; SOCR DEDICATE,’ o- ul AWAIZ wt vba dull aes qe~ My fMC-hi REFACE TO THE NINETEENTH EDITION most dynamic of biological disciplines, while the Phys: cument srence sng exponential change Principles remain unaltered Ree PHYSIOLOGY has one of the longest pedigrees of any publica ques and ©» edition represents a further transformation, ‘The new inaterst eee hres ba tiy and yeadability, Popular Innovations from the las edition have been reinfo ree te ane ta sopie of ECG abnormalities as well as respiratory complications related ta mectoke tenet “This edition helps you to go from gene to the bedside, taking the reader from hraw son process thveush the biology of orchestrated cellular responses in inflammation ant inmmanolory. to huss nunotogy to humar ics, Focus ts to draw your attention in seeking in depth studies as the examination : enging. The text of this book is sufficient to meet requirement ofthe final cane T believe that the new edition in terms of content and presentation is indeed medical text which meet the need of tomorrow's doctors. , as chal How to use this book: For MCOs preparation: Vital facts about the most frequently asked topics are giv: ater Z casy-to-vnderstand format. This will help students to mark correctly the multiple TRUE/FALSE type MCQs & single best.type of MCQs used in MBBS, BDS, FCPS, FRCS, USMLE & PLAB exams 2 £5 For viva proparation: Every physiological concept or fact has been dealt with a bold & unde heading, which, can be used to make viva questions by adding interrogative words. e.g. Bold-X-underlined headings Viva questions T, Human Physiology 1. Define human physiology? 2. Division of ECF -_ 2. What are the divisions of ECF? 3. Internal Environment 3. What do you mean by internal environment? 4. Homeostasis 4. Define homeostasis? 5._Vicious circle 5._What is vicious circle? & For revision of Guyton: Chapters in this book follow the same sequence as in Guyton. In fact, this Yook ~~ isa summary of the more-than-1000-paged textbook by Guyton incorporating important points from GANONG & CHATTERJEE. So, this book can be used to revise major textbooks PHYSIOLOGY in couple of days before exams. ‘Thanks: ~~ Tam grateful to the following friends of mine for their great help: Sarfaraz, Hekmatullah Rahimi, Anwer, Haroon, Kamal, Azher, & my group-fellows. ‘Suggestions: Any suggestion for the improvements of this book will be acknowledged with thi be sent toz anks, Suggestions should Dr. Muhammad Firdaus Medicalstudyzone.comE a RODUCTION, CELL & GENETICS... 2 Introduction Cell Genetics 2) Memn) Musc ae 5 Transport Through Cell Membrane Membrane Potential and Action Potential Nerve Fiber Skeletal Muscle Neuro-Muscular Junction ‘Smooth Muscle HEART. Cardiax SA Nowal Fibers Heart \S 4 Pump Apex Beat Denotes \1.i1.! Valves Rhythmic Excitation OF Heart Overdrive Suppression - Electro-Ca RANE PHYSIOLOGY NERVE & n en 26 2 40 irculation &Lymphatic System In Which Lymphatics Terminate ol Of Local Blood Flow (In Tissues) ‘lis Regulation Of Circulation notional Fainting Pressure And Its Regulation 6) © M BODY FLUIDs.... KIDNEY. BLOOD..... Curve Muscle Bi tr Ine. Venous Resin, Disease — i‘ Blood Flow Maintain Cardiac Faire Low Cardiac Exercise Tet Heart Sound Hear Is Called Thrill Valvular And Congenital Heart Dete Operations Of Intracardial be Circulatory Shock 45 Min Cir Damage Blood Flow Thru Brain Artest Cause 70 16 low, Glomerula Of Filtrate In Urine Formation 1: Renal Blood & Filtration & Their Control Urine Formation Ii P Tubules: Ansulin Is Neither Rea Tubule Control Of ECF Osmolality & Na* Cone. In Addison’s Disease. Regulation Of Blood Vol. And ECF Vol Blood Vol, Regulation Of Urea &K* 2 Other Ions Cone. Dec. To Normal Regulation Of Acid-Base Balance 1 Capi bsorbed Nor Secreted In 99. Introduction to Blood RBC, Anemia & Polycythemnia WBC, Monocyte Macrophage System & Inflammation Immunity and Allergy Blood Groups Hemostasis Medicalstudyzone.com7 = Than schon (8) RESPIRATION o CENTRAL NERVOUS SYSTEM... “Spinal Cord Pulmonary Ventilation Pulmonary Circulation ses thru Resp: Mem. Tranaport of Or & COr Regulationo of Respiration Respiratory Patho-Physiology Introduction Synapses - Senses Receptors Reflex Action Cerebellum Thalamus Transport & Mixing of Food y Function of GIT “Lemon And Absorption In GIT GIT bitters ENDOCRINOLOGY ....000000-5 eee dBS (15) REPRODUCTION... (16) VITAMINS. Introduction Pituitary C Growth Hormone ADH (Vasopressin) nd Oxytocin Thyroid Metabolic Hormones Adrenocortical Hormones Aldosterone Cortisol Adrenal Androgenes Pathology of Adrenal Cortex Epinephrine And Nor-Epinephrin Hormones of Islets of Langerhans Vit. Da, Ca**, POs Bone & Teeth Parathyroid Hormone And Cal Male Physiology Female Physiology Before Pregnancy Pregnancy Lactation Negnatal Physiology Vitamins Vitamin A Vitamin D Vitamin E Vitamin K Vitamin C Thiamine (Vit. Bi) Riboflavin (Vit.B2) Nicotinic Acid (Niacin) And Nicot» raunde Pantothenic Acid (Vit-Bs) Pyridoxine (Vit. B.) Folic Acid (Vit. Bd) Cyanecobalamin (Vit. Bis) Biotin (Vit. H)Study of specific characteristics and mechanisms of ‘human body that make it a living being, is called human physiology. {inside cell is called intracellular fluid ar Fluid (ECF) cell is called extracellular fluid. of ECF rt of ECF present in blood. Fluid or Interstitial Fluid ‘of ECF present in spaces b/w cells: ‘constituents and physical ristics of Extracellular