Animal Physiology & Immunology

Part II · Zoology · Chapter Seven

Animal Physiology & Immunology

Expect 10–14 questions: action potential & synapse types, sliding-filament model, nephron ultrafiltration, cardiac conducting system (SA/AV nodes, ECG waves), ABO blood groups (Landsteiner), IgG vs IgM vs IgA, active vs passive immunity, vaccine types, and HP-angle items (high-altitude polycythaemia, iodine-deficiency goitre in Kullu/Kangra).

Read · 90 min
Revise · 25 min
MCQs · 30

Syllabus Coverage

Nervous system & muscle physiology • Digestion & absorption • Respiration & gaseous exchange • Excretion & osmoregulation • Circulation — blood, heart & vessels • Endocrine system • Innate & adaptive immunity • Vaccines, immune disorders & antibody engineering.

7.1 Neurons & Nervous System

The nervous system is the body’s rapid electrical signalling network, built from two specialised cell types: neurons (signal conductors) and glial cells (support, insulation, nutrition). A typical neuron has a cell body (soma) containing the nucleus, branching dendrites that receive signals, and a single long axon that transmits them. Axons may be wrapped in a myelin sheath formed by Schwann cells in the PNS or oligodendrocytes in the CNS; the gaps between adjacent myelin segments are nodes of Ranvier. Myelinated fibres form white matter; unmyelinated cell bodies and dendrites constitute grey matter.

Camillo Golgi & Santiago Ramón y Cajal — neuron doctrine (1906 Nobel) · Hodgkin & Huxley — action-potential ionic basis 1952 (Nobel 1963) · Otto Loewi — first chemical neurotransmitter (acetylcholine) 1921 (Nobel 1936) · Henry Dale — Dale’s principle, ACh & noradrenaline (Nobel 1936)

Neurotransmitter

A chemical messenger released from the pre-synaptic terminal into the synaptic cleft upon arrival of an action potential; it binds specific receptors on the post-synaptic membrane to produce excitatory or inhibitory responses.

7.1.1 Resting Membrane Potential

At rest a neuron maintains a potential of approximately −70 mV across its plasma membrane (inside negative). This is maintained by the Na⁺/K⁺-ATPase pump, which actively transports 3 Na⁺ out and 2 K⁺ in per ATP hydrolysed. Additional K⁺ leak channels allow K⁺ to diffuse outward down its concentration gradient, further increasing negativity. Na⁺ is largely excluded at rest because Na⁺ channels are closed.

7.1.2 Action Potential

A local depolarising stimulus triggers an action potential (AP) if it reaches the threshold (~−55 mV). The AP proceeds in three phases:

Depolarisation — voltage-gated Na⁺ channels open rapidly; Na⁺ rushes in; membrane potential rises to ~+35 mV.
Repolarisation — Na⁺ channels inactivate; voltage-gated K⁺ channels open; K⁺ flows out; potential returns toward −70 mV.
Hyperpolarisation (undershoot) — K⁺ channels close slowly; membrane briefly overshoots to ~−80 mV before returning to resting potential.

APs are all-or-nothing: they do not vary in amplitude but are frequency-coded. During the absolute refractory period (Na⁺ channels inactivated) a new AP cannot be elicited; during the relative refractory period only a supra-threshold stimulus works. Saltatory conduction in myelinated axons means the AP “jumps” from node to node (up to 120 m s⁻¹ in large myelinated fibres vs ~0.5 m s⁻¹ in unmyelinated C fibres).

Fig. 7.1Myelinated neuron showing nodes of Ranvier (saltatory conduction) and the corresponding action potential trace: depolarisation (Na⁺ in), repolarisation (K⁺ out), and brief hyperpolarisation. Resting potential = −70 mV; peak = +35 mV.

7.1.3 Synapse

The junction between two neurons (or a neuron and an effector) is the synapse. In a chemical synapse an AP arriving at the pre-synaptic terminal triggers Ca²⁺ influx, causing synaptic vesicles to fuse with the membrane and release neurotransmitter into the synaptic cleft (~20 nm wide). The transmitter binds post-synaptic receptors, generating an excitatory postsynaptic potential (EPSP) or inhibitory postsynaptic potential (IPSP). The signal is unidirectional because vesicles are only pre-synaptic. Electrical synapses (gap junctions) allow bidirectional, essentially instantaneous current flow and are found in cardiac muscle intercalated discs, smooth muscle, and some neurons.

**Table 7.1**Major neurotransmitters — type, location, and function
Neurotransmitter	Type	Location / pathway	Key function
Acetylcholine (ACh)	Excitatory / inhibitory	NMJ, parasympathetic, basal ganglia	Muscle contraction; heart rate reduction; memory
Dopamine	Modulatory	Substantia nigra, mesolimbic	Reward, motor control; low in Parkinson’s; excess in schizophrenia
Serotonin (5-HT)	Modulatory	Raphe nuclei, gut	Mood, sleep, appetite; low in depression
Noradrenaline	Excitatory	Locus coeruleus, sympathetic	Fight-or-flight arousal; attention
GABA	Inhibitory	Widely in brain	Main inhibitory transmitter; anxiolytic; benzodiazepines enhance GABA
Glycine	Inhibitory	Spinal cord, brainstem	Motor & sensory inhibition; blocked by strychnine
Glutamate	Excitatory	Widely in brain	Main excitatory transmitter; learning (LTP via NMDA receptors)
Endorphins	Modulatory	Hypothalamus, pituitary	Natural analgesia; euphoria

7.1.4 Reflex Arc

A reflex arc is the simplest functional unit: stimulus → receptor → afferent (sensory) neuron → integration centre (spinal cord/brain) → efferent (motor) neuron → effector. The knee-jerk (patellar tendon reflex) is a monosynaptic arc (one synapse between afferent and efferent). Most reflexes are polysynaptic, involving interneurons. Reflex responses are fast (bypass conscious brain) and involuntary.

Easy to confuse — Myelinated vs Unmyelinated fibres

Myelinated (A & B fibres)

Schwann cells (PNS) / oligodendrocytes (CNS). Nodes of Ranvier. Saltatory conduction; fast (up to 120 m s⁻¹). Form white matter. Motor and proprioceptive signals.

Unmyelinated (C fibres)

No sheath; continuous conduction; slow (0.5–2 m s⁻¹). Form grey matter (cell bodies + dendrites). Carry slow pain, temperature, postganglionic autonomic signals.

7.1.5 Cranial Nerves I–XII

Mnemonic — Cranial Nerves I–XII

“Oh Oh Oh To Touch And Feel Very Good Velvet And Hair”

I Olfactory • II Optic • III Oculomotor • IV Trochlear • V Trigeminal • VI Abducens • VII Facial • VIII Vestibulocochlear • IX Glossopharyngeal • X Vagus • XI Accessory • XII Hypoglossal

Function memory: “Some Say Marry Money But My Brother Says Big Brains Matter Most.” (S=sensory, M=motor, B=both — for I through XII)

**Table 7.2**Cranial nerves I–XII — name, number, type, function
No.	Name	Type	Function
I	Olfactory	Sensory	Smell
II	Optic	Sensory	Vision
III	Oculomotor	Motor	Eye movement (most muscles), pupil constriction
IV	Trochlear	Motor	Superior oblique eye muscle (downward, inward)
V	Trigeminal	Both	Face sensation; mastication (jaw muscles)
VI	Abducens	Motor	Lateral rectus (eye abduction)
VII	Facial	Both	Facial expression, taste (ant. 2/3 tongue), salivation
VIII	Vestibulocochlear	Sensory	Hearing (cochlear) & balance (vestibular)
IX	Glossopharyngeal	Both	Taste (post. 1/3 tongue), swallowing, carotid sinus reflex
X	Vagus	Both	Parasympathetic to heart, lungs, GI tract; speech
XI	Accessory (spinal)	Motor	Trapezius & sternocleidomastoid muscles (shoulder, head rotation)
XII	Hypoglossal	Motor	Tongue movements (speech, swallowing)

Exam Tip: Examiners frequently test which cranial nerve is purely sensory (I, II, VIII) vs purely motor (III, IV, VI, XI, XII) vs both (V, VII, IX, X). The vagus (X) is the only cranial nerve that exits the skull and travels to the thorax and abdomen — it is the main parasympathetic outflow to viscera.

