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1st Year MBBS Physiology - Complete Notes

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UNIT 1: GENERAL PHYSIOLOGY & CELL PHYSIOLOGY

Cell Membrane

• Phospholipid bilayer with embedded proteins (fluid mosaic model)
• Functions: selective permeability, receptor sites, enzymatic activity

Resting Membrane Potential (RMP)

• Normal RMP in nerve = -70 mV; skeletal muscle = -90 mV; erythrocytes = -10 mV
• Maintained by:
  • High K+ permeability (K+ diffuses out) - contributes -94 mV potential
  • Low Na+ permeability (Na+ barely leaks in)
  • Na+-K+ ATPase pump: pumps 3 Na+ out for every 2 K+ in - contributes additional -4 mV
  • Net result: ~-90 mV inside negative

Action Potential (AP) in Nerve

• Threshold: ~-55 mV (stimulus must bring membrane to this level)
• Depolarization: Na+ channels open rapidly → Na+ rushes in → membrane becomes +35 mV (overshoot)
• Repolarization: Na+ channels inactivate, K+ channels open → K+ rushes out → membrane returns to negative
• Hyperpolarization (undershoot): K+ channels stay open briefly → membrane dips below RMP
• Refractory periods:
  • Absolute refractory: Na+ channels inactivated - no AP possible regardless of stimulus
  • Relative refractory: membrane hyperpolarized - needs stronger-than-normal stimulus
• All-or-None law: AP either occurs fully or not at all

Saltatory Conduction (Myelinated Fibers)

• AP jumps from node to node (nodes of Ranvier)
• Faster conduction velocity, less energy expenditure
• Conduction velocity: A-alpha fibers = 70-120 m/s; C fibers = 0.5-2 m/s

Synaptic Transmission

• Chemical synapse: presynaptic terminal releases neurotransmitter into synaptic cleft
• Ca2+ influx into presynaptic terminal triggers vesicle fusion and NT release
• EPSP: Na+ influx → depolarization
• IPSP: Cl- influx or K+ efflux → hyperpolarization
• Summation: temporal (rapid successive stimuli) + spatial (multiple synapses simultaneously)

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UNIT 2: NERVE & MUSCLE PHYSIOLOGY

Neuromuscular Junction (NMJ)

• Motor nerve terminal releases acetylcholine (ACh)
• ACh binds nicotinic receptors on motor end plate
• End plate potential (EPP) → muscle AP → contraction
• ACh inactivated by acetylcholinesterase in cleft

Skeletal Muscle Contraction (Sliding Filament Theory)

• Sarcomere: functional unit (Z disc to Z disc)
• Components: thick filaments (myosin), thin filaments (actin, troponin, tropomyosin)
• Excitation-Contraction Coupling:
  1. AP travels along T-tubules
  2. Triggers Ca2+ release from sarcoplasmic reticulum
  3. Ca2+ binds troponin C → tropomyosin shifts → exposes actin binding sites
  4. Myosin heads bind actin → power stroke → filaments slide
  5. ATP required for myosin head release (rigor mortis = no ATP)
  6. Relaxation: Ca2+ pumped back into SR by SERCA pump

Types of Muscle Contraction

• Isometric: muscle length constant, tension increases (e.g., holding weight)
• Isotonic: tension constant, muscle shortens (e.g., lifting weight)
• Twitch: single stimulus → single contraction
• Summation & Tetanus: rapid repeated stimuli → sustained contraction (incomplete → complete tetanus)

Smooth Muscle

• No troponin - Ca2+ binds calmodulin → activates myosin light-chain kinase (MLCK)
• Slow, sustained contractions; involuntary
• Gap junctions allow spread of excitation (unitary smooth muscle)

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UNIT 3: BLOOD & HEMATOLOGY

Composition of Blood

• Total blood volume: ~5 L (70 mL/kg)
• Plasma (55%): water, proteins (albumin, globulins, fibrinogen), ions, nutrients
• Formed elements (45%): RBCs (99%), WBCs, platelets
• Hematocrit (PCV): Males 42-52%, Females 37-47%

Red Blood Cells (RBCs/Erythrocytes)

