Physiology: blood, nerve, muscle and cardiorespiratory systems

In short

This block covers the physiology of blood (its cells, plasma, groups and clotting), of excitable tissue (nerve and muscle membrane potentials and contraction), and of the cardiovascular and respiratory systems that deliver oxygen and remove carbon dioxide. It is the quantitative, mechanism-heavy core of first-year MBBS under the NMC Competency-Based Medical Education (CBME) curriculum, and the single largest source of marks in Physiology Paper I university examinations. Clinically it underpins the reading of an ECG, a blood gas report, a CBC, a spirometry trace and a coagulation profile - skills tested in every clinical viva, NEET-PG/INI-CET and the National Exit Test (NExT, whose roll-out has been repeatedly deferred, so confirm the current status). Practical competencies examined include haemoglobinometry, blood grouping, bleeding and clotting time, pulse and blood pressure recording, ECG recording and spirometry.

Explained

Blood: composition, cells and plasma

• Volume: about 70-80 mL/kg body weight; roughly 5 L in a 70 kg adult (about 8% of body weight). Plasma volume about 3 L, blood cell volume about 2 L.
• Haematocrit (PCV): fraction of blood volume occupied by cells - 40-50% in adult men, 36-46% in adult women. Rises in polycythaemia and dehydration, falls in anaemia.
• Plasma proteins: total 6-8 g/dL - albumin 3.5-5.0 g/dL (main contributor to plasma colloid osmotic pressure, about 25 mmHg), globulins (transport and immunity), fibrinogen 200-400 mg/dL (clotting), and prothrombin. All but gamma-globulins are made in the liver; A:G ratio normally 1.2-2.5:1.
• Functions of plasma proteins: oncotic pressure, transport of hormones/drugs/iron/copper, buffering (about 15% of blood buffering), clotting and defence, and a protein reserve.
• Erythrocytes: 4.5-5.5 million/µL (men), 3.8-4.8 million/µL (women). Biconcave, non-nucleated, no mitochondria - energy from anaerobic glycolysis; 2,3-BPG from the Rapoport-Luebering shunt. Lifespan 120 days, destroyed in the spleen (the "graveyard of RBCs").
• Erythropoiesis: proerythroblast → early and late normoblast → reticulocyte → erythrocyte. Site: yolk sac (early fetal) → liver and spleen (mid-fetal) → red bone marrow (after birth; restricted to axial skeleton and proximal long-bone ends in adults). Requires erythropoietin (from renal peritubular interstitial cells in response to hypoxia), iron, vitamin B12, folate, pyridoxine, protein, thyroxine and androgens.
• Haemoglobin: 13-17 g/dL (men), 12-15 g/dL (women); 4 haem groups each with ferrous iron, globin chains α2β2 (HbA), α2δ2 (HbA2), α2γ2 (HbF). 1 g Hb carries 1.34 mL O2. Derivatives: oxyhaemoglobin, deoxyhaemoglobin, carboxyhaemoglobin (CO affinity about 210-250 times that of O2), methaemoglobin (ferric), carbaminohaemoglobin (CO2 on globin).
• Haemoglobin catabolism: haem → biliverdin → unconjugated bilirubin → albumin-bound to liver → conjugated with glucuronic acid → bile; iron recycled via transferrin/ferritin.
• ESR: Westergren 0-15 mm/h (men), 0-20 mm/h (women); raised by increased fibrinogen and globulins (rouleaux formation), lowered by polycythaemia and sickle cells.
• Leucocytes: 4,000-11,000/µL. Differential - neutrophils 40-75%, lymphocytes 20-40%, monocytes 2-8%, eosinophils 1-6%, basophils 0-1%. Neutrophils: phagocytosis, first responders, chemotaxis and respiratory burst. Eosinophils: parasites and allergy. Basophils: histamine and heparin. Monocytes → tissue macrophages (reticuloendothelial system). Lymphocytes: T (cell-mediated, thymus-processed) and B (antibody, humoral).
• Platelets: 1.5-4.0 lakh/µL, lifespan 7-10 days, from megakaryocytes under thrombopoietin. Contain alpha granules (PF4, vWF, fibrinogen), dense granules (ADP, ATP, serotonin, Ca2+); no nucleus but have actin/myosin and a canalicular system.

