PNAC UA fey Wiley ESFourth Edition HUMAN PHYSIOLOGY IN NUTSHELL Dr AK Jain M.D., MNAMS Director Prof. & Formerly Head Department of Physiology Maulana Azad Medical College New Delhi an TABLES ARYA PUBLICATIONS (AVICHAL PUBLISHING COMPANY) Industrial Area, Trilokpur Road, Kala Amb 173 030, Distt. Sirmour (HP) Delhi Office: 1002 Faiz Road (opp. Hanuman Murti), Karol Bagh, New Delhi 110 005en published in good te Meeerved. No part of th A RR elec or mechani rien permission of ‘omissions or results “The publisher shall not be poe poke of binding mistake, misprints, or missing {ig replacement of the “i egal matters are tobe settled under Del Published by: ARYA PUBLICATIONS (Avichal Publishing Company) Industrial Area, Trilokpur Road Kala Amb 173030, Distt. Sirmour (HP) Ph: 01702-238688, 238832 Delhi Office: 1002 Faiz Road (opp. Hanuman Murti) Karol Bagh, New Delhi 110 005 (India) Phone: 011-28752745, 28752604 Fax: 011-28756921 E-mail: medical@apcbooks.co.in Website: www.apcbooks.co.in © Author ISBN-978-81-7855-588-1 Second Edition: 2011 Third Edition: 2014 Fourth Edition: 2018 Price: © 375.00 Designed and Typeset at: Laser Tech Prints Printed by: Graphic Prints India Shahdara, Delhi Fc Wythe shor W og 2 sated in any far Geb cre ping ot information rereval y ee be addressed lo the sas ee on cron la steed bra ater a = ith that the material ot Er ahis publication may Be Fe Juding photocopyin fine copyright holder, applica also be obtained before any Par gal action re accuracy and correctne mn ertor changes int yr possiblity of uma aK 7 raration of this work acces eho has been involved in preps spained from use of information Tiable for any direct, consequ ‘book within one month of Pt shi Jurisdiction only. canessof contents of the Book atthe time of seed science either the author pata vsany raponsly for amp I, or incidental damages arising out of the use of ty seithcr ca ay and oar elas ra Le ee ae ope incweaten aeDEDICATED TO My Parents (Late) Shri M.C, Jain and (Late) Shrimati Lajwanti Jain (whose blessings and love have always been with me throughout my endeavour) My wife Shalu, Sons Ashish-Avnish and Daughters-in-law Latika-Nitika (whose support enabled me to complete it) My Grandson-Hridaan (who is world to all of us) My teachers, colleagues and friends (who have made me capable of what I am today) My students (who have been my teachers)Preface to the Fourth Edition Textend my heart-felt thanks to all my readers for their wonderful acceptance given to this book. The purpose of the book remains same as it was in its previous editions—the last minute quick revision of the text just prior to the written and viva-voce examination, Caution: This book must be read in context with last minute quick revision of the text just prior to examination only and NOT to built the concepts in the subject of physiology. It should at No stage be taken as replacement to any textbook in Physiology. Salient features of this edition are: 1, The entire text has been revised, updated and new concepts have been incorporated. 2. More flow charts, summarizing tables and pointwise presentation of the text have been included to help students in their last minute revision of all the topics prior to written and viva-voce examinations. 3. Information on new topics such as yoga, uremia and dialysis therapy has been added. 4. Frequently asked important normal values are given separately in a box at the end of each unit. 5. Handy and student-friendly, the book makes learning of the subject very interesting. 6. The book will be a great help in attempting the questions that require precise answers in about 1-2 lines. Appreciation is extended to Dr. Vipin Gupta and Mr. Arnay Gupta of M/s Arya Publications, Karol Bagh, New Delhi, who helped me to fulfil my dreams in bringing out the book. I extend my sincere regards to Sh. VK Manchanda and Sh. Rajiv Manchanda of M/s Laser Tech Prints for their assistance in the preparation of this book. My deepest love and thanks to my sons Ashish and Avnish and daughters-in-law Ms Latika, and Ms Nitika who helped me to be accurate and balanced in my presentation. Words cannot express the love and support I have received from my wife, Shailesh. She has always encouraged me during hours of study and writing. A new loving entrant to our family - HRIDAAN, my grandson seeks everyone's blessings. 2018 Dr. AK JainContents uNIT 1-THE GENERAL PHYSIOLOGY PEnaneyeno 10. Homeostatic Regulation Cell Membrane Lysosomes Cell Junctions Junctional complexes) Apoptosis: Programmed Cell Death Transport Across Cell Membranes Intercellular Communication: Chemical Messengers Body Water and Body Fluids Units for Measuring Concentration of Solutes The Membrane Potentials UNIT 2—BLOOD pena eenn 10. Composition and Functions of Blood The Plasma Proteins Haemoglobin Erythrocyte—Red Blood Corpuscle (RBC) Jaundice Leucocytes: White Blood Corpuscles (WBCs) Platelets or Thrombocytes Coagulation of Blood Blood Groups Lymphoid Tissues and Immunity UNIT 3—NERVE MUSCLE PHYSIOLOGY SNATe END Structure and Function of Nervous Tissues Properties of the Nerve Fibers Nerve Fiber Types and Function Degeneration and Regeneration in Peripheral Nerves Neuromuscular Junction Skeletal Muscle Cardiac Muscle Smooth Muscle UNIT 4—DIGESTIVE SYSTEM age ene Physiological Anatomy of GIT Salivary Secretion Mouth and Oesophagus Stomach Pancreas Liver and Gall Bladder PY ADLYNNN! 12 13 15 18 a7 30 32 39 40 SEBS 51 Qaa 58 62Small Intestine Large Intestine (Colon) Absorption in the GIT 10. GIT Hormones UL. GIT Reflexes Syen UNIT 5—CARDIOVASCULAR SYSTEM Physiological Anatomy of the Heart The Cardiac Cycle The Electrocardiogram (E.C.G.) General Principles of the Circulation Cardiovascular Regulatory Mechanisms ‘The Heart Rate (HR) The Cardiac Output (CO) The Arterial Blood Pressure (B.P.) The Regional Circulation (capillary, coronary, cerebral, cutaneous) * BBB; Circumventricular organs 10. Cardiovascular Homeostasis * Postural hypotension; effect of “g’; shock and syncope; heart failure; hypertension peNnageenn UNIT 6—THE RESPIRATORY SYSTEM Physiological Anatomy of Respiratory System. Mechanics of Respiration Transport of Gases Regulation of Respiration Hypoxia Physiology of High Altitude Effects of High Atmospheric Pressure Physiology of Exercise and Yoga Yoga peNnageenr UNIT 7—THE EXCRETORY SYSTEM Physiological Anatomy of the Kidney Mechanism of Formation of Urine Renal Clearance Mechanism of Concentration and Dilution of Urine (The Counter Current System) Acidification of Urine Regulation of Volume and Concentration of Body Fluids Physiology of Micturition Regulation of Body Temperature Pee eNO UNIT 8—ENDOCRINE SYSTEM 1. General Principles of Endocrinology 2. The Pituitary Gland 68 70 71 73 74 100 102 108 no 6 ng 123 125 128 