• Normal count: Males 4.5-5.5 million/μL; Females 4-5 million/μL
• Biconcave disc shape - maximizes surface area for gas exchange; deformable
• No nucleus or mitochondria - use glycolysis for energy
• Lifespan: 120 days; destroyed by macrophages in spleen and liver
• Normal Hb: Males 13-17 g/dL; Females 12-15 g/dL

Hematopoiesis

• Origin: bone marrow (after birth); yolk sac (embryo) → fetal liver/spleen → bone marrow
• All cells derived from pluripotent stem cell (hemocytoblast)
• Regulated by: erythropoietin (EPO, from kidneys), thrombopoietin, G-CSF, GM-CSF, IL-3

Hemoglobin (Hb)

• Structure: 4 subunits, each has heme (iron-porphyrin) + globin chain
• Adult Hb A: α2β2 chains; HbA2: α2δ2 (~2.5%); HbF: α2γ2 (fetal, higher O2 affinity)
• HbA1c: glycated Hb; elevated in poorly controlled diabetes mellitus
• Each Hb molecule carries 4 O2 molecules (one per heme)
• Each gram Hb can carry 1.34 mL O2

Oxygen-Hemoglobin Dissociation Curve

• Sigmoid (S-shaped) due to cooperative binding
• P50 = 26-27 mmHg (pO2 at which 50% Hb saturated)
• Right shift (decreased affinity, more O2 unloaded): ↑ CO2, ↑ temperature, ↑ 2,3-DPG, ↑ H+ (acidosis) - Bohr effect
• Left shift (increased affinity, less O2 unloaded): ↓ CO2, ↓ temp, ↓ 2,3-DPG, ↓ H+, HbF, carboxyhemoglobin

White Blood Cells (WBCs/Leukocytes)

• Normal count: 4,000-11,000/μL
• Differential count (mnemonic: Never Let Monkeys Eat Bananas):
  • Neutrophils: 50-70% - first responders to bacterial infection; phagocytic
  • Lymphocytes: 20-40% - B cells (antibodies), T cells (cell-mediated immunity)
  • Monocytes: 2-8% - differentiate into macrophages; phagocytic
  • Eosinophils: 1-4% - parasitic infections and allergies
  • Basophils: 0-1% - release histamine and heparin; allergic reactions

Platelets (Thrombocytes)

• Normal count: 1.5-4 lakh/μL (150,000-400,000/μL)
• Formed from megakaryocytes in bone marrow; lifespan 8-10 days
• Functions: primary hemostasis (plug formation), release clotting factors

Hemostasis & Coagulation

• Primary hemostasis: vascular spasm → platelet adhesion (vWF) → platelet aggregation (fibrinogen/GPIIb-IIIa)
• Secondary hemostasis (coagulation cascade):
  • Extrinsic pathway: tissue factor (III) + factor VII → X activation
  • Intrinsic pathway: XII → XI → IX → VIII → X activation
  • Common pathway: Xa + Va → prothrombin → thrombin → fibrinogen → fibrin
• Thrombin is the key enzyme - amplifies its own production
• Anticoagulants: heparin (activates antithrombin III), warfarin (inhibits vit K-dependent factors: II, VII, IX, X)

Blood Groups

• ABO system: based on antigens on RBC surface and antibodies in plasma
  • A: A antigen, anti-B antibody
  • B: B antigen, anti-A antibody
  • AB: A+B antigens, no antibodies ("universal recipient")
  • O: no antigens, anti-A + anti-B antibodies ("universal donor")
• Rh system: Rh+ have D antigen; Rh- lack it
• Erythroblastosis fetalis: Rh- mother, Rh+ baby - anti-D antibodies cross placenta in 2nd pregnancy

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UNIT 4: CARDIOVASCULAR PHYSIOLOGY

Cardiac Muscle Properties

• Automaticity: can generate its own AP (SA node, AV node, Purkinje)
• Conductivity: AP spreads through specialized system
• Contractility: force of contraction (Frank-Starling law)
• Rhythmicity: regular, rhythmic contractions
• All-or-none law in cardiac muscle