Blood groups, transfusion and haemostasis

• ABO system: antigens A and B on the RBC membrane, with naturally occurring reciprocal IgM antibodies in plasma appearing by 3-6 months. Group O is the "universal donor" (packed cells), AB the "universal recipient" - both only in emergency, as plasma antibodies still matter. Bombay (Oh) phenotype, discovered in Mumbai in 1952, lacks H antigen and can receive only Bombay blood.
• Rh system: D antigen is most immunogenic; about 93-95% of Indians are Rh-positive. No natural anti-D; sensitisation follows exposure. Erythroblastosis fetalis (haemolytic disease of the newborn) occurs when an Rh-negative mother sensitised in a first pregnancy carries a later Rh-positive fetus - prevented by anti-D immunoglobulin to the mother within 72 hours of delivery/abortion.
• Cross-matching: major (donor cells + recipient serum) and minor (donor serum + recipient cells). Transfusion reactions - haemolytic, febrile non-haemolytic, allergic, TRALI, circulatory overload, citrate toxicity, hyperkalaemia, iron overload.
• Indian regulation: blood and blood components are "drugs" under the Drugs and Cosmetics Act, 1940 and its Rules; blood centres are licensed by the State Drugs Controller/CDSCO, and mandatory screening covers HIV, hepatitis B, hepatitis C, syphilis and malaria. National Blood Transfusion Council and State Councils set policy; voluntary non-remunerated donation is the national standard; donation interval normally 3 months (men) / 4 months (women) with minimum Hb 12.5 g/dL - verify current NBTC/CDSCO figures as they are periodically revised.
• Haemostasis in four steps: (1) vascular spasm; (2) platelet plug - adhesion via vWF to collagen through GPIb, activation, secretion of ADP and TXA2, aggregation via GPIIb/IIIa binding fibrinogen; (3) coagulation (fibrin mesh); (4) clot retraction and fibrinolysis.
• Intrinsic pathway: XII → XI → IX → VIII complex → X. Measured by APTT (26-40 s). Extrinsic pathway: tissue factor (III) + VII → X. Measured by prothrombin time (11-16 s; reported as INR). Common pathway: Xa + Va + phospholipid + Ca2+ (prothrombinase) → prothrombin (II) to thrombin → fibrinogen (I) to fibrin → stabilised by XIII.
• Vitamin K-dependent factors: II, VII, IX, X plus proteins C and S. Factor IV is calcium; there is no factor VI.
• Anticoagulants: heparin (antithrombin III potentiator, immediate, monitored by APTT), warfarin (vitamin K epoxide reductase inhibitor, delayed, monitored by PT/INR), citrate and oxalate (chelate calcium - in vitro; CPDA/CPD-SAGM in blood bags), EDTA (CBC samples), DOACs (dabigatran, rivaroxaban).
• Fibrinolysis: plasminogen → plasmin by tPA/urokinase/streptokinase; D-dimer is a degradation product. Bleeding time 2-7 min (platelet/vascular function), clotting time 5-11 min (coagulation).
• Disorders: haemophilia A (factor VIII, X-linked, raised APTT with normal PT), haemophilia B (factor IX), von Willebrand disease (commonest inherited bleeding disorder), ITP, DIC (both PT and APTT raised, platelets and fibrinogen low, D-dimer high), vitamin K deficiency of the newborn.