Fluid INTRODUCTION, CELL & GENETICS : Gran Ly The dagree dh; whith a cutzal ss & Corts) 4 ofpecki VNC system om constemk Candicions Normal Range Approximate Short- | Unit ] Term —_Nonlethal | Limit 40 35-45, 10-1000 mm Hg 40 35-45 5-80 mmHg 142 138-146 115-175 mmol/L. | 42 38-50 159.0 mmol/L - 12 10-14 05-2.0 mmol/L 108 103-112 70-130 mmol/L 28 24-32 8-45 mmol /L [85 75-95 20-1500 mg/dL 98.4 (37.0) 98-98.8 (37.0) 65-110 (183-43.3)__[-F FIO 7A 73-75 69-80 Medicalstudyzone. comow of Physio —— g Jfirdaus™ Fi satornal Environmen Miley Interiour = and nutrient environment aintains same ionic - uM ‘als ‘ot body; 90; ECF is alto called internat foe! ‘ Ive envionment (a cm t conditions in internal ‘Maintenance of static or constan environment is called homeostasis. Negative Feedback ” 9 initial stimulus; it is When final result is opposite l ‘allied negative feedback. Positive Feedback eet 2 ‘when final result i more of initial stimulus; il is called positive feedback. Vicious Circle 4 ‘also called vicious circle; because to save lile, and once started it Positive feedback ii it is defective and fa’ leads to death. Vital Organs of Body ‘Organs of body without which a person cannot survive are called vital organs of body. Fxamples (2) Brain (2) Heart 43) Kidney Different substances that make up cell are collectiv called protoplasm. Compositio substances: (1) Water (2) Electrolytes 12) Carbohydrates (©. Proteins (5) Lipids. Composed mainly ‘of five basic Proteins of Cell (A) Structural proteins e.g. cytoskel 2) Globular proteins, ie. enzymes (3) bucleoproteins. Jeton {ell Structural and functional unit of living matter, cap) of carrying on all life proces s independent! cailed cell Organization of Cell A typical is made up of four basic struct which from outside to inside are (A) Cell membrane (B) Cytoplasm (C) Nuclear membrane and (D) _ Nucleus (A) Cell dembrane Outer covering of cell that isolates i from. s neighbours is called cell membra Composition (1) Lipid Bilayer Q) Proteins and (3) Carbohydrates (1) Lipid Bilayer of Cell Membrane Basic structure of cell membrane bilayer (wo molecules th phospholipids and —cholesjer fl hydrophwbic §'-solubley po towards center ot pil bil hydrophilic (water-suwi', jv tiot towards ints sad uuter surfaces of lpi layer. Functions Prevents free movements of water and w soluble substances from one cell comn. to another. Proteins Of Cell Membrane They are mostly glyco-proteins scattered lipid bilayer, Types Two () Integral Proteins Penetrate all the way thru lipid biiay Functions (a) Provide channels or pores ior ps of water-soluble substanc (b) Some act as carrier proteins that bin with specific substances and trarspe them thru cell membrai (©) Enzymes: — catalyze stirface of membrane (d) Reveptors= Bind to neurotzans™vit of hormones se(ib) Peripheral Proteins Do not penetrate lipid bilayer; but are proteins. Function Act as enzymes. (3) Carbohydrates Of Cell Membrane occur in combination with proteins and lipids forming glyco-proteins and ylyco-lipids. Function objects. saviedicatstudyz adjacent cells Gy) Take parti. amore reactions. Surface oi cell membrane has a hydrate .o9' called glyco-calyx. vi of protoplasm which surrounds = jsupherally bounded by cell Semi-solid. Immediately membrane. Contains micro- Liquified b/w ectoplasm and membrane. Portion of cytoplasm in which or particles and organelles are accumulations of Chapter 1- Intre attached only to one surface of the snembrane or to one of the end of integral (@ Some are negatively charged, so negative cell membrane repel other negative el1& Gonetics | 3 (iv) Peroxisomes () Secretory Vesicle (vi) Ribosomes (vil) Microfilames viii) o and microtubules & ndoplasmic Reticulum (ER) It is a network of interconnected tubular nd flat vesicular structures, bounded by lipid bilayer membrane, endoplasmic matrix, and Space b/w two membranes of do I Parts (@) Granular ER: Has ribosomes attached One.COM -. Functions (a) Granular ER synthesize proteins (©) Agranular ER synthesize lipids (©) Has enzymes for glycogen breakdown (4) Has enzymes to detoxify substances that are damaging to cell. Golgi apparatus It consists of 4-5 layers of flat \csicles closely related to ER. Prominent in secretory cells. Functions Process. (or modify structure of) sub- stances synthesized by ER to torm lysosomes, secretory vesicles, etc filled with mnected with wuble nuclear (ii) Lysosomes These are orgarelles formed by Golgi apparatus and = centain hydrolytic enzymes for intracellular digestion. The interior of lysosome is more acidic than rest of cytoplasm. Fanctions: Provide an intracellular diges- tive system, (@) Contain nucleases for degrading DNA & RNA (b) Contain upases for degrading iipids (©) Contain glycosidases for deg-adinr glycoprorein, proteoglycans & glycolipids. (d) Contain proteases & peptidases ‘or degrading proteins. (©) Contain” bactericiaal agents, lysozymeCe 4 [Firdaus™ Review of Physiology 19th Edition and lysoferrin (f) Responsible for regression of various tissues, eg uterus regress to small size after childbirth. (iv) Peroxisomes ‘These are organelles formed by budding- off from smooth ER. Functions: Provide a detoxifying (or oxidizing) mechanism to cell. Contain oxidases that cause formation of HO: (oxidizing agent) which in association with catalase (oxidizing agent) cause oxidation (detoxification) of poisons and toxins