Physiology
Medical physiology for MBBS: cell and body fluids, blood, nerve and muscle, and the cardiovascular, respiratory, gastrointestinal, renal, endocrine, reproductive and nervous systems, special senses and integrative physiology.
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Definition
The plasma (cell) membrane is a thin (~7.5 nm), selectively permeable lipid bilayer enclosing the cell, described by the Singer–Nicolson fluid-mosaic model.
Composition
- Phospholipid bilayer — hydrophilic heads outward, hydrophobic tails inward
- Proteins — integral (channels, carriers, pumps) and peripheral
- Cholesterol — maintains fluidity and stability
- Carbohydrates — glycocalyx (glycoprotein/glycolipid) for recognition
Functions
- Selective barrier separating ICF from ECF
- Selective transport of substances
- Cell signalling (receptors), recognition and adhesion
- Maintains the resting membrane potential
Transport Across the Membrane — Classification
- Passive (no ATP, down gradient): simple diffusion, facilitated diffusion, osmosis, filtration
- Active (ATP, against gradient): primary (Na⁺–K⁺ pump), secondary (symport/antiport)
- Bulk transport: endocytosis (in), exocytosis (out)
All transport is either passive (down gradient, no energy) or active (against gradient, needs ATP). Type Energy Example Simple diffusion No O₂, CO₂ Facilitated diffusion No Glucose (GLUT) Primary active ATP Na⁺–K⁺ pump Secondary active Ion gradient Glucose–Na⁺ cotransport Applied Aspects
- ORS — glucose–Na⁺ cotransport (secondary active transport)
- Cystic fibrosis — defective CFTR chloride channel
- Digoxin inhibits the Na⁺–K⁺ pump; local anaesthetics block Na⁺ channels
🔑KEY POINTS TO REMEMBER- Plasma membrane = selectively permeable lipid bilayer (fluid-mosaic model).
- Passive transport (no ATP): simple/facilitated diffusion, osmosis, filtration.
- Active transport (ATP): primary (Na⁺–K⁺ pump) and secondary (co-transport).
- Bulk transport: endocytosis and exocytosis.
- Applied: ORS (Na⁺–glucose cotransport), CFTR (cystic fibrosis), digoxin (pump).
📚SOURCES: Guyton & Hall Textbook of Medical Physiology; Ganong’s Review of Medical Physiology; Textbook of Physiology (A.K. Jain).Definition
Total body water (TBW) is ≈ 60% of body weight (≈42 L in a 70 kg adult), distributed between the intracellular and extracellular compartments.
Compartments — the 60–40–20 Rule
- TBW = 60% of body weight (≈42 L)
- ICF = 40% (≈28 L) — two-thirds of TBW
- ECF = 20% (≈14 L) — one-third of TBW
- ECF = interstitial fluid (≈11 L) + plasma (≈3 L) (+ transcellular fluid)
TBW splits into ICF and ECF; ECF splits into interstitial fluid and plasma. Ionic Composition
- ICF — high K⁺, Mg²⁺, phosphate, protein
- ECF — high Na⁺, Cl⁻, HCO₃⁻
- Plasma vs interstitial fluid — differ mainly in protein content
Compartment Marker used TBW Deuterium / tritiated water, antipyrine ECF Inulin, mannitol, radiosulphate Plasma Evans blue, radio-iodinated albumin Measurement (dilution principle: V = amount ÷ concentration)
- ICF = TBW − ECF (indirect)
- Interstitial = ECF − plasma
- Blood volume = plasma volume ÷ (1 − haematocrit)
Applied
- Normal saline (isotonic) → stays in ECF; 5% dextrose → distributes in TBW
- TBW higher in infants (~75%), lower in the elderly and obese
🔑KEY POINTS TO REMEMBER- TBW ≈ 60% body weight; 60–40–20 rule (TBW–ICF–ECF).
- ICF = 2/3 (high K⁺); ECF = 1/3 (high Na⁺) = interstitial + plasma.
- Measured by dilution: TBW (D₂O), ECF (inulin), plasma (Evans blue).
- ICF and interstitial volumes are derived indirectly.