129 131 133 138 143, 146 148 150 155 157 162 165PEN awee The Thyroid Gland Parathyroids, Calcitonin and Vitamin D Adrenal Cortex Adrenal Medulla Pancreas ‘The Thymus The Pineal Gland UNIT 9—REPRODUCTIVE SYSTEM vreNe Physiology of Reproduction Male Reproductive System Female Reproductive System Contraceptive Measures Physiology of Pregnancy UNIT 10—THE NERVOUS SYSTEM Organization of the Nervous System The Synapse Sensory Receptors Reflexes The Sensory System Motor Areas and Descending Tracts Autonomic Nervous System (ANS) Spinal Cord Lesions The Vestibular Apparatus (Labyrinth) Control of Body Movement and Posture |. The Reticular Formation . The Cerebellum . The Thalamus . The Electroencephalogram - E.E.G. . Sleep The Basal Ganglia The Hypothalamus The Cerebral Hemisphere (Cerebrum) . The Limbic System . Higher Functions of the Nervous System (Language/Speech; Learning; Memory and Judgement) UNIT 11—THE SPECIAL SENSES BENE The Smell: Olfaction The Taste ‘The Ear ‘The Eye 173 179 183 189 192 197 198 199 204 209 215 217 225 226 229 231 235 239 242 244 246 247 251 255 255 256 258 261 263 266 268 274 275 277Abbreviations and Symbols Commonly Used Abbre T : Increase ions and Symbols 4: Decrease > + Leads to (4): Stimulation ©: Inhibition +): Mild ++ : Moderate ttt: Severe (] : Concentration of «to: Proportional to CA: Carbonic anhydrase VR : Venous return SBP, DBP, MBP: Systolic, diastolic and Mean BP SV : Stroke volume HR : Heart rate CO: Cardiac output VMC : Vasomotor centre CVC: Cardiac vagal centre Ep : Epinephrine NE : Norepinephrine PR : Peripheral resistance BV: Blood volume COP : Colloidal osmotic pressure S-HT : 5-hydroxytryptamine (serotonin) & : gram m : meterUNIT 1 The General Physiology & HOMEOSTATIC REGULATION he stasis ‘Definition: A variety of physiological mechanisms which act_to stabilize the internal environment of the.cell (ie. oo interieur) in terms of volume (water), composition, 107— concentrations, pH and tempbature=> eayvb> os) ECr oSticde hceaes . B. Wotheostatic regulation se (rolled by negative and positive feedback mechanisms. Ave d- ke 1, Negative feedback mechanisms (i) Most commonly employed mechanisms. ) Here stimulus and response are opposite to each other. Abr. (a stimulus) BR. to normal (cesponse) cong, Coad 2. Positive feedback mechanisms > y2akud > 529, 2.58, (Occur in few situations. i) Here the initial stimulus produces response that increases the original stimulus. (ii) Example: EP in BP (tl sna | 1 od sup to heat 4 myocardial contractility | further fall in BP. (response)—_ 7 2G Human Physiology in Nutshell {iv) It can sometimes be useful > (gag (yscadle- Example: Injury to blood vessel Initiates clotting processes Clotting proceeds Release of chemicals 1 clotting processes ' Seals break in blood vessel wall (also see to page 221) CELL MEMBRANE Structure: Fluid Mosaic Model () Fluid due to presence of cholester (ii) Mosaic (small pieces) of different proteins are 2. Functions of cell membrane proteins: (i) As ion channel allows specific ion to mov (ji) As carrier transports specific substances across For example amino acids, needed to synthesize new proteins, via cartiers. (iii) As receptor recognizes specific ligands and alt ‘ADH binds to receptor in the kidneys and ch membranes. (iv) As enzyme catalyzes reaction inside or outsi (v) As junctional complexes (see below). (wi) A marker (glycoprotein) such as MHC (major histocompatiblity) protein helps in Gell Tecognition. (vii) As pumps which actively transport ions across the lipid layer. For example: Na® — K* pump. (see below) rol which makes membrane quite flexible. ‘embedded. through water-filled pores. membrane by changing shape. enter body cells ers cells function. For example: ange water permeability of cell cell, LYSOSOMES 1. Large irregular structures in the cytoplasm ofa cell filled with small granules which contain variety of enzymes called lysozymes. 2. Acts as a digestive (lytic) system of the cell | 3. When a cell dies, lysosomal enzymes causeGutolysiye the remnant, thus are called suicidal bags. LL JUNCTIONS ( TONAL COMPLEXES) ‘The cells are associated into tissties by 3 means: 1. Tight junction: Here outer membranes of two cells fuse strongly form , r in Taha movements oF Tons amdother solutes front one side To THe aeons ner Sites: Epithelium of the intestinal mucosa, walls ofthe renal tubules, and th i plexus. BBO BI): e choroidUnit 1: The General Physiology I = Fidler junction Here two membranes are separated _by (5-201 space. This holds adjacent cells firmly together in areas that are subjected to stretching, such as the skin. They also resist cell separation during, their corftraction. = 3. Gap jun | Nevus: Here the space between the opposing membranes is traversed. by a/channel that connects the two cells. Thus it permits rapid spread of electrical potential changes from one cell to another (e.g. cardiac and smooth muscle cells)., and direct transfer of ions between the cells without traversing the extracellular space. . Woorosis PROGRAMMED CELL DEATH 1. LyAhfion: Process of programmed cell death in which body cells die and get phagocytosed under genetic control. 2, Mechanisms Activation of inactive enzymes (called as Caspases) _within_the_ mitochondria, The activated apoptotic gene causes the ‘cell to undergo DNA oo jon_and remnants are removed by phagocytosis, a 6 Physiological significances It plays an important role during embryonal development and also in adulthood. For example, it is responsible for: mao 4_regression of duct system during sex differentiation in the foetus; a7 degeneration and regeneration of neurons within the CNS and for the formation of synapse; itt) removal of inappropriate clones of immune cells; Gx cyclical shedding of endometrium at the time of menstruation; and (v) cell shed from the tip of the villi in the small intestine. 4. Appliod: Abnormal apoptosis occurs in autoimmune diseases, degenerative diseases and cancers. rot % Example ° NSPORT A\ ROSS CELL MEMBRANES A, Classification Transport of substances into and out of cells. (Transport process Description — Substances transported A. Passive Processes Requires no cellular energy; Molecules move along their . electro;chemical gradient 1, Diffusion Movement of a substance down i. Simple difiusion its concentration gradient without + Non polar solutes (O,, CO, and the help of membrane transport N, gases); fatty acids; steroids; proteins. fat soluble vitamins. * Polar molecules (urea and alcohol) ii, Facilitated diffusion Movement of a substance down Polar or charged solutes (glucose, its concentration gradient _by fructose, some vitamins and ions transmembrane proteins (carfiers such as K*, Cl-, Na‘, Ca? or channels). 