in cell. (») Secretory Vesicles Secretory substance formed by ER-Golgi apparatus system > Transported into secretory vesicles > Sec vesicle fuses with cell mem. upon suitable stimulus > Release its contents. (vi) Ribosomes These are organelles containing rRNA & protein. They consist of large (60S) & small (40S) subunits. Ribosomes often form polysomes which consist of single messenger RNA (mRNA). Form of Ribosomes Free. polysomes — are the site of synthesis teins destined for the nucleus, ‘or mitochondria. Membrane - bound polysomes - are the site of synthesis of ‘secretary proreins , membrane protein & lysosomal enzymes (vii) Microfilaments And Microtubules Fibrillar protein synthesized by ribosomes > Polymerize into microfilaments > Organize into microtubules. Functions (a) Form cytoskeleton in ectoplasm to support ‘cell membrane. (b) Form flagellum of sperm. (©) Form cilia of ciliated epithelium. (@) Form centrioles and mitotic spindle. (viii) Mitochondria : These are self replicative organelles that synthesize high energy phosphate compound, ie ATP (Adenosine Triphosphate). Structure (a) Two lipid bilayer mem., outer and inner. (b) Shelves formed by infoldings of inne lipid bilayer mem., onto which oxidative enzymes are altached. () Mitochondrial cavity: filled with gi ~ matrix, containing enzymes of citric acid cycle and beta-oxidation, etc. and also its own DNA. Function Synthesize \TPs Power House uy Cell Mitochondria i, © en’vmes for citric acid cycle and beta-oxidation fo: fatty acids, thereby producny, et. rgy. !ibetted energy is wsed for phozplivrviatio. of ADP ty form ATP This is known as ons stive p. sspl>orvlation mitochondria proviice « “sy called power house v: vel! naidation Since TP), so they arc (C) Nuclear Membrane It is covering of nucleus the! s:pa'ey om cytoplasm. Composition It is composed of two membranes outer. Outer “membrane is continuous \.'h endoplasmic reticulum. It has many nuci.. > Functions (1) Prevents free mixing of cytoplasm sit nucleoplasm. (2) Nuclear pores allow protein molecules to pass (D) Nucleus It is the control center of cell. Composition (1) Nucleoplasm Fluid filled in nucleus. (2) Chromosomes Thread-like coiled structures, predominant ‘component of which is DNA Number in Human 23 pairs (46) chromosomes. Types Two ; (i) Somatic Chromosomes or Autosomes 22 Pairs. (ii) Sex Chromusomes 1 pair. (a) Male XY (b) Female XXThe AaRlsh B Fepentsible foe Hhosomal RNA) minthew € reesaMe ANON Mea three morphologically distinet sones: + Granular sone ~ found at the periphery contain ibosomal precursor partic sin various sages of assembly Fibritlar rone ~ centrally located; contains ribonuclear protein fibril Fibrillar center ~ contain DNA that is not being transcribed on of Nucleus Q) Contro! center of cell 2) Controls protein synthesis by forming mRNA. Controls cell division by self replication of DNA molecule. of Coll in four ways Diffusion Facilitated dittusion | Active transport Granular ER synthesize proteins ‘Smooth ER synthesize lipids Golgi apparatus synthesize galactose and ‘sialic acid " Golgi apparatus also synthesize hyaluronic “acid and chondroitin sulfate. ‘of Energy about by mitochoneria, Locomotion; exhibited by WBC fibroblasts. movement; exhibited by cilia of ed epithelium. Flagellum of sperm is tocilium. a ct 5 AU a provous in WIN} Veriton Types Tw () Pinveytosia srgulprocacanicy eas vee @ ules and ECR, WCW formation of ee Ve Datta eg bacteria, OS ONIM® 0 Ima ate , Wis a high ener Triphosphate) Hcl substances are engulfed by ot cell menibrane: ‘BY phosphate compound. (Adenosine Composition Adenosine + Ribose + 3 phosphates Functions Provides energy that helps in (1) Membrane transport @) Synthesis of chemical compounds (8) Mechanical work ATPase Wis an enzyme that cleaves ATP to ADP or AMP, thy releasing energy. tis a segment of long DNA molecule, that codes for a single protein (i.e,, 1 gene > 1 protein). Quantity Theve are 30,000 essential genes which formation of 30,000 types of essentin: proteins Functions: Genes (DNA molecules) contrat sormatie ‘of mRNA which control formation o° Gene Regions Exon : It is the coding region (expression sequen-"s) of the gone (3% of human genome). Antrons: It is the non - coding region (inter: eniny, sequences) of the gene. (97% of human genome). Mnemonic > EXon are EXpressed, INtrons are INactive6 J Firdaus™ Review of Physiology Gene (DNA) RNA eek Protein formation a oe Cell structsre Cell enzymes a ae Cell function [Bocce nes Eg aes ier These are bases which take part in formation of nucleic acids (DNA and RNA). Types Two, (1) Purines Have a 6-membered ring and a 5 membered ring, Include Adenine and guanine. 2) Pyrimidines Have only a 6-membered ring. Include Cytosine, uracil and thymine. Nucleoside ‘Combination of a nitrogenous base with pentose sugar (deoxy-ribose or ribose) is called nucleoside. Nucleotide Combination of a nucleoside (nitrogenous base + pentose sugar) with phosphoric acid, is called nucleotide. Nucleotides of DNA (1) Deoxy-adenylic acid (2) Deoxy-guanylic acid (3) Deoxy-cytidylic acid (4) Deoxy-thymidylic acid Nucleotides Of RNA (1) Adenylic acid "2) Guanyllic acid (3) Cytidylic acid (4) Uridylic reid \ Nucleic Acids | Combination of many nucleotides (poly-nucleotide) is called nucleic acid. Types Two. (1) DNA Deoxy-ribo nucleic acid. Pentose sugar is de: ribose. (2) RNA Ribo nucleic ac'J. Pentose sugar is ribose Deoxy-Ribo Nucleic Acid (DNA) DNé. is a poly-nucleotide formed by combina four types of nucleotides in which pentose s deoxy-ribose. Structure (i) Nucleotides are joined together to form “trand DNA molecule In DNA molecule, two such strands loose bonds b/w nitros,:nous bases While paralleling two strands, adenine bind thymine (AT) & guanine with Two strands are coiled into a helix. DNA is wrapped around a core of histone pr to form nucleosome. A series of nucleoso~ sometimes called “ beads on a string Nucleosome = DNA + Histones. (2) 8) @) 6) Genetic Code Three successive bases in DNA molecule ary calles! 