7.2 Muscle Physiology

Vertebrate muscle falls into three structural and functional categories. Skeletal muscle (striated, voluntary) is attached to bone via tendons and produces locomotion; cells are multinucleate, derived from myoblast fusion. Cardiac muscle (striated, involuntary) forms the myocardium; cells are uninucleate and interconnected by intercalated discs containing gap junctions, allowing electrical syncytial behaviour. Smooth muscle (non-striated, involuntary) lines viscera and vessels; spindle-shaped uninucleate cells contract slowly and sustainably under autonomic/hormonal control.

Easy to confuse — Red (slow) vs White (fast) muscle fibres

Red (Type I) fibres

Rich in myoglobin & mitochondria. Aerobic, slow-twitch. Fatigue-resistant. Used for posture & endurance. Myoglobin gives red colour. Dominant in marathon runners.

White (Type II) fibres

Less myoglobin; fewer mitochondria; more glycolytic enzymes. Anaerobic, fast-twitch. Fatigue rapidly. Used for sprinting, explosive movements. Dominant in sprinters.

7.2.1 Sarcomere — Sliding Filament Model

The functional unit of skeletal muscle is the sarcomere, bounded at each end by a Z-line. Thick filaments are myosin (runs through the A-band, including the H-zone in the centre); thin filaments are actin (anchored to Z-lines, extend into the A-band). During contraction, thin filaments slide over thick ones: the I-band (actin only) and H-zone (myosin only) shorten; the A-band (total myosin length) does not change. The M-line is the midline protein scaffold connecting myosin tails.

Fig. 7.2Sarcomere in relaxed vs contracted state. Sliding filament model: actin thin filaments (green) slide over myosin thick filaments (red) toward the M-line. I-band and H-zone narrow; A-band length remains constant. Z-lines come closer together reducing sarcomere length.

7.2.2 Molecular Events of Contraction

Contraction is triggered by a motor-nerve AP at the neuromuscular junction (NMJ): ACh released from motor neuron binds nicotinic receptors on the sarcolemma, generating an AP that travels down T-tubules into the sarcoplasmic reticulum (SR), triggering Ca²⁺ release. Ca²⁺ binds troponin C on the thin filament; the troponin–tropomyosin complex shifts, exposing actin’s myosin-binding sites. The myosin head (pre-loaded with ADP + Pi) attaches to actin, performs the power stroke (moves actin ~10 nm toward M-line, releasing ADP + Pi), then releases when a new ATP binds. Repeated cross-bridge cycles produce contraction. ATP is also required to pump Ca²⁺ back into the SR for relaxation. Rigor mortis occurs because after death there is no ATP to detach myosin heads, leaving them locked to actin; it resolves when proteases degrade muscle proteins (~24–48 h post-mortem).

Exam Tip: Know what changes and what does not. A-band = constant (myosin length unchanged). I-band and H-zone narrow (actin slides in). The sarcomere shortens but thick/thin filament lengths themselves are unchanged — this is the key concept Huxley & Hanson proposed in 1954. Rigor mortis confirms that ATP is needed for detachment, not for attachment.

7.3 Digestion & Absorption

Digestion converts large, complex food molecules into absorbable monomers. In humans it proceeds through a ~9-metre tube: mouth → pharynx → oesophagus → stomach → small intestine (duodenum, jejunum, ileum) → large intestine (caecum, colon, rectum) → anus. Accessory organs — salivary glands, liver, gallbladder, pancreas — add enzymes and emulsifying agents.

7.3.1 Oral Cavity

Mastication breaks food into a bolus. Three pairs of salivary glands (parotid, submandibular, sublingual) secrete saliva (pH 6.8): chiefly water, mucin (lubrication), and salivary amylase (ptyalin), which begins starch hydrolysis (starch → maltose + dextrins). Saliva also contains lysozyme (antibacterial) and IgA. Chewing increases surface area ∼7-fold.

7.3.2 Stomach

Gastric mucosa contains three secretory cell types: parietal cells (secrete HCl, lowering pH to 1.5–3.5, and intrinsic factor for vitamin B₁₂ absorption), chief (peptic) cells (secrete pepsinogen, activated to pepsin by HCl; pepsin cleaves proteins at Phe, Trp, Tyr residues), and mucous neck cells (protect mucosa). In infants, rennin (chymosin) curdles casein (milk protein) slowing gastric emptying. Gastric emptying is regulated by cholecystokinin (CCK) and secretin from the duodenum.

7.3.3 Small Intestine

The duodenum receives chyme from the stomach plus bile from the liver/gallbladder and pancreatic juice from the pancreas. Bile emulsifies fats (increases surface for lipase) but contains no enzymes. The brush border of intestinal enterocytes carries membrane-bound enzymes completing digestion:

Maltase, sucrase, lactase — disaccharide → monosaccharides (glucose, fructose, galactose)
Aminopeptidase, dipeptidase — small peptides → amino acids

**Table 7.3**Pancreatic enzymes — precursor, activation, substrate, product
Enzyme	Precursor (zymogen)	Activator	Substrate → Product
Trypsin	Trypsinogen	Enterokinase (brush border)	Proteins/peptides → smaller peptides
Chymotrypsin	Chymotrypsinogen	Trypsin	Peptide bonds at aromatic/bulky residues
Elastase	Proelastase	Trypsin	Elastin & other proteins
Pancreatic amylase	Active (no zymogen)	—	Starch → maltose + maltotriose
Pancreatic lipase	Active	Colipase	Triglycerides → fatty acids + 2-monoglyceride
Ribonuclease / DNase	Active	—	RNA / DNA → nucleotides

7.3.4 Absorption Sites

The surface area for absorption is amplified by plicae circulares (circular folds ×3), villi (×10, finger-like projections into the lumen; contain lacteals for lipid + blood capillaries for other nutrients), and microvilli (brush border, ×20). Net amplification ∼600-fold. Glucose and amino acids are absorbed by secondary active transport (Na⁺-coupled cotransporters). Fatty acids and glycerol re-synthesise into triglycerides in enterocytes, package into chylomicrons, and enter lacteals (lymph). Fat-soluble vitamins (A, D, E, K) also enter lacteals. Vitamin B₁₂ requires intrinsic factor (IF) for receptor-mediated absorption in the ileum; IF deficiency causes pernicious anaemia.

**Table 7.4**Gastric juice components — source, nature, function
Component	Secreted by	Nature/pH	Function
HCl	Parietal cells	Acid (pH 1.5–3.5)	Activates pepsin; kills microbes; denatures proteins
Pepsinogen	Chief cells	Zymogen	Activated to pepsin; cleaves proteins
Intrinsic factor (IF)	Parietal cells	Glycoprotein	Binds vitamin B₁₂ for ileal absorption
Mucus	Mucous neck cells	Glycoprotein gel	Protects mucosa from acid and pepsin
Gastrin	G cells (antrum)	Hormone	Stimulates acid and pepsinogen secretion
Rennin (infants)	Chief cells	Protease	Curdles milk casein; prolongs digestion in neonates

Exam Tip: Pepsin is an endopeptidase (cleaves peptide bonds within the chain); aminopeptidase (brush border) and carboxypeptidase (pancreatic) are exopeptidases (cleave terminal residues). Enterokinase (from brush border) activates trypsinogen → trypsin, which then activates all other pancreatic zymogens — this is a cascade amplification. Without enterokinase, the cascade does not start.

Worked example — predicting absorption site

“A patient with surgical removal of the terminal ileum has consistently low serum vitamin B₁₂ despite adequate dietary intake. Predict the mechanism.”

Answer: Vitamin B₁₂-IF complex is absorbed exclusively in the terminal ileum via specific receptors (cubilin). Removing this segment eliminates the absorption site regardless of B₁₂ or IF availability. Treatment: parenteral (IM) B₁₂ injections bypass the gut entirely.