2004 a 2. Osmosis Movement of water moletules Solvent: Water in living systems. across a selective permeable membrane from an area of higher to lower water concentration until, ‘equilibrium is reached.4 Q) Human Physiology in Nutshell B, Active Processes Requires cellular energy in the form of ATP. (as molecules move against their electro-chemical gradient) DL. Primary active A__substance_moves against its Na‘, Kt, Ca®, Ht, Clr ® tragsport “concentration gradient by pumps Examples: Na’ ~ K* pump; Kalb | cll wanes (carriers), ’ Ca? pump; S Sut. alove, Kt - H* pump 2. Secondary active __Coupled active transport of tanapert substances. —— i. Antiporters Move(Na* (or H') and another * Na ~ K* pump which move (counter substance in opposite direction, 3Nat out of the cell in exchange transporter) for 2K* moves into the cell. Na* - H* exchanges in renal r . tubules. ii, Symporters Move Na* (or H*))and another Secondary active transport of (Co-transporter) —— substahGEHTthe-same direction. glucose from GIT. 3. Vesicular transport > “Fy ..:} i. Endocytosis Movement of substance into a cell = yeni in vesicles. (@) Receptor Ligand-gated-receptor complexes mediated ingestion (b) Phagocytosis Cell eating-movement of a solid particle into a cell. (©) Pinocytosis. Cell drinking-movement of ECF Solutes in ECF. (by absorptive into a cell. cells in GIT and kidney) fi, Exocytosis Movement of substances out of a Neurotransmitters, hormones and cell in secretory vesicles. digestive enzymes. B. Factors affecting rate of diffusion of a substance through a membrane (Fick’s law of difusion) 1. Directly proportional to the: (i) Surface area of the membrane ‘ii) Size of the concentration gradient (difference) (Gi) Temperature permed, lgmperature of 37°C diffusion is optimal) if Lipid solubilify that ls why O,,CO, and N, diffuse rapidly through the membrane. Inversely proportional to the: (i) Distance/thickness of the cell membranes. (i) Molecular size (MW between 10,000 to 60,000, that is why glucose diffuses faster _ than large proteins). \Gii” Water solubility, that is why iong glucose and ure cross the membrane slowly. Colts) wi tins -lonic Diffusion © be, Hbposnaczo2® reread. bd) C. Non-ionic Diffusion + Jycliz9- oul bee Loe coe Cote Kare (Weak acids and weak base3 that are quite Soluble ‘in cell] membranes in the undissociated form, cross the membrane with difficulty in the ionic fofm. However, if an undissociated substance diffuses from one side of the membrane to the other end and then dissociates, there occurs net movement of the undissociated substalice from one side of the membrane to another, called non-ionic difusion, This phenomenon is seen in the GIT and kidneys. Yt old? D. Solvent drag? 32,42) ae erttubuser When water flows fkio"Gr Sti of capMlaries, it carries dissolved particles with it. This force is 4 ts small in the body. is called solvent drag. Its effects are very small i y.Unit 1: The General Physiology Q 5 E, Osmosis 1. Definition: It is the passive flow of the sol permeable membrarie, into a region to which the membrane is 2. Osmotic pressure: The _migration (i.e. osm ERM tective solvent (eg. water) acrosé-a'selectively ‘gion where there is a higher concentration of solute permeable. amount of pressure exactly required to prevent solvent is) is called osmotic pressure of the solution. 3. Osmotic pressure (OP) of a solution is related to the = nRT/V where = Nek, n= number of osmotically active particles (crystalldide and colloids - plasma proteins) Since R_ =Gas constant T = Absolute temperature; and V_ = Volume of the solution. irea,-Na*, glucose ete ue Pac} (if "T’ is kept constant, OP is proportionate to the number of particles in a solution per unit volume of solution.) ars Sddidm-potassium (Na’-K*) pump ot Na*=K* ATPase 1. Location: Extend through the membrane of most body cells. 2. Functions ——_ “avo cetsuto. (i) Responsible for maintaining high K* and low Na* concentration in the restn cell by moving 3 Na* from the cell'and take 2K* into the cel for each @uoleQuD> ic ‘ith a coupling anesthe itive charge out of the cell and|keeps ihe inside smotic” equilibrium] Thus helps in regulation normal ‘olume and pressure. a cone. ‘ 3. Physiological e Major energy-using procéssés in the body. and accounts for a large part of the basal metabolic rate. (BMR) 4. Inhibition of the pump () The pump requires binding of Ra, Ko and a for its operation. Therefore, if the@oncenitration“of any of these substances is too low) the pump does not function. (ii) When tempeyature is reduced. (iii) During the lack of oxygen. Z (iv) Metabolic poisons that prevent the formation of ATP. (ii) Produces net movement of and outside of the cell G. Secondary active transport processes Here"the active fransport of Nat coupled to the transport of other substances, i.e. the transport “of many ions and nutrients along their electro-chemical energy gradient, is accomplished by Na*-dependent secondary active transport. For example: 1. Glucose and aminoacids are reabsorbed from the proximal renal tubules or absorbed from the intestinal lumen only if Nat binds to the protein and is transported down its electrochemical gradient at the same time. 4,2. Calcium is exchanged from the cytoplasm of muscle cells for extracellular Na* (Na*-Ca** exchanger). This causes_muscle relaxation ‘¢ 3: Iodide pump. (or Na*/I- symporter)-it helps active I- reabsorption intoG@hyroid> cells against the electrical gradient. ———————=———- = % | 6 Q Human Physiology in Nutshell ESSENGERS INTERCELLULAR COMMUNICATION: CHEMICAL M1 FCF (alle first 1a chemical messengers in the 1. Cells communicate with each other vi messenger) in 3 ways: (i) Neural communication i.e, communication ¥i Example: Neuromuscular junction ca | Gi) Paracrine connmunaton, Here products of cells diffuse into the ECE er the neighbouring cells. (If products of cell bind to rece] the sal . it is called autocrine commumication). synaptic junction. :ptors on U each the cell via the circulating (iii) Endocrine communication in which hormo Rlood) ~ 2. The intracellular mediators are called second messengers; protém kinases, The major protein kinases are: protein kinase C, F dependent Kinases. 3. Mode of action of chemical messenger id. By opening or closing ion channels in the cell membrane; eg. a motor end plate. i) By stimulation of transcription of mRNA. Thyroid and_steroid hormones exert their effects in this fashion. — Gii) By activating phospholipase C with intracellular production of IP; (inositol triphosphate) and DAG (diacylglycerol) which catalyze the formation of second messenger. Angiotensin II and nor-epinephrine act in this fashion. (iv) By altering activity of adenylate cyclase causing increased or decreased intracellular production of cAMP eg. activation of phosphorylase kinase in the liver by epinephrine. (¥)_ By increasing cyclic guanosine monophosphate (CGMP) in cell, Nitric oxide produces vascular vasodilation via this mechanism. wi) Bi wroteinsor GTP (Guanosine triphosphate binding proteins). Once it then_migrat the cell membrane to modulate the activity of target cell in three ways ~~ they generally activate ‘cAMP or cGMP ction of A-ch on (a) interaction with adenylyl cyclase; or (©) interaction with phospholipase C; or (©) directly open an ion-channel. ‘Note Gaecholanins, Ah opioids angiotensin I TSH, FSH, light ee act by activating G-proteins. | BODY WATERAND BODY FLUIDS... 