9 genetic code. Function Controls sequence of amino acids in protein moleciile Ribo Nucleic Acid (RNA) RNA is poly-nucleotide formed by combination four types of nucleotides in which pentose sw ribose. Function \ ‘Acts as intermediate compound thru which DN? (genes). of nucleus control. chemical reactions 9 cytoplasm. » : Types Three, ‘ (1) Messenger RNA (mRNA) Formed from DNA. Single stranded.inction trries genetic information i Jeleus to cytoplasm to control wre fansfer FINA (tRNA) lover leaf like with single anction fansfers activated amino acid: \ }© acids to ribosomes to b Eembled into protein moteeuies ne 8h ibosomal RNA(rRNA) ists of b- Basis of « small sub-unit and a large sub-unit ribosome upon which amino acids are fgembled into protein molecule. Sa n of codon from, I protein formation anticodon in its center iccessive nucleotides are 64 codons jons code for amino acids. emrining 2 codons are stop codons (UAA, LAG). fe is one start codon (initiation codon), AUG, for methicuine. Protein synthesis begins h methionine (Mot) in-cukaryotes and with syImietluvnine (fmet) in prokaryotes. ‘genetic information| jin form of codon, ‘of amino acids in pro! of protein molecul d sequence) in ribosor d (RNA is called trans! sortedicalstudyzote.com of mRNA from DNA is called During traascription genetic code of \) is transferred to which will determine tein molecuie. It le (with specific me with help of Jation. It occurs in Chapter 1- Introduction, Cell & Genetic (4) Mitosis Celt Cyc of Cell Cycle (A) Gap Phase 0 (Gy) Is the resting, phase of the cell, During this phase, the cell cycle 1 suspended (B) Gap phase 1G) (1) Gr is the time between mitosis (4 phase) and the synthesis o deoxyribonucleic acid (Oh phase| (2) RNA, protein, lipid & carbohya synthesis occurs (3) Duration is 5 hours in a typical mammalian cell with 216 he (l) DNA & chromosomal protein 'e.g histones) synthesis occurs. (Q) Duration is 7 hours in a typi mammalian cell with a 16 ~ how cycle. hase 2 (Gr) (1) G2 is the interval between DNA synthesis (S phase) & mitosis (M ell Q) phase) @) Adenosine triphosphate (ATP) synthesis occurs. @) Duration is 3 hours in a typical mammalian cell with a 16 - hour cell cycle. (E) Mitosis (M) phase (1) Cell division occurs during this phase (2) In this one cell splits into two nev cells. (3) Occurs after replication of DNA & chromosome (4) The daughter cell contain same no. & type of chromosomes as in parent cell (8) Ithas 6 stages: (a) Prophase. (b) Prometaphase (©) Metaphase (d) Anaphase. (e) Telophase () Cytokinesis (©) Duration «is 1 hour ‘mammalian cell with cycle. in a typical a 16 - hour cell8 [ Firdaus™ Review, of Physiology 19th Edition Stage of M phase (a) Prophase (1) Chromatin condenses to form well chramosomes, ©) Each chromosome is duplicated during the S defined phase & has specific DNA sequence (centromere) that is required for proper segregation ) A centromere complex that acts as the microtubule organizing centre (MTOC) splits into two halves. The halves move to opposite poles of the cells. The mitotic spindle, which contain microtubules, forms between the centrosomes. @ (1) The nuclear envelop is disrupted, giving the microtubules access to the chromosomes. (@) The nucleolus disappears. 2) Kinetochores (protein compl-xes) assemble al each centromere on the chromosomes. {4) Certain microtubules of the mitotic spir dle bind to the kinetochores (kinetochore microtubt les). (5) Other microtubules af the mitotic sj ndle are polar microtubules and astral microtubul s, Me (1) Chromosomes allign at the metaphase ple e. Q) Cells can be arrested by microtubule i thi ev'chicine). ¢ can be isolated for karyotype analysi: rs 3) {d) Anaphase - (1) The Kinetochores separate, and the chron osomes move to oppasite poles. (2) The kinetochores microtubules shorten. 3) Tis polar microtubules lengthen. + {e)Telophase 1 (1) Gomwsones decondense to form chrom: :n. 2) The nuclear envelop re- forms. (3) Thes nce. lus reappears. (4) The ku eto hor microtubules disappears. (3) The pala: m. rot.ibule continue to lengthe 1. {9 Cytokinesis (1) Cyto lasm cleav ay (2 A dleavage turrow forms around the cei tre of the cell. (3) A contractile ring forms at the cleavag » furrow. The ring is composed of actin anc myosin filament. dix des through the prices of CONTROL OF CELL CYCLE 1A) Control proteins The two main protein families that control the cell cycle are cyclin ~ dependent protein kinases (Cdks) & cyclins, These proteins forms Cdk ~ cyclin complexes the ability of Cdk to phosphorylate target proteins is dependent on the cyclin that forms a complex with it (C) Check points Are points in the cell cycle where cdk ~ protein complexes mediates control G).G) checkpoint + Occurs at the G, > S