7.4 Respiration & Gaseous Exchange

Cellular respiration releases energy from organic molecules; the respiratory system ensures that O₂ reaches cells and CO₂ is eliminated. In mammals, air enters through the nasal cavity (filtered, warmed, humidified) → pharynx → larynx → trachea → bronchi → bronchioles → alveoli. The ~300 million alveoli provide a total exchange area of ~70 m² in adult human lungs, with a diffusion distance of only ~0.5 µm (one-cell alveolar epithelium + capillary endothelium).

7.4.1 Lung Volumes

**Table 7.5**Lung volumes and capacities (approximate adult values)
Volume / Capacity	Approx. value (mL)	Definition
Tidal volume (TV)	500	Air per normal breath
Inspiratory reserve volume (IRV)	3,000	Extra air beyond TV on forced inspiration
Expiratory reserve volume (ERV)	1,100	Extra air expelled after normal expiration
Residual volume (RV)	1,200	Air that cannot be expelled; keeps alveoli open
Vital capacity (VC) = TV + IRV + ERV	4,600	Max air movable in one breath; measured by spirometry
Total lung capacity (TLC)	5,800	VC + RV
Functional residual capacity (FRC)	2,300	ERV + RV; air remaining after normal expiration

HP angle: Residents of Lahaul-Spiti and other high-altitude zones of Himachal Pradesh (above 3,500 m) develop chronic mountain sickness (CMS) / Monge’s disease in some cases, characterised by polycythaemia (RBC count up to 7–8 million/µL vs normal 5 million), raised haemoglobin, and paradoxically excessive hypoxic ventilatory response blunting. The initial compensatory polycythaemia (EPO-driven) is adaptive; CMS represents decompensation. Vital capacity is higher in altitude-adapted individuals due to increased chest volume. This HP physiology context is testable in HPRCA state-TGT papers.

7.4.2 Haemoglobin & Oxygen Transport

Haemoglobin (Hb) is a tetrameric protein with four subunits (adult HbA: 2α + 2β), each containing a haem group with Fe²⁺ at the centre. Each Fe²⁺ binds one O₂ reversibly (oxyhaemoglobin). About 98% of O₂ in blood is carried as oxyHb; only 2% is dissolved in plasma. The O₂-dissociation curve is sigmoidal (cooperative binding): easy loading at high pO₂ (lungs), easy unloading at low pO₂ (tissues). The Bohr effect is a rightward shift of the curve caused by:

Increased CO₂ (carbonic acid lowers pH)
Increased temperature (active tissues)
Increased 2,3-BPG (altitude adaptation)

A rightward shift means Hb releases O₂ more readily — exactly what metabolically active tissues need. The leftward shift (higher affinity, e.g., foetal HbF with 2α + 2γ) allows foetal Hb to load O₂ from maternal HbA across the placenta.

Easy to confuse — Haemoglobin vs Myoglobin

Haemoglobin (Hb)

4 subunits (tetrameric). In RBCs. Sigmoidal O₂ curve (cooperative). Releases O₂ at tissues. Also transports CO₂ (23% as carbamino-Hb) and H⁺ (buffer). Bohr effect = rightward shift.

Myoglobin (Mb)

Single subunit (monomeric). In muscle cells. Hyperbolic O₂ curve (no cooperativity). Higher O₂ affinity than Hb. O₂ storage in muscle. Gives red colour to red muscle fibres. Released in rhabdomyolysis (serum marker).

7.4.3 CO₂ Transport

Carbon dioxide is transported in three forms: (1) 70% as bicarbonate (HCO₃⁻) — CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻; catalysed by carbonic anhydrase inside RBCs; HCO₃⁻ exits into plasma via chloride shift (Hamburger shift) with Cl⁻ entering; (2) 23% as carbamino-haemoglobin (CO₂ + Hb-NH₂); (3) 7% dissolved in plasma. At the lungs, low pCO₂ reverses all these reactions.

7.4.4 Regulation of Breathing

The respiratory centre is in the medulla oblongata (dorsal respiratory group, DRG) and pons (pneumotaxic and apneustic centres). Chemoreceptors respond to: central — pH/pCO₂ of cerebrospinal fluid (CSF); peripheral (carotid and aortic bodies) — low pO₂, high pCO₂, low pH. A rise in CO₂ (not fall in O₂) is the primary respiratory drive in normal individuals.

Easy to confuse — Aerobic vs Anaerobic Respiration (cellular)

Aerobic

O₂ required. Glucose → 36–38 ATP. Products: CO₂ + H₂O. In mitochondria (Krebs cycle + oxidative phosphorylation). Sustained energy for slow-twitch (red) muscle.

Anaerobic (lactic acid)

No O₂. Glucose → 2 ATP. Product: lactic acid (lactate), causing muscle fatigue. In cytoplasm only. Rapid energy for fast-twitch (white) muscle. “Oxygen debt” repaid during recovery.

Exam Tip: Emphysema destroys alveolar walls (reduced surface area, loss of elasticity) → air trapping, raised RV, barrel chest, low diffusion capacity. Asthma is bronchospasm (reversible); emphysema is structural (irreversible). Both reduce FEV₁/FVC ratio (obstructive pattern). Restrictive diseases (fibrosis) reduce TLC with normal or raised ratio.

7.5 Excretion & Osmoregulation

Excretion is the removal of metabolic wastes from the body; osmoregulation is the maintenance of constant internal osmolarity. The kidneys perform both: ~180 L of filtrate is produced per day but only 1.5 L of urine is excreted, meaning ~99% of water and most solutes are reabsorbed.

7.5.1 Nitrogenous Waste Classification

Easy to confuse — Ammonotelic / Ureotelic / Uricotelic

Ammonotelic

Excrete ammonia. Most aquatic invertebrates, bony fish, aquatic amphibians. Ammonia is very toxic but highly soluble; excreted by diffusion into water. Minimum water required per N atom.

Ureotelic

Excrete urea. Mammals, adult amphibians, marine fish, cartilaginous fish. Urea is less toxic; synthesised in liver (urea cycle / ornithine cycle); moderate water needed.

Easy to confuse — Uricotelic vs Ureotelic

Uricotelic

Excrete uric acid. Reptiles, birds, insects, land snails. Uric acid is almost insoluble, so excreted as a paste/pellet — minimum water loss. Energetically costly to synthesise. Adaptation to dry/terrestrial environments.

Ureotelic

Urea is ~100× less toxic than ammonia but requires more water than uric acid for excretion. The ornithine (urea) cycle runs mainly in the liver. Net: 1 NH₃ + CO₂ + 1 NH₃ (from aspartate) → urea.

7.5.2 Nephron Structure & Function

Each kidney contains ~1 million nephrons. Two types: cortical nephrons (short loop of Henle, mostly in cortex; ~85%) mainly concerned with filtration and reabsorption; juxtamedullary nephrons (long loop reaching deep medulla; ~15%) create and maintain the osmotic gradient necessary for urine concentration.

Fig. 7.3Nephron anatomy and countercurrent mechanism. PCT reabsorbs most filtered load. Descending loop of Henle is permeable to water (osmotic withdrawal); ascending limb is water-impermeable but actively pumps NaCl into medullary interstitium, building the 300→1200 mOsm gradient. ADH controls final water reabsorption in collecting duct via aquaporin-2.

7.5.3 Filtration, Reabsorption, Secretion, Excretion

Ultrafiltration: Glomerular filtration rate (GFR) ~125 mL/min (~180 L/day). Driven by blood pressure in glomerular capillaries. Filtrate contains everything except large proteins and cells. PCT: ~67% of Na⁺, Cl⁻, K⁺, HCO₃⁻, and 100% of glucose and amino acids reabsorbed. Loop of Henle: countercurrent multiplier concentrates medullary interstitium. DCT: fine-tuning; aldosterone (from adrenal cortex) inserts Na⁺/K⁺-ATPase pumps via genomic action, increasing Na⁺ reabsorption and K⁺ secretion. Collecting duct: ADH (vasopressin) from posterior pituitary inserts aquaporin-2 channels; absent → dilute urine (diabetes insipidus).

