Human Physiology

Learning Objectives

• Understand the fundamental concepts of Human Physiology
• Apply key formulas and techniques to solve problems
• Practice with exam-level questions to build speed and accuracy
• Analyse clinical scenarios linking organ systems to diseases and disorders
• Master data interpretation from graphs, tables, and experimental setups

Key Concepts

Human Physiology is the study of the mechanical, physical, and biochemical functions of humans. This lesson covers all major organ systems tested in NEET Biology, including digestion, respiration, circulation, excretion, nervous system, endocrine system, locomotion, and coordination. Each section is structured with detailed theory, clinical correlations, comparison tables, solved examples, and exam-focused tip boxes to ensure comprehensive preparation.

The NEET Biology syllabus for Human Physiology typically carries 12–15 questions per year, making it one of the highest-weightage topics. A deep understanding of mechanisms, not rote memorization, is essential for solving application-based questions. Students should focus on understanding feedback loops, countercurrent mechanisms, enzyme cascades, pressure-volume relationships, and hormone-receptor interactions. The ability to integrate knowledge across systems (e.g., how the respiratory and renal systems cooperate in acid-base balance, or how the endocrine and nervous systems coordinate stress responses) is frequently tested in higher-order questions.

Clinical correlations are increasingly emphasized in NEET: expect questions linking anatomical or physiological knowledge to diseases such as diabetes insipidus, pernicious anaemia, myasthenia gravis, Cushing’s syndrome, and renal calculi. Mnemonics, comparison tables, and solved examples in this lesson are designed to build both conceptual clarity and exam speed. Regular practice with the provided MCQs will help consolidate understanding and improve time management.

1. Digestion & Absorption

Digestive System Overview

The human digestive system consists of the alimentary canal and associated digestive glands. The alimentary canal is a continuous muscular tube extending from the mouth to the anus. Its primary functions are ingestion, digestion, absorption, and elimination. The process is regulated by neural and hormonal signals that coordinate peristalsis, secretion, and sphincter relaxation. Understanding regional specialization of each segment is critical for NEET physiology questions.

Alimentary Canal

The alimentary canal is about 8–10 metres long and includes the mouth, pharynx, oesophagus, stomach, small intestine, large intestine, and anus. The mouth contains the tongue and teeth. The tongue is a muscular organ with papillae housing taste buds. The adult dental formula is 2123/2123 (2 incisors, 1 canine, 2 premolars, 3 molars in each half of both jaws). The pharynx is a common passage for food and air. The oesophagus is a 25 cm collapsible muscular tube that conducts food via peristalsis through the diaphragm into the stomach. The stomach is a J-shaped organ (1–1.5 L capacity) divided into the cardiac region, fundus, body, and pyloric region. The gastric wall contains gastric pits lined with chief cells (pepsinogen), parietal cells (HCl and intrinsic factor), and mucous cells (mucus). The pyloric sphincter regulates chyme entry into the duodenum.

The small intestine (about 6 m) is the principal site of digestion and absorption. It has three parts: the duodenum (25 cm, receives bile and pancreatic juice through the hepatopancreatic ampulla), jejunum (2.5 m), and ileum (3.5 m). The large intestine (1.5 m) consists of the caecum (with vermiform appendix), colon (ascending, transverse, descending, sigmoid), rectum, and anal canal. It absorbs water, electrolytes, and vitamins produced by gut flora.

Digestive Glands

Salivary glands (three pairs): parotid (serous secretion, below the ear), submandibular (mixed), sublingual (mucous). Saliva contains salivary amylase (ptyalin) for starch digestion, lysozyme for antibacterial action, and mucus. The liver (largest gland, 1.2–1.5 kg) secretes bile (600–1000 mL/day), stored in the gallbladder. Bile contains bile salts (sodium taurocholate, glycocholate), bile pigments (bilirubin, biliverdin), cholesterol, and phospholipids. Bile emulsifies fats without enzymes. The pancreas (heterocrine gland) secretes pancreatic juice (1.5–2 L/day) containing trypsinogen, chymotrypsinogen, procarboxypeptidase, pancreatic amylase, lipases, and nucleases. The endocrine pancreas has islets of Langerhans: alpha cells (glucagon), beta cells (insulin), delta cells (somatostatin), and F cells (pancreatic polypeptide). Intestinal glands (crypts of Lieberkuhn) secrete succus entericus with disaccharidases (maltase, sucrase, lactase), peptidases, and lipases.

Process of Digestion

Digestion involves mechanical breakdown (mastication, churning, segmentation) and chemical breakdown by hydrolytic enzymes. The process is controlled by gastrointestinal hormones: gastrin, secretin, cholecystokinin (CCK), and gastric inhibitory peptide (GIP).