1, Inan average young adult male, 60% of Posy gpm called total body water \6e (TBW). a3" 2. Distribution of Tavf 70 Kq Mem| Pte Ho Zoy, BEY Oe" (i) Extracellular flat (ECF) Ts approx. volume is 14 L in a normal adult person ie. 20% of body weight or 33% (1/3rd) of TBW.This is the fluid contained in the spaces outside the cell. It includes: a ADL Sata of ECF. It is the fluid portion of the blood. gu iid; It is, the part of ECF that is outside the vascular system. It Intefstit (= aes cells except lood cells and includes lymph. Lymph constitutes val cells tse eet 2.3% of body weight. Sopariii 058-08 oust eds owmcines sys. Bigod. VE+ Hees’ inde tee ceRBs2 SHAK comfrorerd of, Unit 1: The General Physiology 7. HK Tar may (©) Trahscellular fluid: 1.5% Te a % of body weight. It represents fluid irf the lumen_ of structures lined by epithelium, It includes: bile, diges sweat, cerebrospinal fluid (CSE), pleural, peritoneal, “synovial, intraocular. and pericardial fluids. Ihe 8 { Note: Interstitial plus transcellular uid represents 75% of ECF or 15% of body weight. (i) Intracellular fluid (CF): Its approx. volume is 28 L in a normal adult person i 40% of body weight or 67% (2/3rd) of TBW. This is the fluid contained the body cells. nposition of body fluids (in mEq/L) Jon ECF CF Tae ECF 1cF Cations Anions Nav aS 2 TO 8 K+ 5 55) HCO, 27 8 Mg?* 2 15 Phosphate (PO) 2 90 Others 2-2 _— Proteins (Prot) 1560 . Total Cations S454 84) Others = 18 VN ge —T Ber ¢ Total Al i 184, > ree wr 4. Points to remember era (i) Tons constitute approx. 95% of the solutes in the body fluids. 7 (ii) The sum of the concentrations of the cations equals the sum of the concentrations of the anions in each respective compartment, making the fluid in each compartment electrically neutral. mcr Git) Nav, Ca®*, and Care largely extracellular, whereas K+, Mg?, organic phosphate “(PO,>) and proteins (Prot-) are predominantly pres he ICE hiv) Ca concentration gradient on outside to inside the cell is 12,000:1. (v) Essentially, all of the body K* is in the exchangeable pool, whereas only_65%~ 70% of the body Na* is exchangeable (only exchangeable solutes are_ osmotically — (vi)’ Almost alll of the body Ca** (in bone) and most of the body Mg?* (in bone and other cells) are non-exchangeable. UNITS FOR MEASURING CONCENTRATION OF SOLUTES 1. Mole: Mole is the molecular weight of the substance in gram. Thus, 1 mole of KCL (89 + 35.5) = 74.5 g. The millimole (mmol) is 1/1000 of a mole. 2. One-molar (1M or 1 mol/L) solution: It provides a unit of concentration of solutes based upon the number of molecules of the solute in 1 litre of solution. Therefore, IM solution of KCl contains the same number of solute molecules (6 x 10) per litre asa IM solution of glucose or any other substance (1 millimole: mM = 0.001M). 3. Equivalent: It is the standard unit for expressing the solutes in the body which are in the form of charged particles. One equivalent (Eq) is 1 mole of an ionized substance divided by its valency. Therefore, one Eq of K* = 39 g/1 = 39 g; but 1 Eq of Ca? 40 g/2 = 20 g (1 mEq = 1/1000 Eq). Normality of a solution: It is the number of gram equivalent in 1 litre. Therefore, 1N solution of hydrochloric acid contains 1 + 35.5 g/L = 36.5 g/L._—_———— = 8 Q Human Physiology in Nutshell whale supple by 5. Osnfole. The amount of c ‘entrations of osmotically active particles are eXPT* ey osmoles (osm). One osmole equals the gram molecular weight (ie. one mole) ie substance divided by the number of frecly moving particles each molecule libera . The milliosmole (mosm) is 1/1000 of 1 osm. pressed in 1 osm (losmole per litre). (ii) _1-molar solution of NaCl (an ionizing compound would dissociate into and Cl) would supply 2 osmoles of solute per litre of solution, 6. Osmolarity: It ithe number of i 1-molar solution of glucose (a non-ionizing compound) has a concentration of Nat as moles per litre of solution (e.g. plasma), wheres the osmolality is the number of osmoles per kilogram of the solvent. Since osmotically active substances in the body are dissolved in water, and as the density of water is 1, so osmolal concentration is expressed as osm/L of water. 7. Osmolality of normal{h Relative contribution; () Approximately 270 mosm/L by Na’ and its accompanying anions, mainly Cl- and HCO; (these particles are not metabolized). (ii) About mosm/L by the major non-clectrolytes of plasma ie. glucose and urea. ae (ii) Less than 2 mosm/L by the concentration of the plasma proteins (because of their very high molecular weights). Clinical assessment: Plasma osmolality (mosm/L) = 2 [Na*] + 0.055 (glucose) + 0.36 [Blood urea] (mEq/L) (mg/dL) (mg/dL) Clinical singnificance: 3 s * The flow of water in or out of the capillaries dggends ot ‘colloidal osmotic pressure. * Hyperosmolality can cause coma (hyperobmolar coma) by causing cellular _ dehydration. Examples: Coma due tohypergl/cemia (page 197) or_ure 8. Tonicity: It is the osmolality Gf a solutioijrelative to plasma, Solutions that have the same osmolality a3 plasma are said to be isotonic (Examples: 0.9% NaCl, 5% glucose, 10% mannitol and 20% urea solution); those with greater osmolality are hypertonic and those with lesser osmolality are hypotonic. 9. pH and H* concentration —_ (The relation between [H*] and pH: pH = log,o1/{H"] =[—log,olH"]. | (i) Optimal blood pH: 7.35 - 74s{Ga0-= DOS (iii) Blood pH compatible with life. 2.7 to 6.9, (i.e. blood pH where life can exist) (iv) Clinically, blood pH < 7.35 is referred to as acidosis, and blood pH > 7.45 as alkalosis. THE MEMBRANE POTENTIALS A, Resting Membrane Potential (RMP) 1. Definition: It is a constant (or steady) potential difference between the inside and outside of the cell at rest; also termed as steady ot transmembrane potential and “jndicates the resting state jc, state of polarization of the cell membrane. 