phase transition + Cdk - cyclin D and Cdk - cyclin E mediates this transitior © The p53 anti ~ oncogene suppresses the cell cycle ai this check point (2\ echeck point * Occurs at the G2 > M phase transition * Cdk ! - cyclin A and Cdk 1 - cyclin B jediagys this transition. (0) Inactivation of Cyclins * Cyclins are inactivated by —protem degradation during anaphase of the M phase Mitotic Apparatus Zonsists of two ceatrioles at opposite poles of nucleus & microtubes connecting them. Function Causes movement of chromosomes to opposite poles during mitosis, [Interphase Period from end of one mitosis to onset of next, is called interphaseOO 10 [Firdeus™ Review of Physiology ASD Care eae ih tn Aa Cik ya 8 plas Pete rinsed PROMETAPHASE See Sed soc ener RUSE ‘SSC 10 te Sgedumns. Neca, sioryeae Rete eaten meena tat sey sgh ene an nc ntabte of Oana Nal et iene oe St cere machen G Set menahaks nie wane 2 ‘alll polar recat MEAP Retna ieee co Sevan ici ore ANAPIASE inet pra ade Konishi warnhels FLLOMHASE mleoe wha acactt et CVTORINENS SIP stew cal chanape ise it Interphase Lasts 15 hours 4 Last 1 hour tin (vel Se Vincristine (oncovin), Paclitaxel (Texol) are MtMutation A mistake in wanseriphon Feplication, causing app ledes is DNA molecuk Process during DNA we of _inappropria je. is called mutation. a Cancer Uncontrolled mitosis resulting in (lumor) due to mutated gens ner Basic Cause Cancer vecurs becaus eacess cell growth es (or oncogenes) is called mtitaled cells lose normal secdback control for preventing excess growth, Factors Responsible (1) Ionizing radiations, eg X-rays, gamma rays, ete, (2) Chemical substances (carcinogens), eg aniline dye derivatives & cigarette smoke. i (3) Physical uritants (4) Viruses 45) Hereditary Properties Of Cancer Cells (1) They need ne growth limits, oO _ (2) They are not attached to each other, but wander G thru blood & tisstes & form new cancerous growth factor, so they! have no growth . (3) They compete with normal tissues for nutrition; & cancer cells grow, normal cells. suff jonal deathTransport Through Cell Membrane .- Patonnes 9 shapter 2 ‘onic Concentration in ECF And ICF Extracellular] Intracellular Fluid Fluid 142 mEq/L. 10 mEq/L Ss 4mEq/L 140 mEq/L. ae 2.4 mEq/L. 0.0001 mEq/L. ig 1.2 mEg/L 58 mEq/L 1 103 mEq/L. 4 mEq/L LiCOx 28 mEq/L 10 mEq/L. Phosphates amEg/L 75m Eq/L S04 Im Eq/L. 2m Eq/L Chucose 90 mg/dl 01020 mg/dL. eee acids [30mg/dl 200 mg/dl? holesterol eae 0.5g/dl 21095 g/dl eutral fat 7a 35mm Hi 20 mm Hg? O 46mm Hg 50 mm Hg? iat 74 70 teins 2 g/dl © m|i6 g/d! GO m ales) Eg/L sre of Cell Membrane mbra.te consists of : Lipid Bilayer vteins (i) Integral or Transport Proteins Protrude all the way through cell membrane. Two types: (a) Channel Proteins: channels (b) Cor Proteitis: Bind with substance coniormational change > Transport substance across cell mem Have pores oF sr Se ee MEMBRANE PHYSIOLOG NERVE & MUSCL (il) Peripheral Proteins ‘Allached to integral protein on ini Act as enzyme. ner 5 [Transport Through Cell Membrane By Two methods (1)... Diffusion or Passive Transport (ay Simple Diffusion (b) Facilitated Diffusion 2) Active Transport Diffusion or Passive Transport (Random molecular) Movement of subsiatics: co their concentration gradient-either through open in cell membrane or in cgawinanen, Win corti protein, caused by simple kinetic motion 0° ul is called diffusion or passive transport Simple Diffusion Movement of substan membrane without binding wi caused by simple kinetic motion, diffusion. ces through opening ith carrier is called OR Movements of highly permeable molecu! region of higher to lower concentration e.g. C Facilitated Liffusion/Carrier Mediated Diffusion Movement of substance across cell membrane combination with carrier protein towards gradient without utilization of energy, is facilitated diffusion. OR Passage of poorly permeable molecules from a reg of higher to lower concentration via a carrier Example Glucose and Amino acid. Diffusion Thru Lipid Bilayer 1, Lipid soluble substances can easily di through lipid bilayer. Example Oz, Nz, Alcohol, CO:Water, although lipid insolul Marcie through lipid bitayer by” peneteaing Hike ‘bullet cue to ity small size and high KE. “trical charge on ions impede their diffusion igh lipid bilayer in WWO WAYS os i oe wi “| Water molecules attach to sons 3 Hydrated lon > bi ak euch cee Lipid bilayer is polar > =ve" uefave: ve in center > so pa (4ve or =ve) are repelled > sannol diffuse, ties of Pi ls, A lective Permeability. examples), E oa nvely. charged. attract ee eer any other jon >s9 it is, vn selective for Nat. su NS! () Ke channels > smalle# and unehiargeél > = allow only smaller hydrated K* ions > ™ reject bigger-hydrated Na* ions > so it is selective for K*, Gates of Protein Channels examples (a) For Na* Channels > onidutside of nieny. | cap @) For K> Channels > on inside of rem. \copfing of Protein Channels npoppening or closing of protein channels is called Y". Two types : Voltage - Gating In this gates are opened or mf closed due to electrical. potential changes 0, [| across.cell membrane, Examples are a. Nav-gates open when inside of membrane “ becomes less negative or ‘+ve', re J be Kegates oper. when inside of membrane becomes +ve but very slowly, clef) Ligand-Gating .