Nerve and muscle: excitability and contraction

• Resting membrane potential (RMP): about −70 mV in neurons, −90 mV in skeletal muscle, −60 mV in smooth muscle. Caused by high resting K+ permeability, the K+ concentration gradient, impermeant intracellular anions, and the electrogenic Na+-K+ ATPase (3 Na+ out : 2 K+ in) which contributes about −4 mV directly.
• Action potential (AP) phases: (1) local/subthreshold response; (2) depolarisation to threshold (about −55 mV) → voltage-gated Na+ channels open, regenerative Na+ influx, overshoot to +35 mV; (3) repolarisation - Na+ inactivation plus delayed K+ efflux; (4) after-hyperpolarisation from persisting K+ conductance.
• Properties: all-or-none, non-decremental propagation, refractory periods (absolute - no stimulus can excite, due to Na+ channel inactivation; relative - a stronger stimulus can), no summation, no fatigue in nerve.
• Conduction: continuous in unmyelinated fibres; saltatory from node to node in myelinated fibres - faster, and more energy-efficient. Velocity rises with diameter and myelination.
• Nerve fibre classification: A-alpha (70-120 m/s, proprioception and motor), A-beta (touch, pressure), A-gamma (muscle spindle motor), A-delta (pain, temperature), B (preganglionic autonomic), C (unmyelinated - slow pain, postganglionic sympathetic, 0.5-2 m/s). Sensory alternative: Ia, Ib, II, III, IV.
• Nerve injury and degeneration: Wallerian (anterograde) degeneration distal to the cut; chromatolysis in the cell body; regeneration about 1 mm/day along intact neurilemma. Neuropraxia, axonotmesis, neurotmesis. Local anaesthetics block Na+ channels; small unmyelinated C fibres are blocked first, so pain goes before touch and motor power.
• Neuromuscular junction (NMJ): AP reaches the terminal → voltage-gated Ca2+ channels open → quantal acetylcholine release → nicotinic receptors on the motor end-plate → end-plate potential (always suprathreshold, hence 1:1 transmission) → muscle AP; ACh hydrolysed by acetylcholinesterase. Blocked by curare (competitive, non-depolarising), succinylcholine (depolarising), botulinum toxin (prevents release), and autoantibodies in myasthenia gravis; organophosphate poisoning (common in Indian agricultural practice) inhibits cholinesterase.
• Skeletal muscle structure: sarcomere from Z line to Z line; A band (thick myosin, constant length), I band (thin actin only), H zone, M line. Thin filament = actin + tropomyosin + troponin (T, I, C). Triad: one T-tubule with two terminal cisternae of sarcoplasmic reticulum.
• Excitation-contraction coupling: muscle AP → T-tubule → dihydropyridine receptor (voltage sensor) → mechanical opening of the ryanodine receptor RyR1 → Ca2+ released from SR → Ca2+ binds troponin C → tropomyosin shifts → actin-myosin cross-bridge cycling (attach, power stroke, ADP+Pi release, detach with fresh ATP) → sliding filament shortening. Relaxation needs ATP for SERCA to pump Ca2+ back - hence rigor mortis when ATP runs out.
• Muscle mechanics: isotonic (constant load, length changes) versus isometric (constant length, tension changes); length-tension relation peaks at optimal overlap; load-velocity relation is inverse. Twitch → summation → clonus → tetanus (incomplete and complete). Motor unit size and recruitment determine graded force; muscle tone; fatigue is mainly central plus metabolite accumulation.
• Muscle fibre types: Type I (slow oxidative, red, fatigue-resistant, marathon), Type IIa (fast oxidative-glycolytic), Type IIb/x (fast glycolytic, white, powerful, quickly fatigued).
• Smooth versus cardiac muscle: smooth muscle has no sarcomeres or troponin - Ca2+ binds calmodulin → myosin light-chain kinase; it shows latch state, spontaneous tone and plasticity, and single-unit (syncytial, gut and uterus) versus multi-unit (iris, vas deferens) types. Cardiac muscle is striated, syncytial via gap junctions in intercalated discs, with a long plateau (Ca2+ influx) AP, calcium-induced calcium release, no tetanus and no recruitment.