2. Range: -10 mV (in @ RBC) to 100 mV (in the skeletal muscle cell), Minus sign signifies that inside of cell is negative relative to the outside.Unit 1: The General Physiology Q 9 3. Genesis, (why negative inside and p membrane i ve outside the membrane?) - at rest the cell Oe = neable to Nat; Hil o-ring (ii) freely permeable to K* and Cl (K* permeability §0-100 times greater than Na* permeability y (i) effectively impei (iii) practically impermeable to most of intracellular anions (proteins and PO}); (iv) Na*~K* pump is electrogenic at rest with a coupling ratio of 3:2. B, Equilibrium potential It is the membrane potential at which the electric fored is equal in magnitude but opposite in direction to the concentration force” : 1. Equilibrium potential (E) for important ions Ton Neuron Skeletal muscle cell @) Ey.) 460 mV 465 mv OE -90mV 95 mv ()Eg- -90mV -86 mV 2. The magnitude of forces acting across the cell membrane on each ion can be analysed by Nernst equation as follows: _ RT Ejay = — 3p In Cn Coe where, E = equilibrium potential; R = gas constant; T = absolute temperature; Z = ion valency; F = Faraday constant; In = log symbol; C,, and C,,, = concentration Zz of ion inside and outside. . encss + DOL Chey potent & i Definition: The sequence of changes that excitation, 2. Origin: It is due to. changes inthe permeability of ions across the cell membrane (hroduced by alteration in the ion channels} 3. Phases > fokash nae. (i) Resting (polarised) state: RMP in most of neurons: -70mV. (ii) Depolarization means reduction in the membrane potential from its negative value towards zero. It is due to marked (18-20 times) increase in permeability of the membrane to Na*. ii) Repolarization ie. tracing reverses and falls rapidly towards the resting level. When repolarization is about 70% complete, the rate of repolarization decreases and tracing approaches the resting level more slowly (called after depolarization). Repolarization is due to K* efflux. (iv) After reaching the previous resting level, the tracing becomes slightly more negative (magnitude 1-2 mV) and lasts for about 35-40 msec (called after Jiyperpolarization),.It is due to active Na*—K* pump mechanism. (v) The sharp tise and rapid fall is the spike potential of the axon. D. Properties of action potentjal 1. Threshold stimulus (The weakest current strength which can excite a tissue, if allowed to flow through it for an adequate time, is called Pi eel in the membrane potential following10 Q Human Physiology in Nutshell intensity must be within the limi values as a | (ii) The length of time for which a current of twice rheobase | applied to produ response is called chronaxie. Significanc | its value for any given exe therefore cironarie Note: The relationship between the strength which it must be aj “or none response ( If the stimulus is subthreshold, no action potential is produced. : (ii) Once threshold intensity is reached, a full-fledged action potential is produced. (iii) Further increase in the intensity of a stimulus produce: increment in the height | of the action potential but its frequency increases (i. it fires repeatedly). This all or none relationship between stimulus and response is called All or None Law, WX 3 Byfetin oryperiod: If two successive stimuli of more than threshold intensity are Applied to an excitable tissue, the duration for which the tissue remains _non- responsive to the second stimulus is called the refractory period. It is of two typ: (i) Absolute refractory period (ARP) begins from the time the firing level is reached until the repolarization is 1/3rd complete. During this period no stimulus, no matter how strong, can generate a fresh impulse. This is due to inactivation of, the Na* channels. (ii) Relative refractory period (RRP) — begins at the end of ARP to the start of the_ after depolarization. During this period stimulus stronger than normal stimulus ‘can cause excitation. This is due to opening of more Na* channels by the suprathreshold stimulus. 4. Conductivity ie. excitation impulse is spread along the cell membrane as.a wave of _ depolarization. It is due tcirculargcurrent flow and direction of spread of impulse_ Tee Sanne ay current flow direction side Tnside the cell. 5. Accommodation. If an excitable cell is submitted to the passage of a constant strength of current, the site of the membrane under stimulation fails to produce action potential. This is due to the slower opening and delayed closing of the voltage gated K* channels. E. Electrotonic potential-Graded potentials 5@ Diva a ee 1. Application of subthreshold current with cathOde (negative) produces localized depolarizing, potential change, called catelectrotonic potential. 2. Application of subthreshold current with anode (positive) produces localized hyperpolarizing potential change, called anelectrotonic potential. 1. and 2. are together called as electrotonic potentials. 3, At subthreshold intensities of current producing approx. 7mV of depolarization ot hyperpolarization, their size is proportionate to the magnitude of stimulation (called staded potentials). % ov som aUnit 1: The General Physiology QI Graded potential | | ‘Action potential | (0) Ttisnon-propagatingin nature, remains (a) Itis | | spagating (conducting) in nature; travels for considerable distance confined loealy (6) It shows graded response i, stimmation is. possible. Therefore, its Magnitude is proportional to strength of stimulus (©) Tedoes not obey All or None Law. (@) Tt obeys All or None Lar () Ican either be a depolarizing or | hyperpolarizing response. (©) Thas no threshold (9, Whas no refractory period. (4) Mis always a depolarizing response (©) Ithasa threshold thatisusually 10-15 mv. (9. Ithas a refractory period. (©) Itis important in signalling over short (g) tis a long distance signal. atstances F. Extracellular (surface) recording of action potential 1. If both recording electrodes are placed on the surface of an axon, there is no Potential difference between them at rest. When excitable cell is stimulated with threshold stimulus, the record shows an upward deflection followed by an isoelectric interval and then a downward deflection. This sequence is called a biphasic action potential. 2. Useful clinically to record electrical activity of excitable tissues eg. EEG; ECG and EMG. a IMPORTANT VALUES TO REMEMBER 1, Na'-K* pump: coupling ratio 3/2 2 Total body water (TBW) (42 L) i: 60% of body weight 3. Extracellular fluid (ECF) (14 L) ies 20% of body weight or 33% (1/3ed) of TBW 4. Intracellular lid (ICE) (28 L) ies 40% of body weight or 67% (2/3rd) of TBW 5. Plasma: 25% of ECF 6 Lymph: 2-3% of body weight 7. lone composition of body fluids: Refer page 7 8. Normal blood pH: 740405; Blood pH compatible with life: 77 to 69 9. Resting membrane potential (RMP): Range -1OmV (in a RBC) to -100mV (in skeletal muscle cell). 10, Equilibrium potential: Refer page 9.UNIT 2 Blood COMPOSITION AND FUNCTIONS OF BLOOD Composition 1, Total blood volume : 5-6 litres (8% of body weight or 80mL/kg body weight) 2. Viscosity: 4-5 times that of water. 