📚SOURCES: Guyton & Hall Textbook of Medical Physiology; Ganong’s Review of Medical Physiology; Textbook of Physiology (A.K. Jain).Definition
Homeostasis (Cannon) is the maintenance of a constant internal environment (the ‘milieu intérieur’ of Claude Bernard) despite changing external conditions.
Components of a Control System
- Stimulus — a change in the regulated variable
- Receptor (sensor) — detects the change
- Control centre — compares with the set point
- Effector — produces the corrective response
- Response — restores normal (feedback)
Types of Feedback
- Negative feedback — opposes the change (most systems): temperature, BP, blood glucose
- Positive feedback — amplifies the change: childbirth (oxytocin), clotting, LH surge
- Feed-forward — anticipatory control
Negative feedback loop: sense the change, then act to reverse it. Examples
- Body temperature (37°C)
- Blood glucose (insulin/glucagon)
- Blood pressure (baroreceptor reflex)
- Blood pH (7.35–7.45)
- Fluid and electrolyte balance
Applied
- Failure of homeostasis → disease
- Harmful positive feedback (vicious cycle) — e.g. in circulatory shock
Characteristics
- Regulated variables kept within a narrow range (set point)
- Coordinated by the nervous and endocrine systems
- A dynamic equilibrium, not a static state
Feature Negative / Positive feedback Effect Opposes change / amplifies change Frequency Common / rare Example Temperature, BP / childbirth, clotting Outcome Stability / rapid completion of an event 🔑KEY POINTS TO REMEMBER- Homeostasis = constant internal environment (Claude Bernard / Cannon).
- Control loop: stimulus → receptor → control centre → effector → response.
- Negative feedback opposes change (most); positive feedback amplifies it.
- Positive feedback examples: childbirth, clotting, LH surge.
📚SOURCES: Guyton & Hall Textbook of Medical Physiology; Ganong’s Review of Medical Physiology; Textbook of Physiology (A.K. Jain).Definition
The resting membrane potential (RMP) is the steady potential difference across a resting cell membrane, inside negative to outside (≈ −70 mV in neurons, −90 mV in skeletal muscle).
Ionic Basis
- Na⁺–K⁺ pump — 3 Na⁺ out, 2 K⁺ in (electrogenic); builds gradients
- Membrane at rest is most permeable to K⁺ (K⁺ leak channels)
- K⁺ diffuses out → leaves the inside negative
- Non-diffusible anions (proteins) trapped inside add negativity
- RMP lies close to the K⁺ equilibrium potential (Nernst)
K⁺ leaks out while protein anions stay in, so the inside becomes negative. Determinants
- Concentration gradients (set by the Na⁺–K⁺ pump)
- Selective permeability (K⁺ > Na⁺ at rest)
- Described by the Nernst / Goldman equations
Applied
- Hyperkalaemia (↑ ECF K⁺) → RMP less negative → arrhythmias
- RMP is the basis of nerve and muscle excitability
Tissue RMP (mV) Neuron −70 Skeletal muscle −90 Cardiac muscle −90 Smooth muscle −50 to −60 Properties
- Present in every resting (unstimulated) cell
- Maintained by continuous Na⁺–K⁺ pump activity
- A prerequisite for excitability of nerve and muscle
🔑KEY POINTS TO REMEMBER- RMP ≈ −70 mV (neuron), inside negative; near E_K.
- Set by Na⁺–K⁺ pump + high resting K⁺ permeability + trapped anions.
- Na⁺–K⁺ pump is electrogenic (3 out : 2 in).
- Hyperkalaemia destabilises RMP → arrhythmias.
📚SOURCES: Guyton & Hall Textbook of Medical Physiology; Ganong’s Review of Medical Physiology; Textbook of Physiology (A.K. Jain).Definition
The cell is the structural and functional unit of the body, bounded by a plasma membrane and containing cytoplasm with membrane-bound organelles.