Cardiovascular system

• Cardiac muscle properties: autorhythmicity, conductivity, contractility, excitability, long refractory period, all-or-none response by chamber, Starling behaviour.
• Conduction system and conduction velocity: SA node (the pacemaker, 70-80/min, unstable RMP −55 to −60 mV with funny current If) → AV node (40-60/min; AV nodal delay about 0.1 s allows atrial emptying; slowest conduction about 0.05 m/s) → bundle of His → right and left bundle branches → Purkinje fibres (fastest, about 4 m/s).
• Cardiac cycle (0.8 s at 75/min): atrial systole 0.1 s; ventricular systole 0.3 s = isovolumetric contraction + rapid and reduced ejection; ventricular diastole 0.5 s = protodiastole, isovolumetric relaxation, rapid and slow filling (diastasis), atrial systole. Diastole shortens more than systole in tachycardia - coronary filling (which is diastolic for the left ventricle) suffers.
• Pressures: aortic 120/80 mmHg; left ventricle 0-120 mmHg; right ventricle 0-25 mmHg; pulmonary artery 25/10 mmHg (mean about 15); right atrium 0-5 mmHg; pulmonary capillary wedge about 8-10 mmHg.
• Heart sounds: S1 (mitral and tricuspid closure, start of systole, low-pitched long), S2 (aortic and pulmonary closure, sharp, physiologically split on inspiration), S3 (rapid filling - normal in children and athletes), S4 (atrial - usually pathological). Murmurs arise from turbulence at stenotic or regurgitant valves.
• ECG: standard 12 leads at 25 mm/s and 10 mm/mV. P wave = atrial depolarisation (<0.12 s, <2.5 mm); PR interval 0.12-0.20 s (atrial depolarisation plus AV delay); QRS <0.12 s (ventricular depolarisation); ST segment isoelectric (plateau); T wave = ventricular repolarisation; QT interval 0.35-0.44 s (rate-corrected as QTc); U wave sometimes in hypokalaemia. Atrial repolarisation is hidden in the QRS. Uses: rate, rhythm, axis, hypertrophy, ischaemia and infarction (ST elevation, Q waves), electrolyte changes (peaked T in hyperkalaemia), drug effects.
• Cardiac output: 5 L/min at rest (CO = SV × HR; SV 70 mL). Cardiac index about 3.0-3.5 L/min/m². Regulation - Frank-Starling law (force increases with end-diastolic fibre length, i.e. preload, up to optimum), afterload, contractility (sympathetic, catecholamines, digoxin raise it; hypoxia, acidosis, beta-blockers lower it), heart rate. Measured by Fick principle, thermodilution, echocardiography, dye dilution.
• Heart rate control: sympathetic (T1-T4, beta-1 receptors, noradrenaline - positive chronotropic, dromotropic, inotropic, bathmotropic) and parasympathetic (vagus, M2 muscarinic - negative; vagal tone dominates at rest, so cutting both nerves raises the rate to about 100/min). Reflexes - baroreceptor (carotid sinus and aortic arch, via IX and X), Bainbridge, chemoreceptor, Bezold-Jarisch, Cushing reflex, cold pressor.
• Blood pressure: systolic, diastolic, pulse pressure (40 mmHg), mean arterial pressure. Determinants - cardiac output and peripheral resistance; short-term control by baroreflex and chemoreflex, medium-term by capillary fluid shift and renin-angiotensin, long-term by the kidney (renin-angiotensin-aldosterone, pressure natriuresis, ADH). Hypertension in India is defined as ≥140/90 mmHg in most national programme documents (ICMR/NPCDCS, following the WHO/ISH line), while ACC/AHA uses ≥130/80 - state which threshold is being used. Screening and treatment run through the India Hypertension Control Initiative and NP-NCD at HWC/Ayushman Arogya Mandir level.
• Haemodynamics: Poiseuille's law shows resistance depends on the fourth power of radius, so arterioles are the main resistance vessels; velocity is lowest in capillaries (largest total cross-section); veins hold about 60-70% of blood volume (capacitance). Starling forces govern capillary exchange; oedema follows a fall in albumin, a rise in venous pressure, lymphatic block or raised permeability.
• Regional circulations: coronary (autoregulated by adenosine; myocardium extracts about 70-80% of delivered O2 at rest, so flow must rise in exercise), cerebral (autoregulated 60-150 mmHg mean, CO2-sensitive), cutaneous (thermoregulatory), pulmonary (low pressure, hypoxic vasoconstriction), splanchnic, fetal (shunts - ductus venosus, foramen ovale, ductus arteriosus).
• Shock: hypovolaemic, cardiogenic, obstructive, distributive (septic, anaphylactic, neurogenic); compensatory tachycardia, vasoconstriction, fluid shift; stages compensated → progressive → irreversible.