Mouth to Stomach

In the oral cavity, food mixes with saliva. Salivary amylase hydrolyses starch into maltose (optimum pH 6.8). The bolus is pushed into the pharynx by the tongue (voluntary phase), then the involuntary phase involves epiglottis closure and peristalsis. In the stomach, gastrin stimulates gastric secretion. HCl converts pepsinogen into active pepsin, which digests proteins into peptides (optimum pH 1.5–2.0). HCl also kills microorganisms. Rennin (chymosin) coagulates milk in infants. The stomach churns food into chyme over 3–4 hours.

Small Intestine

Chyme enters the duodenum through the pyloric sphincter. Secretin (from S cells) stimulates pancreatic bicarbonate to neutralize acid. CCK (from I cells) stimulates gallbladder contraction and pancreatic enzyme secretion. Trypsinogen is activated by enteropeptidase into trypsin, which then activates chymotrypsinogen and procarboxypeptidase. Pancreatic lipase (with colipase) digests triglycerides. Bile salts form micelles (20–50 nm) to increase surface area for lipase. Brush border enzymes (maltase, sucrase, lactase, aminopeptidase, dipeptidase) complete digestion. Segmentation mixes chyme while peristalsis propels it distally (1 cm/min).

Large Intestine

The ileocaecal sphincter regulates passage into the caecum. The large intestine absorbs water (90% of 500–1000 mL/day), electrolytes (Na+, Cl−), and vitamins (K, biotin, B vitamins from gut flora). Gut flora ferment undigested carbohydrates into short-chain fatty acids. Faeces are stored in the rectum until defecation.

Absorption of Digested Food

The small intestine has circular folds (plicae circulares), villi (40/mm2), and microvilli (brush border, 2000 per cell), providing a total surface area of 200–300 m2. Each villus has a central lacteal and capillary network. Glucose and galactose are absorbed via SGLT1 (secondary active transport with Na+). Fructose uses GLUT5 (facilitated diffusion). Amino acids and dipeptides use sodium-dependent transporters (PEPT1). Fatty acids diffuse into enterocytes, are re-esterified into triglycerides, and packaged into chylomicrons, which enter lacteals and reach the bloodstream via the thoracic duct. Vitamin B12 requires intrinsic factor for ileal absorption. Calcium absorption requires vitamin D; iron absorption is enhanced by vitamin C.

Disorders of the Digestive System

Jaundice: yellowing due to elevated bilirubin (pre-hepatic, hepatic, post-hepatic). Vomiting: reverse peristalsis coordinated by the medullary vomiting centre. Diarrhoea: reduced water absorption causing dehydration. Constipation: excessive water absorption in the colon. Indigestion (dyspepsia): incomplete digestion due to hypochlorhydria or enzyme deficiency. Lactose intolerance: lactase deficiency causing osmotic diarrhoea. Peptic ulcers: gastric/duodenal mucosal erosion due to H. pylori or NSAIDs.

Regulation of Digestion: Gastrointestinal Hormones

Gastrointestinal activity is coordinated by several peptide hormones secreted by specialized endocrine cells in the stomach and intestinal mucosa. Gastrin (produced by G cells in the stomach antrum, stimulated by peptides, amino acids, and vagal activity) acts on parietal cells to increase HCl secretion and promotes gastric motility. Secretin (produced by S cells in the duodenum in response to acidic chyme, pH < 4.5) stimulates pancreatic bicarbonate secretion, inhibits gastric acid secretion, and promotes bile secretion. Cholecystokinin/CCK (produced by I cells in the duodenum and jejunum in response to fats and proteins) stimulates gallbladder contraction, pancreatic enzyme secretion, and relaxes the sphincter of Oddi; it also inhibits gastric emptying and acts as a satiety signal. Gastric inhibitory peptide/GIP (produced by K cells in the duodenum in response to glucose and fats) stimulates insulin secretion (incretin effect), inhibits gastric acid secretion and gastric emptying. Motilin (produced by M cells) stimulates migrating motor complexes during fasting. Ghrelin (produced by P/D1 cells in the stomach fundus) stimulates appetite and GH secretion. Leptin (produced by adipose tissue) inhibits appetite and acts on the hypothalamus. The enteric nervous system (ENS), also called the “second brain,” contains about 500 million neurons organized in the myenteric (Auerbach’s, between longitudinal and circular muscle layers, controlling motility) and submucosal (Meissner’s, in the submucosa, controlling secretion and blood flow) plexuses.

