeabIe to gases. Earthworms, Ieeches and Iarvae oI many Iishes have a vascuIar skin which bIows
diIIusion oI oxygen through it and the entire metaboIic demand is satisIied through it. However, Iarger
animaIs Iike amphibians, and Iish aIso reIy on cutaneous respiration occasionaIIy or continuousIy in
addition to puImonary or giII respiration.
Cutaneous respiration is possibIe onIy when the skin is thin, vascuIar and moist at aII times.
However, animaIs with thin skins are more prone to predation. Cutaneous respiration takes pIace in
smaII crustaceans where chitinization is not very strong. HighIy chitinized crustaceans do not
exchange their gaseous requirement through the skin.
BranchiaI Respiration
SpeciaI respiratory appendages are deveIoped in a number oI aquatic animaIs. These are caIIed gills.
Such organs have originated independentIy and vary in structure Irom animaI to animaI. They range
Irom simpIe IiIamentous epitheIiaI structures to compIex structures comprising hundreds oI
IiIamentous IameIIae encIosed in a giII cavity or branchiaI chamber. GiIIs are suppIied with bIood
vesseIs and are continuousIy IIushed by water IIow so that gaseous exchange is possibIe between
water and bIood oI the giIIs. According to position, giIIs may be externaI or internaI.
EXTERNAL GILLS: These are most simpIe and primitive structures which deveIop as hoIIow
evaginations oI the body waII. In echinoderms, variety oI such hoIIow strucutres deveIop, which are
Fespiration $#
papiIIiIorm in starIishes and branched in case oI sea urchins. These giIIiIorm structures subserve
respiratory Iunction in addition to the tube Ieet which are aIso used Ior exchange oI gases. In anneIids
usuaIIy the skin is used in respiration, but there are speciaIized respiratory structures too. In some
poIychaetes, there are highIy vascuIarized giIIs attached to the notopodium (Glycera, Eunice and
Nereis). In Arenicola a burrowing poIychaete, and Ozobranchus, a Ieech, the giIIs are paired,
segmentaIIy arranged branchiaI tuIts aIong sides oI the body. The tantacIes oI sabeIIids and serpuIIids
are aIso considered respiratory structures.
Among vertebrates, the giIIs occur in the Iarva oI Irogs (tadpoIe) or as a neotenic Ieature oI the
aduIt in saIamanders (axoIotI, Necturus). In some Iishes aIso, externaI giIIs are present during the
IarvaI condition (EIasmobranchs, Dipnoi). The Iarvae oI Protopterus and Lepidosiren have Iour pairs
oI externaI giIIs in earIy IiIe which are repIaced by internaI giIIs when the opercuIum deveIops.
INTERNAL GILLS: ExternaI giIIs have obviousIy a number oI disadvantages. They are a hindrance
during Iocomotion and a source oI attraction Ior predators. During the course oI evoIution, the giIIs
were drawn into partiaIIy cIosed chambers providing protection to the deIicate structures. This aIso
aIIorded streamIining oI the body. One oI the greatest advantages oI the internaI giIIs is the
continuous IIow oI water currents to ventiIate the giII chambers. In majority oI aquatic animaIs
internaI giIIs are present.
In bivaIves, tunicates and some echinoderms, ciIiary activity is responsibIe Ior the circuIation oI
water through the branchiaI chamber. The animaIs receive their oxygen requirements and aIso the
Iood suppIies Irom circuIating water. In crustaceans, various types oI giII structures are present which
are encIosed in weII deveIoped giII chambers. The giIIs are made up oI Iine vascuIarized IameIIate
structures. In case oI gastropod moIIuscs, the giIIs are situated inside the mantIe cavity which receives
continuous water currents.
Aquatic vertebrates have deveIoped a very eIIicient branchiaI respiration. AvaiIabIe inIormation
on the subject is quite exhaustive; however, some saIient Ieatures oI the branchiaI respiration oI
teIeost Iish have been described here. The giIIs are housed in a chamber known as opercuIar chamber.
The oraI cavity draws in water to irrigate the giIIs and the water is Iorced back over the giIIs to come
out Irom the opercuIar cavity.
The IIow oI water over the respiratory epitheIium is continuous and the respiratory current is
produced by muscuIar activities which pump the water. To ensure this, a doubIe pumping mechanism
is said to be in operation (Fig. 13.1) simuItaneousIy. The buccaI cavity Iunctions as a pressure pump
that Iorces water across the giIIs and the opercuIar suction pump draws the water through them. Thus
a continuous IIow is maintained by simuItaneous action oI these two pumps. The buccaI cavity and
the opercuIar opening are guarded by vaIves which are passive but move according to the pressure
gradients across them.
In many aquatic animaIs, especiaIIy Iishes, an important Ieature is that the IIow oI water over the
giII is in one direction and the IIow oI bIood in the opposite direction. This is caIIed counter-current
principIe and ensures a constant gradient oI oxygen tension between the bIood and water.
Tracheae
Aquatic habitat is considered to be the most primitive. ModiIications in the respiratory structures were
consequent upon the change Irom aquatic to terrestriaI habitat. TerrestriaI arthropods, especiaIIy
Animal Physiology $$
insects, have a tracheaI system which is comparabIe to the highIy deveIoped Iung system. TracheaI
system has two Iunctions: (1) it brings air into the body; and (2) distributes it to the ceIIs. Hence, no
other transport system is necessary.
TracheaI tubes are ectodermaI derivatives which deveIop as invaginations oI the body waII and
open to the exterior through spiracIes. In most cases, spiracIes are provided with opening and cIosing
mechanisms controIIed by vaIves. The tracheae have a cuticuIar spiraI, Iorming a Iayer, so that the
tubes can be distended when IuII oI air. However, when the air is drawn out, the chitinous spiraI does
not aIIow the tracheae to coIIapse. Larger tracheae branch into smaIIer anastomosing tracheoIes which
penetrate into the ceIIs oI the body (Fig. 13.2). These tracheoIes are the important physioIogicaI units
oI gaseous exchange.
VentiIation oI the tracheaI system is dependent upon the gaseous diIIusion and is brought about
through the movements oI the body waII. In smaII and Iarge sIuggish insects the oxygen demand is
met adequateIy by the tracheaI ventiIation. However, in Iarge insects which are activeIy running or
FIg. 13.1 Double pumping mechanism illustrating the ventilation of gills in teleost fishes: (a) showing the phase in which
suction pumps are predominant, (c) showing buccal pump forcing water across the gills, (b) and (d) showing
transition phase. Transition phases take about one-tenth of the whole cyele. (After J.D. Jones, Comperative
Physiology of Respiration, Edward Arnold, l972).
Pressure
pump
(c)
(d)
Buccal
cavity
(a)
Suction
pump
Opercular
cavity
(b)
Oral valve Gill resistance
Opercular
valve
Fespiration $%
IIying, the rate oI metaboIism is very high and as such additionaI oxygen demand is met by some
amount oI mechanicaI ventiIation. For this purpose, Iarge air sacs or diIations oI the tracheaI trunks
are present in body cavity (as Iound in honey bees, wasps, etc.) and these carry Iarge air stores.
The respiratory movements in majority oI insects are conIined to the abdomen consisting oI
dorso-ventraI IIattening movements (as in case oI grasshoppers and beetIes). In a Iew cases (as in bees
and IIies), IongitudinaI teIescoping movements oI the abdomen are recognized. The inspiratory and
expiratory movements are controIIed by the spiracIes. SpiracIes have two IunctionaI diIIerences, i.e.
some spiracIes are inspiratory whiIe others are expiratory. In the Iocust, Schistocerca, the thoracic
spiracIes, serve Ior inspiration whiIe the abdominaI spiracIes are Ior expiration. The respiratory
movements are reguIated by impuIses Irom nerve centres. Such respiratory centres Iie either in the
segmentaI gangIia to controI movement oI their own segments or may be in the secondary centres
controIIing movements oI the whoIe insect.
Lungs
In most air-breathing animaIs, the need oI oxygen is greater and cannot be met by cutaneous
respiration. Hence, such animaIs are provided with speciaI respiratory organs having vascuIar
epitheIium caIIed the Iungs. There are many diIIerent Iorms oI Iungs whose eIIiciency depends upon
their structuraI compIexity.
DIFFUSION LUNGS: The simpIest types oI Iungs are Iound in many terrestriaI invertebrates. SmaII
tubuIar Iungs in the Iorm oI book Iungs are Iound in spiders and scorpions. Gastropods have simpIe
puImonary structures Ior gaseous exchange. These Iungs oI terrestriaI invertebrates are devoid oI a
FIg. 13.2 Structure of tracheae in insects.
Animal Physiology $&
ventiIating system and the gaseous exchange depends onIy on diIIusion. ThereIore such Iungs are
reIerred to as diffusion lungs.
VENTILATION LUNGS: TerrestriaI vertebrates have deveIoped air-breathing structures which
perIorm reguIar coordinated movements Ior ventiIation. The gaseous exchange mechanisms ensure
transport oI oxygen Irom Iungs by circuIating bIood. VentiIation Iungs permit greater exchange oI
oxygen to IaciIitate higher metaboIic rate.
Amphibians were, perhaps, the Iirst terrestriaI vertebrates to successIuIIy utiIize their Iungs to
suppIement cutaneous and buccaI respiration. The Iungs oI amphibia are quite simpIe with reIativeIy
Iess eIasticity and aIveoIar spaces as compared to birds and mammaIs. VentiIation oI Iungs is due to a
buccaI Iorce-pump aided by sternohyoid muscIes.
The avian Iung is a more speciaIized organ. Three important Ieatures oI this speciaIization are
enIargement oI the respiratory epitheIium, eIIicient mechanisms Ior ventiIation, and an eIIicient
circuIation. The avian Iung has attained a great deaI oI structuraI compIexity. Instead oI aIveoIi, its
Iung is provided with air capiIIaries so that atmospheric air can eIIicientIy circuIate through the Iung.
The Iungs Iead to non-respiratory structures caIIed the air sacs which act as reservoirs oI air. These air
sacs provide buoyancy to these IIying animaIs.
The air capiIIaries have their waIIs with diameters oI about 10 and these are separated Irom the
puImonary capiIIaries by thin endotheIiaI waII. It is in these air capiIIaries that the gas exchange takes
pIace. VentiIation oI the Iungs and air sacs is due to a costaI suction-pump principIe. During
inspiration, enIargement oI Iungs and air sacs takes pIace. Expiration is due to reIaxation oI the
externaI intercostaIs and Iowering oI the sternum. When the birds are in IIight, ventiIation is IargeIy
achieved by raising and Iowering oI the sternum. The Iungs combined with the air sacs aIIow more
uptake oI oxygen with reIativeIy Iess area Ior gas exchange.
MAMMALIAN LUNGS: The Iung structure in mammaIs shows enormous deveIopment oI air
passages, owing to which an eIIicient exchange oI gases is possibIe. In man, the right Iung has three
Iobes whereas the IeIt one has onIy two. The Iungs are pIaced in the thoracic cavity and covered by a
doubIe IoId oI coeIomic epitheIium caIIed pluera. This divides into two bronchi, each oI which
Iurther subdivides into the tissue oI the Iung into bronchioIes. The bronchioIes are minute air
capiIIaries ending into diIated vesicIes caIIed inIundibuIa, each oI which has its inner surIace thrown
into a number oI rounded pockets caIIed aIveoIi or air sacs. The bIood capiIIaries oI Iungs Iie just
outside the thin epitheIium oI the aIveoIi. Exchange oI gases between the air and bIood takes pIace in
the aIveoIi.
33.E MECHANlSM DF BREATHlNG
The movement oI air into and out oI Iungs is accompIished by expansion and contraction oI the
thoracic cavity. During the act oI inspiration diameter oI the thoracic cavity increases so that the
voIume oI the pIeuraI cavity is increased by about 500 cubic centimeter. Owing to this, Iungs and the
contained air spaces tend to increase correspondingIy in voIume, resuIting in the reduction oI pressure
inside the Iungs. The pressure oI the atmosphere which is now higher exerts its pressure and air
rushes in through the nostriIs in order to restore the pressure. This constitutes inspiration. During
Fespiration $'
expiration the thoracic waIIs contract and pressure is exerted upon the inIIated Iungs Iorcing the air to
move out the way it entered. In the inspiration oI mammaIs, the air is sucked in.
The expansion oI the thoracic cavity is caused by movements oI ribs, sternum, intercostaI muscIes
and the diaphragm. When the externaI intercostaIs contract, each rib is puIIed anteriorwards so that
the sternum is aIso pushed ventraIwards (Fig. 13.3). SimuItaneousIy the diaphragm is aIso stretched,
resuIting in expansion oI thoracic cavity. The contraction oI thoracic cavity is brought about by the
movements oI the same structure in opposite manner. The internaI intercostaI muscIes contract puIIing
the ribs back to their originaI position. At the same time the diaphragm aIso attains its originaI arch
shaped position exerting pressure on Iungs to Iorce out the air.
Air in Lungs
During normaI respiration, a man takes and discharges about 500 cc oI air with each act oI inspiration
and expiration. This is known as tidal air. The Iungs are never deIIated aIter expiration and about
2,500 cc oI air is IeIt behind which is known as stationary air. In deep breathing about 1,500 cc oI
suppIementaI air is inhaIed making the totaI capacity oI the Iungs 4,500 cc. About 3,500 cc are
expeIIed out during expiration. This exhaIed air constitutes 500 cc as the tidaI air, 1,500 cc as the
suppIementaI air and remaining 1,500 cc as complemental, about 1,000 cc oI air stiII remains in the
Iungs which cannot be expeIIed. This is caIIed residual air. The aIveoIi contain Iess oxygen and more
CO
2
. This is because oxygen is exchanged Ior CO
2
in the aIveoIi. TabIe 13.1 gives an anaIysis oI
inspired and expired air.
FIg. 13.3 Respiratory structures involved in breathing mechanism of man.
Expiration
Internal
intercostal muscle
External
intercostal muscle
Sternum
Sternum
Rib
Inspiration
Vertebral column
Animal Physiology %
TabIe 13.1 Analysis of Inspired and Expired Air (in Nan)
Gas 1nsp¡røø a¡r Exp¡røø a¡r AIvøøIar a¡r
Oxygen 20.96 l6.+0 l+.00
Nitrogen 79.00 79.50 80.50
Carbon dioxide 0.0+ +.l0 5.50
Transport of Dxygen
The atmospheric air contains 20.9 per cent oxygen, 0.04 per cent carbon dioxide, and 79 per cent
nitrogen. There are trace amounts oI other gases which, however, are oI no physioIogicaI importance.
The expired air contains about 15 per cent Iess oxygen and about 5 per cent more carbon dioxide as
compared to the inspired air. The percentage oI nitrogen, however, remains unaItered. About one-
Iourth oI the inspired oxygen passes into bIood and is utiIized Ior respiratory purposes. DiIIusion oI
oxygen in water and body IIuids oI the organism takes pIace at a sIow rate.
In aImost aII vertebrates and many invertebrates, the transport oI oxygen is achieved by coIoured
proteins caIIed respiratory pigments. Respiratory pigments have the capacity to IooseIy combine with
oxygen when exposed to high pressures, and reIeasing the gas easiIy at Iower pressures. The pressures
or tensions in the tissues are aIways Iess so that gas can be readiIy reIeased Ior bioIogicaI oxidations.
33.3 RESPlRATDRY PlGMENTS
Respiratory pigments diIIer in their chemicaI constitution in diIIerent groups oI animaIs and even in
the same phyIum, there may be severaI types oI pigments. These pigments incIude the cytochromes,
the IIavoproteins and other coIoured moIecuIes oI proteins caIIed chromoproteins. Here we shaII
restrict our attention to those chromoproteins, which are important in the transport oI gases and impart
a deIinite coIour to the body IIuids. These are circuIating pigments which mediate transIer oI oxygen
at the extraceIIuIar and intraceIIuIar IeveIs. Four important cIasses oI such respiratory pigments have
been recognized: the haemogIobins, the haemocyanins, the chIorocruorins, and the haemerythrins. AII
oI these have a metaIIic atom in their constitution. The distribution oI these pigments and their oxygen
carrying capacity has been given in TabIe 13.2.
HaemogIobin
HaemogIobin is the most characteristic respiratory pigment Iound in bIood oI the vertebrates. This
pigment is Iound in the erythrocytes. Besides, haemogIobins are Iound generaIIy in muscIe ceIIs oI
birds and mammaIs, and occasionaIIy in teIeosts and eIasmobranchs. The chemicaI composition and
structure oI haemogIobin has been described in Chaper 9. HaemogIobin is aIso Iound IreeIy
distributed in the pIasma oI many anneIids and moIIuscs (1erebella, Planorbis).
HaemogIobin has the abiIity to combine reversibIy with oxygen:
Hb ¹ O
2
HbO
2
(oxyhaemogIobin)
Fespiration %
The oxygen combines IooseIy with haemogIobin and its reIease is dependent on the oxygen
tension in the medium surrounding the haemogIobin. Such reIationships have been described in more
detaiI in Section 13.4.
HAEMOGLOBIN FUNCTION IN INVERTEBRATES: The Iunction oI haemogIobin in invertebrates is
rather interesting. It has been Iound that in some invertebrates, haemogIobin transports oxygen at
atmospheric pressures, whereas in others at Iow pressures. Yet in some invertebrates, haemogIobin
stores oxygen during conditions oI hypoxia. Thus the property oI haemogIobin may vary between
groups and sometimes between species. In Fig. 13.4, the oxygen dissociation curves oI three animaIs
have been given where the respiratory pigment is haemogIobin. The oxygen dissociation curves oI
Arenicola, man and pigeon show that the haemogIobins oI the three animaIs become saturated at
diIIerent oxygen tensions, thereby showing diIIerent properties oI the three haemogIobins.
CHLOROCRUORIN: ChIorocruorin is aIso a metaIIo-porphyrin which is cIoseIy reIated to
haemogIobin and cytochromes. This pigment is Iound in the pIasma onIy and its distribution is
restricted to Iour IamiIies oI poIychaeta (AnneIida); SabeIIidae, SerpuIidae, ChIorhaemidae and
Ampheretidae. The oxygen combining capacity oI chIorocruorin is as great as that oI haemogIobin.
HAEMOCYANIN: Haemocyanin pigment is oI wide occurrence and is a non-haeme respiratory
pigment. It is dispersed in the pIasma soIution and has never been Iound in the corpuscIes. The
pigment is Iound in many moIIuscs and arthropods. The metaIIic atom present in the haemocyanin
moIecuIe is copper which gives it a characteristic bIue coIour.
HAEMERYTHRIN: Haemerythrin occurs onIy in a Iew groups oI animaIs and is known oI to be
restricted to Magelona (a poIychaete), most sipuncuIids, Priapulus and Halicryptus (priapuIids),
Lingula and Glottidia (brachiopods). These are aII unreIated phyIa and bear no phyIogenetic
TabIe 13.2 Distribution and Oxygen Carrying capacities of Respiratory Pigments (Adapted from Prosser
and Brown, l96l)
P¡gmønI CøIøur MøIaII¡¿ aIøms S¡Iø An¡maI Ox)gøn vøIumø
pør¿ønI
Haemoglobin Red Fe
++
Corpuscles Nammals l5-30
Bird 20-25
Reptiles 7-l2
Amphibians 3-l0
Fishes +-20
Plasma Annelids l-l0
Nolluscs l-6
Chlorocruorin Creen Fe
++
Plasma Annelids: *
Polychaetes 9
Haemocyanin Blue Cu
++
Plasma Nolluscs:
Castropods l-3
Cephalopods 3-5
Crustaceans l-+
Haemerythrin Red Fe
++
Corpuscles Annelids 2
Animal Physiology %
reIationships. The pigment circuIates in the corpuscIes and contains iron. It has been Iound that three
atoms oI iron are necessary to combine with one moIecuIe oI oxygen. AIthough haemerythrin is
considered a cIose reIative oI haemocyanin, its oxygen transport capacity is very Iow. ProbabIy, it is a
storage pigment.
33.4 PRDPERTlES DF RESPlRATDRY PlGMENTS
Dxygen Transport by HaemogIobin
In aImost aII vertebrates, haemogIobin oI the bIood is responsibIe Ior the transport oI oxygen.
HaemogIobin is contained in the red bIood corpuscIes which are IuIIy packed with this pigment. The
oxygen aIIinity oI the pigment is quite high and is governed by certain gas Iaws. It wouId be
appropriate here to discuss brieIIy the Iaws governing absorption oI gases by Iiquids.
II the pressure oI a gas in a voIume oI water is kept constant, soIubiIity oI the gas is Iowered as
temperature is increased. Since the temperature oI the body remains constant, other Iactors wouId
modiIy the soIubiIity oI gases. The soIubiIity oI a gas in water depends directIy on its pressure,
temperature remaining constant. II the gas is mixed with other gases, its soIubiIity wiII depend upon
its partiaI pressure. The moment an equiIibrium is estabIished between gas and water, the number oI
gas moIecuIes Ieaving it equaIs the number oI gas moIecuIes entering. The property oI a gas to Ieave
the Iiquid is caIIed its tension which is measured by Iinding the pressure or partiaI pressure (in case oI
mixed gases) oI the gas in the atmosphere.
FIg. 13.4 Oxygen equilibrium curves of (a) Arenicola, (b) man, and (c) the pigeon (modified from Comparative Animal
Physiology, Prosser and Brown, l96l, 2nd ed.).
100
80
60
40
20
0
0 10 20 30 40 50 60 70 80
(a)
(b)
%
S
a
t
u
r
a
t
i
o
n
o
f
p
i
g
m
e
n
t
Oxygen tension (mm Hq)
Fespiration %!
The partiaI pressure oI a gas (P) in a mixture oI gases is caIcuIated by muItipIying the pressure oI
the mixture by the percentage oI the gas in it. ThereIore, the partiaI pressure oI oxygen (PO
2
) in
atmosphere at 760 mm Hg is 21/100 760 ÷ 160 mm Hg, where 21 is the percentage oI oxygen in air.
At 38°C, 100 mI oI water can hoId 2.3 mI oI oxygen, 51 mI oI carbon dioxide and 1.2 mI oI nitrogen
when the pressure oI each gas is 760 mm Hg. The approximate voIume oI gases in 100 mI oI bIood
and their tensions are given in TabIe 13.3.
TabIe 13.3 volume And Tension Of Cases In Human Blood
Ox)gøn CarDøn ø¡øx¡øø
mI,JUU mI mI,IUU mI
ø/ Tøns¡øn ø/ Tøns¡øn
DIøøø (mm Hg} DIøøø (mm Hg}
Arterial blood 20 l00 50 +0
venous blood l5 +0 5+ +6
Tissues - 30 - 50
The oxygen-carrying capactiy oI bIood shows marked variations in diIIerent groups oI animaIs. It
has been seen that greater amounts oI oxygen can be heId by bIood oI mammaIs and birds as
compared to coId bIooded vertebrates. The amount oI oxygen dissoIved in bIood, i.e. its percentage
saturation is dependent on the partiaI pressure oI oxygen (PO
2
) in the atmosphere. At high tensions,
the haemogIobin absorbs oxygen, and at Iow tensions oxygen is dissociated Irom the haemogIobin.
The reIationship between tension and percentage saturation oI the bIood is shown in Fig. 13.5
which shows that the reIationship is not a Iinear one. The graph shows sigmoid shaped curves
ensuring the amount oI oxygen given up Ior smaII changes in tension is very great. These curves are
caIIed oxygen equilibrium curves or oxygen dissociation curves. The curves are drawn by determining
the amount oI oxygen which combines with bIood exposed to oxygen at various pressures. At
equiIibrium the amount oI gas combined with the bIood is expressed as the per cent saturation oI
oxygen. From the sigmoid curve, it is cIear that at high tensions oI oxygen Iound in Iungs, aImost
compIete saturation occurs at about 95/100 mm Hg. In the tissues, where the oxygen tension is as Iow
as 40 mm Hg, oxygen is given up. This shows Ioading oI oxygen at high pressures and rapid
unIoading oI oxygen at Iow tensions in the tissues so that the oxygen is made avaiIabIe to the ceIIs.
33.5 FACTDRS AFFECTlNG DXYGEN DlSSDClATlDN
A number oI Iactors inIIuence the dissociation oI oxygen Irom haemogIobin which are brieIIy stated
here.
TEMPERATURE: HaemogIobin saturation is decreased by a rise in temperature. At a temperature oI
38°C and at an oxygen tension oI 100 mm Hg, 93 per cent haemogIobin saturation is obtained,
whereas at 25°C and at the same oxygen tension about 98 per cent saturation is possibIe. It is
interesting to know that the per cent saturation oI haemogIobin at 10 mm Hg tension and at 25°C is
about 88 per cent. whereas at 37°C it is about 56 per cent. The interesting Iact demonstrates that in
warm-bIooded animaIs oxygen dissociates Irom haemogIobin more eIIicientIy and rapidIy than in the
coId-bIooded animaIs.
Animal Physiology %"
ELECTROLYTES: It has been Iound that oxyhaemogIobin reIeases oxygen more readiIy at Iow
tensions in the presence oI eIectroIytes (Fig. 13.6). This has some signiIicance when the bIood passes
through systemic capiIIaries where the oxygen tension is very Iow, the saIts present in the bIood
inIIuence the reIease oI oxygen.
HYDROGEN-ION CONCENTRATION: Dissociation oI oxyhaemogIobin is Iavoured by increase in the
pH. The presence oI carbon dioxide in the bIood increases acidity. Fig. 13.7 shows that increase oI
carbon dioxide tension enhances the reIease oI oxygen Irom oxyhaemogIobin. Carbon dioxide
tensions shiIt the sIope oI the oxyhaemogIobin dissociation curve to the right side and this
phenomenon is discussed in the IoIIowing paragraph.
The Bohr Effect
It has been noted that an increase in temperature and the hydrogen-ion concentration causes a shiIt oI
the oxygen dissociation curve oI haemogIobin to the right. Thus the oxygen binding capacity oI the
haemogIobin is Iowered. Variations in the pressure oI CO
2
(PCO
2
) aIters the pH, thus aIIecting the
oxygen aIIinity oI the haemogIobin. This is caIIed Bohr effect. The Bohr eIIect may be normaI or
negative depending on the rise or IaII in the pH. When enhanced tissue activity takes pIace, as in
muscuIar contraction, CO
2
and Iactic acid are produced which Iower the pH. In Fig. 13.7, increasing
pressures oI CO
2
upon oxygen dissociation curves oI haemogIobin at constant temperature 37°C has
been shown. On the contrary haemocyanins Irom many gastropod moIIuscs show either a reverse
Bohr eIIect or no eIIect. In many Iishes, which show the Bohr eIIect, increased PCO
2
(acidity) exerts
a secondary eIIect on the properties oI haemogIobin. This eIIect is termed root effect in which
FIg. 13.5 Relationship between oxygen tension and percentage saturation of blood.
60
40
80
100
20
0
0 20 40 60 80 100 120 140
P
C
O
=
m
m
H
g
2
40
80
%
S
a
t
u
r
a
t
i
o
n
o
f
h
a
e
m
o
g
l
o
b
i
n
pO
2
Fespiration %#
FIg. 13.6 Oxygen dissociation curves in the presence of electrolytes.
FIg. 13.7 Effect of carbon dioxide pressure (PCO
2
) on oxygen dissociation curves of haemoglobin at 37ºC.
100
80
60
40
20
0
0 20 40 60 80 100
O tension (mm Hg)
2
(a) Curve in absence of electrolytes (b) Curve in presence of electrolytes
%
S
a
t
u
r
a
t
i
o
n
o
f
h
a
e
m
o
g
l
o
b
i
n
w
i
t
h
O
2
a
b
100
80
60
40
20
20
0
0 40 60 80 100
O
m
p
C
O
2
2
0
C
O
2
4
0
P
C
O
2
9
0
P
C
O
2
%
S
a
t
u
r
a
t
i
o
n
o
f
H
a
e
m
o
g
l
o
b
i
n
Oxygen tension (mm Hg)
Animal Physiology %$
haemogIobin cannot be saturated with O
2
at any PO
2
. This means that at Iower pH vaIues Iess O
2
is
carried per unit voIume oI bIood than at higher pH vaIues.
33.8 TRANSPDRT DF CARBDN DlDXlDE
BIood pigments, besides transport oI oxygen, aIso transport carbon dioxide either directIy or in the
Iorm oI buIIers. In a number oI cases, bIood pigments aIso serve to maintain the osmotic pressure oI
bIood coIIoids. SoIubiIity oI CO
2
in water is Iar greater than the oxygen. However, the amount oI CO
2
transported in this way is not adequate Ior most animaIs. GeneraIIy, about one-tenth oI the
requirements oI CO
2
in a mammaI can be met with in this way. Most carbon dioxide is carried as
sodium bicarbonate, though about one-third oI totaI CO
2
is transported in dissoIved condition in the
bIood (Fig. 13.8). In this way, CO
2
is combined with amino groups oI the haemogIobin moIecuIes,
(HHbCO
2
).
FIg. 13.S Diagram to explain chloride shift (A - protein, Hb - haemoglobin).
Carbon dioxide is carried by bIood both in the ceIIs and the pIasma. Large quantities oI carbon
dioxide are taken up by bIood and in spite oI this the pH oI bIood remains aImost constant varying
within very narrow Iimits. The human arteriaI bIood has a pH 7.35 and it may change to 7.32 or 7.34
as it becomes venous. Hence bIood has a remarkabIe seII-buIIering capacity.
Since Iarge quantities oI CO
2
can be heId by the bIood, it is necessary that CO
2
must exist in
other Iorms besides gaseous state. These are: (a) in the Iorm oI carbamino compounds; (b) smaII
amounts oI carbonic acid; (c) in the Iorm oI bicarbonates oI sodium or potassium.
CARBAMINO COMPOUNDS: In haemogIobin soIutions, about 20 percent oI the totaI bIood CO
2
Iorms Iinks with amino groups in the protein portion oI the haemogIobin moIecuIes Iorming
carbamino compounds.
Red cell
Hb