Respiratory system

• Functions: gas exchange, acid-base regulation, heat and water loss, phonation, olfaction, defence (mucociliary clearance), and metabolic roles (ACE activity in pulmonary endothelium, surfactant).
• Mechanics: quiet inspiration is active (diaphragm supplies about 75% of tidal volume, plus external intercostals); quiet expiration is passive elastic recoil. Accessory muscles (sternocleidomastoid, scalenes, serratus) in forced inspiration; abdominals and internal intercostals in forced expiration. Intrapleural pressure −5 cmH2O at end-expiration, about −8 at end-inspiration (always subatmospheric); intra-alveolar swings about −1 to +1 cmH2O.
• Compliance and surfactant: compliance = ΔV/ΔP, about 200 mL/cmH2O for the lung (about 100 mL/cmH2O for the lung-chest wall system). Surfactant (dipalmitoyl phosphatidylcholine from type II pneumocytes, from about 24-28 weeks' gestation, mature by 34-36) lowers surface tension, raises compliance, stabilises alveoli of different size per Laplace's law and prevents transudation; deficiency causes neonatal respiratory distress syndrome. Hysteresis separates the inflation and deflation limbs.
• Lung volumes and capacities: TV 500 mL, IRV 3,000 mL, ERV 1,100 mL, RV 1,200 mL; IC 3,500 mL, FRC 2,300 mL, VC 4,600 mL, TLC 5,800 mL (classic Western values - Indian adults average roughly 20-25% lower, and NIOH/ICMR Indian reference equations should be used for interpretation). RV and FRC and TLC cannot be measured by spirometry - helium dilution, nitrogen washout or body plethysmography are needed.
• Dead space: anatomical about 150 mL (Fowler's method), alveolar, physiological (Bohr's method). Alveolar ventilation = (TV − dead space) × respiratory rate - the figure that actually determines PaCO2; shallow rapid breathing wastes ventilation.
• Spirometry patterns: obstructive (FEV1/FVC < 0.7, low FEV1, raised RV - asthma, COPD) versus restrictive (FEV1/FVC normal or high, low FVC and TLC - fibrosis, kyphoscoliosis, obesity, pleural disease). PEFR is used to monitor asthma.
• Diffusion: across the 0.2-0.6 µm blood-gas barrier, governed by Fick's law (area, thickness, partial-pressure difference, gas solubility). CO2 diffuses about 20 times faster than O2, so hypoxaemia precedes hypercapnia in diffusion defects. Partial pressures - alveolar PO2 100, PCO2 40 mmHg; arterial PO2 95-100, PCO2 40; venous PO2 40, PCO2 46; inspired PO2 about 159 mmHg at sea level.
• Ventilation-perfusion: V/Q ratio about 0.8 overall; apex is better ventilated relative to perfusion (high V/Q, more dead-space-like) and the base is better perfused (low V/Q, more shunt-like) in the erect posture, with both ventilation and perfusion greater at the base in absolute terms. Shunt (V/Q = 0) does not respond well to oxygen; dead space (V/Q = ∞) does.
• Oxygen transport: 97% as oxyhaemoglobin, 3% dissolved. Sigmoid oxygen dissociation curve from cooperative binding; P50 about 26-27 mmHg. Right shift (more unloading) with raised CO2, H+ (lower pH - Bohr effect), temperature, 2,3-BPG and in HbS; left shift with the opposite plus HbF, methaemoglobin and CO. The plateau above 60 mmHg protects saturation at altitude; the steep part aids tissue delivery.
• Carbon dioxide transport: about 70% as bicarbonate (carbonic anhydrase in the RBC, with the chloride shift), 23% as carbamino compounds, 7% dissolved; Haldane effect - deoxygenated Hb carries more CO2.
• Regulation of breathing: medullary dorsal (inspiratory, DRG) and ventral (expiratory, VRG) groups with the pre-Bötzinger complex as rhythm generator; pontine pneumotaxic centre (switches off inspiration) and apneustic centre. Central chemoreceptors in the ventral medulla respond to CSF H+ from CO2 - the main minute-to-minute drive; peripheral chemoreceptors (carotid and aortic bodies, via IX and X) respond chiefly to a PaO2 below about 60 mmHg and become the main drive in chronic CO2 retention. Reflexes - Hering-Breuer inflation, J-receptor, irritant, cough, sneeze.
• Hypoxia: hypoxic (low PaO2 - altitude, hypoventilation), anaemic (low Hb or CO poisoning; PaO2 normal), stagnant/ischaemic (low flow), histotoxic (cyanide). Cyanosis needs about 5 g/dL of deoxygenated Hb, so it appears early in polycythaemia and may be absent in severe anaemia. Acclimatisation to altitude (relevant to Leh, Siachen and the Himalayan high-altitude medical research of DIPAS/DRDO): hyperventilation, polycythaemia, raised 2,3-BPG, more capillaries and mitochondrial enzymes.
• Applied: periodic breathing (Cheyne-Stokes, Biot), dyspnoea, asphyxia, artificial respiration, oxygen therapy and its toxicity, hyperbaric oxygen, decompression sickness, respiratory acidosis and alkalosis and their compensation.