Hormone	Source (Cell Type)	Stimulus for Release	Primary Actions
Gastrin	G cells (stomach antrum)	Peptides, amino acids, vagal stimulation	Stimulates HCl secretion, gastric motility
Secretin	S cells (duodenum)	Acidic chyme (pH < 4.5)	Stimulates pancreatic HCO3−, inhibits gastric acid
CCK	I cells (duodenum, jejunum)	Fats, proteins in chyme	Gallbladder contraction, pancreatic enzyme secretion, satiety
GIP	K cells (duodenum)	Glucose, fats	Stimulates insulin (incretin), inhibits gastric acid
Motilin	M cells (duodenum, jejunum)	Fasting state	Stimulates migrating motor complexes
Ghrelin	P/D1 cells (stomach fundus)	Fasting, empty stomach	Stimulates appetite, GH secretion

Vitamins & Minerals in Human Physiology

Vitamins are organic compounds required in small amounts for normal metabolic functions. They are classified as fat-soluble (A, D, E, K) and water-soluble (B complex, C). Fat-soluble vitamins are stored in the body (liver and adipose tissue); deficiencies develop slowly. Water-soluble vitamins are not stored in significant amounts (except B12); excess is excreted in urine, and deficiencies develop rapidly. Vitamin A (retinol): required for vision (rhodopsin synthesis), epithelial integrity, and immune function. Deficiency causes night blindness (nyctalopia), xerophthalmia, and Bitot’s spots. Vitamin D (cholecalciferol/ergocalciferol): synthesized in the skin from 7-dehydrocholesterol under UVB radiation, hydroxylated in the liver (25-OH-D) and kidney (1,25-(OH)2-D, calcitriol). Functions: increases intestinal Ca2+ and phosphate absorption, promotes bone mineralization. Deficiency causes rickets in children (bowed legs, rachitic rosary) and osteomalacia in adults. Vitamin E (tocopherol): antioxidant, protects cell membranes from lipid peroxidation; deficiency causes haemolytic anaemia and neuropathy. Vitamin K (phylloquinone/menaquinone): required for hepatic synthesis of clotting factors II, VII, IX, X and protein C, S. Deficiency causes bleeding (prolonged PT). Newborns receive vitamin K injection to prevent haemorrhagic disease of the newborn. Vitamin B complex: B1 (thiamine, cofactor in carbohydrate metabolism, deficiency causes beriberi and Wernicke-Korsakoff syndrome), B2 (riboflavin, cofactor in redox reactions, deficiency causes cheilitis, angular stomatitis), B3 (niacin, component of NAD/NADP, deficiency causes pellagra: dermatitis, diarrhoea, dementia), B5 (pantothenic acid, component of coenzyme A, deficiency rare), B6 (pyridoxine, cofactor in amino acid metabolism, neurotransmitter synthesis), B7 (biotin, cofactor in carboxylation reactions, deficiency causes dermatitis, alopecia), B9 (folate/folic acid, one-carbon transfer, essential for DNA synthesis and cell division, deficiency causes megaloblastic anaemia and neural tube defects in pregnancy), B12 (cobalamin, cofactor for methionine synthase and methylmalonyl-CoA mutase, requires intrinsic factor for absorption, deficiency causes megaloblastic anaemia and pernicious anaemia, subacute combined degeneration of spinal cord). Vitamin C (ascorbic acid): cofactor for collagen synthesis (hydroxylation of proline and lysine), neurotransmitter synthesis, antioxidant. Deficiency causes scurvy (bleeding gums, impaired wound healing, petechiae).

Minerals: calcium (bone formation, muscle contraction, nerve transmission, blood clotting; plasma Ca2+ 8.5–10.5 mg/dL, regulated by PTH, calcitonin, vitamin D), phosphorus (bone, ATP, nucleic acids, phospholipids), iron (haemoglobin, myoglobin, cytochromes; absorbed in duodenum as Fe2+ via DMT1, stored as ferritin/hemosiderin; transported by transferrin; deficiency causes microcytic hypochromic anaemia), iodine (thyroid hormone synthesis, deficiency causes goitre and hypothyroidism), sodium (extracellular cation, osmotic balance, nerve impulse transmission), potassium (intracellular cation, membrane potential, cardiac rhythm), magnesium (cofactor for ATP, enzyme function), zinc (cofactor for many enzymes, immune function, wound healing), fluoride (dental enamel, prevents caries), copper (cofactor for cytochrome c oxidase, superoxide dismutase; deficiency in Menkes disease, excess in Wilson’s disease), selenium (antioxidant via glutathione peroxidase), chromium (potentiates insulin action), manganese (cofactor for glycosyltransferases and antioxidant enzymes). Trace elements: essential in very small amounts, including cobalt (component of B12), molybdenum (cofactor for sulfite oxidase and xanthine oxidase).