7.5.4 RAAS — Renin-Angiotensin-Aldosterone System

Low blood pressure → juxtaglomerular cells release renin → cleaves angiotensinogen (liver) → angiotensin I → ACE (lung endothelium) → angiotensin II → (a) adrenal cortex secretes aldosterone (Na⁺ retention, water retention, BP rises); (b) direct vasoconstriction; (c) stimulates ADH release. ACE inhibitors (ramipril, enalapril) and ARBs block this system in hypertension therapy.

Worked example — predicting urine concentration

“A patient is given a large dose of ADH. Predict: concentrated or dilute urine? What happens to urine output?”

Answer: ADH inserts aquaporin-2 water channels into collecting duct principal cell apical membranes. Water moves osmotically from tubular lumen into the hypertonic medullary interstitium and then into peritubular capillaries. Result: concentrated, low-volume urine. Urine osmolality can reach ~1200 mOsm (matching deep medullary gradient). Urine output falls dramatically (<500 mL/day in extreme ADH action).

Exam Tip: Osmotic diuretic (e.g., mannitol) floods the tubule with non-reabsorbable solute, preventing water reabsorption → large-volume dilute urine. Loop diuretics (furosemide) block Na⁺-K⁺-2Cl⁻ cotransporter in ascending limb → destroy the medullary gradient → reduced maximal urine concentration. Thiazides block DCT Na⁺-Cl⁻ cotransporter. These drug mechanisms are directly examinable.

7.6 Circulation — Blood, Heart & Blood Vessels

William Harvey established the principles of blood circulation in Exercitatio Anatomica de Motu Cordis et Sanguinis (1628), showing the heart as a pump driving blood in a closed circuit. The human heart, a four-chambered (double-circuit) organ, maintains pulmonary circulation (right heart → lungs → left heart) and systemic circulation (left heart → body → right heart).

William Harvey 1628 — circulation of blood (double circuit confirmed) · Karl Landsteiner 1900 — ABO blood groups (Nobel 1930) · Alexander Wiener & Landsteiner 1940 — Rh factor · Willem Einthoven 1903 — electrocardiograph (ECG; Nobel 1924)

7.6.1 Blood Composition

**Table 7.6**Blood components — type, count, lifespan, function
Component	Normal count	Lifespan	Key function
Plasma (55%)	—	—	Transport of nutrients, hormones, CO₂, waste; contains fibrinogen (clotting) and albumin (osmotic pressure)
Erythrocytes (RBC)	4.5–5.5 × 10⁶/µL	~120 days	O₂ transport via Hb; biconcave disc; anucleate in mammals; destroyed in spleen
Neutrophils	2,500–7,500/µL (60–70%)	6–12 h	First-line phagocytosis of bacteria; most abundant WBC
Lymphocytes (B, T)	1,500–4,000/µL (20–30%)	Days to years	Adaptive immunity; antibody production (B); cell-mediated killing (T)
Monocytes → Macrophages	200–800/µL (3–8%)	Months	Phagocytosis; antigen presentation; cytokine secretion
Eosinophils	100–400/µL (1–4%)	8–12 days	Parasitic defence; allergy (degranulate with MBP)
Basophils	0–100/µL (<1%)	Few days	Allergy & inflammation; release histamine & heparin
Platelets (thrombocytes)	150,000–400,000/µL	8–11 days	Primary haemostasis (plug); release clotting factors; no nucleus; fragments of megakaryocytes

7.6.2 ABO Blood Groups

Landsteiner’s ABO system (1900) is based on surface antigens (agglutinogens) on RBCs and corresponding antibodies (agglutinins) in plasma. Blood group A: A antigen on RBC, anti-B antibody in plasma. B: B antigen, anti-A. AB: both A and B antigens, no antibodies (universal recipient). O: no antigens, anti-A + anti-B antibodies (universal donor for packed RBCs). Transfusion of incompatible blood → agglutination → haemolysis → potentially fatal.

Worked example — ABO transfusion compatibility

“A group B patient urgently needs a transfusion and only group A blood is available. Can it be given?”

Answer: No. Group B plasma contains anti-A antibodies. Transfused group A RBCs carry A antigens. The recipient’s anti-A antibodies will agglutinate the donor A cells, causing acute haemolytic transfusion reaction (AHTR). In emergency, group O (no antigens) is the universal donor. If AB plasma is available (no antibodies), it is the universal plasma donor.

7.6.3 Cardiac Conducting System

The heart’s intrinsic rhythmicity depends on specialised conduction tissue. The sinoatrial (SA) node in the right atrium wall is the pacemaker (intrinsic rate 70 bpm); its AP spreads across both atria (atrial depolarisation). The signal reaches the atrioventricular (AV) node at the AV junction, where there is a delay of ~120 ms (allowing atria to finish emptying). The AP then travels rapidly via the bundle of His (AV bundle) in the interventricular septum, splits into right and left bundle branches, and reaches the ventricular apex via Purkinje fibres, causing ventricular depolarisation from apex upward.

Fig. 7.4Cardiac conducting system (SA node → AV node → bundle of His → bundle branches → Purkinje fibres) and corresponding ECG waves. P = atrial depolarisation; QRS complex = ventricular depolarisation; T = ventricular repolarisation.

7.6.4 Cardiac Cycle

One complete cycle (~0.8 s at 75 bpm) consists of:

Atrial systole (0.1 s) — atria contract, completing ventricular filling (~25 mL additional).
Ventricular systole (0.3 s) — AV valves close (first heart sound, “lub”); pressure rises; semilunar valves open; blood ejected into aorta & pulmonary artery.
Ventricular diastole (0.4 s) — semilunar valves close (second heart sound, “dub”); ventricles relax and fill.

Stroke volume (SV) ~70 mL/beat; cardiac output (CO) = SV × HR = 70 × 70 = 4,900 mL/min (~5 L/min at rest).

Worked example — cardiac output

“An athlete’s heart at rest has HR = 55 bpm and SV = 95 mL/beat. Calculate cardiac output and compare to an untrained individual (HR 75 bpm, SV 70 mL).”

Answer: Athlete CO = 55 × 95 = 5,225 mL/min ≈ 5.2 L/min. Untrained CO = 75 × 70 = 5,250 mL/min ≈ 5.25 L/min. Both are similar at rest — the athlete achieves the same output with a lower HR and larger SV (cardiac hypertrophy, “athlete’s heart”). During maximal exercise, the athlete can raise CO to 25–30 L/min (vs ~20 L/min untrained) mainly through larger SV.

Easy to confuse — Systolic vs Diastolic / Arterial vs Venous

Systolic / Arteries

Systolic BP = peak pressure during ventricular contraction (normal 120 mmHg). Arteries have thick elastic walls (withstand pressure). Blood flows rapidly, pulsatile. Carry oxygenated blood (except pulmonary artery).

Diastolic / Veins

Diastolic BP = pressure during ventricular relaxation (normal 80 mmHg). Veins have thin walls, valves (prevent backflow), low pressure. Blood returns slowly. Carry deoxygenated blood (except pulmonary vein).

7.7 Endocrine System

The endocrine system coordinates slow, sustained physiological responses using hormones — chemical messengers secreted into the bloodstream and acting on distant target cells via specific receptors. Hormones are classified as: peptide/protein (hydrophilic, act via membrane receptors and second messengers, e.g., insulin, glucagon, GH); steroid (lipophilic, derived from cholesterol, enter cell and act via nuclear receptors, e.g., cortisol, aldosterone, sex hormones); amino-acid derived (adrenaline — membrane receptor; thyroid hormones T3/T4 — nuclear).