Key points

• Haematocrit - cell fraction of blood volume; 40-50% men, 36-46% women; the main determinant of blood viscosity.
• Erythropoietin - renal hormone released on hypoxia; drives erythropoiesis, which is why chronic kidney disease causes normocytic anaemia.
• 1 g Hb = 1.34 mL O2 - the basis of every oxygen-content calculation; oxygen capacity of normal blood is about 20 mL/dL.
• Vitamin K factors II, VII, IX, X - warfarin targets these; PT/INR tests the extrinsic pathway and APTT the intrinsic.
• Haemophilia A - factor VIII deficiency, X-linked, prolonged APTT with normal PT, normal bleeding time and platelet count.
• Anti-D prophylaxis - given to an Rh-negative mother within 72 hours of delivery or abortion to prevent haemolytic disease in later pregnancies.
• RMP - set by high resting K+ permeability near the K+ equilibrium potential, maintained by Na+-K+ ATPase.
• Absolute refractory period - due to Na+ channel inactivation; it limits the maximum firing frequency and prevents tetanus in cardiac muscle.
• Saltatory conduction - node-to-node jumping in myelinated fibres; faster and metabolically cheaper than continuous conduction.
• End-plate potential - always suprathreshold, giving a one-to-one relation between nerve and muscle action potentials at the NMJ.
• Excitation-contraction coupling - T-tubule depolarisation → DHPR → RyR1 → SR Ca2+ release → troponin C → cross-bridge cycling.
• ATP in relaxation - needed by SERCA to remove Ca2+; its absence explains rigor mortis, not contraction failure alone.
• Frank-Starling law - stroke volume rises with end-diastolic volume (preload) up to an optimum, matching the two ventricles' outputs.
• AV nodal delay (about 0.1 s) - the slowest conduction in the heart; it lets the atria empty before ventricular systole and protects the ventricles in atrial fibrillation.
• PR interval 0.12-0.20 s, QRS <0.12 s - the two intervals most often asked on an ECG strip at 25 mm/s (1 small square = 0.04 s).
• FEV1/FVC < 0.7 - the cut-off that defines airflow obstruction; a normal or high ratio with low FVC suggests restriction.
• Alveolar ventilation, not minute ventilation - determines PaCO2; dead space makes rapid shallow breathing inefficient.
• Bohr and Haldane effects - CO2/H+ shift the O2 curve right (better unloading); deoxygenation lets blood carry more CO2.

Formulas and examples

Example 1 - Red cell indices and anaemia type. A 24-year-old woman from a rural district has Hb 8.4 g/dL, PCV 27%, RBC 4.2 million/µL.

• MCV = (27 × 10) / 4.2 = 270/4.2 = 64.3 fL (low).
• MCH = (8.4 × 10) / 4.2 = 84/4.2 = 20 pg (low).
• MCHC = (8.4 × 100) / 27 = 840/27 = 31.1% (low).
• Interpretation: microcytic hypochromic anaemia - in India most often iron deficiency; confirm with serum ferritin, and consider thalassaemia trait where ferritin is normal. Anaemia Mukt Bharat uses the same indices after Hb screening.

Example 2 - Cardiac output, ejection fraction and MAP. Echo shows EDV 120 mL, ESV 50 mL, heart rate 72/min, BP 124/82 mmHg, BSA 1.7 m².

• SV = 120 − 50 = 70 mL.
• EF = 70/120 × 100 = 58.3% (normal).
• CO = 0.070 × 72 = 5.04 L/min; cardiac index = 5.04/1.7 = 2.96 L/min/m².
• Pulse pressure = 124 − 82 = 42 mmHg; MAP = 82 + 42/3 = 82 + 14 = 96 mmHg.
• If heart rate doubles to 144/min with no change in stroke volume, CO = 10.08 L/min - but in reality diastole shortens, filling falls, so the gain is less.