Organelles & Functions
- Nucleus — holds DNA; controls cell activity and division
- Mitochondria — ATP production (power house)
- Rough ER — protein synthesis; Smooth ER — lipid/steroid synthesis, detoxification
- Ribosomes — protein synthesis
- Golgi apparatus — processing, packaging, secretion
- Lysosomes — intracellular digestion (hydrolytic enzymes)
- Peroxisomes — oxidation and detoxification
- Cytoskeleton — shape, movement, intracellular transport
Each organelle performs one job, so the cell runs many processes at once. Organelle Function Mitochondria ATP (aerobic respiration) Rough ER Protein synthesis Golgi apparatus Packaging & secretion Lysosome Intracellular digestion Applied
- Lysosomal storage diseases (Tay–Sachs, Gaucher)
- Mitochondrial disorders (maternally inherited)
Cell Membrane & Cytoplasm
- Plasma membrane — selective barrier (fluid-mosaic)
- Cytoplasm/cytosol — site of many metabolic reactions
- Inclusions — stored glycogen, fat, pigment
🔑KEY POINTS TO REMEMBER- Cell = structural & functional unit; membrane-bound organelles divide labour.
- Mitochondria = ATP; RER = protein synthesis; Golgi = packaging; lysosome = digestion.
- Smooth ER = lipids/detox; ribosomes = protein synthesis.
- Applied: lysosomal storage diseases, mitochondrial disorders.
📚SOURCES: Guyton & Hall Textbook of Medical Physiology; Ganong’s Review of Medical Physiology; Textbook of Physiology (A.K. Jain).Definition
The Na⁺–K⁺ ATPase pump is a primary active transporter that pumps 3 Na⁺ out and 2 K⁺ in per ATP, against their gradients.
Mechanism
- Binds 3 intracellular Na⁺ + ATP
- Phosphorylation → shape change → 3 Na⁺ expelled
- Binds 2 extracellular K⁺ → dephosphorylation → 2 K⁺ taken in
One ATP moves 3 Na⁺ out and 2 K⁺ in — an electrogenic pump. Functions
- Maintains Na⁺ and K⁺ gradients
- Contributes to RMP (electrogenic)
- Prevents cell swelling (osmotic balance)
- Drives secondary active transport
- Regulates cell volume
Applied
- Inhibited by digoxin / ouabain → ↑ intracellular Ca²⁺ → ↑ cardiac force
- Uses a major share of the body’s basal energy
Features
- A carrier protein with ATPase activity
- Electrogenic — net positive charge pumped out
- Present in all cell membranes
- Activity ↑ by ↑ intracellular Na⁺, thyroid hormone and insulin
Other Membrane Pumps (for comparison)
- Ca²⁺ ATPase — pumps Ca²⁺ out of the cell
- H⁺–K⁺ ATPase — secretes gastric acid
- All are primary active transporters (use ATP directly)
Feature Detail Stoichiometry 3 Na⁺ out : 2 K⁺ in Energy 1 ATP per cycle Nature Electrogenic — net +1 charge out Inhibitor Ouabain, digoxin 🔑KEY POINTS TO REMEMBER- Na⁺–K⁺ ATPase: 3 Na⁺ out, 2 K⁺ in, per ATP (electrogenic).
- Maintains gradients, RMP, cell volume; drives secondary active transport.
- Inhibited by digoxin/ouabain → ↑ cardiac contractility.
📚SOURCES: Guyton & Hall Textbook of Medical Physiology; Ganong’s Review of Medical Physiology; Textbook of Physiology (A.K. Jain).Definition
Osmosis — water movement across a semipermeable membrane from low to high solute concentration. Osmolarity — osmoles of solute per litre of solution. Tonicity — effect of a solution on cell volume (non-penetrating solutes).
Tonicity — Effect on the Cell
- Isotonic (≈290 mOsm/L, 0.9% saline) — no change
- Hypertonic — water leaves → cell shrinks (crenation)
- Hypotonic — water enters → cell swells / bursts (haemolysis)
Tonicity tells you whether a cell shrinks, stays the same, or swells. Applied
- IV fluids must be ≈ isotonic
- Osmotic diuretics (mannitol) pull water out of tissues
- Normal plasma osmolarity 285–295 mOsm/L
Term Meaning Osmolarity Osmoles per litre of solution Osmolality Osmoles per kg of water Tonicity Effect on cell volume (non-penetrating solutes) Osmotic pressure Pressure that just prevents osmosis (van’t Hoff) Notes
- Effective osmoles set tonicity (urea is an ‘ineffective’ osmole)
- Osmotic pressure ∝ number of particles
🔑KEY POINTS TO REMEMBER- Osmosis = water to the higher-solute side; osmolarity = particle count.