Cardiac Action Potential

• SA node (pacemaker): slow spontaneous depolarization (funny current, If)
  • Phase 4: gradual depolarization (Na+ and Ca2+ leak in)
  • Phase 0: Ca2+ channels open (no fast Na+ channels)
  • Phase 3: K+ channels open → repolarization
• Ventricular myocyte (5 phases):
  • Phase 0: rapid depolarization - fast Na+ channels open (+30 mV)
  • Phase 1: partial repolarization - transient K+ outward current
  • Phase 2 (Plateau): Ca2+ influx = K+ efflux - unique to cardiac muscle; ~250 ms
  • Phase 3: K+ channels dominate → rapid repolarization
  • Phase 4: resting potential (-90 mV)
• Long refractory period due to plateau phase - prevents tetanus (essential for pumping)

Conduction System

• SA node (sinoatrial): pacemaker, 60-100 bpm; right atrium
• AV node: 40-60 bpm; delays impulse (0.1 sec) - allows ventricular filling
• Bundle of His → right & left bundle branches → Purkinje fibers: 20-40 bpm
• Dominant pacemaker: SA node (fastest intrinsic rate)
• If SA node fails → AV node takes over (ventricular escape rhythm)

Cardiac Cycle

• Duration: ~0.8 sec at 75 bpm
• Systole (0.3 sec): isovolumetric contraction → rapid ejection → reduced ejection
• Diastole (0.5 sec): isovolumetric relaxation → rapid ventricular filling → slow filling (diastasis) → atrial systole
• Heart sounds:
  • S1 ("lub"): closure of mitral + tricuspid valves (start of systole)
  • S2 ("dub"): closure of aortic + pulmonary valves (end of systole)
  • S3: rapid ventricular filling (normal in children; heart failure in adults)
  • S4: atrial contraction against stiff ventricle (hypertension, LVH)

Cardiac Output (CO)

• CO = Stroke Volume × Heart Rate
• Normal CO = 5 L/min; Cardiac index = CO/BSA = 3.2 L/min/m²
• Stroke Volume (SV) = EDV - ESV = ~70 mL (EDV ~130 mL, ESV ~60 mL)
• Ejection fraction (EF) = SV/EDV = 55-70%
• Frank-Starling Law: ↑ preload (EDV) → ↑ SV (within limits) - heart pumps what it receives
• Preload: ventricular filling pressure (EDV); influenced by venous return
• Afterload: resistance to ejection (aortic BP/peripheral resistance)
• Contractility (inotropy): intrinsic force; increased by sympathetic stimulation, digitalis; decreased by acidosis, hypoxia

Regulation of Heart Rate

• Chronotropic effects: sympathetic (↑ HR via β1 receptors), parasympathetic/vagal (↓ HR)
• Dromotropic effects: conduction velocity; sympathetic ↑, parasympathetic ↓ at AV node

Arterial Blood Pressure

• Systolic BP: ~120 mmHg; Diastolic BP: ~80 mmHg
• Pulse pressure = Systolic - Diastolic = 40 mmHg
• Mean Arterial Pressure (MAP) = Diastolic + 1/3 Pulse Pressure ≈ 93 mmHg
• Also: MAP = CO × Total Peripheral Resistance (TPR)
• Regulation:
  • Short-term: baroreceptors (carotid sinus, aortic arch) → autonomic reflex
  • Long-term: kidneys (RAAS, pressure natriuresis)

Microcirculation & Edema

• Capillary exchange: Starling forces
  • Filtration: capillary hydrostatic pressure + interstitial oncotic pressure
  • Absorption: plasma oncotic pressure + interstitial hydrostatic pressure
• Edema causes: ↑ capillary pressure, ↓ plasma proteins, ↑ capillary permeability, lymphatic obstruction

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UNIT 5: RESPIRATORY PHYSIOLOGY

Lung Volumes & Capacities

• RV and FRC cannot be measured by spirometry (use helium dilution or body plethysmograph)

Mechanics of Breathing

• Inspiration: diaphragm + external intercostals contract → chest expands → lung volume ↑ → pressure ↓ → air flows in
• Expiration: passive at rest (elastic recoil); active with abdominal muscles + internal intercostals during exercise
• Compliance: change in volume per unit change in pressure; ↓ in fibrosis, ↑ in emphysema
• Surfactant (type II pneumocytes): reduces surface tension, prevents alveolar collapse; deficient in IRDS (premature neonates)
• Laplace's law: P = 2T/r; smaller alveoli collapse into larger without surfactant