H
+
HCO
3

H
+
Hb
HHb CO
2
CO
2
Carbamino
reaction
H CO
3 2
CO
2
H O
2
Carbonic
anhydrase
H CO
3 2
H O
2
CO
2
H
+
HCO
3

A
HA NaHCO
3
Na
+
Slow reaction
NaHCO
3
HCO Na
3
+
Cl

CO
2
CO
2
Tissues
Plasma
Fespiration %%
The Iormation oI carbamino compounds is very rapid.
CARBONIC ACID: The amount oI CO
2
physicaIIy dissoIved in the bIood is not very Iarge. When
CO
2
reacts with water carbonic acid is Iormed in the presence oI carbonic anhydrasea zinc
containing enzyme. Carbonic anhydrase is present in erythrocytes but not in the pIasma.
The reaction is reversibIe and can be shown as:
2H
2
O ¹ 2CO
2

carbonic
anhydrase
H
2
CO
3
¹ H
¹
¹ HCO
3

It takes pIace sIowIy in the absence oI the enzyme and moves in either direction, but when CO
2
enters the capiIIaries, cataIytic action oI enzyme hastens the reaction, thereby Iavouring more CO
2
to
enter the bIood corpuscIes.
FORMATION OF BICARBONATES: CO
2
tends to accumuIate in the bIood in the Iorm oI carbonic acid,
but very IittIe CO
2
can be transported in this way since the presence oI carbonic acid has a
unIavourabIe eIIect on the pH. Any major shiIt in the bIood pH wouId be harmIuI. ThereIore most oI
the carbonic acid is converted into bicarbonate compounds oI Na
¹
, and K
¹
ion needed to Iorm the
bicarbonate comes Irom the NaCI oI the bIood, and K
¹
comes Irom the haemogIobin itseII, since it is
a potassium saIt. The reaction wouId take pIace in the IoIIowing manner:
KHb ¹ H
2
CO
3
KHCO
3
¹ HHb
NaCI ¹ H
2
CO
3
NaHCO
3
¹ HCI
33.7 BUFFER SYSTEMS DF BLDDD
HaemogIobin Effect
HaemogIobin has remarkabIe buIIering capacity. The carbonic acid and HCI are both transported in
the erythrocytes without producing an acidic eIIect. How couId this be achieved? The behaviour oI
haemogIobin and oxyhaemogIobin is responsibIe Ior this curious phenomena. HaemogIobin occurs as
a potassium saIt and thereIore K
¹
ions are abundantIy present in it. This protein compound reacts with
acids Iike HCI and H
2
CO
3
and gets neutraIized. Thus haemogIobin and oxyhaemogIobin react to Iorm
neutraI KCI and aIkaIine NaHCO
3
and haemogIobin and oxyhaemogIobin are set Iree. H
¹
ions so
Iiberated combine with Iree proteins which act as buIIers within the corpuscIes. These reactions are
iIIustrated in Fig. 13.9.
The buIIer action transIorms oxyhaemogIobin to haemogIobin which is weakIy acidic. The
buIIering eIIect oI pIasma proteins has immense importance since they reIease cations Ior the
transport oI at Ieast 10 percent oI the totaI CO
2
.
The phosphates present in the erythrocytes aIso exert some buIIer action and account Ior about 25
per cent oI the totaI CO
2
carried. However, the buIIering roIe oI haemogIobin and oxyhaemogIobin
N
H
H
Hb CO
2
+ N
H
COO

Hb + H
+
Animal Physiology %&
has a major share in the transport oI CO
2
and accounts Ior about 60 per cent oI its transIer. Under Iow
oxygen tension in the tissues, reduction oI oxyhaemogIobin takes pIace by giving oII O
2
to the tissues.
Thus, reduced haemogIobin is Iormed. At this stage CO
2
oI the tissues enters the bIood Iorming
H
2
CO
3
. This H
2
CO
3
dissociates into H
¹
and HCO
3

. H
¹
ions are accepted by reduced haemogIobin
Iorming HHb (acid-reduced haemogIobin). At this point, there is no signiIicant change in the pH.
However, when the bIood goes back to the Iungs, these H
¹
ions are reIeased owing to the Iormation oI
oxyhaemogIobin which is a stronger acid. H
¹
ions are again reIeased which are quickIy neutraIized by
HCO
3

. This reaction is oI utmost importance in the Iiberation oI CO
2
in the Iungs.
ChIoride Shift
About 85 per cent oI the CO
2
transport capacity resides in the red bIood ceIIs, about 60 per cent
contributed by the haemogIobin and about 25 per cent by the red bIood ceII phosphates. This wouId
mean that the buIIering capacity oI the whoIe bIood shouId be Iar greater than the pIasma aIone.
When bIood is Ioaded with CO
2
, the bicarbonate ions are present in Iarge quantities in the red
bIood ceIIs. These HCO
3

ions Irom the red ceIIs diIIuse through the capiIIaries into the pIasma and
CI

ions enter into the red ceII to maintain eIectricaI neutraIity. This phenomenon is caIIed `chloride
shift¨ or Hamburger phenomenon. We shaII see here how this is achieved.
The movement oI the ions across the membrane oI the red ceIIs takes pIace by Donnan
equiIibrium. The membrane is impermeabIe to protein ions, and cations Iike K
¹
and Na
¹
, whereas
anions Iike CI

and HCO

3
can diIIuse across the membrane. The movement oI the anions take pIace
in such a way that equaI distribution oI CI

and HCO

3
ions is achieved with respect to inside and
outside the ceII membrane. The shiIt takes pIace rapidIy and is eIIected within a second.
The haemogIobin, Iike aII other proteins, is negativeIy charged. The negativeIy charged
haemogIobin combines with H
¹
ions Iormed due to ionization oI H
2
CO
3
giving rise to haemogIobinic
acid (HHb).
H
2
CO
3
H
¹
¹ HCO

3
H
¹
¹ Hb

HHb
Thus HCO

3
ions accumuIate in the red ceIIs and tend to diIIuse away into the pIasma. For every
bicarbonate ion that comes out oI the red ceIIs, one CI

ion moves into the red ceII Irom the pIasma to
baIance the eIectricaI neutraIity. The chIoride shiIt has been iIIustrated in Fig. 13.8.
Acid-base BaIance
It has been noted above that bIood has a remarkabIe buIIering capacity, and as such a proper baIance
in the ratio oI H
¹
and OH

ions in bIood is maintained (Fig. 13.9). This is known as the acid-base
balance. It has been seen that the onIy Iree acid in the bIood is the carbonic acid (H
2
CO
3
) which is
Iormed by the union oI CO
2
and H
2
O. Besides this, the onIy aIkaIi present in the bIood is in the Iorm
oI NaHCO
3
. The standard bicarbonate can be caIcuIated Irom the Henderson-HasseIbaIch equation
which is deIined as HCO

3
ions at a PCO
2
oI 40 mm Hg when the haemogIobin oI the bIood is IuIIy
oxygenated at 38°C. The pH oI the bIood may be determined by the ratio HCO

3
/ H
2
CO
3
.
Fespiration %'
Any change in the pH may be due to aIteration oI HCO

3
ions with H
2
CO
3
being normaI or due to
aIteration in H
2
CO
3
when HCO

3
ions remain normaI. These changes are due to aIteration in H
2
CO
3
concentration or PCO
2
during respiration. The ratio oI these two substances is 20:1 which is
represented by pH 7.4. The pH oI bIood may vary within narrow Iimits, i.e. variations Irom 7.3 to 7.5
may be considered normaI.
Disturbances in the acid-base baIance Iead to speciIic disorders which are not toIerated by the
tissues since they are highIy susceptibIe to such changes. Three departures Irom the normaI condition
have been recognized:
(a) A IaII in pH causes respiratory acidosis, whereas rise in pH causes respiratory aIkaIosis.
(b) Bicarbonate ions are either raised or Iowered.
(c) The carbonic acid content (PCO
2
) oI the bIood may be raised or Iowered.
33.8 AClD-BASE DlSTURBANCES DF RESPlRATDRY DRlGlN
Acidosis
Lungs have a key roIe in acid-base reguIation. Respiratory acidosis is generaIIy caused by deIective
puImonary excretion oI CO
2
Ieading to an increase in the H
2
CO
3
oI bIood. Consequent upon this, a
IaII in the pH oI bIood is recorded. However, iI the HCO

3
and H
2
CO
3
are somehow baIanced, the pH
wouId be normaIIy adjusted. In case the removaI oI CO
2
Irom the Iungs is insuIIicient, return to
normaI condition wiII not be restored. In such circumstances return oI pH towards normaI is
accompIished by the kidneys. The kidneys reabsorb more oI HCO
3
ions and Na
¹
ions and excrete H
¹
ions. Thus in respiratory acidosis CO
2
content oI bIood increases with consequent increase in the
bicarbonate ions. This wouId resuIt in a situation where both carbonic acid and bicarbonates wiII be
higher than normaI. The respiratory acidosis is then 'compensated¨.
FIg. 13.9 Buffering action of haemoglobin: (A) in lungs-higher pH releases CO
2
, and (B) in tissues-lower pH releases
O
2
in tissues.
A
Lungs
(venous circulation)
B
Tissues
(Arterial
circulation)
HHb HHb
HHb
HCO

3
H O
2 CO
2
(Expired air)
HbO

2
O
2
H
+
HbO

2
HbO

2
O
2
H
+
HCO

3
H CO
2 3
H O
2
CO
2
Metabolism
HCO

3
H CO
2 3
Animal Physiology &
Respiratory AIkaIosis
Due to excessive Iosses in the CO
2
content oI bIood, the pH is raised causing aIkaIosis. The rate oI
eIimination oI CO
2
Iar exceeds the rate oI CO
2
production in the tissues so that a IaII in the H
2
CO
3
content oI the arteriaI bIood is noticed. The partiaI pressure (PCO
2
) in the aIveoIar air aIso IaIIs. As a
resuIt oI these disturbances, the acid-base ratio is aItered. Respiratory aIkaIosis occurs due to
overbreathing, either voIuntary or Iorced.
33.8 AClD-BASE DlSTURBANCES DF
NDN-RESPlRATDRY DRlGlN
MetaboIic Acidosis
Disturbances in the acid-base baIance due to changes in the bicarbonate oI bIood are said to be
metaboIic in origin. MetaboIic acidosis is caused by a decrease in the bicarbonate Iraction without any
change in the carbonic acid Iraction. This occurs very commonIy in uncontroIIed diabetes mellitus.
MetaboIic AIkaIosis
MetaboIic aIkaIosis occurs when excess oI bicarbonates accumuIate in the bIood without any change
in the carbonic acid content. In aIkaIosis vomiting may resuIt due to Ioss oI hydrogen ions resuIting
Irom Ioss oI gastric secretions. In pyIoric stenosis (intestinaI obstruction), persistent vomiting resuIts
in rapid Ioss oI eIectroIytes causing aIkaIosis.
TabIe 13.4 Disturbance of
P
H and Acid-Base Ratio of the Blood
Cønø¡I¡øn pH Basø-a¿¡ø Pøsp¡raIør) NørmaI a¿¡ø- Nøn-røsp¡raIør)
raI¡ø ø¡sIurDan¿ø Dasø DaIan¿ø ø¡sIurDan¿ø
Normal 7.+0
20
l
-
2+
l2
-
Acidosis 7.0
8 0
l
2+
3
-
9 6
l2