3. pH: 7A + 005; alkaline 4. Cells: 45% of total blood volume, called packed cell volume (PCV) or haematocrit (i) Erythrocytes (RBCs): 5 million /uL (Gi) Leucocytes (WBCs): 4000-11000/yL (iii) Platelets (Thrombocytes): 1.5~4 lacs/yL 5. Plasma: 55% of total blood volume (5% of body weight) 6. Plasma proteins: (Total) 64-83 g/dL omponenis (55% Albumin 1 35 g/aL. io ()38% Globulin + 28 g/at |G ratio“ 2721) (iii) 7% Fibrinogen : 03 g/dL (iv) Prothrombin + 40 mg/dL 7. Now-proten nitrogenous (NPN) substances ie., derivatives of food and products of tissue catabolism, Normal: 28-40 mg/dL. It includes: (i) Urea + 20-40 mg/dL (ii) Uric acid 24 mg/dL. (iii) Creatine : 1-2 mg/dL (iv) Creatinine 2 06-12 mg/dL (*)Xanthine, hypoxanthine: Traces 8. Others (i) Neutral fats (triglycerides): 30-150 mg/dL (ii) Phospholipids + 150-300 mg/dL. (ii) Glucose (fasting) + 70.90 mg/dL (iv) Cholesterol 120-200 mg/dL. Functions 1. Respiratory: transport of gases: (O; from lungs to tissues and CO, from tissues to lungs). 2. ‘Nutritive: conveys absorbed nutrients from the GIT to the tissues, 3, Ereretory: transports metabolic wats tothe Kidneys, skin and intestine forthe removal. 4, Homeostatic: (page 1). : ; 5, Regulation of ody temperature: Water in blood has high specific heat, high conductiy; ‘and high latent heat of evaporation. ae ity 2Unit 2: Blood Q 13 6. Chemical for communication, protection and regulation of haemostatic (clotting) mechanism, 7. Act as a reservoir of protein (see below). Serum '. Blood after clotting shrinks and gives out serum, I is thus plasma minus fibrinogen and clotting factors II, V and VILL 2. Has higher serotonin (5-HT) content due to breakdown of pl jatelets. THE PLASMA PROTEINS Plame ee x) 1. In Embryo : Mesenchymal cells ee 2. In Adults Albumin fibrinogen and prothrombin from liver. (ii) Globulin from tissue macrophage system, pl lasma cells and lymphocytes. 3. Normal Value: (Total) 64-83 g/dL. Forms of Plasma Proteins Type Normal plasma level 1, Pre-albumin 0.03 g/dL 2. Albumin 35 g/aL (Av: 48 g/dL) Functions Binds Thyroxine (T,) and tri-iodothyronine (T,). ( Controls colloidal osmotic pressure. (ii) Helps in transport of ions, dyes, drugs, hormones, fatty acids, metals, amino acids, enzymes and bilirubin, 3.Globulin (4, B23 g/dL See below. and 7) (Av: 23 g/dL) 4. Fibrinogen 03 g/dL Helps in blood clotting (precursor of fibrin). i 5. Prothrombin 40 mg/dL. Helps in blood clotting (precursor of thrombin). Forms of Globulin 1. Glycoprotein: Carbohydrate plus protein. 2. Lipoprotein: oz-globulin plus lipid. Sub-types (i) High density lipoprotein (HDL) also called good cholesterol: o-lipoprotein. (ii) Low density lipoprotein (LDL) also called bad cholesterol: contains large amounts of glycerides. Very low density lipoprotein (VLDL). (iv) Chylomicrons (2% proteins and 98% triglycerides). | Important Note: In healthy individuals, proportion of HDL is high but in coronary artery disease (CAD) patients, proportion of ‘B-lipoproteins (LDL and VLDL) increases. | 3. Transferrin: c-B-globulin; helps in iron transport and regulates iron absorption from | Git, 4. Haptoglobins: o,-globulin; prevents loss of haemoglobin in urine; thus protects the kidney from damage. 5. Ceruloplasmin: a.-globulin; binds with copper and helps in its transport and storage. Its deficiency produces hepato-lenticular degeneration (Wilson’s disease). 6. Coagulation factors: ct, B-globulin.14 Human Physiology: in Nutshell | 7. Angiotensinogen: o-globulin 8. Hacmagglutinins ic., antibodies against red cell antigens. 9. Immunoglobulins (Ig): y-globulins. Forms of Cell Proteins Itis based on Whipple’s experiment: Standard plasma depleted dog. 1. Fixed cell proteins or indispensable cell proteins: not mobilized even when serum plasma protein level is less than 2 g/dL; required for all essential metabolic activity of tissues and play no role in compensatory mechanisms. 2. Dispensable reserve proteins: Called upon for energy purposes in starvation and malnutrition etc, Examples: Endogenous proteins from skeletal muscle and glands. 3. Labile reserve proteins: They move out immediately into the blood stream and compensate for protein loss such as in haemorrhage, burns, etc. Main sites: Liver; RE system. Variations in Plasma Protein Concentration 1. Decrease (Hypoproteinaemia): Haemorrhage, burns, pregnancy, _ starvation, malnutrition. 2. Increase (Hyperproteinaemia | or dehydration. | 3. Decrease in Albumin Physiological: (@ Infancy and newborns (because of hepatic immaturity). Gi) Pregnancy. | Pathological | Secondary to water (or fluid) loss e.g. extensive burns (® Impaired protein synthesis ~ liver diseases, malnutrition, malabsorption. (ii) Excessive protein loss ~ Burns, kidney diseases. 4. Increase in albumin ~ Dehydration, congestive cardiac failure. Increase in y-globulin — Secondary to extensive tissue destruction. 6. Decrease in y-globulin — Nephritis, hypogammaglobulinaemia. s Functions of Plasma Proteins 1. Helps in coagulation of blood. Helps to maintain colloidal osmotic pressure (COP) across the capillary wall. Normal: 25-30mmHig. This helps to maintain the exchange of fluid at tissue level. The rate of fluid exchange at any point along a capillary depends upon a balance of forces, called Sigg forees (Fig. 2.1). Afteriolar end Capillary wall Venous end COP: 25-30 mnt —> v ® HP = 37 mmHg HP = 15 mmbig Pressure gradient (HP-COP): Pressure gradient (COP — HP): 37 ~ 25 = 12 mmHg = 15 = 10 mmbig {leads to filtration] [leads to absorption} ering forces: Prossur0 gradiont across capilary wal (In most vascular bods) Fig. 2.1 Starling forces’ Pgcoure Le, prosaure due fo cololds (plasma protein) and crystalokds oreo acoae) HP: hydrostatic pressure: due to water molecules) a ea SS =Unit 2: Blood OQ 15 COP due to Plasma proteins alone is called the Oncotic pressure. 80 because of I of COP is due to album’ xX ast molecular weight and maximum concentration, : He. COP w antoef Applied: Hypoprot = 1 con, increase filtration at artérial end and decrease in d at venous end — abnormal collection of fluid in “mia. | of blood at low level, since 80% of total plasma protein imin. Not hone b calla GG absorptio interstitial spaces, called /oed 3. Helps in maintaining vis, concentration is due to albui Provides ® stability to blood due to presence of globulin Helps in maintaining the acid base b amphoteric in nature (i.e. behave buffering cap: and fibrinogen, palace in the body because plasma proteins are as acids or bases depending on conditions). Their acity is 1/6th (15-16%) of the total buffering capacity of blood. 6. Transport and reservoir of hormones, drugs and metals 7. Provides immunity due to +-globulin fraction of the plasma proteins, ordsides upémostosin “P Structure o 1, Haem (iron containing porphyrin, called iron protoporphyrin 1X) (i) Iron in ferrous (Fe) form. (ii) Each Fe®* combines loosely and reversibly with one molecule of O, (called “oxygenation and not oxidation). ~ ) Oxygen is cartied as molecular oxygen (not as idic oxygen). 