\\In this, gates aresopened or closed due to binding of another niolécule with channel protein (binding substances: = ligand). Example Acetyl choline binds: with Ach- channels and opens it. Increasing Diffusion Through Protein hy, J Pressure gradient ere -Chapter 2: Membrane Physiology Now & Muse Acti ort Movement combination concentration gr Is called Activ OR Moververit’ of moteeitos fron higher concentration with VCH) SE NGHEY eXpenaitiee 4 AY Cotransport sing ehemleat gradiont ey Cat ATPase Substances acroue cell membrane carrier radient cause Transport Prowin ay 4 by, UUIIZ,II) of ener Fe BION Of lower | WNL Warts anotlior Na) QINA+/ shicose » Mechanism of Active Transport Nts mechanism can be electrogenic pump Na’~ K° Electrogenic Pump ‘Transports’ Na‘ ions out’oF éell transports 2K> ions into cell Functions molecule K pump ymiporter illustrated by Nar’ & ‘nd sinmiltanedlis (1) Maintains Na’ and K* one. differtice aetoss cell membrane. @) Contributes ~ 4 mv to tatiana Potential (-90 mV) @) Controls cell volume Carrier Prot yin of Na*~ k* Pump Has two glolular proteins, smaller one has ufksguia funetions, bv | larger one has three functions (a) 3 rece nots for Na* ions on inside (6) 2 rece Hors for K* ions on outside (©). Inside »ortion has ATP ase activity Wren two 1 ions bind of the prctiens $tsree Na becomes activ ited, libe outside of ear jons'on inside, the ATP rating energy from ATP. Th energy causes 3 conformational change in putt expelling three Nat ions to the outside & two K* ion to the inside of 1 sombrane. Why Called Elec vogenic? Since Na*- K+ pu up, pumps 3 Na* out of cell anit K* sinto, cell.) It creates negativity inside ul membrane. So itis. lled electrogenic pump. Calcium Pump Two Cats pumps, (@) One sin cell, menbrane> pumps Cat > outside, (b) Other pumps Ca: into vesicular oijanelles cells. SoCa** cone in cytoplasm is 10)000'tim Jess than ECR, Hydrogen Pump Present in14 [Firdeus™ Review of Physiology rr Os nolality No of osmoles © osmolality: eB» 90M MOs/kg: srietal cells of gastric glands. Latte distal tabute ” Kidney & cortical collecting ducts of Secondary Active Transport In secondary active tr oI (ransport energy is not provided by ATP, but itis provided by cone gradient of Nee tons across cell membrane ; (a) Ne-Cotransgort of Glucose and Amino Acid artier protein has two sites on outside, one for Nav and other for glucose or amino acid > when both bind > cone. gradient of Na* cause conformational change in ci Be IN cartier protein > Glucose or amino acid co-transported with Na to inside. : 2 Found in Epitheliuny of GIT and renal tubules. Na’-Counter Transport — This occurs in ppesite rection, je Na* fs transported to inside and other substances to opposite si Used for rece Exchange of Na* with K+, Ca‘, H+ ) Osmosis Diffusion of water from higher water conc. to lower water conc. ie from dilute solution to concentrated solution through a semipermeable membrane, is called asmosis. Osmotic Pressure “Pressure required to stop osmosis completely is called osmotic pressure” OR. “Pressure with which water molecules move from dilute solution to concentrated solution is called osmotic Pressure”.OR “Sucking pressure of concentrated solution that causes movement of water molecules from dilute solution to concentrated solution is called osmotic pressure”. Dependence ‘Osmotic pressure depends upon No. of particles per unit volume of cone, solution. Osmole (a) No. of particles in one mole (gram mol.wt.) of undissociated solute is called one osmole. Value 1 osmole = 6.02 x 10° particles; eg 180 gm. of glucose (1 mole) = 6.02 x 10® particles = 1osmole. (b) If a solute dissociates into two ions, its 1 gm mol. wt, will be equal to 2 osmoles; eg Na’ CY. Osmolarity Osmoles per Tremendous me membrane due ‘gradients Is called bu! i) * Responsible for RMP. @ @) @ te per liter of wat meat oxmoiaiity of 1 f solu fitter of solution Ss." yarn These are « i’ Nav Leak Channels Bc proteins in cell mem. the which K” 2 : Ean normally leak towards cone, Brod i ‘are 100 times more permeable 'o an Voltage-Gated Na‘-Channels Flas two sol: (a) Activation Gate: On outside. Remo closed at normal resting membron potential (-90 mV). Activated or oper: ‘when mem. becomes less -ve b 70 and -50 mV. So, Na® ions influx ) opened at Inactivated or closed when mem. potent: becomes +35 mV. So, Nat ions inilux blocked. Increased Permeability of Na‘-Channe's when Ca‘ * Decreases Ca* binds \ exterior of Na*-channel protein molecule > Difficult to open. So, when Ca** cone. dec »ermeability of Na*-channels ine. Voli \ge-Gated K*-Channels Has only on activ ‘ion gate on inside that remains closed a RMP ‘-90 mV). Slowly activated or openc when mem. potential rises from -90 m' toward. zero. So, K* ions outfux te caus repolari. tion. Slow Ca “- Na‘ Channels These are. in heart n uscle and SnOgiRieele, Slow tet activated nd they allow diffusion of Ca** an Nav ics. “heir slow but prolonged activatic acauses plates a muscles where they are Present in Cell Mombrane Na-K" Electrogonic Pump asamonr ve out of cell and at the same time a thereby creating negativity incite ett {ll Contributes 4 mV in RMP (00 my Me™ @ Calcium Pump — Transports cs gytoplasm into ECF or into. vyto tt, an plastic membrane Potential! 