Alkalosis 7.60
70
l
2+
03+
-
8+
l2
33.30 REGULATDRY PRDCESSES lN RESPlRATlDN
The respiratory movements have to be reguIated to ensure proper suppIy oI oxygen whose
composition varies with composition oI bIood. AII such movements have to be coordinated without
which oxygen suppIy to the tissues and eIimination oI carbon dioxide Irom the tissues cannot be
eIIectiveIy reguIated. A number oI reguIatory processes are at work, some oI which wiII be described
in the IoIIowing paragraphs.
Fespiration &
ChemicaI ReguIation
As shown by HaIdane, O
2
content oI bIood and aIveoIar air is IargeIy responsibIe Ior the reguIation oI
respiration in mammaIs. II oxygen does not reach the bIood, asphyxia occurs. Reduction in the suppIy
oI oxygen to the tissues causes hypoxia, whereas iI the tissues are compIeteIy deprived oI oxygen, the
condition is known as anoxia. The inhaIation oI air containing 5-10 percent CO
2
causes increase in
ventiIation. Respiratory movements are increased and become vioIent. This causes increased eIIort on
part oI the muscIes resuIting in many symptoms Iike vasoconstriction, saIivation, contraction oI
pupiIs, etc.
Effect of Carbon Dioxide
SeveraI mechanisms operate to maintain the composition oI aIveoIar air. SmaII increases in the CO
2
Iraction oI the bIood have a deIinite eIIect on the meduIIary respiratory centres. There is normaIIy
0.03 per cent carbon dioxide present in the inspired air. II the meduIIa is cut oII Irom the sensory
input, and the carbon dioxide content oI the inspired air is raised to 6.5 per cent, meduIIa shows weII
deIined respiratory potentiaIs. The eIIect oI CO
2
on ventiIation is shown in Fig. 13.10. At higher
concentrations ventiIation increases sharpIy. Many individuaIs can toIerate about 8 per cent carbon
dioxide in the inspired air, but higher concentrations produce depression and unconsciousness and
uItimateIy respiratory paraIysis may occur. In mammaIs, breathing is generaIIy increased due to the
action oI CO
2
on chemoreceptors Iocated centraIIy in the meduIIa and peripheraIIy in the carotid and
aortic bodies (See Chapter 10).
FIg. 13.1û Effect of CO
2
on ventilation.
120
100
80
60
40
20
0 20 0 40 60 80 100
b
lo
o
d
NaHC 3
O
Water
P
r
e
s
s
u
r
e
o
f
C
O
p
e
r
1
0
0
v
o
l
u
m
e
s
2
Pressure of CO per (mm Hg)
2
0
Animal Physiology &
Low CO
2
tension oI the bIood causes a decrease in Iung ventiIation and an increase raises
ventiIation. The partiaI pressures oI carbon dioxide express the ventiIation oI Iungs more preciseIy.
The normaI PCO
2
is 40 mm Hg and iI it increases to 60 mm Hg, ventiIation increases at Ieast ten
times. II the tension oI CO
2
is Iowered, such as by voIuntary deep breathing, CO
2
is Iowered in the
bIood, as a resuIt oI which the respiratory centre is temporariIy inhibited. Low CO
2
tension in the
bIood causes acapnia and in this condition the excitabiIity oI the respiratory centre is bIocked causing
cessation in breathing.
Effect of Low Dxygen SuppIy
Oxygen tension in the bIood is the determining Iactor Ior reguIation oI breathing. It depends IargeIy
on the percentage oI O
2
in the atmosphere and upon the atmospheric pressure. At sea-IeveI the
percentage oI oxygen is Iess but the breathing remains normaI. II the oxygen tension is Iurther
Iowered, breathing is stimuIated in order to inhaIe more oxygen into the aIveoIi. A simpIe experiment
can be done to demonstrate this principIe. II a person is subjected to breathe in an air-tight coIIapsibIe
bag through a soda Iime container, the person becomes bIue. The outgoing CO
2
is absorbed by the
soda Iime but renewaI oI oxygen is not possibIe. Thus oxygen Iack causes unconsciousness and even
death.
Effect of Acidity
Carbon dioxide inIIuences the respiratory centre to increase the acidity (H
¹
) oI the ceIIs. Increased
acidity oI the bIood enhances ventiIation, aIthough the pH may not vary extensiveIy. However, it
seems quite IikeIy that to some extent, increase in pH is due to CO
2
tension. According to GeseII
(1939), intravenous injection oI NaHCO
3
wiII increase the CO
2
tension and thus stimuIate respiration.
On the other hand, injection oI Na
2
CO
3
heIp in Iowering CO
2
tension in the tissues making bIood
aIkaIine. This depresses respiration.
NeuraI ControI of Respiration
We have aIready noted that the most important Iactor in the reguIation oI respiration is the carbon
dioxide tension. Carbon dioxide oI bIood stimuIates the respiratory centre whose activity is modiIied
by aIIerent impuIses arriving at the meduIIa. The impuIses originate Irom the receptors in the chest-
waII and inIIuence the vagus nerves, and the nerves Irom the carotid body and the carotid sinus. It is,
however, emphasized that the act oI breathing is quite compIicated and invoIves the movement oI
voIuntary muscIes. The controI oI aII these muscIes is exerted by the respiratory centre in the brain
stem or meduIIa. The voIuntary muscIes contract when they receive impuIses Irom the respiratory
centre. The intercostaI muscIes are suppIied by motor nerves arriving Irom the spinaI cord. The
diaphragm is served with the phrenic nerves which take oII Irom the Iourth and IiIth spinaI nerves.
From the respiratory centre, impuIses arrive at the diaphragm through phrenics. Certain other Iibres
carry impuIses to the externaI-intercostaI muscIes which contract to cause respiration. ReIaxation oI
intercostaIs causes expiration.
The controI oI breathing by respiratory centre has been studied in mammaIs and it is beIieved that
there are three stepwise controIs in the process:
Fespiration &!
(1) pneumotaxic centre; (2) expiratory centre; and (3) inspiratory centre. Respiratory controI
invoIves:
1. Adjustments due to variations in the composition oI environmentaI gases or body IIuids.
2. CentraI nervous system.
3. CentraIIy mediated acts oI respiration.
The meduIIa contains two groups oI neurons that controI inspiratory and expiratory centres in aII
vertebrates (Fig. 13.11). It controIs aII rhythmic respiratory activities and is aIso dependent on the
higher centres. II the meduIIa is sectioned Irom the spinaI cord, aII respiratory activities wiII cease. II
the brain is cut between the meduIIa and the Iower pons, respiratory activity becomes abnormaI
showing the inIIuence oI higher centres.
The pneumotaxic centre is the controIIing centre situated in the craniaI part oI the pons which
controIs activity oI neurones oI the Iower part. The expiratory centre exerts controI over the muscIes
oI expiration. The inspiratory centre is said to be in a constant state oI excitabiIity and it sends
impuIses to inspiratory muscIes, but it aIso sends impuIses to the pneumotaxic centre (Fig. 13.11). The
pneumotaxic centre in turn transmits impuIse to the expiratory centre which wiII aIso send inhibitory
impuIses to the inspiratory centre.
FIg. 13.11 Diagram showing respiratory control centres of the brain and their possible interconnections.
Medulla
(–)
(+)
(–)
(–)
(+)
Higher centre
Pneumotaxic
centre
Apneustic
centre
Inspiratory
muscles
Spinal cord
Expiratory
muscles
Vagus
( ) ´ (–)
Pons
(–) (Excitation)
(+) (Inhibition)
Animal Physiology &"
Chemoreceptors
Certain chemoreceptors sensitive to changes in the partiaI pressures oI oxygen and carbon dioxide
aIso controI the respiratory activities. These are present in the carotid bodies Iocated at the biIurcation
oI internaI and externaI carotids and in the aortic bodies on the dorsaI aorta. II the PO
2
in the bIood
and tissues IaIIs, there is increase in the Irequency oI respiration. Both carotid and aortic bodies
receive a proIuse arteriaI bIood suppIy. They can perceive changes in the PO
2
oI water, especiaIIy in
aquatic vertebrates. Low PO
2
acts as stimuIant oI respiratory activities. In mammaIs a IaII in PO
2
to
50 mm Hg increases the Iiring rate oI chemoreceptors. During asphyxia, when PCO
2
is more and PO
2
Iow, the receptors are activated.
VagaI ControI
There are numerous stretch receptors or inIIation receptors scattered throughout Iungs which respond
to the distension oI Iungs during inspiration. The vagus nerve suppIy to the Iungs has some aIIerent
Iibres which end up in these receptors. During the inspiratory cycIe these receptors are stimuIated and
send impuIses to the expiratory centre through vagus Iibres. This centre than sends inhibitory
impuIses to the inspiratory centre to stop inspiration. This is a reIIex termed Hering-Breuer reflex in
which the vagus centre during inspiration is aIIected indirectIy in the opposite direction by the
impuIses which inhibit respiratory centre. The Iungs get deIIated mechanicaIIy. This, however,
happens in quiet breathing. During Iaboured breathing, sudden coIIapse oI Iungs stimuIates deIIation
receptors which send impuIses to the inspiratory centre causing Iorced respiration. This reIIex is an
important mechanism Ior the controI oI breathing in many animaIs and aIso Ior a short time in the
newborn baby. In aduIt man, it is weak or even absent.
As a resuIt oI metaboIic activities certain waste products are Iormed. The major waste products are
carbon dioxide, water and nitrogenous compounds. These wastes, iI retained in the body, wiII have
harmIuI eIIects. Hence their removaI becomes necessary. RemovaI oI these wastes Irom the tissues oI
the body to the outside is caIIed excretion.
34.3 DRGANS DF EXCRETlDN
The organs or the tissues responsibIe Ior the eIimination oI waste products are caIIed excretory
organs. These organs eIiminate the wastes in the IoIIowing ways:
(i) by eIiminating nitrogenous wastes.
(ii) by adjusting water baIance oI the body.
(iii) by maintaining ionic composition oI the extraceIIuIar IIuids.
Major organs oI the body which heIp in the excretion process are: integument, giIIs, Iiver,
intestine, Iungs and kidneys. In certain Iower animaI groups such as protozoa and poriIera, excretion
oI wastes takes pIace directIy through the ceIIuIar membranes. In such cases, simpIe mechanisms Iike
osmosis and diIIusion may be Iound very eIIective. In certain species, however, excretion is done
through contractiIe vacuoIes as in Amoeba and Paramecium. In higher invertebrates and vertebrates,
deIinite excretory organs are Iound which do the speciaIized job oI excretion. Integument or the skin
heIps in the eIimination oI urea through the sweat gIands. AIong with the urea, certain inorganic saIts
are aIso removed by the skin. The giIIs and the Iungs are heIpIuI in removing gaseous products Iike
carbon dioxide. Liver is one oI the most important gIands in the body oI vertebrates which heIps in
the removaI oI choIesteroI, biIe saIts and excess oI caIcium and iron saIts. These are generaIIy
eIiminated by the intestine aIong with the IaecaI matter. The intestinaI epitheIium aIso excretes some
inorganic saIts which are in excess. Rubidium, potassium, caIcium and magnesium, etc., are excreted
in part through the intestinaI waII. Kidneys are the major excretory organs in aII vertebrate groups and
-N?HAJE
+ 0 ) 2 6 - 4
"
Animal Physiology &$
aIso in some invertebrates which eIiminate urea, excess oI water, saIts and other nitrogenous wastes.
The renaI mechanisms are responsibIe Ior maintaining ionic reguIation or IIuid baIance in majority oI
animaIs.
34.E TYPES DF EXCRETDRY PRDDUCTS
The end-products oI metaboIism IaII under two major categories: (i) carbon dioxide; and (ii)
compounds containing nitrogen. Besides these products, water Iorms an important product which
requires to be eIiminated iI Iound in excess, and aIso it Iorms a vehicIe Ior the transport oI waste
products to the exterior. Here we shaII give our attention mainIy to the production oI nitrogenous
wastes and their eIimination.
Nitrogenous Wastes
In Iiving organisms, nitrogen is never eIiminated in the Iorm oI Iree nitrogen but resuIts in the
Iormation oI nitrogenous end-products. Proteins are the main nitrogen containing compounds which
are metaboIized to Iorm end-products Iike ammonia, urea and uric acid. These end-products are
derived Irom the degradation oI proteins, amino acids, pyrimidines and purines.
Proteins are important dietary constituents needed Ior the buiIding, growth, and repair work oI the
body. Proteins are broken down to smaIIer protein moIecuIes (peptides and dipeptides) upon
hydroIysis. These subunits can be Iurther hydroIyzed to yieId amino acids which are metaboIized to
yieId ammonia and urea as nitrogenous end-products.
NormaIIy, aduIts are said to be in a state oI nitrogen balance when the nitrogen Ioss equaIs to the
nitrogen intake. II the nitrogen baIance is disturbed in an animaI, it experiences a new situation and
tries to adjust itseII to a new nitrogen IeveI. This new IeveI can be achieved by an adjustment between
increase or decrease oI nitrogen excretion. Nitrogen excretion Iosses Irom the body are generaIIy
measured by anaIysis oI the urine and Iaeces.
Ammonia
Ammonia is the chieI breakdown product oI amino acids and is removed by oxidative deamination
process. Deamination chieIIy occurs in the Iiver, but kidney aIso heIps in the process.
Ammonia is a toxic substance, and is constantIy being produced in the tissues by deamination oI
amino acids. It is removed very rapidIy Irom the body by one oI the IoIIowing reactions:
(1) amination oI keto acids.
(2) amidation oI gIutamic acid.
(3) Iormation oI urea in the Iiver.
The rapidity with which ammonia is removed Irom the body ensures a very Iow concentration oI
it in the bIood oI most animaIs. MammaIs cannot withstand ammonia in their bIood in concentrations
more than 0.0001 to 0.0003 mg/100 mI. However, the bIood oI amphibians, reptiIes and Iishes can
withstand a higher concentration oI ammonia (Iess than 0.1/100 mI). Many invertebrates show a
higher toIerance Ior ammonia.
Excretion &%
Urea
Urea is derived Irom organic compounds Iike amino acids and purines, and Iiver is beIieved to be the
chieI organ capabIe oI making it. It is highIy soIubIe in water and Iess toxic than ammonia. The
human bIood normaIIy contains 18 to 38 mg oI urea per 100 mI. However, higher concentrations oI
urea can be toIerated by man which, oI course, indicates uremic condition.
Urea Iormation in Iiver has been studied by Krebs and HanseIeit and has been expIained in a
series oI reactions (Fig. 14.2).
Ornithine, citruIIine and arginine are the three amino acids which participate in the Iormation oI
urea. Liver contains an enzyme arginase which hydroIyzes arginine to ornithine and urea is Iormed as
a byproduct. This is aIso known as Ornithine cycle.
The ornithine cycIe has been studied mostIy in the mammaIian Iiver. In many vertebrates which
Iack arginase, urea is not Iormed and instead uric acid is the chieI end-product oI nitrogen
metaboIism.
The steps invoIved in urea Iormation are as IoIIows:
1. CitruIIine is Iormed by the addition oI CO
2
and ammonia to ornithine. This CO
2
and ammonia
come Irom Carbamyl phosphate.
2. CitruIIine gives rise to arginine in two intermediate steps. In the Iirst step, citruIIine and
aspartate Iorm arginosuccinate in the presence oI ATP and magnesium ion. It is a reversibIe
reaction. In the second step, arginine is Iormed Irom arginosuccinate by spIitting oI Iumarate.
The Iumarate is Iater converted to maIate and oxaIoacetate in citric acid cycIe, and gives rise to
aspartate (Fig. 14.3).
Ammonia is highIy soIubIe in water and in majority oI aquatic animaIs, it is Iost by diIIusion in
the surrounding water. In a number oI animaIs ammonia does not Iorm the excretory waste, but heIps
in maintaining acid-base baIance. In mammaIs, ammonia is obtained chieIIy by deamination oI
gIutamine oI bIood by gIutaminase (Fig. 14.1). This happens in kidney where ammo-nitrogen is
increased, which reacts with hydrogen ions so that more ammonium ions (NH
4
¹
) are secreted. This
aspect oI acid-base baIance wiII be treated in more detaiIs whiIe discussing the roIe oI kidney.
Ammonia is aIso Iormed Irom urea by the action oI urease.
FIg. 14.1 Deamination of glutamine results in the production of NH
3
. Clutamine is synthesized from glutamic acid by
glutamine synthetase.
CH
2
CONH
2
CH
2
CH-CH
2
COOH
CH
2
COOH
CH
2
CH-CH
2
COOH
H O
2
NH
2
H O
2
NH
3
Glutaminase
gln. synthetase
Glutamine Glutamic acid
Mg
+
ATP
++
Animal Physiology &&
FIg. 14.2 Urea formation in the liver by ornithine cycle.
FIg. 14.3 Metabolism of citrulline.
ORNITHINE CYCLE
(CH )
2 3
NH
2
CH.NH
2
COOH
H N
2
C
O
Urea
Arginase
Ornithine
NH
3 CO
2
HN C
NH
2
NH
NH
2
(CH )
2 3
CH.NH
2
COOH
Arginine
H O
2
O C
NH
2
NH
(CH )
2 3
CH.NH
2
COOH
Citrulline
NH
3
H O
2
H O
2
Oxaloacetate
Citrulline Aspartate + Arginosuccinate
ATP AMP + P P
H O
2
Aspartate
Malate
Arginine
Fumarate
H O
2
Arginosuccinase
Mg
++
Excretion &'
Uric Acid
Uric acid is the most important nitrogenous waste in the urine oI birds, reptiIes, some snaiIs and
insects. It is Iormed Irom ammonia and contains Iess hydrogen than any other nitrogenous waste. Uric
acid is Iess toxic and being insoIubIe in water, may be stored or excreted in crystaIIine Iorm.
Formation oI uric acid is an adaptation Ior the conservation oI water since its eIimination requires
very IittIe water.
Uric acid is Iormed in the Iiver oI birds, and in insects it is made in the MaIpighian tubes. Uric
acid is Iormed either as an end-product oI purine metaboIism or as a product oI waste nitrogen
derived Irom the protein. In man, uric acid is the end-product oI purine metaboIism. In subprimate
mammaIs, as aIso in a number oI insects, uric acid is Iurther oxidized to aIIantoin. Thus aIIantoin is
the main end-product oI purine metaboIism in such animaIs (Fig. 14.4). Further breakdown products
oI aIIantoin are derived as IoIIows:
FIg. 14.4 Conversion of uric acid to allantoin.
O
C
C
C
HN
OC
N
H
N
H
H
N
Uric acid
urate oxidase
(urico-oxidase)
C
C
OC
N
H
N
H
NH
COOH
NH
OH
CO
CO
C
N
H
CO
OC
N
H
H
NH
2
H
N
Hydroxyacetylene–diuretine–carboxylic acid
(intermediate)
Urate–oxidase (urico–oxidase)
Excreted by
primates
birds
uricotelic reptiles
insects (other than diptera)
Allanto n i
Mammals (other than primates)
insects (diptera only)
gastropods
CO
Animal Physiology '
Dther Nitrogenous Constituents
The excretory nitrogenous products come Irom nucIeic acid metaboIism. There are purine
compounds, viz. adenine and guanine. Pyrimidine nitrogen is excreted as urea or ammonia. Traces oI
pyrimidine may be excreted as such aIso.
(a) Guanine: Guanine is the main nitrogenous excretory product in some arthropods (spiders), but
is conspicuousIy absent in insects. It is IaintIy soIubIe in water and its mode oI Iormation is
rather unknown.
(b) Xanthine and hypoxanthine: In a number oI insects (Melophagus, Galleria and Pieris, etc.)
xanthine and hypoxanthine are excreted.
(c) 1rimethylamine oxide: Marine teIeost Iishes, which have a diet rich in trimethyIamine, excrete
trimethyIamine oxide.
(d) Hippuric acid and ornithuric acid: Hippuric acid is Iormed in mammaIs. The diet oI mammaIs
contains traces oI benzoic acid which is a toxic substance. This benzoic acid combines with
amino acid gIycine to Iorm a Iess toxic substance hippuric acid. In case oI birds, dietary
benzoic acid combines with ornithine and is excreted in the Iorm oI ornithuric acid.
(e) Creatine and creatinine: Creatine is present in the muscIe, brain and bIood in the Iree state as
weII as combined state (as phosphocreatine). Traces are present in the urine aIso. Three amino
acidsgIycine, arginine, and methionine are invoIved in the synthesis oI creatine. Some oI the
creatine is converted into creatinine which is an anhydride oI creatine. It is Iormed IargeIy in
muscIes and occurs in the bIood and urine in Iree state.
(I) Pterydines: Pterydines are aIso regarded as excretory products which are important pigments
in insects. The synthesis oI pterydines resembIes that oI uric acid. In some insects
(Oncopeltus) traces oI pterydines are excreted in the Iaeces, whereas in butterIIies (Pieris
brassicae) pterydines are deposited in the wings, Iat body, etc. OnIy traces are excreted in the
urine.
Uric acid
Allantoin
Allantoic acid
Urea
+
Glyoxylic acid
Uricase
Allantoinase
Allantoicase
Urease
Ammonia
CO
2
FIg. 14.5 Breakdown of uric acid to ammonia and CO
2
.
Excretion '
34.3 PATTERNS DF EXCRETlDN
We have seen that diverse types oI nitrogenous excretory products are Iormed in animaIs, and more
than one type oI such products may be excreted in an individuaI. The dietary proteins are digested in
the stomach and the intestine by way oI enzymatic hydroIysis which Iiberates amino acids. Most oI
the amino acids are absorbed as such, whiIe some may be Iost by way oI excretion. Thus the Ioss oI
amino acids Irom the body may prove injurious to the heaIth oI the organism. Amino acids are
required as the buiIding bIocks Ior the synthesis oI the bIood and tissue proteins. Due to
transamination reactions nitrogen is Iormed which may be eIiminated in severaI Iorms (urea,
ammonia, etc.) as described above. Based upon the type oI nitrogenous compound excreted, animaIs
have been cIassiIied into severaI broad categories.
AmmonoteIic AnimaIs
AnimaIs in which ammonia is the chieI metaboIic waste are caIIed ammonoteIic. Ammonia is highIy
soIubIe in water and diIIuses rapidIy Irom the body surIace into the surrounding aquatic medium.
Aquatic vertebrates excrete Iarge amounts oI ammonia which is Iormed by hydroIysis oI urea present
in the bIood. The presence oI ammonia in bIood is toxic, hence requires pIenty oI water Ior rapid
eIimination. The amount oI ammonia Iiberated in the body varies with the diet and the species oI the
animaI. Certain protozoans Iike 1etrahymena and Paramecium excrete Iarge quantities oI ammonia.
Sea anemones excrete about 52.7 per cent ammonia in the Iorm oI nitrogenous waste. Echinoderms
and poIychaetes are aIso ammonoteIic. CephaIopods and peIecypods, both Ireshwater as weII as
marine Iorms, excrete Iarge quantities oI ammonia.
The crustaceans excrete ammonia predominantIy aIthough they Iorm amino acid nitrogen aIso. In
aquatic insects aIso ammortoteIic behaviour is Iound. In Sialis Iarvae, Ior exampIe, about 90 per cent
oI nitrogen in the Iorm oI ammonia is Iiberated. Aquatic habitat oI animaIs appears to be an important
requirement Ior ammonoteIic behaviour and may be said to be an aquatic adaptation. An interesting
behaviour in earthworms has been described by BahI (1947). It was experimentaIIy demonstrated that
earthworms kept in naturaI moist surroundings produce more urea than ammonia. However, iI the
earthworms are kept immersed in water they start excreting ammonia (DeIaunay, 1934).
Freshwater Iishes Iet out more ammonia than urea, a major proportion oI which diIIuses out