Gas Exchange

• Alveolar pO2: ~100 mmHg; arterial pO2: ~95 mmHg
• Alveolar pCO2: ~40 mmHg = arterial pCO2
• Alveolar gas equation: PAO2 = PiO2 - (PaCO2/R) where R = 0.8
• Diffusion governed by Fick's law: rate ∝ surface area × driving pressure / thickness

Oxygen Transport

• Dissolved O2: 0.3 mL/dL (minimal)
• Hb-bound O2: ~20 mL/dL (majority, ~98.5%)
• Normal O2 saturation (SpO2): 97-99%

CO2 Transport

• Dissolved: 5-7%
• As HCO3-: ~70% (via carbonic anhydrase in RBCs: CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-)
• Carbaminohemoglobin (bound to globin): ~23%
• Chloride shift: HCO3- moves out of RBC, Cl- moves in to maintain electrical neutrality

Control of Ventilation

• Central chemoreceptors (medullary): respond to ↑ pCO2/↑ H+ in CSF - PRIMARY driver
• Peripheral chemoreceptors (carotid + aortic bodies): respond to ↓ pO2 (<60 mmHg), ↑ pCO2, ↑ H+
• Normal stimulus: pCO2 (most sensitive regulator)
• Hypoxic drive: takes over when CO2 drive blunted (e.g., COPD)

Ventilation-Perfusion (V/Q) Ratio

• Normal V/Q = 0.8
• V/Q = 0 (shunt): perfused but not ventilated (pneumonia, atelectasis)
• V/Q = ∞ (dead space): ventilated but not perfused (pulmonary embolism)
• Apex of lung: V/Q > 1 (over-ventilated relative to perfusion)
• Base of lung: V/Q < 1 (over-perfused relative to ventilation)

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UNIT 6: RENAL PHYSIOLOGY & BODY FLUIDS

Body Fluid Compartments

• Total body water (TBW): 60% of body weight (42 L in 70 kg man)
  • ICF: 40% BW = 28 L (2/3 of TBW)
  • ECF: 20% BW = 14 L (1/3 of TBW)
    • Plasma: 5% BW = 3.5 L
    • Interstitial fluid: 15% BW = 10.5 L
• Osmolarity: 285-295 mOsm/L

Renal Structure & Blood Flow

• Renal blood flow (RBF): 1200 mL/min (20-25% of CO)
• Renal plasma flow (RPF): ~660 mL/min
• Filtration fraction (FF) = GFR/RPF = 125/660 = ~0.19 (19%)

Glomerular Filtration

• GFR: 125 mL/min (males); 110 mL/min (females); ~180 L/day filtered
• Filtration force (net) = (Capillary hydrostatic + Bowman's oncotic) - (Capillary oncotic + Bowman's hydrostatic)
• Net filtration pressure ≈ +10 mmHg
• Filtration barrier: fenestrated capillary endothelium + basement membrane + podocytes (slit diaphragm)
• Autoregulation: maintains GFR between MAP 80-180 mmHg (myogenic + tubuloglomerular feedback)

Tubular Reabsorption

Hormonal Regulation

• Aldosterone (adrenal cortex): ↑ Na+ reabsorption, ↑ K+ secretion in collecting duct → ↑ blood volume/pressure
• ADH/Vasopressin (posterior pituitary): ↑ H2O reabsorption (aquaporin-2 insertion) → ↑ urine concentration
• ANP (atrial natriuretic peptide): ↑ Na+ excretion, ↓ BP; released with ↑ atrial stretch
• RAAS: ↓ BP → renin (JG cells) → angiotensin I → ACE → angiotensin II → aldosterone + vasoconstriction + ADH release

Renal Clearance

• Clearance (C) = (U × V) / P (mL/min)
• Inulin clearance = GFR (freely filtered, not reabsorbed/secreted)
• PAH clearance ≈ RPF (completely cleared in one pass)
• Creatinine clearance ≈ GFR (clinical estimate; slight overestimate due to secretion)
• If Cx > GFR: substance is secreted; if Cx < GFR: substance is reabsorbed