Mnemonic — Anterior Pituitary Hormones (FLAT PIG)

FSH (follicle-stimulating) • LH (luteinising) • ACTH (adrenocorticotrophic) • TSH (thyroid-stimulating) • Prolactin • Inhibins (negative feedback) • GH (growth hormone = somatotrophin)

Posterior pituitary stores and releases ADH (vasopressin) and Oxytocin — both made in hypothalamus

**Table 7.7**Key hormones — gland, chemical class, target, action, deficiency/excess
Hormone	Gland	Target	Major action	Deficiency / Excess disease
GH (somatotrophin)	Anterior pituitary	Liver, bone, muscle	Growth (IGF-1); protein anabolism; lipolysis	Dwarf (childhood def.) / Gigantism (childhood excess) / Acromegaly (adult excess)
TSH	Anterior pituitary	Thyroid	Stimulates T3/T4 synthesis & release	Hypothyroidism if TSH deficient
ACTH	Anterior pituitary	Adrenal cortex	Stimulates glucocorticoid (cortisol) synthesis	Cushing’s (excess ACTH/cortisol); Addison’s (def.)
ADH (vasopressin)	Hypothalamus → post. pituitary	Kidney collecting duct	Aquaporin-2 insertion; water reabsorption; VC	Diabetes insipidus (def.); SIADH (excess)
Oxytocin	Hypothalamus → post. pituitary	Uterus, mammary	Labour contractions; milk ejection; social bonding	—
T3 & T4	Thyroid follicular cells	All cells	Metabolic rate, growth, thermogenesis; require iodine	Cretinism/myxoedema (def.); hyperthyroidism/Graves’ (excess)
Calcitonin	Thyroid C-cells	Bone, kidney	Lowers blood Ca²⁺ (inhibits osteoclasts)	—
PTH	Parathyroid	Bone, kidney, gut	Raises blood Ca²⁺ (activates osteoclasts; 1,25-OH Vit D)	Hypo: tetany; Hyper: bone resorption, kidney stones
Insulin	Pancreatic β cells	Liver, muscle, fat	Lowers blood glucose; promotes glycogenesis, lipogenesis	Type 1 DM (autoimmune β cell destruction); Type 2 DM (insulin resistance)
Glucagon	Pancreatic α cells	Liver	Raises blood glucose; promotes glycogenolysis, gluconeogenesis	Glucagonoma (rare tumor)
Cortisol	Adrenal cortex (zona fasciculata)	Widespread	Raises blood glucose; anti-inflammatory; stress response	Cushing’s syndrome (excess); Addison’s (def.)
Aldosterone	Adrenal cortex (zona glomerulosa)	Kidney DCT/CD	Na⁺ reabsorption, K⁺/H⁺ secretion; BP regulation	Conn’s syndrome (excess); Addison’s (def.)
Adrenaline (epinephrine)	Adrenal medulla (chromaffin)	Heart, vessels, liver	Fight-or-flight: ↑HR, ↑BP, glycogenolysis, bronchodilation	Phaeochromocytoma (excess)
Testosterone	Testicular Leydig cells	Reproductive organs, muscle	Spermatogenesis; secondary sexual characteristics; anabolic	Hypogonadism (def.)
Oestrogen	Ovarian follicle/corpus luteum	Reproductive organs	Follicular growth; secondary sex characteristics; bone density	Osteoporosis (post-menopausal def.)

HP angle: Iodine-deficiency goitre has historically been prevalent in the inland hill districts of Himachal Pradesh — Kullu, Kangra, Mandi, and Chamba valleys — because glacial/river water and local food sources are iodine-poor. TSH rises compensatorily (thyroid enlargement = goitre) when T3/T4 synthesis is impaired by iodine lack. The problem has been largely resolved by mandatory iodisation of salt (iodised salt scheme) under India’s National Iodine Deficiency Disorders Control Programme (NIDDCP). Endemic cretinism (foetal hypothyroidism due to maternal iodine deficiency) was a notable public health concern before iodisation. This is a standard HPRCA HP-specific question.

Worked example — identifying hormone deficiency from symptoms

“A patient has excessive thirst and urination; blood glucose is normal; urine is very dilute (osmolality 80 mOsm/kg). Identify the hormone deficiency.”

Answer: Normal blood glucose rules out diabetes mellitus. Very dilute urine despite dehydration points to inability to concentrate urine. This is central diabetes insipidus — deficiency of ADH (vasopressin) from the posterior pituitary/hypothalamus. Without ADH, aquaporin-2 channels are not inserted into collecting duct; water passes out as large volumes of dilute urine. Treatment: synthetic ADH (desmopressin, DDAVP).

7.8 Immune System — Innate & Adaptive Immunity

The immune system defends against pathogens, aberrant cells, and foreign molecules. It is divided into two functional arms: innate (non-specific), providing immediate but general defence, and adaptive (acquired/specific), providing targeted, memory-generating responses.

Edward Jenner 1796 — smallpox vaccine (cowpox cross-protection) · Louis Pasteur 1885 — rabies vaccine (first human use of attenuated pathogen) · Emil von Behring 1901 — diphtheria antitoxin (first Nobel in Physiology/Medicine) · Paul Ehrlich 1908 — selective toxin/antibody theory (Nobel with Metchnikoff) · Frank Macfarlane Burnet 1957 — clonal selection theory (Nobel 1960) · Georges Köhler & César Milstein 1975 — monoclonal antibody hybridoma (Nobel 1984) · Susumu Tonegawa 1987 — antibody diversity (gene rearrangement, Nobel)

7.8.1 Innate Immunity

Innate immunity is present from birth, acts within minutes/hours, and does not improve with repeated exposure. It recognises pathogen-associated molecular patterns (PAMPs) via pattern-recognition receptors (PRRs) such as Toll-like receptors (TLRs).

Physical barriers: skin (keratin layer); mucous membranes; cilia (ciliary escalator in respiratory tract); tight junctions.
Chemical barriers: lysozyme (tears, saliva, sweat — cleaves bacterial peptidoglycan); gastric HCl; defensins in skin/gut; sebum (fatty acids); lactoferrin (iron sequestration).
Cellular effectors: Neutrophils (phagocytosis, NET formation); macrophages (phagocytosis, cytokine release, antigen presentation — link innate to adaptive); dendritic cells (professional APCs, bridge to adaptive); NK (natural killer) cells (kill virus-infected and tumour cells lacking MHC-I, via perforin + granzymes); mast cells and basophils (inflammation mediators).
Inflammation: vasodilation, increased permeability, recruitment of leukocytes. Mediators: histamine, prostaglandins, leukotrienes, cytokines (IL-1, IL-6, TNF-α). Signs: calor (heat), dolor (pain), rubor (redness), tumor (swelling), functio laesa (loss of function).
Complement system: ~30 plasma proteins activated in a cascade (classical, lectin, or alternative pathways); outcomes: opsonisation (C3b coating), membrane attack complex (MAC, lyses bacteria), inflammation (C3a, C5a anaphylatoxins).
Interferons (IFN-α, IFN-β): secreted by virus-infected cells; signal neighbouring cells to activate antiviral proteins (RNase L, PKR); IFN-γ is from T cells and NK cells (immunomodulatory).

7.8.2 Adaptive Immunity

Adaptive immunity is antigen-specific, slow (days) on first exposure, and produces immunological memory (faster, stronger secondary response). Two branches:

Humoral immunity: B lymphocytes → (antigen + T-helper signals) → plasma cells → antibody secretion. Protects against extracellular pathogens.
Cell-mediated immunity (CMI): T lymphocytes recognise antigen only when presented on MHC molecules by APCs. Protects against intracellular pathogens, tumour cells, grafts.

7.8.3 Lymphocytes — B Cells and T Cells

Easy to confuse — B cells vs T cells

B Cells (Bone-marrow matured)

Origin & maturation: bone marrow. Activated by antigen + Th2/Th cell help. Differentiate into plasma cells (secrete antibodies) and memory B cells. BCR = surface IgM/IgD. Humoral immunity. Recognise free/soluble antigens directly.

T Cells (Thymus-matured)

Origin: bone marrow; maturation: thymus. TCR recognises antigen only as peptide–MHC complex. Subtypes: CD4⁺ T helper (Th) — coordinate both humoral and CMI; CD8⁺ cytotoxic T (Tc) — kill infected cells; T regulatory (Treg) — prevent autoimmunity.