through the giIIs. The amount oI nitrogen excreted out through urine is comparativeIy Iess.
UreoteIic AnimaIs
UreoteIic animaIs excrete most oI their nitrogen in the Iorm oI urea. It is the predominant organic
substance present in the urine oI animaIs. The probIem oI water conservation in aduIt mammaIs has
necessitated reabsorption oI water in the kidney tubuIes, thus excreting urea in a concentrated Iorm.
In desert animaIs, Iow water intake has resuIted in active tubuIar secretion oI urea. In ruminants, urea
excretion is greatIy reduced and is retained in the rumen which acts as a protein source. It has been
suggested that Iow protein diet Ieads to a marked decrease in urea output, whereas a high protein diet
increases urea production.
Animal Physiology '
Amphibians are predominantIy ureoteIic, as aIso the eIasmobranch Iishes. The synthesis oI urea
in Irogs takes pIace in the Iiver, and in eIasmobranchs aII tissues except brain and bIood are capabIe oI
synthesizing it by the same cycIe as occurring in mammaIs.
UricoteIic AnimaIs
TerrestriaI animaIs Iike insects, Iizards, snakes and birds excrete their nitrogen in the Iorm oI uric
acid. As aIready described, uric acid is Iormed by deamination and oxidation oI purine bases (guanine
and adenine). Uric acid production is aIso reIated to the probIem oI water conservation in these
animaIs.
In insects uric acid is the most important nitrogenous constituent oI urine. When pIenty oI water
is avaiIabIe to insects, uric acid remains in soIution in the MaIpighian tubuIes. However, during
scarcity oI water, uric acid crystaIIizes in the Iorm oI crystaIIine spheres. In Rhodnius, the urine is
dried and consists oI about 64-84 percent oI uric acid (Brown, 1937). In Iizards, snakes and birds, the
urine is in the Iorm oI a soIid or a semi-soIid mass and contains Iarge quantities oI uric acid.
GuanoteIic AnimaIs
In some arthropods such as spiders, guanine is a predominant excretory product eIaborated by the
MaIpighian tubuIes and cIoacaI sacs. The Iormation oI guanine Irom protein nitrogen is stiII not
adequateIy known.
TrimethyIamine Dxide
Marine teIeosts excrete trimethyIamine oxide as the major nitrogenous product which is soIubIe in
water and nontoxic in nature. It is, however, absent in marine eIasmobranchs. Marine teIeosts are
Iaced with the probIem oI maintaining osmotic baIance by retaining water in the body which is aided
by trimethyIamine oxide. This compound is present in smaII quantities in the muscIe, and bIood oI the
marine Iish which diIIuses out through the membrane. This compound has a IouI smeII and is
probabIy derived Irom the breakdown products oI Iipoproteins. ConsiderabIe quantities oI
trimethyIamine oxide are Iormed in octopus, squids, crabs and barnacIes. It occurs in traces in the
urine oI certain animaIs Iike echinoderms, oysters, gastropods and tunicates. Its presence in marine
teIeosts is, however, reIated to the maintenance oI concentration in the body. It has been suggested
that this substance is not produced endogenousIy, and rather comes Irom the Iood oI the Iish.
TabIe 14.1 Percentage of Nitrogen Products Excreted in Different Forms
An¡maI NH
5
Urøa Ur¡¿ a¿¡ø Am¡nøa¿¡ø Pur¡nø OInørs
Annelids
S¡pun¿uIus 50 9.7 0 l6.6 +.l l9.+
LumDr¡¿us (fed) 72 5 l.+ - - l6 undetermined
PnørøI¡ma +2 50 0 0.6 - Creatine 7.8
Echinoderms
AsIør¡as 39.3 ll.7 trace 23.8 3.6-l0 l6-26
CønIø.
Excretion '!
Molluscs
Søp¡a 67 l.7 2.l 7.8 +.9
L¡mnaøa +2 l+ 5 - 39
(F.W., summer)
Crustaceans
Car¿¡nus 68 3 0.7 8.7 3.2
AsIa¿us 60 ll 0.8 l0.l +.+
Insects
Pønøn¡us (l day
post feeding) 0 trace 90.92 0 - + creatine
Aøøøs aøg)pI¡ 6.+ ll.9 +7.3 +.+ - l9
CuIøx p¡pøns l0 7.9 +6.9 5.5 - 20
Fish
C)pr¡nus 60 6.2 0.2 6.5 - 22
Tørpøøø l.7 85.3 - l.7 -
Amphibians
Bu/ø (Iarva} 80 - - - - -
Bu/ø (adult) l5 - - - - -
Birds
Hen 3.+ l0 87 - - -
Mammals
Dog 2.7 88 0.+ - - Allantoin 3.6
Man +.8 86.9 0.65 - - Creatine 3.6
undetermined +.0
*Based on Prosser and Brown, CømparaI¡vø An¡maI Pn)s¡øIøg), 2nd ed. (l96l).
34.4 CHANGES lN NlTRDGEN EXCRETlDN WlTH LlFE CYCLE
PrincipaI wastes come Irom the metaboIism oI purines, pyrimidines and amino acids. It is a known
Iact that the production oI nitrogenous wastes may vary during the deveIopment and aduIt IiIe;
variations may be due to environment and diet aIso. In amphibians, Ior exampIe, urea is a
predominant waste in the aduIts, whereas IarvaI amphibians are ammonoteIic. EnvironmentaI
inIIuence is perhaps more important in shiIting the production oI nitrogenous substances. II animaIs
producing ammonia are transIerred to a medium containing more saIt, their capacity oI urea
production is enhanced. Higher concentrations oI urea are heIpIuI in maintaining osmoreguIatory
Iunctions.
Embryonic history oI animaIs reveaIs that the patterns oI metaboIism change with the
diIIerentiation oI organ systems. The metaboIic machinery oI the individuaI is geared to suit the
individuaI to its environment. In case oI the tadpoIe oI Bufo, 80 per cent oI nitrogen is excreted as
ammonia which graduaIIy decIines to 15 per cent untiI the aduIt stage is reached. Needham has
proposed existence oI recapituIation in patterns oI nitrogen excretion on the basis oI excretory pattern
in the chick. In a three-day oId chick embryo, ammonia is the chieI excretory product. The percentage
oI ammonia graduaIIy decIines. On the IiIth day, ammonia decIines considerabIy and the percentage
CønIø.
Animal Physiology '"
oI urea increases to a maximum untiI the eighth day. AIter this, urea aIso starts decIining and uric acid
increases rapidIy. About the eIeventh day uric acid concentration in the urine is maximum with a
concomittant drop in urea. The cycIe oI events in the embryonic IiIe oI the chick shows that up to Iour
days the chick was ammonoteIic, Iater on it became ureoteIic, and about the eIeventh day, it became
uricoteIic and continued to be so throughout its aduIt IiIe.
34.5 DlETARY lNFLUENCE DN NlTRDGEN EXCRETlDN
Diet inIIuences the pattern oI excretion to a great extent. Insects provide the best exampIes to
demonstrate this Iact. In a reduvid bug Rhodnius, immediateIy IoIIowing a bIood meaI, considerabIe
quantity oI urea is excreted in the urine which contains excess oI water and saIts. AIter a Iew hours
urine becomes rich in uric acid. In the meat eating Iarvae oI Calliphora and Lucilia (bIowIIy) the
excreta is rich in ammonia. However, in the pupaI stage excretion oI ammonia is repIaced by uric
acid. Thus the excretion depends on the substances present in excess in the diet and aIso on the
production oI waste substances in metaboIism.
Earthworms Iurnish yet another exampIe where the excretory wastes depend on the nutritionaI
state. In a normaI weII-Ied Lumbricus, urea appears in smaII quantities, i.e. 8-15 per cent oI the totaI
excretory nitrogen, whiIe ammonia is predominant. During the state oI starvation urea increases up to
85 per cent and percentage oI ammonia decIines considerabIy.
34.8 EXCRETDRY DEVlCES lN lNVERTEBRATES
Excretory devices met with in the organisms are essentiaIIy the adaptive capabiIities evoIved in
reIation to their habitat. AnimaIs may reside in one oI the IoIIowing surroundings: Ireshwater, marine
and Iand. Diverse excretory devices have been deveIoped in animaIs in order to ensure ionic
reguIation oI the body IIuids.
Protozoans
AIthough protozoa do not have speciaIized excretory organs, the wastes are discharged through
ceIIuIar membranes. SeveraI mechanisms Iike osmosis, diIIusion, etc. are responsibIe Ior waste
eIimination through the membranes. However, in a number oI species, contractiIe vacuoIes serve as
excretory organeIIes. The Iunction oI contractiIe vacuoIes has been extensiveIy studied in
Paramecium. The vacuoIes are membrane bound vesicIes Iormed temporariIy, which coIIect excess
amount oI water and discharge on the surIace oI the organism. These vacuoIes may be oI wandering
type and may IoIIow a deIinite path Ior eIimination. OnIy Ireshwater protozoans possess such
vacuoIar mechanisms Ior waste reguIation.
CoeIenterates
CoeIenterates aIso do not possess speciaIized excretory organs and processes Iike diIIusion osmosis
and active transport to reguIate the IIuids in the body. The need Ior organs oI excretion in
coeIenterates is greatIy restricted.
Excretion '#
PIatyheIminthes
The animaIs oI this phyIum are characterized by having a speciaIized flame cell system. The IIame
ceII is a Iarge ceII bIinded at one end and bearing many cytopIasmic processes. There are series oI
such ceIIs which open in an excretory duct. The nucIeus is dispIaced generaIIy towards the bIind end
side and the cytopIasm bears many secretory dropIets. A bunch oI ciIia arises in the hoIIowed out
cytopIasmic region which keep on moving to produce a directed IIow oI IIuids. The excretory
products enter the IIame ceIIs in a IIuid state Irom the parenchymatous ceIIs by diIIusion. Excess oI
water aIongwith metaboIic wastes are thus discharged by the IIame ceIIs.
AnneIida
The excretory organs are in the Iorm oI tubuIar and coiIed structures caIIed nephridia which are
metamericaIIy arranged. These nephridia are open at both ends, hence known as metanephridia. In
some anneIids, protonephridia are present in pIace oI metanephridia, which are branched and open
bIindIy in the coeIom. A metanephridium diIIers Irom a protonephridium in having a ciIiated IunneI
or nephrostome. These nephridia receive IIuid waste Irom the bIood and the coeIomic IIuid and
eIiminate urine rich in urea and ammonia.
MoIIusca
In moIIuscs, the excretory organs are in the Iorm oI kidneys and pericardial gland. The kidneys are
mesodermaI organs which communicate with the coeIom, whereas the epitheIiaI Iining oI the
pericardium containing gIanduIar tissue serves as pericardiaI gIand. In cephaIopods, the nitrogenous
wastes are eIiminated in the Iorm oI guanin, whiIe uric acid and urea in case oI opisthobranchs and
bivaIves respectiveIy.
Arthropoda
Excretory organs in arthropods are oI severaI types and incIude nephridia, coxaI gIand, green gIand,
sheII gIand and MaIpighian tubuIes, etc. Except MaIpighian tubuIes, these organs are derived Irom
coeIomoducts. In the present context, we shaII deaI with the mechanism oI excretion by MaIpighian
tubuIes as they have proved to be the most eIIicient organs oI excretion in terrestriaI arthropods.
These tubuIes open into the Iumen oI the intestine through their proximaI end and their distaI bIind
end remains suspended within the haemocoeIomic spaces. The excretory products pass out through
the aIimentary canaI.
The MaIpighian tubuIes coIIect and transport soIutions Irom the haemoIymph into the hindgut
where water and some physioIogicaIIy important compounds are absorbed by the hindgut epitheIium.
These tubuIes are characteristic organs oI insects which heIp in removing wastes and sometimes to
conserve water. The physioIogy oI these tubuIes has been exceIIentIy described in mosquito Iarvae by
Ramsay (1953) and in Rhodnius by WiggIesworth (1965). The tubuIes are bathed in the haemoIymph
Irom where they absorb potassium ions. The absorption oI potassium ions takes pIace by active
transport mechanism which aIso heIps in the diIIusion oI water and substances oI Iow moIecuIar
weight such as inorganic saIts, gIucose and urea into the tubuIes. A continuous IIow oI such
substances Irom the haemoIymph into the hindgut takes pIace via these tubuIes. In the hindgut,
Animal Physiology '$
recovery oI essentiaI compounds and water takes pIace by reabsorption and thus onIy wastes are
eIiminated. The rectaI gIands oI insects are responsibIe Ior conservation oI water. GeneraIIy the
MaIpighian tubuIes Iie IreeIy in the body cavity, but in certain insects the terminaI portions are
intimateIy attached to the waII oI the rectum (Fig. 14.6). This condition is Iound in Iepidopterous
Iarvae, coIeoptera and some tenthredinid Iarvae and is associated with the conservation oI water in dry
habitats.
In Rhodnius, a cIearcut regionaI distinction has been Iound in the MaIpighian tubuIes.
WiggIesworth (1942) Iound that the upper portion is concerned with the secretion and the Iower
portion with reabsorption. For this reason, the Iower portion contains uric acid granuIes and the upper
portion contains cIear IIuid.
34.7 EXCRETlDN DEVlCES lN VERTEBRATES
RENAL PHYSlDLDGY
Kidney
Kidneys are the chieI organs Ior excretion oI wastes in vertebrates and, thereIore, deserve speciaI
attention. Besides their excretory Iunction, kidneys Iunction in a signiIicant manner in the
maintenance oI internaI environment oI the body.
FIg. 14.6 Malpighian tubule of an insect.
O P Na K
1 6 3 14 10
1 5 7 6 1 2 3
1 6 7 6 1 1 2
Haemolymph
Intestine
SIMPLE TYPE
Midgut
Malpighian
tubule
Rectal gland
CRYTONEPHRIDIAL TYPE
Excretion '%
STRUCTURE OF KIDNEY: MammaIian kidney couId be taken as an exampIe to expIain the structure
and Iunction oI a typicaI vertebrate kidney. The kidneys are paired organs which are generaIIy bean-
shaped structures. When seen in a sagittaI section, it shows two main divisions. The outer portion is
caIIed the cortex, and the inner region Iorming the main mass oI the kidney is caIIed the medulla. The
meduIIa is composed oI severaI pyramids containing renaI tubuIes projecting into a cavity towards the
inner region oI kidney, caIIed the pelvis. PeIvis is the region where the renaI artery and vein enter
kidney. The cortex contains a Iarge number oI MaIpighian bodies and convoIuted tubuIes (Fig. 14.7).
FIg. 14.7 L.S. of vertebrate kidney.
HistoIogicaI examination oI kidney shows that it is made up oI a Iarge number oI secreting units,
caIIed nephrons. Each nephron is composed oI a sphericaI structure known as the MaIpighian body
and a convoIuted tubuIe. MaIpighian bodies have a doubIe-waIIed capsuIe encIosing a network oI
capiIIaries caIIed glomerulus. The capsuIe opens into a Iong tubuIe through a narrow neck and takes a
rather tortuous course in the cortex, and Iater descends down in the meduIIary region. Here it makes a
loop of Henle and through ascending and descending Ioops terminates into a coIIecting tubuIe
(Fig. 14.8). The tubuIes are surrounded by a network oI bIood capiIIaries which heIps in the exchange
oI materiaIs between the bIood and the ceIIs oI the tubuIes. The capsuIe has very thin Iayer oI
endotheIiaI ceIIs, whiIe the ascending and descending Ioops are Iined with cuboidaI ceIIs. The Iumen
oI the tubuIes is very narrow.
Pyrimid Cortex
Calyx
Pelvis
Ureter
Renal
artery
Fat
Medulla
Artery
Tubules in
cross section
Animal Physiology '&
BLOOD SUPPLY: Kidneys receive a very rich suppIy oI bIood. An aduIt kidney receives about 1.3
Iitres oI bIood per minute. The bIood suppIy oI kidney comes Irom a short renaI artery which arises
Irom the abdominaI aorta. AIter entering the kidney, the renaI artery divides into a number oI
arterioIesafferent arterioles. The afferent arterioles Iurther branch into capiIIaries and enter into
each gIomeruIus. These capiIIaries then join to Iorm another arterioIe caIIed efferent arteriole which
Iurther opens into another set oI capiIIaries, caIIed peritubular capillaries surrounding the proximaI
tubuIe, the thin Ioop and the distaI tubuIe oI the same nephron. Having taken this tortuous course, this
FIg. 14.S Structure of a nephron.
Proximal convoluted tubule
Distal convoluted tubule
Efferent arteriole
Afferent arteriole
Descending loop
of Henle
Glomerulus
Veins
Capillary
Ascending loop of Henle
Collecting tubule
Artery
Excretion ''
capiIIary opens into avenuIe which joins with other venuIes to Iorm IinaIIy the renaI vein. The renaI
vein opens into the inIerior vena cava.
At this stage, it wouId be interesting to know as to how the pressure Ior bIood IIow is maintained
through aIIerent and aIIerent arterioIes, and peritubuIar capiIIaries. The renaI artery is thick and short
and thus the pressure drop in reaching the bIood to the kidney is smaII. The aIIerent arterioIes which
are Iarger than other arterioIes in the body Iower the pressure to some extent to about 60 mm Hg
which is cIose to the hydrostatic pressure in the gIomeruIi. The eIIerent arterioIes bring the pressure
Iurther down to about 15 mm Hg. This causes Iurther decrease in the hydrostatic pressure in the
peritubuIar capiIIaries and aIIows movement oI IIuid into the capiIIaries. Further, the aIIerent and
eIIerent arterioIes are subjected to vasomotor changes to aIter the bIood pressure in the gIomeruIi.
Constriction oI the aIIerent arterioIes decreases the pressure within the capiIIaries and aIIows Iess
bIood IIow. On the other hand, diIation oI these arterioIes causes more bIood to IIow through them.
EIIerent arterioIes, upon contraction, raise the bIood pressure in the gIomeruIus capiIIaries and
consequentIy decrease the bIood IIow.
Functions of kidneys: The principaI Iunctions oI kidney are:
(1) To eIiminate certain nonvoIatiIe waste products oI the body Iike urea, suIphates, etc.
(2) To reguIate hydrogen-ion concentration oI bIood by eIiminating any excess oI nonvoIatiIe
acids and bases.
(3) To remove excess oI certain nutrients such as sugar and amino acids when their concentration
increases in the bIood.
(4) To remove Ioreign or injurious substances Irom the bIood, such as, iodides, pigments, drugs
and bacteria, etc.
(5) Maintenance oI osmotic pressure oI the bIood by reguIation oI the excretion oI water and
inorganic saIts, thus keeping constant the voIume oI circuIating bIood.
(6) Kidneys reguIate the arteriaI bIood pressure by secreting the hormone renin.
URINE FORMATION: In mammaIs each kidney is composed oI tens oI thousands oI uriniIerous
tubuIes which Iorm the urine. Urine is Iormed Irom the bIood circuIating in the gIome-
ruIus (Fig. 14.9). Thus urine is a IiItrate oI the bIood which goes into the tubuIes as a diIute IIuid
resembIing the pIasma deIicient in coIIoids. This diIute IIuid is concentrated in the tubuIar region by
reabsorption oI the excess portion oI the IIuid and certain saIts and thus repIaced in the bIood stream.
Besides, certain susbstances may aIso be secreted by the tubuIar epitheIium into the urine. Formation
oI urine by the kidneys is considered to be due to three types oI activitygIomeruIar IiItration,
seIective secretion and tubuIar reabsorption.
FUNCTION OF THE GLOMERULUS: In the middIe oI the nineteenth century, Ludwig proposed a
theory oI physicaI IiItration and diIIusion. According to him, noncoIIoidaI constituents oI bIood were
removed by the thin membranes oI the gIomeruIus by IiItration and onIy cIear diIute IiItrate was
aIIowed to enter the tubuIes where excess amount oI water was reabsorbed making the urine
concentrated. Later, Cushny in 1914 proposed a partiaI modiIication oI Ludwig`s theory and
suggested that aIongwith water, the noncoIIoidaI constituents oI the pIasma IiIter through the
gIomeruIus. As the Iiquid passes through the tubuIar region, some oI the water, saIts, gIucose, amino
acids and certain other constituents useIuI Ior the body are reabsorbed by the tubuIar epitheIium and
sent back to the bIood.
Animal Physiology !
We shaII now consider the process oI IiItration in the Iight oI the current ideas. The structure oI
the gIomeruIus suggests that it is best suited Ior the purpose oI IiItration which wouId depend on three
conditions: (1) semipermeabIe nature oI the gIomeruIar membranes; (2) osmotic pressure exerted by
the contents on either side oI the membrane and; (3) bIood pressure in the gIomeruIi.
Filtration: The semipermeabIe nature oI gIomeruIar membrane wouId aIIow to pass through it
proteins oI Iow moIecuIar weights. Egg aIbumin (MW: 35,000), geIatin (MW: 35,000) and
haemogIobin (MW: 64,500) and substances around these moIecuIar weights can be expeIIed through
it. Proteins oI high moIecuIar weight such as casein (200,000), serum gIobuIin (160,000) and serum
aIbumin (72,000) are not excreted. Such membranes exert osmotic pressure to eIIect IiItration. The
coIIoids oI the bIood exert an osmotic pressure, against IiItration and may cause diIIusion oI water
into the bIood. However, the hydrostatic pressure oI bIood wouId try to Iorce the water Irom the bIood
into the tubuIes. This suggests that bIood pressure is higher than the osmotic pressure to cause
IiItration and the energy oI IiItration is derived Irom the hydrostatic pressure. The hydrostatic pressure
oI bIood in the aIIerent gIomeruIar artery is about 75 mm Hg, whereas the osmotic pressure exerted
by the pIasma proteins is about 20 to 30 mm Hg. The interstitiaI pressure acting on the capiIIaries is
10 mm Hg. ThereIore the IinaI pressure or the actuaI driving Iorce is 25-30 mm Hg which may be
expressed as IoIIows:
P
b
P
o
P
c
÷ P
f
where P
b
÷ hydrostatic pressure oI the bIood, P
o
÷ osmotic pressure oI proteins, P
c
÷ totaI oI
interstitiaI pressure and movement pressure, and P
f
÷ IinaI driving Iorce.
Glomerular filtration rate (GFR): About 1 Iitre oI bIood is IiItered per minute by both the
kidneys. When the net IiItration pressure is about 25 mm Hg, about 120 mI oI gIomeruIar IiItrate is
Iormed at the Bowman`s capsuIe. ThereIore GFR is about 120 mI per minute, which is actuaIIy the
voIume oI pIasma IiItered per minute. It may be expressed as:
FIg. 14.9 Structure of a Bowman´s capsule.
Vas
efferens
Vas
efferens
Endothelium
Glomerula
membrane
Capsule
epithelium
Membrane
propria
Tubule
Excretion !
GFR ÷
UJ
P
where U ÷ mg oI the IiItered substance per mI urine, J ÷ mI oI urine per minute, and P ÷ mg oI
IiItered substance per mI oI pIasma.
FUNCTION OF THE TUBULE: The composition oI urine is quite diIIerent Irom the gIomeruIar
IiItrate. The gIomeruIar IiItrate contains some essentiaI substances Iike water, gIucose, amino acids,
chIorides, sodium and other wastes Iike urea, creatinine, and uric acid. The essentiaI substances are
retained to carry on normaI metaboIism, and this seIective Iunction is carried out by the tubuIes oI the
kidney. Thus by secretion and reabsorption the gIomeruIar IiItrate is transIormed into urine.
TUBULAR REABSORPTION: Certain substances which appear in normaI quantities are reabsorbed
compIeteIy, but appear in the urine when normaI IeveIs are exceeded. Such substances are known as
threshold substances. Amino acids and gIucose are such threshoId substances which are eIIicientIy
reabsorbed by the tubuIar ceIIs (Fig. 14.10).
FIg. 14.1û Schematic diagram of a urinary tubule showing functional regions of secretion and reabsorption of various
substances.
Creatinine
REABSORPTION
Creatinine, Urea
H O, Glucose
2
aa, Na , Uric acid
+
K , M , Ca
+ + + ++
g
P O , Cl , HCO 3
– – – –
4
Na (70%) Obligatory
+
H O (87.5%) Obligatory
2
Urea (40%)
Na
+
pH
7.4
Filtrate
pH 7.4
SECRETION
SO , – Hippuric acid