Acid-Base Balance

• Normal pH: 7.35-7.45 (acidosis <7.35, alkalosis >7.45)
• Buffers: bicarbonate (ECF main), phosphate, proteins, Hb
• Henderson-Hasselbalch: pH = 6.1 + log([HCO3-] / 0.03 × pCO2)
• Normal values: HCO3- = 22-26 mEq/L; pCO2 = 35-45 mmHg

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UNIT 7: GI PHYSIOLOGY

Gastrointestinal Motility

• Peristalsis: coordinated sequential contraction/relaxation - propels food aborally
• Segmentation: mixing movements; no net propulsion
• MMC (migrating motor complex): "housekeeper" contractions during fasting
• Gastric emptying: regulated by CCK, secretin, fat/protein content

GI Secretions

• Intrinsic factor (parietal cells): required for vitamin B12 absorption (terminal ileum)
• Absence of intrinsic factor → pernicious anemia

Gut Hormones

• Gastrin (G cells, antrum): ↑ HCl, ↑ pepsinogen, ↑ motility; stimulated by protein, vagus
• Secretin (S cells, duodenum): ↑ pancreatic HCO3-, ↓ gastric acid; stimulated by acid in duodenum
• CCK (I cells, duodenum): ↑ pancreatic enzymes, gallbladder contraction, ↓ gastric emptying; stimulated by fat/protein
• GIP (K cells): ↑ insulin release (incretin effect); stimulated by glucose

Absorption

• Carbohydrates: broken to monosaccharides; absorbed by SGLT1 (glucose/galactose) and GLUT5 (fructose)
• Proteins: broken to amino acids + di/tripeptides; absorbed by Na+-coupled transporters
• Fats: emulsified by bile salts → micelles → absorbed → chylomicrons → lymphatics
• Fat-soluble vitamins (A, D, E, K): absorbed with fat via micelles
• Vitamin B12: requires intrinsic factor; absorbed in terminal ileum
• Iron: absorbed as Fe2+ in duodenum (acidic pH); ferritin = storage form; transferrin = transport

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UNIT 8: ENDOCRINE PHYSIOLOGY

Hormones - General Concepts

• Peptide/protein hormones: water-soluble; bind surface receptors; fast action (sec-min)
• Steroid hormones: lipid-soluble; cross cell membrane; bind intracellular receptors; slow action (hours)
• Thyroid hormones: lipid-soluble but use transporters; bind nuclear receptors

Hypothalamo-Pituitary Axis

• Hypothalamus releases releasing/inhibiting hormones into portal blood → anterior pituitary
• Key axes:
  • TRH → TSH → Thyroid hormones
  • CRH → ACTH → Cortisol
  • GnRH → FSH/LH → Sex steroids
  • GHRH → GH; somatostatin inhibits GH
  • Dopamine inhibits prolactin (tonic inhibition)

Thyroid Gland

• T3 (triiodothyronine) - more potent, shorter half-life
• T4 (thyroxine) - prohormone, converted to T3 in periphery
• Effects: ↑ BMR, ↑ protein synthesis, normal growth and development, ↑ sensitivity to catecholamines
• Critical for brain development in fetus/neonate (cretinism if deficient)
• Synthesis requires iodine; inhibited by propylthiouracil (PTU), methimazole

Adrenal Gland

• Cortex (from mesoderm):
  • Zona Glomerulosa: Aldosterone (mineralocorticoid) - Na+ retention, K+ excretion
  • Zona Fasciculata: Cortisol (glucocorticoid) - ↑ gluconeogenesis, anti-inflammatory, immunosuppressive, ↑ protein catabolism
  • Zona Reticularis: Androgens (DHEA)
  • Mnemonic: GFR (salt, sugar, sex from outside in)
• Medulla (from neural crest): Epinephrine (80%) and norepinephrine (20%)
  • Stress response ("fight or flight"): ↑ HR, ↑ BP, ↑ glucose, bronchodilation

Pancreatic Hormones

• Insulin (beta cells): ↑ glucose uptake (GLUT4 in muscle/fat), ↑ glycogen synthesis, ↑ protein/fat synthesis; secreted when glucose ↑
• Glucagon (alpha cells): ↑ glycogenolysis, ↑ gluconeogenesis; secreted when glucose ↓
• Somatostatin (delta cells): inhibits both insulin and glucagon