1 potential across cell mem. is called meme aes! ™ {) Under “resting” condition, outside inside is -ve. 2) During “activity” or “action potential”, outside becomes -ve and inside +ve, Membrane Potential (RMP) ‘Mem. potential of nerve fiber when it is not transmitting signals or in resting condition, is called RMP. Value 90 mV on inside. Origin of Normal RMP~90 MV (1) Contribution by K" Diffusion Potenti: K* conc. inside is 140: mEq/L and outside is 4 mEq/L > so, K* diffuses thru K* ~ Na* leak channels to outside until mem. potential becomes -94 mV inside > - 94 mV prevents further outflux of Kt, hence called Nemst potential for K* > so, K* diffusion potential is — 94 mv. acne Contribution by Na* Na+ conc. outside is 142 mEq/L > so, Na diff channels to inside becomes +61 mV inside > + further influx of Na*, hence potential for Na* > But K*-Na* 100 times less permeable to N Na* “diffusion potential” is not but it is +8 mV. 7 Contribution by Na-K" mp Na’-K* electrogenic pump . ions to exterior while 2 K* ions to interior, | (3) ea Chapter 2: Mo : Pte” 2: Membrane Physiology Norve & Muscie 15 ibuites 4 mV to RMP Not RMP. (1K diftuston potential = -9 (2) Na? dihuston polential ate or Contribution & K° ele Pur 4 mv : hem. potential = 9 Cause of Negativity ins ns, organic phosphate compounds and soltate ‘annot diffuse out of eel So. they nance inside cell mem. when posits from interior of cell Nemst Potential Potential difference across cell mem. that can block the difsion of an to completely towatds on Examples Laelia Q) Normally K+ ions channels, because their cone. insid. their cone. inside is greater tia Outside. But, when inside of becomes -94 mV, this potential can completely block K* diffusion towards cone. gradient, 1 from inside to outside of cell, because ~94 nV attracts +ve K> ions. So, this is called Nernst potential for K: Nernst potential for Na is +61 mV inside cell mem. diffuse out thru 2 Nernst Equation * It is used tr calculate Nernst potential for any univalent ion: * EMF (mV)= +61 log conc.inside = * cone. outside * Sign is +ve for -ve ions & vice versa Condition For NP tc develop: by diffusion of ions, two © conditions sre required. (1) Selec ive permeability Q) Con gradient. Goldman Equation It gives ¢ iffusion (mem.) potential when mem. is _ permeabk to more than one jon: EMF (mV, = ~ 61 log C Nai PNa + Cki PK + Clo © PCI/C Nac Pra + Cko PK + CCl PCL SUiaian Pot ata! Q) Transp rt of ions across cell mem. due to a stimulu. to change mem. potential from normal46] Firauet™ Review of F /olo9\ 19th Edition -ve value to 4ve value and then back to ve value, giving rise to an impulse, is called action potential. OR (2) Changes in mem. potential that occurs during activity are collectively called action potential (3) _ Rapid changes in membrane potential resulting in generation of an impulse. Stages of Action Potential (1) Resting stage (RMP) = ~ 90mv. 2) Depolarization = Change of RMP from ~ 90 mV to O and then overshoot to +35 mV is called depolarization. Due to Na* influx thru voltage- gated Na*-channels, Repolarization = change of mem, potential from +35 to again -90 mV (RMP) is called repolarization. Due to K* outflux thru voltage- gated K*-channels. + + When a stimulus is applied, membrane begins to depolarize. After an initial 15mV of depolarization, the rate of depolarization increases, this point is called FIRING LEVEL. Membrane potential then rapidly rises in the +ve direction. It then reverses & falls rapidly back to resting level. In large nerve fibers the potential soverhoots zero ‘to +ve, but in smaller fibers & many CNS neurons, the potenti a the ial very a Dies Initial very large change in mem, po} spike potential. Also called nerve im At termination of spike returns slowly to i negative after pot Occurs potential level this is called After 4 series of repe. Causes Build-up of K+ immediately outside cell mem. after repeated action potential that slows down K- outflux. Positive After Potential (Hyperpolarization) Alter action potential is over, mem. potential becomes more negative; this is called positive after potential or hyperpolarization. action potentials. merely approaches zero & does “> overshoot to +ve level. xy Kechannels remain ope Cais to K* outtlux (1) First gt is due at cases more several ie e more negativity is due to © | @) Prolonged cate et" Buimnp tha pumped ou! causes negativil ‘a group of ner jgompound! 2c ‘Compound Action potential fibers, eg sciatic 1 i ial fnitiate actior ion of action -50 mV) due to Na* channel threshold, yt u (©) Uther i @ ‘Mec ranical stimuli, (a) crushing (b) Pinching (©) Pricking @) Ele -tireal Stimuli, eg (a, Cathode current (b) Anode current inhibits 4 (4) ‘The. ral stimuli Subthreshold °otential Potential belov. threshold level that action potential .: called subthreshold p ‘of Safety Factor a Ratio of action po ential to threshold for called safety factor Note For normal propa ation of impulse should be greate- th n 1.Nerve Fiber A *On of neuron is c Kinds Two, a Prev Myelin Sheath Xt is. lipoprotein layer thar ace fents flow of ions across ner, ts of: Multiple y Schwann ceil mem. Each layer of Schwann cell mens is composed of ay Outer and in @) ner protein layers and Sphingomyelin in between Manner is which myelin sheath is formed is called myelination. kes Several turns around axon. Later, “cytoplasm of leaving multiple concentric layers of cell mem. of Schwann cells, which together constitute myelin sheath. where myelin sheath is absent exchange for action potential tolake pace; these ae called nodes eon Neurolemma vr Sheath of Schwann It is a sheath of Schw, ‘ann