7.8.4 MHC (Major Histocompatibility Complex)

MHC molecules display peptide fragments for T-cell surveillance. MHC class I (HLA-A, B, C in humans): expressed on all nucleated cells; presents peptides from intracellular proteins (viral, tumour); recognised by CD8⁺ cytotoxic T cells. MHC class II (HLA-DR, DP, DQ): expressed on professional APCs only (dendritic cells, macrophages, B cells); presents exogenous antigen peptides; recognised by CD4⁺ T helper cells. Mismatched MHC causes graft rejection — basis of tissue typing in transplantation.

7.8.5 Antibody Structure and Classes

first antibody in primary response; best complement activator IgE Lowest serum conc.; binds mast cells / basophils; allergy & anti-parasitic IgD Mainly B-cell surface receptor (BCR); role in B-cell activation signalling

Fig. 7.5Antibody (immunoglobulin) structure: Y-shaped; two heavy + two light chains; variable (V) regions at both Fab arms form the antigen-binding site; constant (C) regions in Fc tail mediate effector functions. Five classes: IgG, IgA, IgM, IgE, IgD.

**Table 7.8**Immunoglobulin (Ig) classes — structure, concentration, key functions
Class	Structure	Serum %	Key properties
IgG	Monomer (7S)	~80%	Long half-life (23 days); crosses placenta (neonatal immunity); secondary response; opsonisation; complement activation
IgA	Dimer in secretions	~13%	Secretory IgA (sIgA) dominant in gut, respiratory, urogenital secretions & breast milk; first-line mucosal defence
IgM	Pentamer (19S)	~6%	First antibody synthesised in primary response; most efficient complement activator; B-cell surface receptor
IgE	Monomer	<0.001%	Binds FcεRI on mast cells/basophils; type I hypersensitivity (allergy, anaphylaxis); anti-helminth defence
IgD	Monomer	<1%	B-cell surface BCR; involved in B-cell activation; minor effector role

Easy to confuse — Primary vs Secondary Immune Response

Primary Response

First antigen encounter. Lag phase 5–10 days. Main antibody: IgM (first to rise, first to fall). Lower antibody titre. Produces effector cells + long-lived memory cells.

Secondary (Anamnestic) Response

Same antigen again. Lag phase 1–3 days. Main antibody: IgG (higher affinity, class switching). Much higher titre (10×–100×). More sustained. Basis of vaccine booster shots.

Easy to confuse — Humoral vs Cell-Mediated Immunity

Humoral (Antibody-Mediated)

B cells → plasma cells → antibodies. Targets extracellular pathogens (bacteria, free viruses, toxins). Antibodies neutralise, opsonise, activate complement. Transferred by serum.

Cell-Mediated (CMI)

T cells. CD4⁺ Th co-ordinate; CD8⁺ Tc kill intracellular-infected, viral, cancer cells. Cytokines (lymphokines) direct response. Transferred by T cells (not serum). Graft rejection is CMI-mediated.

Easy to confuse — Active vs Passive Immunity

Active Immunity

Own immune system produces antibodies. After natural infection or vaccination. Slow onset (days–weeks). Long-lasting (memory cells). Examples: post-infection immunity; BCG; measles vaccine.

Passive Immunity

Pre-formed antibodies from another source. Immediate protection. Short-lived (no memory). Natural: maternal IgG (placenta), IgA (breast milk). Artificial: antitoxin (tetanus, diphtheria), antivenin (snake), monoclonal antibodies (IVIG).

7.9 Vaccines, Immune Disorders & Antibody Engineering

7.9.1 Vaccine Types

**Table 7.9**Vaccine types — mechanism, examples, advantages, limitations
Type	Mechanism	Examples	Advantage / Limitation
Live attenuated	Weakened pathogen; replicates, mimics infection	BCG (TB), OPV (Sabin polio), MMR, Varicella, Yellow fever	Strong, durable immunity; risk of reversion; contraindicated in immunocompromised
Killed / inactivated	Whole pathogen killed; cannot replicate	IPV (Salk polio), Hep A, Rabies (some), Flu (killed)	Safer; shorter duration; multiple doses needed
Toxoid	Inactivated exotoxin; stimulates anti-toxin antibodies	Tetanus toxoid (TT), Diphtheria toxoid (DTP/DPT)	Highly effective; very safe; boosters needed
Subunit / conjugate	Purified antigen(s) only; no whole organism	Hep B (HBsAg), Hib, Pneumococcal (PCV), HPV (Gardasil)	Minimal side effects; may need adjuvant; conjugate improves T-dependent response in infants
mRNA vaccine	mRNA encoding antigen injected; host cells translate into protein → immune response	COVID-19 (Pfizer-BioNTech BNT162b2, Moderna mRNA-1273)	Rapid development; lipid nanoparticle delivery; cold chain requirement
Recombinant / DNA	Antigen gene inserted into vector (e.g., adenovirus)	AstraZeneca COVID (ChAdOx1), Janssen, Covishield	Can combine antigens; stable; some pre-existing immunity to vector

Easy to confuse — Vaccine vs Antibody therapy

Vaccine (prophylactic)

Given before infection. Active immunity — body makes its own antibodies. Leads to memory. Long-lasting protection. Cheap to manufacture at scale.

Antibody (passive, therapeutic)

Given after exposure or for treatment. Passive immunity — ready-made antibodies. No memory. Short-lived. Monoclonal antibodies (mAbs) e.g., Rituximab, Herceptin, Pembrolizumab.

7.9.2 Immune Disorders

Autoimmune diseases arise when the immune system attacks self antigens, breaking tolerance. Examples: Type 1 diabetes mellitus (autoimmune destruction of pancreatic β cells by CD8⁺ T cells; anti-insulin antibodies; insulin-dependent); Rheumatoid arthritis (RA) (anti-IgG = rheumatoid factor; synovial joint destruction); Systemic lupus erythematosus (SLE) (anti-dsDNA, anti-nuclear antibodies; multi-organ); Multiple sclerosis (MS) (demyelination of CNS by autoreactive T cells against myelin basic protein).

Allergy (Type I hypersensitivity): First exposure → sensitisation → plasma cells secrete IgE → binds FcεRI on mast cells. Second exposure → allergen cross-links surface IgE → mast cell degranulation → histamine, leukotrienes → symptoms (rhinitis, urticaria, bronchospasm). Anaphylaxis = systemic, life-threatening. Treatment: antihistamines, epinephrine.

Immunodeficiency: Primary (congenital) — SCID (severe combined immunodeficiency; ADA deficiency is most common form; “bubble boy disease”); DiGeorge syndrome (thymic aplasia, no T cells). Secondary (acquired) — AIDS: HIV-1 infects CD4⁺ T helper cells (via gp120 binding CD4 + CCR5/CXCR4 co-receptors), depletes them below 200 cells/µL → loss of adaptive immunity coordination → opportunistic infections (PCP, CMV retinitis, Cryptococcal meningitis, Kaposi’s sarcoma).

7.9.3 Monoclonal Antibodies — Hybridoma Technology

Köhler and Milstein (1975, Nobel 1984) developed hybridoma technology: immune mouse B cells (specific antibody) + immortal myeloma cells → hybridoma (immortal + antibody-producing). Clonal selection → single hybridoma clone → identical (monoclonal) antibodies with defined antigen specificity. Applications: diagnostics (ELISA, pregnancy tests, HIV tests), cancer therapy (Rituximab — anti-CD20, B-cell lymphoma; Herceptin/trastuzumab — anti-HER2, breast cancer; pembrolizumab — anti-PD-1, checkpoint inhibitor), antivenom, passive immunotherapy.