4 P
r
o
x
i
m
a
l
r
n
d
D
e
s
c
e
n
d
i
n
g
l
i
m
b
A
s
c
e
n
d
i
n
g
l
i
m
b
K
+
H
+
NH
3
+
D
i
s
t
a
l
t
u
b
u
l
e
pH 6.0
ADH
Acts here
K
+
Na (12%)
+
H O (Facultative)
2
Urea
ADH H O ADH Controlled
2
Urine

Animal Physiology !
Reabsorption of glucose: In a normaI aduIt, when the GFR is 120 mI/minute, about 120 mg oI
gIucose are transIerred into the IiItrate per minute. NormaIIy, except onIy a Iew mg, the entire quantity
oI gIucose is reabsorbed. The absorption takes pIace in the proximaI part oI the tubuIe by active
transport mechanism associated with phosphoryIation. In men, the maximum rate at which gIucose
can be reabsorbed by the tubuIe is 350 mg/minute. This is known as the tubuIar maximum Ior gIucose
(TmG). In women TmG is about 300 gm/minute. Sometimes considerabIe amounts oI gIucose are
Iound in the urine, a condition known as gIycosuria. GIycosuria can be artiIiciaIIy caused by
administering Phlorizin which inhibits phosphoryIation.
Reabsorption of vater: The osmotic pressure oI the pIasma remains more or Iess unchanged and
is due to the presence oI inorganic saIts which act as eIectroIytes. II Iarge quantities oI water are
taken, this might cause diIution oI the pIasma. This causes reduction in the osmotic pressure which
resuIts in the excretion oI Iarger amounts oI water in the urine. Thus the kidney deIends osmoIarity oI
the pIasma by excreting excess amount oI water. Increased rate oI urine secretion is known as diuresis
and the substances which produce this eIIect are caIIed diuretics. Urea has a diuretic eIIect. Certain
saIts such as NaC1 and Na
2
SO
4
aIso have diuretic eIIects.
NormaIIy 150 to 180 Iitres oI gIomeruIar IiItrate is produced every day, and out oI this
approximateIy 80 per cent oI the IiItrate is reabsorbed in the proximaI part oI the tubuIe. This is caIIed
obIigatory reabsorption.
Reabsorption of inorganic salts: Sodium, chIoride and bicarbonate ions are seIectiveIy
reabsorbed in proximaI tubuIar portion. AIong with the reabsorption oI Na
¹
there is paraIIeI
reabsorption oI it so that regaining oI NaCI heIps in the return oI water. Reabsorption oI Na
¹
is aided
by the adrenaI corticaI hormone.
Potassium is aIso present in smaII quantities in the gIomeruIar IiItrate. NormaIIy aII the potassium
IiItered is reabsorbed by the proximaI tubuIe. However, iI any potassium appears in the urine, it
originates as a tubuIar secretion Irom the distaI tubuIe which is responsibIe Ior acid-base equiIibrium.
The secretion and reabsorption oI sodium and potassium are controIIed by a hormone, aldosterone,
which is secreted Irom the adrenaI cortex. Sodium reabsorption is Iowered during osmotic diuresis
and glucocorticoids (costisoI and corticosterone) increase the tubuIar reabsorption oI Na
¹
in exchange
oI H
¹
and aIso reabsorption oI Na
¹
with CI

.
DIURESIS: When the rate oI urine secretion is increased, the condition is caIIed is diuresis and the
substances which cause this are known as diuretics. GIucose and urea have marked diuretic eIIects.
Besides these, other compounds Iike caIIeine and deoxycorticosterone acetate aIso act as diuretics.
Increased water content in the bIood resuIts in diuresis. The soIutes oI the gIomeruIar IiItrate
which are not absorbed in the proximaI tubuIe exert an osmotic pressure so that more water passes out
oI the tubuIes thereby increasing the concentration oI soIutes in the bIood. Such is the state when
gIucose and urea are present in higher concentrations in the bIood. II suIIicient water is avaiIabIe to
the organisms, the excretion oI water runs paraIIeI with that oI urea. AnimaIs consuming a high
protein diet wiII Iorm more urea in the body and wouId require Iarger voIumes oI intake oI water,
otherwise a miId diuresis occurs. Diabetic patients aIso excrete Iarger voIumes oI urine so that the
IiItered Ioad oI gIucose exceeds TmG resuIting in a condition known as poIyuria.
Excretion !!
In some cases, diuretics bring about an increased bIood IIow through the kidney which is mainIy
the Iunction oI vasomotor nerves. AIthough no direct nervous controI oI the kidney has been
demonstrated, yet sometimes under emotionaI stress, diuresis or decrease in urine excretion are
observed. This may be caused by vasomotor nerves which bring about vasoconstriction or diIation oI
renaI arteries and arterioIes, thus aItering the kidney secretion.
CLEARANCE: The maximum amount oI the bIood pIasma that can be cIeared by the kidney in one
minute is caIIed the cIearance.
CIearance tests are done with reIerence to the pIasma. MathematicaIIy, caIcuIation oI pIasma
cIearance oI any substance can be represented as:
C ÷
UJ
P
where C ÷ pIasma cIearance in mI per minute, U ÷ concentration oI the substance in urine in gm/100
mI, J ÷ voIume oI urine passed in mI/minute, and P ÷ concentration oI the substance in the pIasma in
gm/100 mI.
To take a speciIic exampIe, iI the pIasma contains 0.05 gm oI inuIin per 100 mI, the urine 6.25 gm
inuIin per 100 mI, and the rate oI urine excretion is 1 mI per minute, then inuIin cIearance rate wouId
be
6 25
0 05
.
.
1
÷ 125 mI/minute
Homeostasis
LiIe is an extension oI non-Iiving processes. The physico-chemicaI Iaws which are appIicabIe to the
non-Iiving systems are appIicabIe to the Iiving systems as weII in many ways, a Iiving process can be
considered as a kind oI super-chemistry and is an exampIe oI interactions between matter and energy
to produce a highIy compIicated and weII organised seII-dupIicating automatic system. Thus Iiving
system is not a closed system but an open system with matter and energy that IIow into the system
being in a steady state with the matter and energy that IIow out oI the system. Living organisms create
and maintain their essentiaI orderIiness at the expense oI their environment and this tendency to
maintain themseIves in a steady state condition is known as homeostasis.
In the nineteenth century, physioIogist CIaude Bernard deveIoped an idea that the ceIIs and tissues
oI the body which are bathed in an internaI IIuid constitute the internaI environment or milieu interior,
whereas the externaI environment oI the whoIe organisms constitutes milieu exterior. The internaI
environment is maintained at a constant, irrespective oI the organism`s externaI environment. In
animaIs a number oI homeostatic mechanisms are at work which serve to maintain internaI
environment such as osmotic and ionic reguIation, temperature reguIation, buIIer mechanisms, active
transport and excretion. The detaiIs oI these homeostatic mechanisms have been described in
appropriate pIaces oI this book.
Animal Physiology !"
34.8 CDMPDSlTlDN DF URlNE
The voIume and composition oI urine varies remarkabIy and such variations are governed by the type
oI Iood consumed by the individuaI, and voIume oI IIuid intake. In a normaI aduIt about 1-1.5 Iitres oI
urine is Iormed daiIy. In warm cIimates, urine voIume is Iess since a good amount oI water is Iost
through perspiration. II the voIume oI water intake is increased, urine voIume is aIso increased.
The normaI urine is transparent and straw coIoured. PaIe yeIIow coIour is due to the presence oI
pigment caIIed urochrome. SpeciIic gravity oI urine varies Irom 1.005 to 1.040 and it is generaIIy
acidic with a pH 6.0. Upon standing, urine becomes aIkaIine because conversion oI ammonia Irom
urea takes pIace.
The concentration oI the constituents in urine varies with individuaIs. It consists oI a number oI
soIids, haII oI which is urea. Average concentration oI principaI constituents is given in TabIe 14.2.
TabIe 14.2 Composition of Normal Human Urine (volume of urine l.250 mlf2+ hours)
CønsI¡IuønIs Grams pør 2÷ nøurs
Water l2,l+0
Total solids 58.5
Total nitrogen l5.5
Urea 25.0 - 28.5
Uric acid 0.6
Creatine l.5
Ammonia 0.7
Hippuric acid 0.60
Allantoin 0.0l
Carbohydrates 0.90
Oxalates as oxalic acid 0.0l5
Lactates as lactic acid 0.0l
Ketone bodies, acetone 0.0l
Free amino acids, etc. 3.0
Chlorides l2.0
Phosphates as phosphoric acid 2.3
Sulphates as H
2
SO
+
l.8
Potassium 2.0
Sodium 6.0
Calcium as CaO 0.2
Magnesium 0.2
Iron 0.006
The constituents oI urine may be broadIy cIassiIied into three categories: (1) nitrogenous wastes;
(2) nitrogen-Iree organic compounds; and (3) inorganic saIts.
Excretion !#
PrincipaI Constituents
(1) UREA: It is diamide oI carbonic acid and is the most abundant substance oI the urine. The urea
content depends on protein cataboIism oI an individuaI. AnimaIs having Iow protein diet
produce Iess urea, whereas in animaIs whose diet is rich in protein, urea content increases. It
normaIIy contains 60-90 per cent oI totaI nitrogen.
(2) AMMONIA: Fresh urine contains IittIe ammonia. However, on standing urea is converted into
ammonia which occurs mainIy in the Iorm oI saIts such as urates and chIorides.
(3) CREATININE AND CREATINE: Creatinine contents oI urine are IairIy constant. The concentrations
oI creatinine are as IoIIows:
20-26 mg/kg body weight/day in normaI man.
14-22 mg/kg body weight/day in normaI woman.
Creatine is aIso present in the urine oI inIants.
(4) URIC ACID: It is the most important end-product oI purine metaboIism in the body. In certain
diseases, Iike Ieukemia, Iiver disease and gout, the uric acid output is increased.
(5) AMINO ACIDS: GIycine, histidine, gIutamine and cystine are principaI amino acids Iound in the
urine. Other amino acids are aIso present, but in very smaII quantities. About 200 mg oI amino
acids are excreted per day in urine oI a normaI man.
(6) ALLANTOIN: This compound occurs in very smaII quantities in human urine. However, in other
mammaIs its content is more where it is Iormed due to purine metaboIism. This is aIso derived
Irom the partiaI oxidation oI uric acid.
(7) HIPPURIC ACID: SmaII quantities oI hippuric acid are Iound in the urine. It is Iormed by
conversion oI benzoic acid, which otherwise cannot be oxidized easiIy. Conversion is
generaIIy accompIished by the intestinaI bacteria.
In addition to the above mentioned substances, smaII amounts oI chIorides, suIphates, phosphates,
oxaIates, mineraIs, vitamins and steroid hormones and gonadotropins are aIso present in the urine.
TabIe 14.3 Some Constituents Urine and Plasma Compared
PIasma mg ¾ Ur¡nø mg ¾ 2÷ nøur ur¡nø gm
Clucose 80.0 0.0 0.0
Urea 2.5 l,600 2+.0
Uric acid +.0 53 0.8
Creatinine l.5 l00 l.5
pH 7.+l 6.0 6.0
Animal Physiology !$
34.8 CDUNTERCURRENT MECHANlSM
GeneraIIy, with variations in the intake oI IIuid and soIutes, the osmotic pressure oI the pIasma
remains unaItered. The osmoIarity oI the pIasma oI many animaIs is around 285-300 mOsm/Iitre oI
water which depends on its inorganic saIt contents. II Iarge voIumes oI water are taken, the kidney
adjusts the osmoIarity oI the pIasma by excreting Iarger amount oI water. However, in some animaIs
hyposmotic or hyperosmotic urine may be produced under certain conditions.
In order to achieve these conditions, certain mechanisms are at work. Hyposmotic IiItrate may be
produced iI sodium chIoride is reabsorbed in the ascending Iimb oI the tubuIe. On the other hand, the
tubuIar IiItrate becomes more concentrated, as much water without soIute is reabsorbed in the
descending Iimb, thus producing hyperosmotic urine. Fishes and amphibians are capabIe oI producing
hyposmotic urine whereas reptiIes produce hyper-osmotic urine. It is onIy in case oI birds and
mammaIs where hyposmotic as weII as hyperosmotic urine may be produced. The mechanism by
which these conditions can be achieved is caIIed countercurrent mechanism.
The countercurrent mechanism has certain speciaI Ieatures which are as IoIIows:
(1) The descending Iimb oI HenIe`s Ioop is permeabIe to water, whereas the ascending Iimb has
poor water permeabiIity.
(2) The ascending Iimb oI the nephron is the site Ior active transport oI sodium.
(3) The reguIatory inIIuence oI the antidiuretic hormone (ADH) is exerted on the permeabiIity oI
the distaI tubuIes and the coIIecting ducts. High hormone IeveIs increase water permeabiIity
and its absence reduces it to a Iow IeveI.
FIg. 14.11 A scheme of the countercurrent mechanism.
300
600
300
600
300
1200
H O
2
H O
2
Na
Na
H O
2
Urea
300
300 300
300
300
300
300
300
300
300 300
Urea
600
1200
600 600
1000
1200
Urea
400
800
1200
100
400
600
800
800
1000
1000
800
400
600
800
1000
1200
Nacl
Nacl H O
2
H O
2
H O
2
Cortex
Outer zone of medulla
Inner zone of medulla
C B A
Excretion !%
The countercurrent mechanism is a process in which urine is rendered hyposmoIar as it passes
through diIIerent portions oI the tubuIes.
From the structure oI the urinary tubuIes, it is seen that the descending, ascending and coIIecting
tubuIe are very cIose to each other. The IIow in the ascending tubuIe runs counter to that in the
descending and the coIIecting tubuIe. Sodium and other ions are transported out oI the IiItrate in the
proximaI tubuIe where water aIso moves out. By the time urine reaches the Ioop oI HenIe, about 80
per cent oI totaI IiItrate is out oI the tubuIe. The Ioop oI HenIe absorbs Iot oI sodium and chIoride and
hands over to the surrounding tissue, making the urine concentrated or hyperosmoIar.
In the ascending tubuIe and the Ioop oI HenIe, there is no movement oI water consequent upon
the active transport oI sodium, making the IiItrate Iess concentrated. The IIuid returned to the distaI
tubuIe is hypotonic, but this segment is abIe to reabsorb water and the IIuid reaching the coIIecting
tubuIes is isotonic. There is Iurther transport oI sodium Irom the coIIecting duct, but as the IIuid
passes through the meduIIa, water diIIuses out oI the IiItrate and the IIuid reaching the peIvis oI the
kidney is the concentrated Iorm oI urine. From Fig. 14.11 it wiII be seen that aII aIong the system the
concentration gradient is aIways about 200 mOsm/Iitre and never greater than this. However, the
concentration oI the IiItrate progressiveIy increases Irom 300 mOsm/Iitre to 1200 mOsm/Iitre by the
time it passes out oI the coIIecting tubuIe.
The countercurrent mechanism is aIso maintained by the vasa rectae. In vasa recta the IIow oI
bIood run counter to the IIow oI urine. The IIow oI bIood in the meduIIary tissue is downward and in
the cortex it is upward. As the bIood IIows through the meduIIa, water diIIuses out and sodium
diIIuses in, whereas reverse movement takes pIace in the cortex, Ieaving most oI the sodium to remain
in the meduIIary interstitiaI IIuid circuIation.
34.30 AClD-BASE REGULATlDN
The kidney reguIates both voIumes oI water and mineraI saIts. Apart Irom this, another important
Iunction perIormed by the kidney is acid-base reguIation. Kidneys provide a seII-correcting device by
means oI which cations Iike sodium are conserved. Excess oI sodium ions is exchanged Ior hydrogen
ions in the proximaI tubuIes, whereas exchange oI sodium and potassium ions Ior hydrogen ions takes
pIace in the distaI tubuIe.
During metaboIism hydrogen ions and ammonia are produced in excessive amounts which must
be buIIered to maintain the baIance. In protein metaboIism, certain nonvoIatiIe acids, such as Iactic
acid, the ketone bodies, suIphuric acid, etc., are produced which must be eIiminated by some
mechanism. In the course oI metaboIism oI phosphoIipids, phosphoric acid is produced. These acids
are buIIered by sodium ions mainIy and eIiminated by IiItration in the gIomeruIus. Sodium ions thus
Iost are recovered by tubuIar reabsorption in exchange Ior hydrogen ions.
In the proximaI tubuIe, carbonic acid is Iormed Irom CO
2
and water in the presence oI carbonic
anhydrase. This carbonic acid is ionized to reIease H
¹
ions which are mobiIized out oI the tubuIe and
is exchanged Ior sodium bicarbonate as shown in Fig. 14.12. This resuIts in the Iormation oI carbonic
acid in the tubuIar IiItrate, which again decomposes to set Iree CO
2
and water; CO
2
thus set Iree again
diIIuses back into the ceIIs oI the tubuIe and hydrogen ions are reutiIized.
Animal Physiology !&
AImost aII bicarbonate ions are reabsorbed in the proximaI tubuIe and the remaining are absorbed
in the distaI tubuIe. In the distaI tubuIe, the hydrogen ions are exchanged Ior sodium ions oI Na
2
HP
4
increasing the acidity oI urine. Figure 14.13 gives a summary oI the secretion oI hydrogen ions in the
distaI tubuIe.
FIg. 14.12 Mobilization of hydrogen ions in the proximal tubule.
FIg. 14.13 Secretion of hydrogen ions in the distal tubule.
The distaI tubuIe heIps in the eIimination oI hydrogen ions by yet another process. The ceIIs
produce ammonia by deamination oI amino acids which combines with the hydrogen ions so that
ammonium (NH
4
¹
) ions are produced. Such a mechanism operates when sodium chIoride is present in
suIIicient amount in the tubuIar IiItrate. The mechanism is summarized in Fig. 14.14.
Blood Proximal tubule cells Tubular filtrate
CO
2
H O
2
HCO
3
Na
+
CO
2
CO
2
H O
2
H O
2
H O
2
HCO
3
HCO
3
Na
+
Na
+
Carbonic annydrase
H
+
H
+
H CO
2 3
H CO
2 3
– – –
Blood Distal tubule cells Tubular filtrate
CO
2
H O
2
HCO
3
Na
+
CO
2
H O
2
HCO
3
Na
+ Na
+
Carbonic annydrase
H
+
H
+
H CO
2 3
Na
+
+ H + HPO
4
2 Na + HPO
+
4
(pH 7.4)
pH 6.0
To urine
Formed at glomerulus
(pH 7.4)
– –
– –

Excretion !'
34.33 RENAL CDNTRDL MECHANlSMS
SeveraI controI mechanisms operate to maintain constancy oI the composition and the voIume oI the
extraceIIuIar IIuid.
The osmoIarity oI urine changes without any variation in the amount oI saIt excreted. Any gain or
Ioss in the amount oI water is dependent upon the action oI the antidiuretic hormone (ADH) secreted
Irom the posterior Iobe oI the pituitary. The ADH IeveI is controIIed by changes in the osmotic
pressure oI the extraceIIuIar IIuid. There are speciaI osmoreceptors` situated in the hypothaIamus or
in the waIIs oI the bIood vesseIs going in it. These receptors are sensitive to changes in the osmoIarity
oI the bIood. ADH secretion is thought to be due to nervous impuIses originating in the hypothaIamus
and passing into the posterior Iobe oI the pituitary. When the extraceIIuIar osmoIarity is Iowered, the
ADH secretion is suppressed which in turn decreases water reabsorption. However, higher IeveIs oI
ADH stimuIate water reabsorption. The ADH has a speciIic site oI action acting at the distaI tubuIe
and the coIIecting ducts.
This controI mechanism can be exempIiIied by a disease, Diabetes insipidus. The disease is
caused due to damage oI certain centres in the brain stem inhibiting ADH secretion. Such patients
dischange Iarge amounts oI urine, sometimes exceeding 40 Iitres a day. In order to compensate the
excessive Ioss oI water, the patients drink Iarge amount oI water. Administration oI ADH injections
cures this disease.
The mechanisms which maintain the voIume oI extraceIIuIar IIuids are poorIy understood.
However, the hormone oI the adrenaI cortex, aIdosterone, a sodium conserving hormone, is
considered to be signiIicant in this regard. The site oI action oI this hormone is the distaI tubuIe.
AIdosterone remains in circuIation and its IeveIs are inIIuenced in two possibIe ways:
(1) Low sodium concentration in the extraceIIuIar IIuid, provides a stimuIus to the adrenaI cortex
Ior aIdosterone secretion.
FIg. 14.14 Sectetion of ammonia ions in the distal tubule.
Blood Distal tubule cells Tubular filtrate
CO
2
H O
2
HCO
3
Na
+
CO
2
H O
2
HCO
3
Na
+
Na
+
H
+
NH
4
+
H CO
2 3
Cl