- Tonicity effect: hypertonic → shrink, isotonic → no change, hypotonic → swell.
- Plasma osmolarity 285–295 mOsm/L; IV fluids must be near-isotonic.
📚SOURCES: Guyton & Hall Textbook of Medical Physiology; Ganong’s Review of Medical Physiology; Textbook of Physiology (A.K. Jain).Definition
The Gibbs–Donnan effect is the unequal but predictable distribution of diffusible ions across a semipermeable membrane when one side holds non-diffusible charged particles (e.g. proteins).
Principle
- Non-diffusible anions (protein⁻) fixed on one side
- They attract diffusible cations, repel diffusible anions
- Product of diffusible ion concentrations is equal on both sides
- More total particles → higher osmotic pressure on the protein side
Trapped protein anions force a predictable unequal distribution of diffusible ions. Significance
- Contributes to the resting membrane potential
- Plasma proteins → oncotic pressure (hold water in vessels)
- Cells counter it with the Na⁺–K⁺ pump (pump–leak balance)
Consequences
- Slightly more cations and total solute on the protein side
- ↑ intracellular osmotic pressure → tendency of cells to swell
- A membrane potential develops (Donnan potential)
Where It Operates
- Across the capillary wall (plasma proteins)
- Across the red-cell and other cell membranes
- Influences glomerular filtration in the kidney
Consequence Effect Ion distribution Diffusible ions unequally distributed Osmotic pressure Higher on protein side Membrane potential Small potential generated Cell volume Would swell without Na⁺-K⁺ pump 🔑KEY POINTS TO REMEMBER- Donnan effect: non-diffusible protein anions → unequal diffusible-ion distribution.
- More particles/water on the protein side (↑ osmotic pressure).
- Basis of plasma oncotic pressure; countered by Na⁺–K⁺ pump.
📚SOURCES: Guyton & Hall Textbook of Medical Physiology; Ganong’s Review of Medical Physiology; Textbook of Physiology (A.K. Jain).Definition
The Nernst equation gives the equilibrium potential of a single ion — the membrane voltage at which its electrical and chemical gradients balance (no net movement).
The Equation
- E = (RT/zF) × ln([ion]outside / [ion]inside)
- Simplified (37°C, monovalent cation): E = 61 × log₁₀([out]/[in]) mV
Typical Equilibrium Potentials
- E_K ≈ −90 mV
- E_Na ≈ +60 mV
- E_Cl ≈ −70 mV
- E_Ca ≈ +120 mV
The Nernst equation converts an ion’s concentration ratio into its equilibrium voltage. Uses / Applied
- Explains RMP (near E_K) and the AP peak (near E_Na)
- Goldman–Hodgkin–Katz equation combines several ions
Assumptions / Notes
- Applies to one ion at a time
- Assumes the membrane is permeable to that ion
- For the real RMP use the Goldman equation (weights permeabilities)
Related Concepts
- Driving force on an ion = Vm − E_ion
- Goldman–Hodgkin–Katz equation — handles several ions together
- Equilibrium potential is not the same as resting potential
Ion Equilibrium potential (mV) K⁺ −90 to −94 Na⁺ +60 to +61 Cl⁻ −70 to −86 Ca²⁺ +130 🔑KEY POINTS TO REMEMBER- Nernst = equilibrium potential of one ion; E = 61·log₁₀(out/in) mV.
- E_K ≈ −90, E_Na ≈ +60, E_Cl ≈ −70, E_Ca ≈ +120 mV.
- RMP is near E_K; AP peak near E_Na; GHK combines ions.