HP angle: Berberis aristata (daruharidra, found widely in HP including Kullu and Chamba) contains berberine, a compound used in traditional Ayurvedic/folk medicine for jaundice (hepatoprotective claims), diarrhoea, and eye infections. Modern studies show berberine has anti-inflammatory and immunomodulatory properties, inhibiting NF-κB. While evidence-based medicine requires clinical trials, the recognition of this HP folk-medicine link is relevant to HPRCA biodiversity and applied biology questions. Similarly, iron-rich traditional HP foods (locally grown rajmash/kidney beans, kala chana, leafy vegetables in mid-hill zones) are discussed in the context of anaemia prevention and haemoglobin synthesis.

7.10 Quick-Reference Tables

**Table 7.10**Vitamins — type, source, deficiency disease
Vitamin	Type	Major source	Deficiency disease
A (retinol)	Fat-soluble	Liver, dairy, carrots (β-carotene)	Night blindness; xerophthalmia; keratomalacia
D (calciferol)	Fat-soluble	Sunlight (skin); fish oil, fortified milk	Rickets (children); osteomalacia (adults)
E (tocopherol)	Fat-soluble	Vegetable oils, nuts, green vegetables	Haemolytic anaemia (rare); peripheral neuropathy
K (phylloquinone)	Fat-soluble	Green leafy veg; gut bacteria synthesise K₂	Bleeding tendency (clotting factor synthesis impaired)
B₁ (thiamine)	Water-soluble	Whole grains, legumes	Beriberi (dry: peripheral neuropathy; wet: cardiac); Wernicke’s
B₂ (riboflavin)	Water-soluble	Milk, eggs, liver	Ariboflavinosis (angular stomatitis, glossitis)
B₃ (niacin)	Water-soluble	Meat, fish, peanuts	Pellagra (dermatitis, diarrhoea, dementia — 3Ds)
B₉ (folic acid)	Water-soluble	Green leafy veg, liver, legumes	Megaloblastic anaemia; neural tube defects (pregnancy)
B₁₂ (cobalamin)	Water-soluble	Meat, dairy, eggs (nil in plants)	Pernicious/megaloblastic anaemia; subacute combined degeneration of cord
C (ascorbic acid)	Water-soluble	Citrus, amla (Emblica officinalis), guava	Scurvy (collagen synthesis impaired; bleeding gums, petechiae)

Quick Recap

Neuron: resting −70 mV (3 Na⁺ out / 2 K⁺ in by pump); AP = depol (Na⁺ in) → repol (K⁺ out) → hyperpol; saltatory conduction (myelinated); chemical synapse via neurotransmitter into cleft.
Cranial nerves I–XII: purely sensory = I (olfactory), II (optic), VIII (vestibulocochlear); purely motor = III, IV, VI, XI, XII; mixed = V, VII, IX, X. Vagus (X) = main parasympathetic to viscera.
Muscle: A-band unchanged on contraction; I-band and H-zone narrow; Z-lines approach. Ca²⁺ from SR → troponin → tropomyosin shifts → cross-bridge cycles (ATP needed for detachment). Rigor mortis = no ATP.
Digestion: Salivary amylase (pH 6.8, starch) → pepsin (HCl, pH 1.5–3.5, protein) → bile (emulsify) + pancreatic enzymes (trypsin, chymotrypsin, lipase, amylase) → brush-border enzymes (maltase, lactase, sucrase). Vitamin B₁₂ absorbed ileum with IF from parietal cells.
Respiration: 98% O₂ as oxyHb; Bohr effect (low pH/high CO₂) = right shift; CO₂: 70% HCO₃⁻, 23% carbamino-Hb, 7% dissolved. Vital capacity = TV + IRV + ERV.
Excretion: Ammonotelic (fish), ureotelic (mammals), uricotelic (birds/reptiles). GFR ~125 mL/min. PCT reabsorbs 100% glucose, 67% Na⁺; loop of Henle = countercurrent multiplier; DCT = aldosterone (Na⁺ in, K⁺ out); collecting duct = ADH (water, aquaporin-2).
Heart: SA node (pacemaker) → AV node (delay 120 ms) → bundle of His → bundle branches → Purkinje fibres. CO = SV × HR (~5 L/min at rest). ECG: P = atrial depol; QRS = ventricular depol; T = ventricular repol.
Blood groups (Landsteiner 1900): O = universal donor (no antigens); AB = universal recipient (no antibodies). Rh: Rh⁺ have D antigen.
Endocrine: Anterior pituitary (FSH, LH, ACTH, TSH, prolactin, GH); posterior pituitary stores ADH + oxytocin (made in hypothalamus). T3/T4 need iodine; def. → goitre/cretinism. Insulin (B cells, lowers glucose); glucagon (A cells, raises glucose).
Immunity: Innate (fast, non-specific: neutrophils, NK cells, complement, interferons); adaptive (slow, specific, memory: B cells → IgM then IgG; T cells → CD4⁺ helper, CD8⁺ cytotoxic). MHC I: all nucleated cells, CD8⁺; MHC II: APCs only, CD4⁺.
Antibodies: IgG (most abundant, crosses placenta); IgA (mucosal, dimer); IgM (pentamer, primary response, first); IgE (allergy, mast cells); IgD (BCR). Active immunity = long-lasting + memory; passive = immediate, short-lived.
Vaccines: live attenuated (BCG, OPV, MMR), killed (IPV, Hep A), toxoid (TT, DTP), subunit (Hep B, HPV), mRNA (COVID-19), recombinant. Monoclonal antibodies: Köhler-Milstein 1975, hybridoma technology, Nobel 1984.

Chapter 7 Cheatsheet

Neuron & Action Potential

Resting: −70 mV; Na⁺/K⁺ pump 3:2
AP: depol (Na⁺ in) → repol (K⁺ out) → hyperpol
Saltatory conduction → myelinated = fast
Synapse: vesicle → cleft → receptor (unidirectional)
GABA = main inhibitory; Glutamate = main excitatory
Dopamine low → Parkinson’s; serotonin low → depression

Muscle & Sarcomere

A-band = constant; I-band & H-zone narrow on contraction
Ca²⁺ → troponin → tropomyosin shift → cross-bridges
ATP for detachment; rigor mortis = no ATP
Red (type I) = slow, aerobic; White (type II) = fast, glycolytic
Cardiac = striated, involuntary; intercalated discs; syncytial

Digestion

Salivary amylase: starch → maltose (pH 6.8)
Pepsin: protein (HCl-activated, pH 1.5–3.5)
Enterokinase: activates trypsinogen → trypsin cascade
Bile: emulsify fats (liver); no enzymes
Vit B₁₂: IF (parietal cells) + ileum absorption
Lactase def. → lactose intolerance

Respiration

Hb: 4 subunits, 4 O₂; sigmoidal curve; Fe²⁺
98% O₂ as oxyHb; Bohr shift = right = more O₂ release
CO₂: 70% HCO₃⁻; 23% carbamino-Hb; 7% dissolved
Vital capacity = TV + IRV + ERV
HP altitude → polycythaemia (EPO-driven compensation)

Kidney & Excretion

Ammonotelic = fish; ureotelic = mammals; uricotelic = birds
GFR 125 mL/min; filtrate 180 L/day; urine ~1.5 L/day
PCT: 100% glucose, amino acids; 67% Na⁺
Loop: countercurrent multiplier (300→1200 mOsm)
ADH (vasopressin): aquaporin-2 → concentrated urine
Aldosterone: Na⁺ in, K⁺ out (DCT)
RAAS: low BP → renin → Ang II → aldosterone

Heart & Blood

SA node 70 bpm (pacemaker) → AV delay → His → Purkinje
ECG: P atrial; QRS ventricular depol; T repol
CO = SV × HR; normal ~5 L/min
Lub (AV close) — Dub (semilunar close)
ABO: O = universal donor (no Ag); AB = universal recipient
Landsteiner 1900 (ABO); Wiener 1940 (Rh)

Endocrine

Ant. pit: GH, TSH, ACTH, FSH, LH, Prolactin (FLAT PIG)
Post. pit stores: ADH + Oxytocin (hypothalamic origin)
Thyroid: T3/T4 (iodine); calcitonin (lowers Ca²⁺)
PTH: raises Ca²⁺
Insulin (β): lowers glucose; glucagon (α): raises
Cortisol: raises glucose, anti-inflammatory; Addison’s vs Cushing’s
HP: iodine def. goitre (Kullu/Kangra; solved by iodised salt)

Immunity & Vaccines

Innate: fast, non-specific; neutrophils, NK, complement, IFN
Adaptive: B (IgM → IgG); T (CD4⁺ helper, CD8⁺ cytotoxic)
IgG: abundant, placenta; IgA: mucosal; IgM: first/primary
MHC I: all nucleated; MHC II: APCs only
Jenner 1796; Banting-Best 1922; Köhler-Milstein 1975
Active = long-lasting + memory; passive = quick, no memory

Practice Questions

The resting membrane potential of a neuron is approximately: HPRCA-pat.