H
+
Deamination of
amino acids
NH
3
+
NH
3
+
Carbonic
anhydrase
Animal Physiology !
(2) The extraceIIuIar IIuid voIume inIIuences the secretion, increase in voIume enhances, whiIe
decrease in voIume suppresses aIdosterone secretion.
The possibIe mechanism oI aIdosterone secretion may be expIained as IoIIows: speciaI ceIIs oI
the renaI cortex (ischemic region) secrete a proteoIytic enzyme, renin, that goes into the bIood by
renaI vein. The impact oI renin reduces the gIomeruIar IiItration rate and consequentIy deIivery oI
sodium to the distaI tubuIe is decreased. Loss oI sodium induces shrinkage in the IIuid voIume.
Whenever there is a IaII in the IIuid voIume, the gIomeruIar IiItration rate is aIso Iowered. Renin acts
upon angiotensinogen, a gIobuIin present in the pIasma, and converts it to angiotensin. Angiotensin,
increases the rate oI heart beat and arteriaI bIood pressure thereby stimuIating aIdosterone secretion.
AIdosterone promotes sodium reabsorption by the renaI tubuIes, and to maintain proper osmotic
baIance, water is retained to keep up the IIuid voIume. Thus sodium chIoride is an important
eIectroIyte which reguIates the extraceIIuIar IIuid voIume.
Living organisms have a unique property to respond to changes in the environment. The inIormation
received by the organism is coordinated through the nervous system so that the organism can act
eIIectiveIy under any circumstance. The inIormation is obtained in the Iorm oI a stimuIus. A stimuIus
is a change in the environment which evokes a response Irom the organism. The types oI stimuIi are
many and diverse, such as caused by Iight, heat, sound, temperature, pressure, gravity, chemicaI, etc.
AII such inIormation is responsibIe to evoke a response Irom the organism by chieIIy aIIecting the
receptor organs and may be perceived simuItaneousIy. The mechanism oI perception is a highIy
compIicated one invoIving a number oI sensory structures in the body.
Some oI the inIormation is used consciousIy by the organism so as to inIIuence its behaviour.
InIormation may be gathered and used unconsciousIy as weII, such as contraction oI muscIes, bIood
pressure, posture oI the body, etc. AII these inIormation inIIuence the behaviour oI the organism
invoIving nervous system. In order to process diverse inIormation Irom an animaI`s environment, the
nervous system has to Iunction in three principaI ways:
(1) It shouId receive externaI and internaI stimuIi to provide sensory inIormation about itseII and
its own environments.
(2) It shouId integrate aII this inIormation so that meaningIuI interpretation oI the data Ied in by
sensory organs may be made.
(3) It shouId reguIate intraceIIuIar activity to maintain coordination oI movement oI the whoIe
organism (This may invoIve stimuIation oI muscIes, gIands and neurons concerned with
perception, Iearning and memory, etc.).
In order to understand the Iunctioning oI nervous system, it is necessary to consider the basic
structure and properties oI its structuraI components.
Nerve FhysioIogy
+ 0 ) 2 6 - 4
#
Animal Physiology !
35.3 UNlTS DF THE NERVDUS SYSTEM
The nervous system may be divided Ior the sake oI convenience into: (1) the centraI nervous system
incIuding the brain and the spinaI cord; and (2) the peripheraI nervous system consisting oI craniaI
nerves, spinaI nerves and (3) the autonomic nervous system. The IunctionaI units oI the nervous system
are caIIed neurons which are distributed throughout the body (vide inIra). They have a Iarge number oI
diIIerent kinds oI synapses through which inIormation can be transmitted.
Sympathetic
trunk
Nerve trunk
(a)
Posterior
rootganglion
Sympathetic
ganglion
(b)
FIg. 15.1 Diagram showing the anatomical relationships of (a) somatic and (b) autonomic nervous system.
Nerue Physiology !!
In higher organisms, the process oI cephaIization has resuIted in the concentration oI nerves as weII
as neurons which has given rise to brain. CephaIization oI the highest order is Iound in mammaIs and
birds, where a weII deveIoped centraI nervous system (CNS) consisting oI a spinaI cord, brain stem,
meduIIa obIongata, cerebeIIum and the cerebrum. The peripheraI system consists oI nerves that are
directIy connected with the brain and suppIy to the peripheraI organs.
In the centraI nervous system, there is a somatic division or somatic nervous system and the
autonomic nervous system. The somatic nervous system is characterized by the presence oI certain
speciaI connections caIIed synapses Iying within the spinaI cord, whereas in the autonomic system the
synapses Iie outside the spinaI cord (Fig. 15.1).
Main Iunctions oI the centraI nervous system are to receive impuIses, to give rise to various
patterns oI responses, and aIso to modiIy them. As soon as the stimuIus is given, a response is
conducted which is spontaneous. In order to transmit impuIses, nervous system has certain basic
IunctionaI units which have been reIerred to as neurons. These are a part oI the grey matter.
Neurons
The existence oI neurons was Iirst discovered by His
and ForeI. Neurons are eIongated nerve ceIIs; a vast
majority oI them are Iocated in the spinaI cord and
brain. A neuron is a microscopic structure consisting
oI a main ceII body, dendrites, a Iong axon Iibre and a
number oI terminaI Iibres (Fig. 15.2). The axon is a
hoIIow cyIinder IiIIed with cytopIasm which diIIers in
its chemicaI composition Irom the surrounding IIuid.
The axon takes part in the Iormation oI a nerve.
The part oI the neuron containing the ceII body
aIongwith the nucIeus is not needed to conduct waves
oI impuIses, but it is mainIy needed Ior growth,
maintenance and repair. II an axon is severed oII Irom
the nucIeated ceII body it wouId be regenerated. II the
ceII body is destroyed, the axon cannot be regenerated.
The axon is generaIIy covered with a myeIin
sheath, which acts as an insuIator. This sheath is
highIy deveIoped in vertebrate neurons. The myeIin
sheath over the axon is not continuous but Ieaves smaII
areas naked which occur at reguIar intervaIs oI about 1
mm. These naked areas are caIIed nodes oI Ranvier.
The ceII body and aIso the terminaI Iibres are not
enveIoped by this sheath. These two naked areas are
the regions oI input and output respectiveIy (Figure
15.3).
FIg. 15.2 Diagram of motor neuron with its axon.
Dendrites
Nucleus
Soma
Myelin sheath
Node of Ranvier
A
x
o
n
Motor
nerve ending
Animal Physiology !"
In invertebrates, the neurons are usuaIIy encIosed by a singIe Iayer oI sheath ceIIs caIIed Schvann
cells (Fig. 15.4). However, some invertebrate neurons are naked. A nerve is made up oI severaI such
neurons. The ceII body contains protopIasm and a weII deIined nucIeus. Within cytopIasm are minute
nissle bodies.
FIg. 15.3 Schematic diagram to show the functional components of a neuron.
Schwann
cell
axon 1
2
3
FIg. 15.4 Diagram of schwann cells.
Axon can be distinguished Irom dendrites as it is Ionger and carries neurosecretory vesicIes within
its distaI tip. Dendrites branch in the immediate vicinity oI the ceII body and provide an increased
surIace area Ior reception oI stimuIi Irom the externaI environment or Irom other neurons.
PhysioIogicaIIy speaking, axons diIIer Irom dendrites in two ways. FirstIy, the dendrites receive
stimuIi Irom the externaI environment and Irom neighbouring neurons and convert them into
impuIses. SecondIy, the dendrites usuaIIy carry the stimuIi toward the ceII body, whereas the axons
carry impuIses Irom their origin (in the ceII body) to the terminaI Iibres at the distaI end.
Conductile region
(axon)
Input region Output region
Nerue Physiology !#
Neurons exist in a bewiIdering variety oI shapes and sizes, but aII share common Ieatures. Neurons
can be cIassiIied on the basis oI the number oI ceII processes, Iunctions and whether they are
myeIinated. A myeIinated neuron is encIosed in a sheath which is composed oI one to severaI Iayers
oI membranes derived Irom schwann ceIIs. The membrane contains choIesteroI and phosphoIipids.
StructuraIIy, the neurons may be cIassiIied on the basis oI the number oI ceII processes Ieaving the
ceII body. A unipolar neuron has one axon that carries the impuIse towards or away Irom the axon. A
bipolar neuron has two processes arising Irom the ceII body, and a multipolar neuron has severaI
dendrites at one end, an axon on the other.
On the basis oI Iunction, neurons can be cIassiIied into Iour major types: (1) motor neurons which
convey inIormation Irom the centraI nervous system to the eIIector organs, such as muscIes, gIands, etc.;
(2) sensory neurons, which transmit sensory inIormation Irom the peripheraI parts oI the body to the
centraI nervous system; (3) internuncial neurons which Iie between motor (eIIerent) and sensory
(aIIerent) neurons, transmit signaIs in severaI directions by modiIying them in a way best suited to the
need oI the animaI; and (4) neurosecretory neurons that are speciaIized Ior the production oI hormones.
Functioning oI the nerves depends on the neurons and this can be demonstrated by cutting the nerve
Irom the neuron which renders the ceII IunctionIess. CajaI propounded his Iamous neuron theory and
suggested that the dendrites arising Irom the neuron Iorm a compIex network in the grey matter and aII
oI them are in contact with each other. Sherrington (1897) suggested that the dendrites are not
continuous but continuous. CajaI`s theory was Iater discarded in Iavour oI Sherrington`s.
The NeurogIiaI CeIIs
In some invertebrates, aII the axons are devoid oI the surrounding sheath and remain naked. In most
invertebrates and aII vertebrates, neurons are Iused with sateIIite ceIIs or neurogIiaI ceIIs. These are
huge ceIIs with Iarge membrane potentiaIs and Iow eIectricaI resistance. AIthough their Iunctions are
poorIy understood, they are supposed to serve many important Iunctions in inIIuencing the nervous
activities.
A primary Iunction oI these neurogIiaI ceIIs seems to be exchange oI nutrients and waste products
since they are rich in gIycogen deposit and Iipid granuIes. They aIso heIp in giving structuraI support
Ior neurons and appear to be invoIved during degeneration and regeneration oI nervous eIements.
They do not produce any action potentiaIs and are not invoIved in the eIectricaI activity oI the centraI
nervous system.
35.E lRRlTABlLlTY
IrritabiIity can be deIined as the capacity to react to changes in the environment, both internaI and
externaI. IrritabiIity is aIways expressed in some kind oI response. Organisms possess certain
mechanisms oI irritabiIity and respond to various stimuIi. GeneraIIy strong stimuIi produce a response
which is spread over a Iarge area. This is due to Iormation and conduction oI wave oI excitation
passing aIong the ceII membrane. The sequence oI events is; (a) stimuIation; (b) excitation; (c)
conduction; and (d) response.
Animal Physiology !$
When a stimuIus is given, there is a deIay (Iatent period) beIore the response is observed. This
deIay is due to the time taken Ior conduction oI the wave oI excitation Irom the point oI stimuIation.
35.3 ELECTRlCAL PHENDMENA DF NERVES
Resting PotentiaI
The inside oI a neuron, when not excited is negative to the outside. This diIIerence in charge is known
as the membrane potential or resting potential. The resting potentiaI may be deIined as the net
diIIerence in the charge between inside and outside oI a neuron requiring IittIe or no expenditure oI
energy. In a neuron this resting potentiaI is about 70mV, so Iong as the neuron is in a non-excitabIe
state, and is maintained aImost constant. The IoIIowing paragraphs wouId expIain the mechanism
invoIved in the resting potentiaI.
The neuron, Iike aII other Iiving ceIIs, is encIosed by a semipermeabIe membrane containing Iarge
quantities oI protein moIecuIes. These moIecuIes are unabIe to penetrate through the membrane, and
bear a net negative charge. However, smaIIer ions oI potassium (K
¹
), sodium (Na
¹
) and chIoride
(CI

) can diIIuse across the membrane. Na
¹
ions are Iound in higher concentration outside the ceII,
and in Iow concentration inside the ceII. ConverseIy, K
¹
ions are distributed in high concentration
inside the ceII and in Iow concentration outside the ceII. The reIative concentrations oI some oI these
ions inside and outside the squid axons and Irog muscIe are Iound to be as IoIIows (in mM
concentration):
TabIe 15.1 Ionic Concentration of K
+
, Na
+
and Cl
-
, on Either Side of the Nembrane of Squid Axon and
Frog Nuscle Fibre
Squ¡ø axøn Frøg mus¿Iø /¡Drø
1øn 1ns¡øø OuIs¡øø (DIøøø} BIøøø Mus¿Iø
K
+
+00 20 2.5 l+0
Na
+
50 ++0 l20 9.2
Cl
-
+0 560 l20 3.+
These reIative concentrations given in TabIe 15.1 suggest that Na
¹
behaves diIIerentIy as compared
to K
¹
. Na
¹
ions are more outside the Iibre (or membrane) making it positiveIy charged in reIation to the
inside. How is it that. the Na
¹
ions do not migrate inside aIong their concentration gradient to take the
pIace oI K
¹
? German physioIogist Bernstein (1902) propounded a hypothesis to expIain the reason Ior
this phenomenon (ionic equiIibrium) which exists during resting potentiaI. He suggested that the
membrane is seIectiveIy permeabIe to K
¹
ions and impermeabIe to Na
¹
ions during this state. Potassium
ions which are sIightIy smaIIer can however, IIow out to make the outside more and more positiveIy
charged thereby buiIding up a negative potentiaI inside (Fig. 15.5). As a resuIt oI this an ionic
equiIibrium wouId be attained, when the potentiaI diIIerence reaches to about 60 mV between inside
and outside. Such an equiIibrium wouId prevent a Iurther outIIow oI K
¹
ions.
Nerue Physiology !%
EIectricaI Activity in a StimuIated Neuron
A stimuIus couId be in the Iorm oI an eIectricaI, chemicaI, physicaI, eIectromagnetic or pressure change.
Once a stimuIus is given to a nerve ceII, it produces certain eIectricaI events which bring about a
potentiaI change and this couId be measured with the heIp oI a cathode ray osciIIoscope. For this
purpose, microeIectrodes are pIaced on the nerve and connected to the cathode ray osciIIoscope through
an ampIiIier. Changes in the potentiaI are recorded in the Iorm oI verticaI deIIections as they move on
the osciIIoscope screen.
Chronaxie
There are two parameters which determine the excitabiIity oI the tissue: (1) minimaI strength oI the
current when aIIowed to IIow Ior any Iength oI time wiII produce excitation, and (2) a deIinite amount
oI current shouId IIow Ior a minimaI time to produce excitabiIity. In order to evoke a response, the
stimuIus must act Ior certain duration. This was shown by Lapicque who demonstrated the existence
oI a deIinite reIationship between the strength oI the stimuIus and its duration. The minimaI time
required to evoke a response is caIIed excitation time. The stronger the stimuIus, shorter is the
excitation time. This couId be shown with the heIp oI Fig. 15.6.
A strong stimuIus oI 300 mV requires a brieI Iength oI time, but Ior a weaker stimuIus greater
Iength oI time is needed. In Fig. 15.7, 100 mV is considered to be the threshoId strength oI the
stimuIus which is appIied Ior a Ionger duration. A weaker stimuIus than this wouId be ineIIective and
wiII not evoke a response. II the strength oI the current is increased, the excitation time is Iowered.
Lapicque gave a term chronaxie to expIain this principIe. Chronaxie deIined as the time required Ior
a current twice the rheobase to excite a nerve. Thus the eIIiciency oI a stimuIus is determined by its
intensity, its duration, and the speed with which it is appIied.
Action PotentiaI
The most IamiIiar activity oI the excited neurons is the action potentiaI. The equiIibrium condition oI
the resting potentiaI can be disturbed by appIying an outside energy source.
When the neuron is excited, there is a marked change in the potentiaI Irom the resting IeveI zero
and then it becomes 20 or 30 mV. This reversaI oI poIarity caIIed the overshoot (Fig. 15.7). SuddenIy
the potentiaI then reverts to the resting IeveI, that is about 70 mV. In certain cases, it may IaII even
FIg. 15.5 Distribution of ions in a nerve fibre during resting potential.
Na
Na
K
K
Na
Na
K
K
Na
Na
K
K
Na
Na
K
K
Na
Na
K
K
Animal Physiology !&
FIg. 15.6 Strength-duration curve of sartorius muscle of frog (chronaxie).
FIg. 15.7 Diagram of the action potential.
M
i
l
l
i
v
o
l
t
s
Rheobase
Msec
Chronaxie
Rheobase 2
+ 20
– 60
– 40
– 20
0
– 60
0 2 4 6 8 10 12
Resting potential
Threshold potential EPSP
Spike potential
Milliseconds
M
i
l
l
i
v
o
l
t
s
Nerue Physiology !'
beyond that. AII these changes together cause an action potentiaI. The rise and IaII oI the action
potentiaI is caIIed the spike potential, and the short phase oI the action potentiaI beIore reaching the
resting potentiaI is caIIed the negative after-potential. The portion oI the curve which IaIIs beIow the
resting IeveI is caIIed the positive after-potential.
The reversaI oI the membrane poIarity that occurs due to a stimuIus provided to it, has been
expIained on the basis oI sodium theory or membrane potential theory. Both the K
¹
and the Na
¹
ions
oI the neuron and the surrounding IIuid, take part in reversing the poIarity. During the resting
potentiaI stage, Na
¹
ions are ten times more in concentration outside than inside the ceII, whereas K
¹
ions are twenty times more inside than outside. When a stimuIus is provided, there is a rapid inward
movement oI Na
¹
ions to make the inside positiveIy charged. Consequent upon this sudden inward
surge oI positiveIy charged ions, the resting potentiaI is disturbed causing the charge diIIerentiaI to
disappear, resuIting in depoIarization oI the membrane (Fig. 15.8).
FIg. 15.S Sequence of events in a nerve fibre during the conduction of an impulse.
Action
+ 40
+ 20
0
– 20
– 40
– 60
– 80
K
+
Na
+
Na
+
action
+ 40
+ 20
0
– 20
– 40
– 60
– 80
+ 40
+ 20
0
– 20
– 40
– 60
– 80
K
+
Na
+
Na
+
Na
+
Na
+
Potential
Resting potential
1
Axon
M
e
m
b
r
a
n
e
p
o
t
e
n
t
i
a
l
(
m
i
l
l
i
v
o
l
t
s
)
M
e
m
b
r
a
n
e
p
o
t
e
n
t
i
a
l
(
m
i
l
l
i
v
o
l
t
s
)
M
e
m
b
r
a
n
e
p
o
t
e
n
t
i
a
l
(
m
i
l
l
i
v
o
l
t
s
)
Minimum refractory period
Na
+
Na
+
2
3
K
+
K
+
Animal Physiology !
However, soon aIter the reversaI oI poIarity, penetration oI sodium ions stops aItogether IoIIowed
by an overshoot oI about 50 mV in the nerve ceII. At this stage K
¹
ions now begin to IIow tiII such
time the state oI resting potentiaI is restored. This process oI action potential Iasts Ior just 5 to 10
miIIiseconds (Fig. 15.9).
FIg. 15.9 Effect of depolarization on the conductance of Na
+
and K
+
ions. (a) Changes in Na
+
and K
+
conductance
resulting from a step depolarization of 56 mv applied at time 0. Na
+
conductance reaches a maximum and
then declines. K
+
conductance rises after some time delay and remains hight.
The best expIanation oI the action potentiaI was given by Hodgkin, HuxIey and Katz. When the
neuron is stimuIated, sodium ions suddenIy move into the ceII and cause a positive potentiaI. Since
the sodium ions move into the ceII due to excitation, the resting potentiaI changes Irom 70 mV
towards the positive side acceIerating the movement oI sodium ions. This inIIux is due to an increase
in the membrane permeabiIity. The expIanation given by Hodgkin and HuxIey is summarized beIow.
56 mV
20
10
10
20
0
0 2 4 6 8 10
Potassium
conductance
Sodium
conductance
Internal
potential
Time (in sec)
Nerue Physiology !
(1) An eIectricaI stimuIus depoIarizes the membrane increasing its sodium permeabiIity.
ConsequentIy, inIIux oI Na
¹
ions takes pIace. II the inward IIow is sIow, it is counterbaIanced
by the outward IIow oI K
¹
ions, which are more mobiIe. II the initiaI depoIarization is Iarge
enough, that is, iI the membrane becomes suIIicientIy depoIarized, Na
¹
ions move Iaster than
K
¹
ions Ieaving the Iibre. This causes the membrane potentiaI to drop stiII Iurther (about 10-20
mV) when the outIIux oI K
¹
ions can no Ionger keep pace with the Iaster inIIux oI Na
¹
. This
causes an action potentiaI. The reIationship between sodium permeabiIity arid the membrane
potentiaI is shown in Fig. 15.10.
(2) The inIIux oI sodium ions does not continue indeIiniteIy and Ior some reasons, it is haIted near
the peak oI action potentiaI. As a resuIt oI this Na
¹
permeabiIity IaIIs to its resting IeveI and K
¹
ions aIso move outward. The stoppage oI sodium entry may be partIy due to sodium
inactivation and partIy because the membrane potentiaI reaches a IeveI where the net inward
driving Iorce acting on Na
¹
ions becomes zero.
(3) Soon aIter attaining the peak oI the spike, sodium permeabiIity stops and potassium
permeabiIity oI the membrane rises above the resting state. ConsequentIy, eIIIux oI K
¹
ions
takes pIace restoring the membrane potentiaI. At the end oI the spike, originaI IeveI oI
potentiaI is restored but the sodium permeabiIity is stiII in an inactive state. This is absolute
refractory period when it is impossibIe to initiate another action potentiaI. AIter this negative
FIg. 15.9 (b) Changes in sodium (g
Na
) and potassium (g
K
) conductance in a squid axon. (Adapted from N.S. Cordon,
Animal Function: Principles and Adaptations, l968).
g
Na
g
K
10
20
30
0 1 2 3 4
12 mV
EK
m sec
(b)
Ena
115 mV
Animal Physiology !
aIter-potentiaI is reached where the membrane can be retriggered to eIicit another action
potentiaI response (Fig. 15.9).
EIectrotonic PotentiaIs
SubIiminaI stimuIus IaiIs to eIicit a spike potentiaI, aIthough there is a smaII change in the potentiaI
diIIerence between inside and outside the ceII, and the potentiaI may be aItered in either direction.
The direction oI change depends upon the current used. An anodaI current causes the potentiaI to
become more negative, whereas the cathodaI current makes it Iess negative. PotentiaIs produced in
this way are caIIed electrotonic potentials.
lonic Basis of Resting and Action PotentiaIs
It is weII estabIished that the interior oI aII nerve and skeIetaI muscIe Iibres is negative with respect to
outside. Bernstein`s (1902) hypothesis postuIated that the membrane is seIectiveIy permeabIe to K
¹
ions and impermeabIe to Na
¹
, chIoride and other organic ions. As such the excitation is deveIoped
due to depoIarization oI the membrane caused by increased permeabiIity oI cations. LateIy,
Bernstein`s hypothesis has been modiIied in view oI certain objections to it. Excitation does not cause
simpIy depoIarization. A reversaI oI potentiaI is deveIoped. The modern concept presupposes a
'cation pump¨ in the membrane which aIIows rapid entry oI K
¹
than Na
¹
ions and the Ieakage oI Na
¹
into the ceII is controIIed by the sodium pump (Fig. 15.11). Hence most physioIogists beIieve that the
bio-eIectric potentiaIs arise Irom a combination oI concentration gradients and membrane
permeabiIity to generate action and resting potentiaIs.
In a system Iike the one expIained above, the membrane separating the two soIutions is
speciIicaIIy permeabIe to onIy one type oI ions. The potentiaI diIIerence across the membrane is given
by Nernst equation.
E
m
÷
R1
F