2. Globin . 7? ontgat (i) Built from 4 polypeptide chains: two @ and two B chains, therefore, adult haemoglobin is HbA (a,8;), (ii) Each of a-chain contains 141 aminoacids and each of B-chain_146 aminoacids. (ii) Each polypeptide chainis associated with one haem group) thus one haemoglobin molecule can carry 4 molecules (8 atoms) of oxygen. (iv) Shifting affinity of haemoglobin for oxygen results i (a) Sigmoid shape of oxygen-haemoglobin curve. (page 116) (©) Oxygenation of haemoglobin is very rapid_(<0.01sec), similarly is deoxygenation. Important Definitions 1. Oxyhaemoglobin (HbO,) ie., haemoglobin combines with oxygen. As concentration of 2, 3, DPG rises within The RBCs, the affinity of haemoglobin for oxygen falls. 2_Reduced (deoxygenated) haemoglobin (Hb). Haemoglobin from which oxygen has been removed. 3. Carbaminohaemoglobin. CO, reacts with haemoglobin to form this compound. 4. Carboxyhaemoglobin or Carbonmonoxy haemoglobin. Carbon monoxide (CO) combines with haemoglobin to form it. The affinity of haemoglobin for CO is 210 times than its affinity for oxygen. 5. MetMhemoglobin (HUOE) ie. when the ferrous (Fe) in the haemoglobin is oxidised to ferric (Fe). Disadvantages: It cannot unite reversibly with gaseous oxygen. (ii) It is dark coloured_and when present in >1.5 g/dL in circulation it mimics (resembles feyanosis [blue colouration of skin).EY Too -_.2._—_——_ a 16 _Q_ Human Physiology in Nutshell Normal Values, asin, WO" se 1. Atbirth: 238/dL (as RBC count is more). At the end of 3 months: 10.5g/dL (infant totally on milk feed). At the end of 1 year: 125 g/dL. Adults: Males (14-18 g/dL); Females (12-155g/dL). Clinically ‘14.8g/dL haemoglobin is 100% haemoglobin. 1g/dL of haemoglobin when fully saturated combines with 1.34mL oxygen (an index of oxygen-carrying capacity of blood; Normal - males: 21mL/dL; females: 18mL/dL). aneen Functions 1. Transport of gases (O, and CO,). (page 12) 2. Acts as an excellent acid base buffer (being a protein); responsible for 70% buffering power of whole blood. 3 3. Promotes vasodilation in the tissues as it has additional nitric oxide (NO) binding site on the B-chain. Free Haemoglobin 1. Definition: Haemoglobin dissolved in the plasma, 2. Disadvantages (i) Increases blood viscosity causing blood pressure to rise. (i) Interferes with fluid exchange between capillaries and tissue spaces (page 14). (ii) Loss in urine (haemoglobinuria) + kidney damage by forming acid haematin. (iv) Taken up and rapidly destroyed by the tissue-macrophage system. Synthesis 1. Proteins ~ helps in globin formation. 2. Minerals (@) Iron — helps in formation of haem. (i) Copper and cobalt — help in promoting the absorption, mobilization and utilization of iron. (iii) Calcium — increases iron absorption from GIT. 3. Vitamins - Vitamin C, vitamin B,, and folic acid help in synthesis of nucleic acid (required for the development of RBCs). Catabolism 1, Old RBCs are destroyed in tissue macrophage system (page 32). 2. Fate (i) Haem gives rise to: (2) Fe? + Apoferritin (tissue protein) — Ferritin (stored in the liver). (©) Biliverdin and bilirubin pigments. (ii) Globin - enters amino acid pool and is re-used. Vbrieties A. Adult Haemoglobin (HbA) 1. Types ; (i) Haemoglobin A(a8,) - predominant.Unit 2: Blood O17 (ii) Haemoglobin A,(a,5,) (9) Bechains replaced by 5:chains which also contain 146 amino acids but 10 _ individual amino acids differ from those in the f-chain. (b) Contributes 2.5% of total haemoglobin. (©) Produces no abnormality. 2. Appearance Amount of HbA) of the total haemoglobin) (i) At 20 week of intra-uterine life : 6% (rest is HbF) (ii) At birth 20% (iii) At 2 months (post-natal) : 50% (iv) At 4 months (post-natal) 90% (W)More than 1 year [599% (<1% is HbP) B. Foetal Haemoglobin (HbF-c.;1,) 1. B-chains replaced by y-chains containing 146 amino acids but have 37 amino aci differ from those in the B-chains. 2. More resistant to the action of alkalies than H 3. Greater affinity for oxygen (because of poor _20 mmHg pO, (HDA is only 30-35% saturated at this pO,) 4. Life span: Less, 80 days (compared to HbA" jay tna a PELE 45. Disappears 2-3 months after birth; its persistence beyond the age of 4-6 months > or B thalassaemia (due to deficient production of a or B-chains respectively). ling of 23 DPG); 70% saturated at ialassaemia is more common. 6. Differentiating features between major and minor (thalassaemia. ‘Major B-thalassaemia (also called Cooley's anaemia or Minor B-thalassaemia ‘Mediterranean anaemia) 1. Occurrence: Less common. 1. More commonly seen. 2. Transmission: ‘Homozygous’ 2. ‘Heterozygous’. 3. Anaemia: Moderate to severe. 3. Mild, 4. Basic defect: Total absence of B-chain synthesis. 4. Partial synthesis of -chain. 5. HOF levels: +++ 7. 5. Normal or + 1. 6. Life span: Shorter, average age of death 17th year. 6. Longer. SON Haemoglobin s (HbS) 1, Inherited as Mendelian dominant. 2. One glutamic acid in each f-polypeptide chain of HbA at position 6 js replaced by v 3. When reduced (e.g. in hypoxia or low pH), it becomes much less soluble than HbA —> precipitates into crystals within RBCs —> (i) 1s RBCs fragility (ii) RBCs become sickle shape —» 4 blood flow (i and (ji) — severe anaemia (sickle cell anaemia)————_—____ ,. 18_Q Human Physiology in Nutshell ERYTHROCYTE—RED BLOOD CORPUSCLE (RBC) Structure ‘i ; able change of | Circular, biconcave, non-nucleated disc; ean withstand consider 6 osmotic pressure and easily pass through capillaries. 19) 2 Life span 120 days (depends on glucose metabolism for its energy supply &: Spectrin: maintains the shape, flexibility and also contains specific blood group substance, the antigen, 4. Dimensions (Diameter; 6,5-8.8 ym (average: 7.3 pm) Thickness: 2-24ym (periphery); 1.2-1.5pm (centre) (iii) Surface area: 140 am? (iv) Volume + 78-98 pm? or FL (86 + 8 jm? or fL) | - Count (Clinically 5 million/pL: 100% RBC count) (At birth: 6-7 million/pL, Gi) Adults - Males: 5-6million /yL; Females: 4.5-Smillion/pL. Sites of destruction: Tissue macrophage system. 