cells (not Schawen cell mem) that closely inv sts peripheral nerves, both ted ar unmyelinated. Woe SIE 1 regener of neve fiber * nibAA CE hte Conduction ¢ age Poll in mycinateireanae i ad fi ae Ld ‘ 4 slater conducag STMT sorter18 [Firdaus™ Review of Physiology Importance Q) Velocity of transmission is ine @ Conserves energy nly Nodes depolarize Rheobase Minimum current need muscle is called rheobas: ‘ Utilization Time Time needed for stimula tion by Pheabase ca utilization time. : a Chronaxie Time needed for stimulation by ® current double the theobase, is called chronaxie. ms ‘onttractile tissue of body is called muscle. Types (1) Striated Muscle (2) Skeletal muscle (Voluntary) (b) Cardiac muscle (Involuntary) (2) Unstriated Muscle (involuntary) smooth muscle, Present in viscera. ‘Skeletal Muscle that type of muscle, which is present in skeleton, voluntary in action and striated in appearance, is called skeletal muscle. Skeletal Muscle Fiber Functional and structural unit of muscle is called muscle fiber. it is cell mem. of muscle fiber that (2) Sarcoplasm: It is matrix present in muscle fiber (3) Sarcoplasmic Reticulum. It contain a protein called “calsequestrin”. Which can bind up to 40 times more Ca** 14) Myofibrils (5) Each muscle fiber is innervated by one nerve ending in center | Sigel wcities UREN TR Each muscle fiber contains. in its sarcoplasm hundreds of myofibrils. Composition Each myofibvril contains: thick) fi thin) filaments Structural Pecullarities Actin and myosin filaments partly interargitate causing alternate dark and light bands: (01 Band: Light band containing only actin filament. tsotropic to polarized light 2) A Band: Dark filamer polarized ligh (3) H Zone: Light area in center of A band. See When muscle is stretched beyond its resting length, due to pulling apart of actin filaments. (4) M Line: Dark line in the center of H zone. d containing actin and myosin hey overlap. Anisotropic ZDisc It is a disc (plate) of filamentous protein to which actin filaments are attached. Funetion Z disc passes from myofibril to myofibril and attach them together. SARCOMERE: Portion of myofibril b/w two successive Z discs is called sarcomere. Resting Length: of sarcomere is 2p Myosin Filament It consists of 200 myosin molecules. Each myosin ‘molecule consists of two heavy chains and four light chains, Structural Peculiarities @) Tail Formed by two heavy chains which coil into a helix. (2) Head_ Formed by the other end of helix together with four light chains. it has ATP-ase activity. (3) Body Formed by tails of all myosin molecules. (4) Arry_ Part of tail that protrude out from body is, Callsd arm. (5) Cress Bridge Arm and head together are called excss bridge. Absent in center. (6) Tvo Hinges Movable point of myosin filament is called hinge. One hinge is present where arm le: ves body and other where head is attached to arn, Actin Filament ‘ Com) osed of: (2) F-Actin Strands _(F = filamentous). Two 5 strands are wound into helix, Each strand of act n molecules is made by polymerization act n (G = globular) protein molecules. E:molecule has one ADP thay , ch interact du ring slid) yyosin Strand wo myosin ate coiled inte Nethe that 5 Paactin strane Bach ymerization of tropomy fon Wn resting st cally cover activessit _ preventing muscle contraction Troponin Complex Mis atlached 2/9 distane, along each tropomyosin molecule Consists of 3 globular proteins (a) Troponin I; to attach with actin fb) Troponin T; to altach with tropomyosin {@ Troponin C; to attach with Cass Function Troponin complex attaches F-actin strands with tropomyosin strands, of Actin Filament resting condition, tropomyosin strand ly covers active site (ADP) of actin strand. ng interaction occurs b/w actin and myosin to muscle contraction. of Actin Filament By ° in muscle mem. > Ca** released iculum 9 Ca’ binds with ational change > Pushes groove b/w two F- ADP) on F-actin strands actin and myosin > iN molecule Hopomyesin strands of Feactiny = (a) (2) @) bridge of myosin (they walk is pulled inward over myosin over each otler > Z dises pul shorten > Muscle contracts. ied Walk Along Theory Of Muscle wore When active site of actin filament * ‘of cross bridge attaches to active ys alignment of inter-molecular forces Head he Chaptor é of myosin filament > Membrann Physiology Merve & Muscio§) 19 “0% Aetic fi 10D Head ds towards >A n Hament move brid nt, pulling a ere Molecular Events in Muscle Contraction Actin 40 Retin: Myosin are Process of Muscle Contraction In relaxation phase, the head of myosin hydrolyzes ATP to ADP + Pi, but these remain bound to myosin. ADP-Pi-myosin complex is now in high-energy conformation When contraction is stimulated, head of myosin binds to active sites on actin é& forms actin- myosin-ADP-Pi complex. Formation of this complex promotes the release of Pi, which intiates power stroke, This is followed by release of ADP, & is accompanied by a large conformational change in myosin head in relation to its tail, pulling actin about 10 nm towards the center of sarcomere. This is the power stroke. The myosin is now in a low-energy state. (4) Andther molecule of ATP binds to myosin head. forming actin-myosin-ATP complex. (6) Myosin-ATP has a low affinity for actin, so actin is released. This last step is a key component of felaxation & is dependent upon the ot binding Reeser complex. (Depletion of ATP Mortis).