(Penetrating ion outside)
(Penetrating ion inside)
÷ 58 Iog
10
(ion outside)
(ion inside)
miIIivoIts
E
m
is the equiIibrium potentiaI at which the Iorce exerted by the concentration gradient is exactIy
baIanced, R1/F denotes the conversion Iactor oI gas constant (absoIute temperature, vaIence and
Faraday units). For a positiveIy charged cation, E
m
is the inside potentiaI. It has been demonstrated
FIg. 15.1û Relationship between Na
+
permeability and the membrane potential.
Depolarization
of the membrane
Increase in Na
permeability
+
Entry of Na
+
Nerue Physiology !!
now that the resting membranes oI nerves and muscIe Iibres are not onIy excIusiveIy permeabIe to K
¹
ions, but aIso permeabIe to CI

ions and partiaIIy to Na
¹
ions. According to GoIdman, the potentiaI
deveIoped across a membrane permeabIe to aII these ions can be IormaIIy described thus:
E
m
÷
R1
F
Iog
e

P P P
P P P
o o i
i i o
K Na CI
K Na CI
K) Na) CI)
K) Na) CI)
( ( (
( ( (


where i and o reIer to inside and outside respectiveIy and P denotes the permeabiIity constant; CI

reIers
to ions Ior which there is no active transport.
The ionic composition and equiIibrium potentiaIs have been extensiveIy worked out Ior Irog muscIe
and Ior squid axons (TabIe 15.2).
The resting potentiaI arises Irom the potassium concentration gradient and the membrane behaves
Iike a potassium eIectrode.
FIg. 15.11 Nodel illustrating the sodium pump showing ionic composition inside and outside a resting nerve cell (After
Eccles. Scient. Amer. 2l2 (l) 55, l965)
Exterior
Surface
membrane
Interior
Diffusional
fluxes
K ion
fluxes
+
K –Na
pump
+ +
Metabolic
drive
of pump
Na
ionic
fluxes
+
Diffusional
flux
Animal Physiology !"
35.4 THEDRlES DF EXClTATlDN
A number oI theories have been propounded which attempt to expIain the phenomenon oI excitation.
However, not a singIe theory is compIete in itseII and aII expIain the intricate phenomenon partiaIIy
onIy. Some oI these theories wiII be considered here.
Nernst Theory of Excitation
This is the oIdest theory which accounts Ior the quantitative IormuIation oI the excitation phenomena. In
a resting ceII, Iree movement oI ions does not take pIace, but when the ceII is stimuIated eIectricaIIy,
ionic movement into and out oI the ceII takes pIace. Nernst excited the ceII by a constant current and
noted that a current oI high Irequency does not produce excitation at very high intensity. This Ied him to
suggest a reIationship oI strength-duration by a IormuIa,
i t ÷ K
where i is the strength oI the current enough to excite, t is the time duration, and K is the constant Ior
the ceII which is excited. Nernst IormuIa has been improved upon by severaI workers. NevertheIess, it
has IaiIed to account Ior some changes taking pIace in the eIectricaI potentiaIs.
Membrane-permeabiIity Theory
This theory takes into account the Iact that whenever a ceII is excited, there is a change in the
permeabiIity oI the surIace membrane oI the protopIasm. Studies perIormed on the giant axon oI
squid reveaIed that by using eIectrodes to measure the impedance to aIternating current across the
axon, impedance was greatIy reduced in a reversibIe manner. AIter cessation oI the stimuIus the
resistance was restored. This means that the axon sheath permits an increased permeabiIity to ions
when excited.
TabIe 15.2 Concentration of Ions in the Cytoplasm and in the Blood Plasma of Squid Axons and Frog
Nuscle and Equilibrium Potentials Calculated from Nernst Equation
Squ¡ø axøn Frøg mus¿Iø
m-møIø,Kg ø/ waIør
(K
+
) inside +l0 l25
(K
+
) outside 22 2.6
E
K
- 7+ mv - 98 mv
(Na
+
) inside +9 l5
(Na
+
) outside +60 ll0
E
Na
+ 56 mv + 50 mv
(Cl
-
) inside l23 l.2
(Cl
-
) outside 560 77
E
Cl
- 38 mv - l0+ mv
(TaDIø aøapIøø /røm HøøgK¡n (l95l), Biol. Rev. 26; Kø)nøs (l96+), J. Physiol. l69.)
Nerue Physiology !#
CaIcium-reIease Theory
HeiIbrunn proposed a theory that excitation causes certain caIcium-protein compounds to reIease Ca
¹¹
ions that induce changes in the protopIasm. The Ca
¹¹
ions so reIeased near the ceII surIace cause
IiqueIaction oI the geI-cortex oI the ceII so that Ca
¹¹
ions diIIuse to the ceII interior, IiqueIaction is
temporary and is IoIIowed by geIation.
AcetyIchoIine-production Theory
When the ceIIs are excited, acetyIchoIine is reIeased and its reIease is Iinked with the caIcium-reIease
theory. When a neuron is excited, acetyIchoIine is Iiberated Irom some compIex which changes the
properties oI the ceII membrane causing movements oI ions. Na
¹
and K
¹
are mainIy concerned with
this. Na
¹
ions start moving into the ceII to increase the concentration and are responsibIe Ior the rising
phase oI the action potentiaI ConverseIy, K
¹
ions start moving out oI the ceII across the membrane
which corresponds to the IaIIing phase oI the action potentiaI. AcetyIchoIine cannot stay Ionger and
immediateIy, it is hydroIyzed by an enzyme acetyIchoIinesterase marking the reIractory period, aIter
which the membrane is again ready Ior another excitation. The caIcium ions are IargeIy responsibIe to
activate the enzyme acetyIchoIinesterase.
Dsterhout's Theory
Based on the study oI excitation phenomenon in the aquatic pIant Nitella, Osterhout postuIated that K
¹
ion concentration oI the sap and the surrounding soIution is responsibIe Ior an action potentiaI.
Excitation induces movement oI K
¹
ions. This theory takes into account the movement oI K
¹
ions
onIy and it has been suggested that the movement oI other ions must aIso be considered.
35.5 FACTDRS lNFLUENClNG EXClTATlDN
AND PRDPAGATlDN
The process oI excitation oI a nerve, and the propagation oI the impuIse is inIIuenced by a number oI
Iactors, some oI which are brieIIy described here.
Repetitive StimuIi
The excitabiIity and conductivity oI a nerve is hampered by repeated stimuIation provided the intervaI
between two stimuIi is not Iess than reIative reIractory period. II the intervaI between two stimuIi is
shorter than the reIractory period, the subsequent stimuIi produce progressiveIy smaIIer spikes as
compared to the Iirst. By continuous stimuIation the negative and positive aIter-potentiaIs increase.
The excitabiIity and veIocity oI conduction become subnormaI during the positive aIter-potentiaIs.
Temperature
The excitatory process as weII as the propagation oI the nerve impuIse are greatIy inIIuenced by
temperature changes. Lowering oI temperature brings about bIockade oI impuIse transmission. In
mammaIs and Irogs, a temperature oI 0°C aIways suspends the excitatory process.
Animal Physiology !$
Drugs
Administration oI certain drugs Iike cocaine, novocaine, etc., do not aIter the spikes, but the excitabiIity
and aIter-potentiaI are greatIy aIIected.
35.8 lMPULSE PRDPAGATlDN
When a stimuIus is provided in nerve tissues, a IocaI depoIarization is initiated and it spreads out
rapidIy over the ceII membrane in the Iorm oI a wave known as the nerve impuIse. The conduction oI
an impuIse is a bioeIectricaI phenomenon. This impuIse is propagated aIong the axon undisturbed.
The nerve impuIse obeys all-or-none principIe; once initiated it is propagated down the axon without
any change in its intensity or veIocity.
The impuIse is initiated at the dendritic end oI a ceII and it traveIs aIong the axon towards the
terminaIs (output zone).
There are certain aspects oI the nerve conduction which shouId be taken into account. These are
excitabiIity threshoId, reIractory period and accommodation. Excitation causes depoIarization oI the
ceII membrane and the magnitude oI the stimuIus required to activate a neuron varies with the state oI
the ceII. ExcitabiIity threshoId is the criticaI IeveI when the membrane potentiaI is deveIoped at which
the net rate oI entry oI Na
¹
becomes exactIy equaI to the net rate oI exit oI K
¹
ions. During the spike
potentiaI, the neuron wiII not respond to any stimuIus, however strong it may be. This period is the
absoIute reIractory period (Fig. 15.7). ThereaIter, untiI the beginning oI the negative aIter-potentiaI,
there is reIative reIractory period. During this period excitabiIity is higher than at rest. During the
negative aIter-potentiaI excitabiIity is Iow, whereas during the positive aIter-potentiaI it is higher than
at rest. PhysioIogicaIIy speaking, during the reIractory period sodium permeabiIity is inactivated, but
the K
¹
ions permeabiIity is greater than the normaI.
Nerves aIso show the power oI accommodation. II the nerves are stimuIated by graduaIIy
increasing currents, they do not show a response because oI the accommodation oI the stimuIus.
Accommodation may be either due to proIonged potassium permeabiIity or to inactivation oI sodium
permeabiIity mechanism.
Action PotentiaI Conduction
We have outIined beIore that action potentiaI is initiated with the depoIarization oI the membrane and
the Na
¹
ions start diIIusing inside the nerve Iibre. This brings about aIteration in the membrane
poIarity making outside oI the ceII negative in reIation to inside. Such changes are Iirst initiated at the
point where stimuIus is provided and at this particuIar point the poIarity oI the remaining area oI the
membrane is undisturbed. Because oI the attraction oI positive charges towards the negative ones,
positive charges IIow in towards the negative setting up a IIow oI current (Fig. 15.12). Since the
positive charges are removed Irom the point, the potentiaI diIIerence between the two sides oI the
membrane is Iowered, making the resting potentiaI Iess negative at that point. This increases
permeabiIity oI the membrane to Na
¹
ions which quickIy move in. Again this portion oI the
membrane undergoes reversaI in poIarity making the outside positive. The entire sequence is repeated
and a sequence oI action potentiaIs is deveIoped which moves in either direction Irom the point oI
Nerue Physiology !%
FIg. 15.12 Conduction of action potential in nonmyelinated squid axon fibre. Horizontal scale represents conduction
velocity of 20 mfsec.
(A) Change in membrane potential, broken lines showing zero potential and Nernst potentials for Na
+
and K
+
; (B) Polarity of potential difference across the membrane and ionic move ments; (C) variation in
Na and K permeabilities; (D) Local circuit current flow; (E) variation in total membrane conductance; (A
to C, after Hodgkin and Huxley (l952), J. Physiol, ll7, 530; D to E, after Cole and Curtis (l939) J. Cen
Physiol, 22). E
m
for K ions = E
K
, E
Na
for Na ions = E
Na
Na
K
B
0 1 2 3 4 5 6
0 2 4 6 8 12 10
m sec
cm
E
D
E
Na
A O
E
K
C
P
Na
P
K
Direction of propagation
Animal Physiology !&
stimuIation. This is how the impuIse is generated in a nonmyeIinated neuron. However, in case oI
myeIinated neurons, the situation oI impuIse propagation is somewhat diIIerent.
Conduction in MyeIinated Nerves
The mechanism oI impuIse propagation in myeIinated Iibres is diIIerent Irom that oI unmyeIinated ones.
The conductivity oI nonmyeIinated nerve Iibres is Iower because oI the absence oI insuIating
materiaI. In myeIinated nerves, there are points oI nodes of Ranvier where meduIIary sheath is aImost
absent. These points are highIy excitabIe. In the process oI conduction, the excitation jumps Irom one
node to another aIong the Iength oI the nerve (Fig. 15.13).
FIg. 15.13 Diagram illustrating the local circuit theory in (a) nonmyelinated fibre and (b) myelilnated fibre (saltatory
conduction). (After A.L. Hodgkin (l957), Proc. Roy. Soc. B. l+8)
This jumping mechanism has been caIIed saItatory condition. In this process, active generation oI
the current is conIined to the nodaI points due to the entry oI sodium ions, whereas the internodaI parts
oI the nerve are depoIarized by IocaI circuit action. However, the IocaI circuits act much ahead oI the
region oI activity since the conduction activity oI internodaI portions is quite high. SaItatory conduction
was demonstrated by HuxIey and StampIIi (1949).
Events in lmpuIse Propagation
The action potentiaI is characterized by a series oI events that can be studied with the heIp oI two sets
oI eIectrodes. One set is used to give a stimuIus and the other is used to record the voItage across the
ceII membrane.
When a stimuIus is appIied, a short Iatent period occurs which is actuaIIy the time Iapse between
the appIication oI the stimuIus and the response. FoIIowing the Iatent period, the nerve membrane is
depoIarized with the consequent reduction oI transmembrane potentiaI. II a subthreshoId stimuIus is
passed through a nerve, the impuIse propagation IaiIs to occur, but onIy a IocaI potentiaI appears.
LocaI potentiaIs are non-propagative and graded. By graduaIIy increasing the strength oI the stimuIus,
a threshoId IeveI oI the stimuIus is reached which produces a critical potential. When the criticaI
Repolarization Depolarization Resting
Impulse
Axoplasm
NaNaNa
Axoplasm
Direction of impulse Myelin sheath
Active node
or Ranvier
Outward flow of
current depolarizes
node
(b) (a)
Nerue Physiology !'
potentiaI is reached, the impuIse is propagated in the Iorm oI spike. At this moment, depoIarization oI
the membrane occurs due to the inIIow oI sodium ions. The duration oI the spike varies with the speed
oI conduction and Iibre size.
AIter depoIarization the membrane potentiaI decIines in its negative vaIue, passes through zero
potentiaI and becomes positive. The moment spike height attains its peak, the potentiaI reaches its
maximum positive vaIue. This is how action potentiaI is caused. AIter this the membrane potentiaI is
restored causing repoIarization. This is due to diIIusion oI potassium ions to the outside. A positive
after-potential is soon reached in which case voItage is more negative than the resting potentiaI.
FoIIowing this, another event oI negative after-potential is reached when the voItage is Iess negative
than the resting potentiaI (Fig. 15.7).
During the positive aIter-potentiaI the nerve has a greater threshoId excitabiIity. AII these events
described above constitute an action potentiaI. AIter the ceII membrane has been depoIarized, a
refractory period occurs which continues untiI the resting potentiaI is restored, and during this period
the nerve recovers. The chemicaI changes accompanying the eIectricaI event are probabIy connected
with the recovery process. During reIractory period the portion oI the Iibre through which the impuIse
has aIready been propagated is not responsive to stimuIi. But, aIter the recovery process the nerve is
again excitabIe and stimuIus at this time wouId create another puIse. AII such impuIses are conducted
aIong the nerve at a constant ampIitude and veIocity. Thus, the propagation is in the Iorm oI a series
oI puIses which are aII aIike. This principIe is caIIed pulse-coded analog principIe since a nerve Iibre
conducts an impuIse intermittentIy.
VeIocity of the Nerve lmpuIse
The veIocity oI the nerve impuIse diIIers in nerve Iibres oI diIIerent animaIs. The nerve impuIse veIocity
can be measured with the heIp oI a cathode-ray osciIIoscope utiIizing two parameters: (1) the diIIerence
between the duration oI two Iatent periods, and (2) the Iength oI nerve between the two points oI
excitation. The Iatent period can be determined by knowing the time Iapse between the appIication oI
nerve stimuIus and the moment the muscIe begins to contract.
In the sciatic nerve preparation oI Irog at room temperature, the veIocity is about 30 metres per
second, whereas in the human motor nerve it is about 120 metres per second. In nonmeduIIated nerve
Iibres, the veIocity oI conduction is much sIower, as Iow as I cm per second in some invertebrates.
Variations in the veIocity are due to severaI parameters. Diameter oI the nerve Iibres is the most
important Iactor. The veIocity oI impuIse conduction is proportionaI to the diameter (v/d ratio). The
veIocity oI conduction is very sIow in the sensory nerve Iibres oI the skin as compared to the motor
nerves having Iarger caIibre. For this reason, the nerve Iibres carrying sensation oI pain are very sIow
in their conduction.
Other Iactors which aIIect the veIocity are temperature, conductivity oI the medium, sheath
thickness, etc.
Nature of a Nerve lmpuIse
Any disturbance aIong the Iength oI a nerve may cause a change in its potentiaI at any point.
PhysioIogists beIieve that the change in the potentiaI may be either a (1) physicaI change brought
about by movement oI ions, or a (2) chemicaI change accompanied by Iiberation oI chemicaI energy
Animal Physiology !!
(viz. oxygen consumption, Iormation oI CO
2
and Iiberation oI heat are some evidences oI chemicaI
change), or (3) a physicochemicaI change.
The passage oI nerve impuIse causes chemicaI changes in the nerves aIIecting their metaboIic rate.
It has been demonstrated that the nerves under stimuIation produce more CO
2
as compared to the
resting ones. Excitation aIso increases oxygen consumption by nerves. This has been shown
experimentaIIy by keeping nerve preparations in oxygen-Iree atmosphere when they Iose their
excitabiIity. Excitation oI nerve aIso resuIts in greater heat production.
35.7 SYNAPTlC TRANSMlSSlDN
The Synapse
As aIready noted, the neurons are the basic units Ior communication. The communication may not be
possibIe unIess the inIormation induces an eIIector organ or ceII to act by secreting a chemicaI
messenger or a transmitter substances across a gap. The gaps between neurons are caIIed synapses.
The discovery oI synapse was made by CajaI at the end oI the nineteenth century. FoIIowing this
discovery, a controversy was raised over the transmission oI impuIse across the gap. Some thought that
the synaptic transmission was eIectricaI, whiIe others thought that it is mediated by a chemicaI
messenger. Synapses exhibit three important characteristics: (1) the mode oI transmitting the impuIse
across the synapse; (2) one-way transmission pattern; and (3) modiIication oI impuIse transmission.
The nerve endings are buIb-Iike having a synaptic membrane investing in the terminaI region
synaptic vesicIes. For conduction, the impuIse reaching the presynaptic membrane must be strong
enough to depoIarize the presynaptic membrane to start an impuIse in the postsynaptic
neuron (Fig. 15.14).
FIg. 15.14 Diagram to show the structure of a synapse.
Glial
membrane
Mitochondrion
Synaptic
vesicles
Subsynaptic
membrane Synaptic cleft
Presynaptic
membrane
Nerue Physiology !!
An impuIse may be propagated in the neuron in either direction. However, iI the neurons are
arranged in a chain, the impuIse can traveI in onIy one direction because oI the synapse Iormation.
UsuaIIy at a synapse the impuIse is transmitted Irom the terminaI knobs oI the axon oI one neuron to
the dendrites, or ceII body oI the secondary neuron. It cannot be transmitted in the opposite direction
since the dendrites and the ceII body do not reIease any transmitter substance.
II a postsynaptic neuron is stimuIated, the impuIse wiII be conducted to the dendrites and the
presynaptic neuron wiII remain unaIIected. Synaptic transmission wiII continue as Iong as there is
adequate suppIy oI oxygen and ATP. In the absence oI these, the synapse wiII Iatigue. On the contrary,
the neurons do not undergo Iatigue and the nerve constituting them wiII continue to produce action
potentiaIs. The synaptic Iatigue is due to the deIiciency oI transmitter substance.
Drugs aIso aIIect synapses. There are some drugs which stimuIate, whiIe there are others which
have inhibitory inIIuence. The inhibitory drugs bIock the reIease oI transmitter substance, and the
excitatory drugs bIock the reIease oI inhibitory transmitter substance.
TYPES OF SYNAPSES: AIthough synapses vary between diIIerent types oI ceIIs, they have certain
common properties. GeneraIIy, the presynaptic Iibres divide into Iine branches which terminate in
synaptic knobs. These knobs are not in intimate contact with the membrane or the dendrites oI the
postsynaptic ceII but Iie very cIose to them. EIectron microscopicaI studies have reveaIed that the pre-
and postsynaptic membranes are separated by narrow gaps or cIeIts about 250 A wide. The synaptic
cIeIts oIIer very IittIe resistance when eIectricaIIy excited and there is very IittIe spread oI the current
through the postsynaptic membrane. Two types oI synapses have been recognized: (1) eIectricaI
synapses; and (2) chemicaI synapses.
Electrical synapses: EIectricaIIy transmitting synapses have severaI Ieatures worth noting. They
have a Iarge synaptic area oI contact, the junction between the two ceIIs is very tight and there is
aImost no resistance to the IIow oI the current. ConsequentIy, there is no synaptic deIay and the
current IIow is aImost instantaneous across the synaptic cIeIt. The eIectricaI coupIing between the
presynaptic ceII (PRC) and the postsynaptic ceII (PTC) is an intimate one so that enough current
IIows Irom the presynaptic ceII to the postsynaptic ceII to cause depoIarization. The depoIarization
caused by an eIectric current is regenerative and produces an aII-or-none eIIect which is propagated in
the Iorm oI a spike without any decrement. EIectricaI synapses can normaIIy transmit in either
direction unIike chemicaI synapses and are generaIIy non-ampIyIying types.
EIectricaI synapses were considered a property oI invertebrates onIy, but IateIy they are Iound to
occur in severaI vertebrates aIso.
EIectricaI stimuIus Increases Na
¹
DepoIarization
conductance B
Spike
These synapses can be divided into two types on the basis oI the depth oI the synaptic cIeIts. First
type oI synapses are excitatory in which case the synaptic cIeIt is about 300 to 400 A deep. The
synaptic membrane is usuaIIy thicker and provided with dark staining dense patches. In other types oI
synapses, the synaptic cIeIt is about 150-200 A deep. The subsynaptic membrane is thin and enIarged
by the presence oI IoIds. The neuromuscuIar junctions are oI the Iatter type and are caIIed inhibitory
Animal Physiology !!
synapses. AIthough it is diIIicuIt to distinguish between excitatory and inhibitory synapses on
morphoIogicaI grounds, the gamma-aminobutyric acid (GABA) acts as the inhibitory transmitter in
vertebrates. The probabIe mode oI action oI GABA is simiIar to that oI acetyIchoIine. The reIease oI
transmitter substance causes a temporary increase in permeabiIity to K
¹
and CI