−90 mV
−70 mV
−55 mV
+35 mV

Answer: B — −70 mV

Maintained by the Na⁺/K⁺-ATPase (3 Na⁺ out, 2 K⁺ in) and K⁺ leak channels. −55 mV is the threshold; +35 mV is the peak of the action potential.

The ionic basis of the depolarisation phase of an action potential is:

K⁺ influx
Na⁺ efflux
Na⁺ influx
Cl⁻ influx

Answer: C — Na⁺ influx

Voltage-gated Na⁺ channels open at threshold; Na⁺ rushes in down its electrochemical gradient, reversing membrane polarity to ~+35 mV. K⁺ efflux drives repolarisation.

Which cranial nerve is responsible for the gag reflex and taste sensation from the posterior third of the tongue?

Facial (VII)
Vagus (X)
Glossopharyngeal (IX)
Trigeminal (V)

Answer: C — Glossopharyngeal (IX)

CN IX carries taste from the posterior one-third of the tongue and mediates the afferent limb of the gag (pharyngeal) reflex. CN VII carries taste from the anterior two-thirds. CN X mediates the efferent limb of the gag reflex.

In the sliding filament model, which band remains constant during muscle contraction? HPRCA-pat.

I-band
H-zone
A-band
Distance between Z-lines

Answer: C — A-band

The A-band spans the entire length of the thick myosin filament; since myosin does not change length, the A-band is constant. The I-band (actin only) and H-zone (myosin only, no actin overlap) both narrow as actin slides in. The sarcomere (Z-to-Z distance) shortens.

Intrinsic factor (IF), necessary for vitamin B₁₂ absorption, is secreted by:

Chief cells of the stomach
G cells of the gastric antrum
Parietal cells of the stomach
Brunner’s glands of the duodenum

Answer: C — Parietal cells

Parietal cells secrete both HCl and intrinsic factor. IF binds B₁₂ in the duodenum and the complex is absorbed by cubilin receptors in the terminal ileum. Loss of parietal cells (autoimmune atrophic gastritis) causes pernicious anaemia.

The Bohr effect on the oxygen-dissociation curve of haemoglobin refers to: HPRCA-pat.

Leftward shift caused by high pH and low pCO₂
Rightward shift caused by low pH (or high pCO₂), favouring O₂ release
Increased O₂ affinity at low temperatures
Decrease in haem groups under hypoxic conditions

Answer: B — Rightward shift, favours O₂ release

Active (acidic, warm) tissues release CO₂ lowering pH; this causes Hb to release O₂ more readily (right shift). The opposite (left shift = higher affinity, e.g., foetal HbF) allows foetal Hb to “steal” O₂ from maternal HbA across the placenta.

The animals that excrete nitrogenous waste mainly as uric acid are called:

Ammonotelic
Ureotelic
Uricotelic
Ureothelic

Answer: C — Uricotelic

Uric acid is almost insoluble; excreted as paste, minimising water loss. Characteristic of birds, reptiles, and insects. Mammals (including humans) are mostly ureotelic; bony fish/aquatic animals are ammonotelic.

The pacemaker of the human heart is the: HPRCA-pat.

AV node
Purkinje fibres
Sinoatrial (SA) node
Bundle of His

Answer: C — SA node

The SA node (Keith-Flack node) in the right atrial wall has an intrinsic firing rate of ~70 bpm and sets the cardiac rhythm. AV node (40–60 bpm), bundle of His, and Purkinje fibres (20–40 bpm) can act as subsidiary pacemakers if SA fails.

In the ECG, the QRS complex represents:

Atrial depolarisation
Ventricular repolarisation
Ventricular depolarisation
AV nodal delay

Answer: C — Ventricular depolarisation

P = atrial depolarisation; QRS = ventricular depolarisation (and is the largest wave, reflecting the mass of ventricular myocardium); T = ventricular repolarisation. The P-R interval includes AV nodal delay.

Blood group “O” is called the “universal donor” because: HPRCA-pat.

Group O individuals have both A and B antibodies in plasma
Group O RBCs lack both A and B antigens on their surface
Group O RBCs carry both A and B antigens
Group O plasma has neither anti-A nor anti-B antibodies

Answer: B — Group O RBCs lack A and B antigens

Since O RBCs carry no A or B antigens, they will not be agglutinated by anti-A or anti-B antibodies in any recipient. However, group O plasma does contain anti-A and anti-B, so whole blood from group O can cause problems; packed O RBCs are the safest donor product.

Which hormone is produced in the hypothalamus but stored and released from the posterior pituitary?

Growth hormone (GH)
Luteinising hormone (LH)
Antidiuretic hormone (ADH)
Thyroid-stimulating hormone (TSH)

Answer: C — ADH (vasopressin)

Both ADH and oxytocin are synthesised in the hypothalamic paraventricular and supraoptic nuclei, transported along axons, and stored in and released from the posterior pituitary. GH, LH, TSH are synthesised in the anterior pituitary.

The first antibody produced during a primary immune response is: HPRCA-pat.

Answer: C — IgM

IgM (pentameric) is the first antibody secreted during a primary response; it is the most efficient complement activator. In the secondary response, class switching produces predominantly IgG (longer-lived, higher affinity, crosses placenta).

Hybridoma technology, used to produce monoclonal antibodies, was developed by:

Jenner and Pasteur
Köhler and Milstein
Behring and Ehrlich
Burnet and Medawar

Answer: B — Köhler and Milstein

Georges Köhler and César Milstein (1975) fused immune B cells with immortal myeloma cells to create hybridomas. Awarded Nobel Prize in Physiology or Medicine in 1984.

Which immunoglobulin class crosses the placenta to provide passive immunity to the newborn? HPRCA-pat.

Answer: D — IgG

IgG is the only antibody class that crosses the placenta via FcRn (neonatal Fc receptor). IgA is provided in breast milk (colostrum), giving mucosal passive immunity. IgM cannot cross the placenta (pentamer, large).

The ADH deficiency leads to: HPRCA-pat.

Diabetes mellitus (Type 2)
Addison’s disease
Diabetes insipidus
Conn’s syndrome

Answer: C — Diabetes insipidus

ADH (vasopressin) deficiency impairs aquaporin-2 insertion in collecting duct principal cells; water cannot be reabsorbed → large volumes (up to 20 L/day) of very dilute urine. Blood glucose is normal (not diabetes mellitus). Treated with desmopressin (DDAVP).

Which vaccine uses an attenuated live organism and is given orally? HPRCA-pat.

Salk polio vaccine (IPV)
Hepatitis B vaccine
Sabin polio vaccine (OPV)
Tetanus toxoid

Answer: C — Sabin OPV

Sabin’s oral polio vaccine (OPV) uses live attenuated poliovirus; induces mucosal (intestinal) IgA as well as systemic immunity. Salk’s IPV uses killed virus, is injected. Hep B is recombinant subunit; tetanus is a toxoid.

Assertion (A): Saltatory conduction in myelinated nerve fibres is much faster than continuous conduction in unmyelinated fibres.
Reason (R): Action potentials jump from one node of Ranvier to the next because the myelin sheath is electrically insulating and allows current to travel rapidly in the internodal region.

Both A and R are true and R is the correct explanation of A
Both A and R are true but R is not the correct explanation of A
A is true but R is false
A is false but R is true