Example 3 - Oxygen content and anaemic versus hypoxic hypoxia. Patient A: Hb 15 g/dL, SaO2 70%, PaO2 40 mmHg. Patient B: Hb 7.5 g/dL, SaO2 98%, PaO2 95 mmHg.

• A: (1.34 × 15 × 0.70) + (0.003 × 40) = 14.07 + 0.12 = 14.19 mL/dL.
• B: (1.34 × 7.5 × 0.98) + (0.003 × 95) = 9.85 + 0.285 = 10.14 mL/dL.
• Normal: (1.34 × 15 × 0.98) + (0.003 × 95) = 19.70 + 0.285 = 19.98 mL/dL (about 20 mL/dL).
• A has hypoxic hypoxia (low PaO2, cyanosis likely, responds to oxygen); B has anaemic hypoxia (normal PaO2, no cyanosis as deoxygenated Hb cannot reach 5 g/dL, responds poorly to oxygen alone - needs haemoglobin).

Example 4 - Alveolar ventilation and the effect of breathing pattern. Dead space 150 mL.

• All three move 6 L/min, yet alveolar ventilation ranges from 2.4 to 5.1 L/min - so the rapid shallow pattern will retain CO2 despite a "normal" minute volume.

Example 5 - Alveolar gas equation and A-a gradient. A patient on room air (FiO2 0.21) at sea level (Patm 760 mmHg) has PaO2 70 mmHg and PaCO2 32 mmHg.

• PAO2 = 0.21 × (760 − 47) − 32/0.8 = 0.21 × 713 − 40 = 149.7 − 40 = 109.7 mmHg.
• A-a gradient = 109.7 − 70 = 39.7 mmHg - well above the expected (age/4 + 4 ≈ 10-15 mmHg in a young adult), so this is a gas-exchange defect (V/Q mismatch or shunt), not simple hypoventilation (which would raise PaCO2 with a normal gradient).

Where it is used

• Clinical diagnostics and laboratory medicine: CBC and red-cell indices, PT/INR and APTT, blood grouping and cross-matching in NABL-accredited labs (Dr Lal PathLabs, SRL, Metropolis, Thyrocare) and hospital blood banks licensed under the Drugs and Cosmetics Rules.
• Cardiology and critical care: ECG interpretation, echocardiographic stroke volume and ejection fraction, invasive haemodynamics and ventilator settings in ICUs - the direct application of cardiac output, compliance and V/Q physiology.
• Pulmonary function and occupational health: spirometry in COPD and asthma clinics, pre-employment and periodic medical examinations under the occupational safety and health provisions now consolidated in the OSH and Working Conditions Code (in force with the four Labour Codes from 21 November 2025), and silicosis/byssinosis surveillance in mining and textile industries.
• Public health programmes: Anaemia Mukt Bharat and the National Health Mission (Hb screening, iron-folic acid supplementation), India Hypertension Control Initiative and NP-NCD screening at Ayushman Arogya Mandirs, and the National Tobacco Control Programme for respiratory disease.
• Research, sports and defence physiology: ICMR institutes, AIIMS and DRDO's DIPAS work on high-altitude acclimatisation for troops in Ladakh and Siachen; SAI and National Centre of Sports Science use VO2 max, lactate threshold and fibre-type testing.
• Careers and exams: physiology demonstrator and postgraduate (MD Physiology) posts, clinical trial and medical-affairs roles in pharma, medical-device companies selling monitors, ventilators and dialysis equipment, and the physiology component of NEET-PG, INI-CET, AIIMS/PGI/JIPMER entrance tests and AFMC/armed forces medical selection.