ions (Na
¹
ions are not
aIIected) so that the resting potentiaI is equaI to the equiIibrium potentiaI.
Chemical synapses: Majority oI the synapses that have been investigated IaII in the category oI
chemicaIIy transmitting types. A simpIe synapse invoIves two neurons in a chain. In case oI knee-jerk
reIIex two neurons pIay the part Irom reception oI the stimuIus to causing the response. This is caIIed
a monosynaptic reflex. In a number oI cases, many internunciaI neurons are invoIved so that the
situation becomes compIicated. This is, however, accompIished by integrating the inIormation at the
synaptic junctions.
There is a cIearcut distinction between transmission oI an impuIse aIong nerve and transmission
across a synapse. The passage oI an impuIse across the synapse is unidirectionaI and is accompIished
by the reIease oI a chemicaI transmitter substance. The synaptic knobs contain a Iarge number oI
synaptic vesicIes which are probabIy the sites oI manuIacture and reIease oI the transmitter. For the
impuIse to traveI across the synapse, there is some time deIay caused by the reIease and diIIusion oI
the transmitter substance across the synaptic cIeIt. The depoIarization oI the presynaptic membrane
generates an action potentiaI which is transIerred to the postsynaptic membrane aIter a deIay oI about
0.4 to 10 msec.
In aImost aII chemicaI types oI synapses, synaptic cIeIt is present. The neuromuscuIar junctions
resembIe such synapses in aII essentiaI detaiIs where the impuIse transmission is much Iaster. In 1936,
DaIe and coworkers demonstrated that acetyIchoIine is the neuro-transmitter substance which is
reIeased at the motor nerve terminaI in the neuromuscuIar junction. ConsequentIy, a postsynaptic
potentiaI or an end-pIate potentiaI (EPP) is deveIoped which is IocaIized to the end-pIate onIy and
begins about 1 msec aIter the arrivaI oI the impuIse in the nerve terminaI.
Very IittIe is known about the mechanism oI Iormation oI the transmitter substance. However, it
has been estabIished that many oI the synapses are chemicaIIy transmitting types and oI the nature oI
neuromuscuIar junctions.
The entire mechanism oI chemicaI transmission is very compIex, and is onIy partiaIIy understood.
The transmitter substance aIters the permeabiIity oI the postsynaptic membrane reversing the poIarity
thereby making it more permeabIe to Na
¹
ions. Such synapses are caIIed excitatory synapses, which
reIease an inhibitor substance enhancing the permeabiIity to K
¹
ions which tend to diIIuse outward.
This makes the inside oI the postsynaptic membrane more negative resuIting in the increase oI
potentiaI across the postsynaptic membrane. This is caIIed hyperpolarization.
Most oI the synapses have acetyIchoIine as the transmitter substance. When a nerve impuIse
reaches the presynaptic buIb, the vesicIes burst open and reIease acetyIchoIine into the synapse which
diIIuses in aII directions. The chemicaI causes depoIarization in postsynaptic membrane and thus the
excitation traveIs in one direction onIy. As soon as acetyIchoIine is reIeased in the cIeIt, it is quickIy
hydroIyzed by an enzyme acetylcholinesterase. Thus acetyIchoIine does not remain in the cIeIt Ior
more than a miIIisecond.
Nerue Physiology !!!
AcetyIchoIine H ChoIine Acetic Acid
2
acetyIchoIinesterase

AcetyIchoIine is not the onIy chemicaI transmitter in aII the neurons. AcetyIchoIine is the
transmitter substance in case oI vertebrate centraI nervous system. Other transmitter chemicaIs are
adrenaIine (epinephrine) and serotonin (5-hydroxytryptamine). AdrenaIine is secreted by the synaptic
buIbs oI the nerves suppIying to smooth muscIes, gIand ceIIs and heart Gamma-amino-butyric acid
(GABA) is an inhibitory neurotransmitter and prevents antagonistic muscIes Irom contracting.
InIormation about the externaI worId is received through the receptors or sense organs and integrated
in a way so as to produce a meaningIuI response. In the integration oI sensory inIormation, aII
speciaIized parts incIuding the nervous system and the receptor-eIIector system are invoIved. This
inIormation is processed through eIaborate neuraI mechanisms. The receptors are responsibIe Ior
gathering more precise and compIete sensory inIormation, whereas the eIIectors are concerned with
the eIIective execution oI the reactions oI the nervous system to such inIormation.
Each sense organ is an organized group oI ceIIs around a group oI receptor ceIIs which are
speciaIized to receive speciIic type oI stimuIus. There are two types oI sense organs: simpIe and
compIex. SimpIe types oI sense organs such as sensilla occur in arthropods which contain a Iew nerve
ceIIs. CompIex type oI sense organs are composed oI severaI nervous and non-nervous tissues in a
singIe organ. These incIude the organs oI speciaI senses oI vertebrates such as the vision, audition
(hearing), taste and oIIaction. Our eyes respond to Iight waves oI speciIic waveIengths, our ears to
vibrations in the air, our taste buds and oIIactory (smeII) organs to chemicaI substances. But the
perception oI speciIic stimuIi is not an independent Iunction oI receptors aIone. The receptors have to
communicate with the nervous system as weII so that a stimuIus is transIated into a nerve impuIse.
A study oI sensory mechanisms is oI great interest to us since the Iunction oI the nervous system
is dependent on such mechanisms. The nervous Iunction is adapted to the sensory input which is aIso
responsibIe Ior reguIating the overaII activity oI the centraI nervous system. In this chapter, our aim
wiII be to study the sensory mechanisms invoIved in the perception oI various kinds oI stimuIi. In this
context, the reader is advised to go through the neuron structure and the physioIogy oI the impuIse
transmission through a nerve which wouId be oI immense vaIue in the understanding oI receptor
mechanism.
38.3 CLASSlFlCATlDN DF RECEPTDRS
The point oI contact between the nervous system and the environment is the receptor ceII. A receptor
5ensory Mechonisms
+ 0 ) 2 6 - 4
$
Sensory Mechanisms !!#
ceII may exist independentIy or outside a sense organ and may detect most readiIy onIy certain stimuIi
Ior which it is speciaIized. When an eIIective stimuIus impinges upon a suitabIe sensory ceII, it
generates an impuIse to be communicated to the nervous system. This is ca1Ied sensory transduction.
The impuIse traveIs in a certain direction with a speciIic speed depending upon the quaIity and
duration oI the stimuIus.
There are severaI types oI receptors in an animaI body and these have been cIassiIied variousIy by
diIIerent authors. The oIdest cIassiIication, based on their position in the body, recognized two types
oI receptors-exteroceptors and enteroceptors. Exteroceptors respond to stimuIi Iike Iight, temperature,
and pain, whereas the enteroceptors Iocated inside the body respond to internaI changes such as
hydrogen-ion concentrations, osmotic pressure, and oxygen tension.
Receptors may aIso be cIassiIied according to their source oI stimuIus. These are: exteroceptors
Iocated at the surIace oI the body responsive to stimuIi emanating Irom the environment;
proprioceptors Iocated in the deeper regions oI the body sensitive to the position oI the body; and
enteroceptors Iocated in the Iining oI the digestive system and responsive to stimuIi coming Irom
within the body oI the organism. The cIassiIication oI receptors as proposed by Parker, based on the
nature oI stimuIus, is given beIow:
(1) Chemoreceptors: Receptors which respond to stimuIi by chemicaIs are termed as
chemoreceptors. They incIude: (a) oIIactory receptors; and (b) gustatory receptors (taste).
(2) Mechanoreceptors: They respond to mechanicaI stimuIi oI various modaIities and incIude: (a)
muscIe receptors; (b) pressure receptors oI the skin; (c) gravity receptors; (d) audio receptors;
and (e) nociceptors.
(3) Radioreceptors: These are excited by the eIIects oI radiant energy such as heat and Iight, and
are: (a) photoreceptors; and (b) thermoreceptors.
38.E CHEMDRECEPTDRS
The chemoreceptors respond to chemicaI stimuIi and heIp the animaI in Iocating the Iood, Iinding
mates and escaping the enemies. There are two types chemicaI receptors-oIIactory receptors and taste
receptors. In the simpIest animaIs such as invertebrates, the chemicaI senses are wideIy distributed
over the body and their deIinite roIe in chemoreception can be ascertained by studying the nature oI
response to speciIic chemicaIs.
DIfactory Receptors
OIIactory receptors are primariIy concerned with the sense oI smeII. In vertebrates the oIIactory
receptor is innervated by the Iirst craniaI nerve and consists oI a group oI highIy speciaIized receptors
responding to chemicaIs that are voIatiIe. These sense organs vary in structuraI detaiIs in diIIerent
animaIs, but in generaI they are composed oI a group oI neurons Iocated near the body surIace. Each
neuron sends out a Iong dendritic IiIament into some space which may be a pit, peg-Iike or hair-Iike
papiIIa. Pit-Iike sense organs are present in mammaIs whereas peg-Iike or hair-Iike sense organs are
Iound IargeIy in arthropods.
Animal Physiology !!$
OLFACTORY RECEPTORS IN VERTEBRATES: The oIIactory sense in vertebrates is Iocated in the nasaI
region. We may describe here the human sense oI smeII providing a good basis oI understanding. The
oIIactory passage in the nose is Iined by the oIIactory epitheIium or mucosa. The mucosa contains
basaI ceIIs, supporting ceIIs and the oIIactory bipoIar ceIIs (Fig. 16.1). The bipoIar ceIIs are the actuaI
neurosecretory oIIactory ceIIs having at their Iree ends hair-Iike processes. These ceIIs possess a
dendrite, caIIed the olfactory rod, which extends beyond the oIIactory epitheIium.
FIg. 16.1 Diagram showing the bipolar cells of the olfactory epithelium in vertebrates.
SmeII receptors receive stimuIation Irom odours coming Irom distant sources which deveIop
sIowIy generator potentiaIs in the bipoIar ceIIs. The bipoIar ceII has a duaI Iunction: it Iunctions as a
receptor ceII as weII as a gangIion ceII. But, how are diIIerent odours discriminated? Very IittIe is
known about the sense oI discrimination in oIIaction. Seven categories oI primary odours have been
identiIied: these are camphoraceous, musky, IIoraI, pepperminty, ethereaI, pungent and putrid.
AIthough each receptor has a certain degree oI speciIicity in identiIying a particuIar odour, yet
overIapping is possibIe. However, the speciIicity oI the receptor ceII is abIe to provide enough cIues to
the brain Ior discrimination. A stereochemical theory has been proposed to expIain odour
discrimination. The theory postuIates that the odoriIerous substance is a voIatiIe one and each
substance has a speciIic moIecuIar conIiguration. In order to perceive seven diIIerent primary odours,
there are at Ieast seven types oI oIIactory ceIIs each oI which is capabIe oI perceiving a moIecuIe oI a
speciIic conIiguration. OI course, morphoIogicaIIy such receptors are diIIicuIt to be identiIied.
Axons
Basement
membrane
Endoplasmic
reticulum
Sustentaclar
cell
Receptor cell
Cilia
Dendrite
Sensory Mechanisms !!%
OLFACTORY RECEPTORS IN INVERTEBRATES: OIIactory receptors are Iound in Iower invertebrates
aIso but they are scattered aII over the skin. Such receptors are aIways oI primitive kind and are
devoid oI any synapse between the receptor ceII and the nerve Iibre joining the nervous system. SmeII
receptors oI sea anemones are oI this nature which show sensitivity to Ioods and other substances
present in water. However, primitive receptors oI this type are Iound in aII animaIs.
Gustatory Receptors
The organs oI taste or gustation consist oI taste buds Iocated chieIIy on the dorsum oI the tongue.
They are aIso Iound in the epigIottis, soIt paIate, and the pharynx. The structure oI taste buds is IairIy
uniIorm in vertebrates, and each consists oI a cIuster oI neurosensory ceIIs and supporting ceIIs
arranged in a gobIet-shaped structure embedded in a stratiIied epitheIium (Fig. 16.2), The supporting
ceIIs Iorm the outer covering whiIe neurosensory ceIIs remain in the interior. Each neurosensory ceII
is Iong and narrow with a thin taste hair at its Iree end and a sensory nerve Iibre at its base. The taste
hairs are ciIia-Iike and project into a depression caIIed taste pore in mammaIs. In some animaIs, the
hairs project above the surIace oI the epitheIium. In such cases, the taste pores are absent.
FIg. 16.2 Taste buds in vertebrates.
Taste buds are wideIy distributed in Iishes, Iocated in the mouth, pharynx, branchiaI cavities,
outer surIace oI the head, and in some even occurring over the entire body surIace. In vertebrates, the
taste buds are innervated by eighth, ninth and tenth craniaI nerves that carry the taste Iibres to the
meduIIa. Some oI the taste Iibres end up in a nucIeus outside oI the soIitary tract within the meduIIa.
The taste sensations are carried to the thaIamus and the cerebraI cortex.
In mammaIs various kinds oI papiIIae are Iound on the tongue containing taste buds. The taste
buds can perceive taste when substances are in soIution. In man, Iour primary sensations oI taste have
been recognized; they are sweet, saIty, bitter and sour. These quaIities are dependent upon the
Iunction oI speciIic receptors which are distributed in speciIic areas oI the tongue. The receptors Ior
Pore
Epithelium
Receptor cell
Nerve fibres Taste bud
Basement
membrane
Animal Physiology !!&
sweet taste are Iocated mostIy on the tip oI the tongue, Ior bitter taste at the root, and Ior sour and
saIty taste on the sides oI the tongue.
Since the taste buds are innervated by neurons that enter Irom the base, it is probabIe that the
nerve Iibres are stimuIated directIy by dissoIved substances that enter the taste pore. The inside oI the
taste bud is negative to the outside with a potentiaI diIIerence oI about 70 mV. StimuIation oI taste
buds occurs when the hair-Iike processes are sensitized which is possibIe when substances in soIution
come in contact with the taste buds changing the potentiaI to Iess negative. The magnitude oI the
receptor potentiaI is directIy proportionaI to the intensity oI the stimuIus; i.e. the concentration oI the
substances which increases the rate oI Iiring. The rate oI Iiring oI the sensory neurons increases with
the increasing rate oI stimuIi.
38.3 MECHANDRECEPTDRS
The mechanoreceptors respond to mechanicaI stimuIi oI diIIerent modaIities. These incIude muscIe
sense, sense oI equiIibrium, touch and hearing. The simpIest kind oI mechanorceptores are the
pressure or touch receptors Iocated in the skin and responding to stimuIi emanating by movement or
pressure exerted by an object against the receptor. The sense oI hearing or audition is adapted to
record mechanicaI disturbances Irom any source through a medium consisting oI air, water or earth.
The gravity receptors respond to any deviation in the orientation oI the body in reIation to the IieId oI
gravity.
MuscIe Receptors
The vertebrate muscIes have a speciaI kind oI receptor ceIIs which convey responses to the centraI
nervous system when the muscIes are stretched or reIaxed. In addition to their occurrence in muscIes,
the receptors may aIso occur in joints or tendons. The receptors oI the joints have a position sense,
whereas those oI the tendon heIp keep the muscIes within IunctionaI Iimits. Both oI these do not have
the muscIe sense. The muscIe receptors are important since they Iie in the body oI the muscIe cIose to
the intraIusaI muscIe Iibres (Chapter 17). IntraIusaI muscIe Iibres are striated Iibres but diIIer Irom
them in having sensory nerve endings and a motor suppIy. A typicaI muscIe spindIe oI vertebrates
consists oI intraIusaI muscIe Iibres with sensory nerve endings (Fig. 16.3).
The muscIe spindIes show a ready response to stretching. When a receptor is stretched the motor
neurons are activated to generate impuIses so that the muscIe exhibits a shortening response. As the
muscIe shortens, the activation oI the muscIe diminishes, causing diminution oI the excitation in the
motor neuron. SimpIe rcIIexes oI vertebrates are the best exampIes oI this mechanism in which the
spinaI cord exerts a controI. However, this system is aIso under the controI oI higher centres to
produce voIuntary movements. In such cases, impuIses Irom the higher centres are reIayed to the
motor neurons oI the intraIusaI muscIe Iibres (gamma motoneurons) which cause the Iibres to
contract in a graded manner. The spindIes aIso contain extraIusaI muscIe Iibres (aIpha motoneurons)
which are inIIuenced by the activity oI gamma motoneurons. SIow voIuntary movements are produced
by activation oI both gamma and aIpha motoneurons. VioIent muscuIar activity is due to aIpha
motoneurons, whereas in steady state position gamma motoneurons controI the muscuIar activity.
Sensory Mechanisms !!'
Pressure Receptors
The pressure receptors are oI two types: externaI and internaI. The externaI pressure receptors occur
as smaII bodies distributed aII over the skin and possess aIIerent nerve endings. They are Iound in the
outer Iayers as weII as in the deeper Iayers oI the skin. InternaI pressure receptors have many branched
nerve endings extending to the muscIe Iibres. The Iibre terminations are the pressure receptors which
are excited by muscIe contractions.
SeveraI types oI pressure receptors have been described in animaIs which incIude crustacean
stretch receptors, amphibian muscIe spindIes and mammaI-ianpacinian corpuscIes.
Pacinian corpuscles are typicaI pressure receptors Iound in the deeper Iayers oI the skin, in the
mesentary oI the viscera, in the connective tissues oI the tendons, muscIes and joints. Each corpuscIe
is a Iarge structure, about 1 mm Iong, and consists oI a number oI connective Iayers surrounding a
thin granuIar mass having a Iree terminaI oI nonmyeIinated nerve (Fig. 16.4) The spaces between the
connective Iayers are IiIIed with a IIuid which is heIpIuI in transmitting pressure changes to the non
myeIinated nerve ending. The myeIin sheath extends Ior some distance in the corpuscIe and one node
occurs the ceII.
The naked nerve ending in the pacinian corpuscIe can be excited by a very smaII movement such
as 0.5 Ior a duration oI 0.1 msec. The corpuscIes can be excited by eIectric currents aIso and eIectric
responses are in the Iorm oI generator potentiaIs which are graded. In case a mechanicaI disturbance
FIg. 16.3 Intrafusal muscle fibres with sensory nerve endings.
Tendon
organ
Gamma
motoneuron
Spindle
receptor
neuron
Alpha motoneuron
Extrafusal
fibre
Intrafusal
fibres
Capsule of
muscle spindle
Tendon organ
receptor neuron
Animal Physiology !"
FIg. 16.4 Pacinian corpuscle.
is appIied at a point, the generator potentiaIs that are produced go on decaying when measured at a
distance Irom the point oI stimuIus. II the naked Iibre is stimuIated at two points separated by some
distance (about 0.5 mm), a singIe Iarge generator current is produced as an additive eIIect.
Gravity Receptors
Gravity receptors are aIso termed as equiIibrium receptors which respond to change in position or
orientation oI the body with respect to the gravitationaI IieId. Statocysts oI crustaceans are speciaIized
mechanoreceptors concerned with reactions to gravitationaI IieId. A statocyst is a sac-Iike organ Iined
by sensory ceIIs and has a centraI core made oI statoIith (otoIith). The sensory ceIIs have sensory hairs
or transducing membranes at their Iree ends. By mechanicaI stimuIus the statoIiths produce vibrations
in the hairs and this inIormation is transmitted through the sensory ceIIs to the nervous system and the
animaI becomes aware oI its position with respect to the gravity. Statocysts are phyIogeneticaIIy very
primitive organs Iound in coeIenterates, IIatworms and crustaceans. FormerIy, they were supposed to
have an auditory Iunction, but experiments have proved that these are gravity receptors which may be
Iikened to structures Iike saccuIe and utricIe oI the inner ear oI higher animaIs.