Parathyroid Hormone (PTH) vs. Calcitonin

• PTH (parathyroid glands): ↑ Ca2+ (↑ bone resorption, ↑ renal Ca2+ reabsorption, ↑ vit D activation → ↑ gut absorption)
• Calcitonin (thyroid C cells): ↓ Ca2+ (opposes PTH; inhibits osteoclasts)
• Vitamin D (1,25-dihydroxycholecalciferol, calcitriol): ↑ Ca2+ and PO4 absorption from gut

Growth Hormone (GH)

• From anterior pituitary; secreted during deep sleep
• Direct effects: lipolysis, anti-insulin (diabetogenic)
• Indirect effects (via IGF-1 from liver): linear growth, protein synthesis
• Deficiency in childhood: dwarfism; excess: gigantism (child), acromegaly (adult)

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UNIT 9: NEUROPHYSIOLOGY

Organization of Nervous System

• CNS: brain + spinal cord
• PNS: somatic (voluntary) + autonomic (involuntary - sympathetic & parasympathetic)

Autonomic Nervous System

Sensory Pathways

• Pain & Temperature: spinothalamic tract (crosses immediately at entry level)
• Fine touch, vibration, proprioception: dorsal column-medial lemniscal pathway (crosses at medulla)
• Gate control theory of pain: Aβ fibers can inhibit pain transmission at dorsal horn

Cerebellum

• Functions: coordination, balance, fine motor control, motor learning
• Neocerebellum (lateral): planning and coordination of voluntary movements
• Spinocerebellum (vermis + intermediate): gait and posture
• Vestibulocerebellum (flocculonodular lobe): balance and eye movements
• Cerebellar lesions → ipsilateral deficits (ataxia, dysmetria, intention tremor, dysdiadochokinesia)

Basal Ganglia

• Involved in initiation and modulation of movement; procedural learning
• Direct pathway: ↑ movement (thalamus disinhibited)
• Indirect pathway: ↓ movement (thalamus inhibited)
• Dopamine (from substantia nigra): ↑ direct, ↓ indirect = promotes movement
• Parkinson's: ↓ dopamine → bradykinesia, rigidity, resting tremor, postural instability
• Huntington's: ↓ GABA in indirect pathway → hyperkinesia (chorea)

EEG Rhythms

Sleep Physiology

• NREM sleep (Stages 1-3): progressive slowing of EEG; stages 3 = slow-wave deep sleep
• REM sleep: low-voltage, mixed-frequency EEG (like wakefulness); dreaming; muscle atonia; eye movements
• Sleep cycles: 90 min cycles; REM increases toward morning
• GH released during stage 3 NREM; cortisol peaks in early morning

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UNIT 10: REPRODUCTIVE PHYSIOLOGY

Male Reproductive Physiology

• Spermatogenesis: begins at puberty; ~74 days; occurs in seminiferous tubules (34°C)
• Sertoli cells: support spermatogenesis, blood-testis barrier, secrete inhibin, respond to FSH
• Leydig cells: produce testosterone (stimulated by LH)
• Testosterone functions: spermatogenesis, secondary sex characteristics, protein anabolism, bone growth, libido

Female Reproductive Physiology

• Oogenesis: begins in fetal life; arrested at prophase I until ovulation
• Menstrual cycle (28 days):
  • Follicular phase (days 1-14): FSH → follicle growth → estrogen ↑ → LH surge → ovulation (day 14)
  • Luteal phase (days 15-28): corpus luteum → progesterone + estrogen → prepares endometrium
  • If no fertilization: corpus luteum degenerates → progesterone ↓ → menstruation

Key Hormones in Female Cycle

• Estrogen: proliferative phase of endometrium, ↑ LH receptors, positive feedback (high estrogen → LH surge)
• Progesterone: secretory phase, maintains pregnancy, ↑ basal body temperature, inhibits uterine contractions
• FSH: follicle development, aromatase activity
• LH: ovulation trigger, corpus luteum maintenance, testosterone in theca cells

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KEY NORMAL VALUES - Quick Reference

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Notes Index