7. Functions (0 same as that of haemoglobin (page 16) | Gi) helps in identifying blood groups. Variations fia ~ Reduced oxygen carrying capacity of blood due to either {RBC count (<4 million/yL) or their content of haemoglobin (<12 g/dL) or both, - Polycythemia — T RBC count >6 million/pL. Causes | Z (Physiological (a) at birth tk (b) high altitude (due to hypoxia) (ii) Pathological ON (a) congenital heart disease (b) dehydration (6) shock (@) tumour of bone marrow called polyeythemia vera (RBC count may increase upto 7-8 million/L and is associated with presence of immature RBCs in the peripheral blood). ropoiesis finition: Development of RBCs. Note: Haemopoiesis is development of all blood cells. ing intrauterine life — 3 stages. : arcauail stage (upto 3 months) from mesoderm of yolk sac, erythropoiesis) foes (ii) Hepatic stage (after 3 months) from liver and se : (iii) Myeloid stage (after middle of foetal life) from the bone marrow, (Stages 2 and 3 are extravascular crytrapoiesis) 2. In children: All bones with red marrow; Liver and spleen. (intravascularUnit 2: Blood 19 3. In adults from red bone marrow, such as end of long bones, skull, vertebrae, ribs, sternum, and pelvis. Stages Terminology Special feature Remarks 7 ra 1. Haemocytoblast Mitosis present As the cell attains maturity: S (stem cell) 1. Cell size Ls 2. Proerythroblast 2 Active mitosis 2. Cytoplasm amount Ts y sen 3 3. Nucleus size gradually i Early normoblast & Active mitosis decreases to disappear finally WAL Intermediate Haemoglobin starts 4+. Staining reaction changes Ap" ormablat eet from deep basophilic to i polychromatophilic and finally 5. Late normoblast 1 Mitosis stops to acidophilic 6. Reticulocyte B Juvenile RBC; No nucleus, remnants of RNA 7. Erythrocyte (Gee to page 18) Note: Normal (normoblastic) bone marrow contains 30% proerythroblast plus early normoblast cells and 70% of intermediate plus late normoblast cells julation 1. General factors: Hypoxia (i) Most potent Stimulus. (i) Effect is mediated by erythropoietin (Ep.) within 24 horus of hypoxic stimulus. iii) Erythropoietin sources (a) 85%: kidneys (interstitial cells of the peritubular capillaries) (b) 15%: extrarenal - liver, tissue macrophage system. (iv) Formation, release and mode of action of Erythropoietin ‘Kidney os |—— ss — | Renal erythropoietic Enythropoietinogen factor (a-globulin) Exythropoietin Eyton sestive > roentobat stem cells re (v) Factors affecting Erythropoietin production (a) Increase by: Hypoxia, T,, androgens, anterior pituitary hormones. (b) Decrease by: less androgen, (that is why, in females, RBC count is less as compared to males), kidneys and liver diseases. (vi) Mode of action (a) potentiates stages of erythropoiesis > T RBC count in 2-3 days. (b) 7 release of reticulocytes from the bone marrow. (©) T haemoglobin synthesis in already existing normoblasts.20 Q Human Physiology in Nutshell 2. Special maturation factors (responsible for final maturation of RBCs) (i) Dietary factors: helps in synthesis of haemoglobin (page 16). (ii) Castle's intrinsic factor (IF) produced by parietal (oxyntic) cells of stomach and | ps in absorption of vitamin By» from ileum. i (iii) Extrinsic factors: Vitamin By, and folic acid. IF with extrinsic factors form | aeinatbite principle which helps in conversion of proerythroblast to mature RBC, therefore, deficiency of any one of them causes maturation failure and leads to megaloblastic anaemia. Anaemia Definition: Page 18, Grading 1, Mild: Haemoglobin 8-12 g/dL 2. Moderate : Haemoglobin 5-8 g/dL 3. Severe: Haemoglobin <5 g/dL Classification 1, Etiological: based on the cause. (i) Haemorrhagic due to blood loss. (ii) Dietary deficiency due to proteins, iron, vitamins. (iil) Abnormal haemopoiesis -» Aplastic anaemia Causes: (a) X-rays/yrays exposure (b) hypersensitivity of bone marrow to drugs. (iv) Hemolytic anaemias ie., excessive destruction of RBCs. Causes: (@) intracorpuscular defects (hereditary); examples: congenital spherocytosis; sickle cell anaemia; thalassaemia (©) extracorpuscular defects (acquired); examples: antigen antibody reaction; infections (malaria); drugs (quinine, aspirin); hypersplenism. 2. Morphological: Based on size of RBC and its haemoglobin concentration Ne Normachilé Hypechromie (@) ‘Normocytic’ (i) After acute haemorrhage (i) All haemolytic anaemias except Thalassaemia (iil) Aplastic Anaemia () ‘Macrocytic’ All megaloblastic anaemias due to deficiency of Vitamin B,3; folic acid or intrinsic factor (©) Microcytic’ Chronic infections After chronic haemorrhage Secondary to liver disease (i) Iron deficiency anaemia Gi) Thalassaemia Note: Iron deficiency anaemia is microcytic hypochror type. Pernicious (or Addison's) Anaemia: destructive or injurious anaemia 1, Cause: Lack of intrinsic factor — failure in abs 2. Characteristic features (i) Bone marrow: Megaloblastic hy normoblasts (normal 30%); orption of vitamin By. yperplasia - 70% proerythroblasts + early 30% intermediate + late normoblasts. (normal 70%).Unit 2: Blood Q 21 (ii) Blood changes (a) RBC: Macrocytic normochromic; count +++ L. (b) Haemoglobin ~ decreases, (c) Reticulocyte count > 5% (normal <1%). (d) Hemolyti undice (due to exce: ive destruction of RBCs). Changes in GIT: Deficiency of IF; achlorhydria; GIT disturbances. (iv) Changes in nervous systems: demyelination of dorsal and lateral columns (subacute combined degeneration of spinal cord) — tingling and numbness in limbs, motor and psychological disturbances. (v) Others (a) Plasma vi amin B,2 4 (normal: 300-400 pg/mL). xi] min B,2 excretion in faeces T (normal: 30-40%). fe Vitamin B,) excretion in urine decreases, 3. Signs of improvement after beginning treatment with vitamin Byy (i) Generalized improvement in health; patient feels stronger. (ii) Reticulocytic response, i.c., reticulocytes T upto 30-40%, (iii), Normoblastic reaction of the bone marrow. (page T3 (iv) Serum bilirubin returns to normal. Se retumns to normal. Note: Treatment with vitamin B,, prevents further progression of CNS lesions, but cannot reverse the damage already done and changes in the stomach remain unaffected. That is why this anaemia is called pernicious (ic., destructive) anaemia, Folic acid deficiency anaemia It also produces megaloblastic anaemia without neuropathy. Causes 1. Less dietary intake. : 4 » Fe dsy 2. Poor absorption. if alepleare. | 3. Increased demand (e.g. pregnancy). 4. Antifolate drugs (eg., anticancer drugs). What will happen if folic acid is given to pernicious anaemia patients? It will improve the blood picture but cannot protect against ‘neuropathy’ and may even erate the development of nervous lesions. iency anaemia—most commonly seen Definition: Any anaemia which responds to adequate dosage of iron. 2. Causes 7 e (i) Decreased iron intake, e.g. milk fed infants. (ii) Increased iron loss (haemorrhage). (iii) Increased iron demand (pregnancy, infancy, menstruation). (iv) Defective utilization of iron due to decreased absorption from GIT. 3. Characteristic features : () RBC - Microcytic hypochromic; count: normal. (ii) Bone marrow: Normoblastic hyperplasia. (ii) Blood a) S. iron decreases (normal: 60-160 ng/dL). (b) Total iron binding capacity (TIBC) - increases (normal: 150-350 g/dL). (iv) Nails: dry, soft, spoon shape, with longitudinal striations.