📚SOURCES: Guyton & Hall Textbook of Medical Physiology; Ganong’s Review of Medical Physiology; Textbook of Physiology (A.K. Jain).Definition
Fluid compartment volumes are measured by the indicator (dilution) principle: Volume = amount of indicator injected ÷ its final concentration.
Compartment Marker TBW Deuterium/tritiated water, antipyrine ECF Inulin, mannitol, radiosulphate Plasma Evans blue (T-1824), radio-iodinated albumin Derived (Indirect)
- ICF = TBW − ECF
- Interstitial fluid = ECF − plasma
- Blood volume = plasma volume ÷ (1 − haematocrit)
A known marker, once mixed, reveals the volume from how dilute it becomes. Ideal Marker Criteria
- Non-toxic; distributes evenly in that compartment only
- Not metabolised or excreted too quickly; easily measured
🔑KEY POINTS TO REMEMBER- Dilution principle: Volume = amount injected ÷ concentration.
- TBW — D₂O; ECF — inulin; plasma — Evans blue.
- ICF and interstitial volumes are derived indirectly.
📚SOURCES: Guyton & Hall Textbook of Medical Physiology; Ganong’s Review of Medical Physiology; Textbook of Physiology (A.K. Jain).Definition
A second messenger is an intracellular signalling molecule produced when a hormone (first messenger) binds a surface receptor — it relays and amplifies the signal inside the cell.
Major Second Messengers
- cAMP (adenylyl cyclase, via Gs) — glucagon, adrenaline
- cGMP — ANP, nitric oxide
- IP₃ & DAG (phospholipase C) → ↑Ca²⁺, activate PKC
- Ca²⁺ — acts via calmodulin
The hormone acts outside; the second messenger relays and amplifies the signal inside. Significance / Applied
- Signal amplification (one hormone → many molecules)
- Cholera toxin → persistent ↑cAMP → watery diarrhoea
- Many drugs act through these pathways (e.g. ↑cAMP relaxes airways)
2nd messenger Enzyme / source Example cAMP Adenylyl cyclase Adrenaline, glucagon IP₃ / DAG Phospholipase C α₁ agonists Ca²⁺ Channels / ER Muscle contraction cGMP Guanylyl cyclase ANP, nitric oxide 🔑KEY POINTS TO REMEMBER- 2nd messenger relays & amplifies a hormone signal inside the cell.
- Main ones: cAMP, cGMP, IP₃/DAG, Ca²⁺.
- Cholera toxin → ↑cAMP → diarrhoea.
📚SOURCES: Guyton & Hall Textbook of Medical Physiology; Ganong’s Review of Medical Physiology; Textbook of Physiology (A.K. Jain).Definition
Apoptosis is programmed cell death — an active, energy-dependent, genetically-controlled ‘cell suicide’ without inflammation (contrast necrosis).
Features
- Cell shrinkage; chromatin condensation
- Nuclear fragmentation; formation of apoptotic bodies
- Cell membrane stays intact → no inflammation
- Apoptotic bodies phagocytosed by neighbours
Pathways
- Intrinsic (mitochondrial) — cytochrome c release → caspases
- Extrinsic (death receptor) — Fas/TNF → caspases
- Executioner caspases carry out cell death
Both pathways converge on caspase enzymes that dismantle the cell cleanly. Feature Apoptosis / Necrosis Nature Programmed / Accidental Energy ATP-dependent / passive Inflammation Absent / Present Cell membrane Intact / Ruptured Significance / Applied
- Embryogenesis (removes webbing between fingers)
- Removes damaged and self-reactive cells
- ↓ apoptosis → cancer; ↑ apoptosis → neurodegeneration
🔑KEY POINTS TO REMEMBER- Apoptosis = programmed, tidy, ATP-dependent cell death, no inflammation.
- Pathways: intrinsic (mitochondrial) & extrinsic (death receptor) → caspases.
- Necrosis = accidental, messy, with inflammation.
- ↓ apoptosis → cancer; ↑ → degeneration.
📚SOURCES: Guyton & Hall Textbook of Medical Physiology; Ganong’s Review of Medical Physiology; Textbook of Physiology (A.K. Jain).