Interview questions

• Q: Why is the resting membrane potential close to the potassium equilibrium potential? A: Because the resting membrane is far more permeable to K+ than to Na+, so K+ diffusion dominates the potential, with a small contribution from the electrogenic Na+-K+ pump and impermeant intracellular anions.
• Q: What causes the absolute refractory period, and why does it matter clinically? A: Inactivation of voltage-gated Na+ channels. It caps the maximum firing rate and, in cardiac muscle, prevents tetanic contraction so the heart can always relax and refill.
• Q: Why does the heart not undergo tetanus? A: Its action potential has a long plateau phase and a correspondingly long refractory period that outlasts most of the contraction, so a second stimulus cannot arrive before relaxation begins.
• Q: Why is ATP needed for relaxation as well as contraction? A: ATP is hydrolysed by SERCA to pump Ca2+ back into the sarcoplasmic reticulum and is required for myosin to detach from actin - without it the muscle stays stiff, as in rigor mortis.
• Q: State the Frank-Starling law and its physiological purpose. A: The force of contraction increases with the end-diastolic length of the muscle fibres; it automatically matches stroke volume to venous return and keeps the right and left ventricular outputs equal.
• Q: Why does the AV node conduct slowly? A: Small-diameter cells with few gap junctions and a slow calcium-dependent upstroke. The resulting 0.1 s delay lets the atria empty and shields the ventricles from very fast atrial rates.
• Q: A patient has a prolonged APTT with normal PT, platelet count and bleeding time. What is likely? A: An intrinsic-pathway factor deficiency - most often haemophilia A (factor VIII) or B (factor IX); von Willebrand disease would usually also prolong the bleeding time.
• Q: Why does carbon monoxide poisoning not cause cyanosis despite severe hypoxia? A: CO forms cherry-red carboxyhaemoglobin and also shifts the O2 curve left; PaO2 and so arterial colour stay normal while oxygen content and delivery are low.
• Q: What shifts the oxygen dissociation curve to the right and why is it useful? A: Raised CO2 and H+ (Bohr effect), raised temperature and 2,3-BPG - all conditions found in exercising tissue, where easier unloading of oxygen is exactly what is needed.
• Q: Why must you never give high-flow oxygen carelessly to a patient with long-standing CO2 retention? A: Their respiratory drive depends on peripheral chemoreceptor hypoxia rather than CO2; abolishing the hypoxic stimulus can depress ventilation, and loss of hypoxic pulmonary vasoconstriction worsens V/Q mismatch, raising PaCO2 further. Controlled, titrated oxygen is used instead.
• Q: Two patients breathe 6 L/min; one retains CO2. Explain. A: Alveolar ventilation, not minute ventilation, clears CO2 - a rapid shallow pattern wastes a larger fraction of each breath on the 150 mL dead space.
• Q: Why is residual volume not measurable by spirometry, and how is it measured? A: Spirometry records only air moved in and out; the air remaining after maximal expiration never leaves the lung. It is measured by helium dilution, nitrogen washout or body plethysmography.
• Q: How does surfactant prevent small alveoli from collapsing into large ones? A: By Laplace's law the pressure in a small alveolus would be higher; surfactant lowers surface tension more as the alveolus shrinks, equalising pressures and stabilising alveoli of different sizes.

Common mistakes

• Writing that depolarisation is caused by K+ influx, or that the Na+-K+ pump directly generates the action potential - the pump maintains gradients; the AP is a passive ionic flux down them.
• Mixing up the two coagulation screens: PT/INR tests the extrinsic and common pathways (and warfarin), APTT the intrinsic (and heparin).
• Saying group O blood can be given to anyone without qualification - only packed O-negative cells in an emergency; plasma antibodies and other antigen systems still matter.
• Confusing total minute ventilation with alveolar ventilation, and forgetting to subtract dead space before multiplying by respiratory rate.
• Reversing the V/Q story: both ventilation and perfusion are greater at the lung base, but the *ratio* is higher at the apex.
• Treating oxygen saturation as oxygen content - a severely anaemic patient can be 99% saturated and still profoundly hypoxic; always compute content from haemoglobin.
• Quoting Western lung volume and haemoglobin reference values for Indian patients without noting that Indian spirometry reference equations are lower, and misreading cyanosis as a reliable sign of hypoxia in anaemia or polycythaemia.
• In the lab: timing bleeding time with a needle prick of uncontrolled depth, ignoring the correct anticoagulant tube (EDTA for CBC, citrate for coagulation), and not checking the ECG calibration (25 mm/s, 10 mm/mV) before measuring intervals.

Related topics

Physiology: renal, gastrointestinal, endocrine and nervous systems · Gross anatomy: limbs, thorax, abdomen and pelvis · Histology and embryology · Clinical biochemistry: organ function tests · Carbohydrate metabolism · Nutritional biochemistry