Vitamin	Chemical Name(s)	Solubility	Dietary Sources	Deficiency Disease	Key Function
A	Retinol, retinal, retinoic acid	Fat	Carrots, liver, spinach, eggs	Night blindness, xerophthalmia	Vision, epithelial health, immunity
D	Cholecalciferol (D3), ergocalciferol (D2)	Fat	Sunlight, fish liver oils, fortified milk	Rickets (children), osteomalacia (adults)	Ca2+ & phosphate absorption, bone health
E	Tocopherol, tocotrienol	Fat	Nuts, seeds, vegetable oils, green leafy vegetables	Haemolytic anaemia, neuropathy	Antioxidant, membrane protection
K	Phylloquinone (K1), menaquinone (K2)	Fat	Green leafy vegetables, gut flora synthesis	Bleeding, prolonged PT	Clotting factor synthesis (II, VII, IX, X)
C	Ascorbic acid	Water	Citrus fruits, tomatoes, peppers, broccoli	Scurvy	Collagen synthesis, antioxidant, iron absorption
B1	Thiamine	Water	Whole grains, legumes, pork	Beriberi, Wernicke-Korsakoff syndrome	Carbohydrate metabolism (TPP cofactor)
B3	Niacin, nicotinamide	Water	Meat, fish, poultry, peanuts, whole grains	Pellagra (dermatitis, diarrhoea, dementia)	NAD/NADP synthesis, redox reactions
B9	Folate, folic acid	Water	Green leafy vegetables, legumes, fortified grains	Megaloblastic anaemia, neural tube defects	DNA synthesis, one-carbon metabolism
B12	Cobalamin	Water	Meat, fish, eggs, dairy (only animal sources)	Pernicious anaemia, subacute combined degeneration	DNA synthesis, myelin maintenance, methionine synthase

Enzyme	Source	Substrate	Product(s)	Optimum pH
Salivary amylase	Salivary glands	Starch	Maltose, dextrins	6.8
Pepsin	Stomach (chief cells)	Proteins	Peptides, proteoses	1.5–2.0
Trypsin	Pancreas	Proteins, peptides	Dipeptides, amino acids	7.8–8.4
Chymotrypsin	Pancreas	Proteins	Peptides	8.0
Pancreatic amylase	Pancreas	Starch	Maltose, glucose	7.0
Lipase	Pancreas	Triglycerides	Monoglycerides + fatty acids	7.5–8.0
Maltase	Intestinal brush border	Maltose	Glucose	5.5–7.0
Sucrase	Intestinal brush border	Sucrose	Glucose + fructose	5.5–7.0
Lactase	Intestinal brush border	Lactose	Glucose + galactose	5.5–7.0
Carboxypeptidase	Pancreas	Peptides	Amino acids	7.5–8.0

2. Breathing & Gas Exchange

Respiratory System Anatomy

The respiratory system is divided into the conducting zone (nostrils to terminal bronchioles) and the respiratory zone (respiratory bronchioles, alveolar ducts, alveoli). The lining has ciliated pseudostratified columnar epithelium with goblet cells, forming the mucociliary escalator.

Conducting Zone

External nostrils open into the nasal cavity divided by the septum. Nasal conchae create turbulent airflow for warming and humidification. The pharynx is divided into nasopharynx, oropharynx, and laryngopharynx. The larynx contains nine cartilages (thyroid, cricoid, epiglottis, arytenoids, corniculates, cuneiforms). The trachea (10–12 cm, C-shaped cartilages) bifurcates at the carina into right and left primary bronchi. The right bronchus is shorter, wider, and more vertical, making it the common site for foreign body aspiration. Bronchioles (diameter < 1 mm) lack cartilage and are regulated by autonomic innervation: sympathetic (β2, bronchodilation) and parasympathetic (muscarinic, bronchoconstriction). Anatomical dead space is about 150 mL.

Respiratory Zone

Respiratory bronchioles have scattered alveoli budding from walls, leading to alveolar ducts and alveolar sacs. About 300–500 million alveoli provide 70–100 m2 surface area. Type I pneumocytes (squamous, 95% of surface) facilitate gas exchange; type II pneumocytes (cuboidal) secrete pulmonary surfactant (dipalmitoylphosphatidylcholine, DPPC) that reduces surface tension and prevents alveolar collapse (Laplace’s law). The respiratory membrane (0.2–0.5 μm thick) consists of alveolar epithelium, fused basement membranes, and capillary endothelium.

Mechanism of Breathing

Breathing follows Boyle’s law: pressure is inversely proportional to volume at constant temperature.

Inspiration

An active process. The diaphragm (primary muscle) contracts and flattens. External intercostals elevate the ribs (pump-handle and bucket-handle movements). Thoracic volume increases, intrapleural pressure drops from −2.5 to −6 mmHg, and air flows in until alveolar pressure equals atmospheric pressure. Accessory muscles (scalene, sternocleidomastoid, pectoralis minor) assist during forced inspiration. Tidal volume is about 500 mL.

Expiration

Normal expiration is passive: inspiratory muscles relax, elastic recoil decreases thoracic volume, intrapleural pressure returns to −2.5 mmHg, and air flows out. Forced expiration involves internal intercostals and abdominal muscles (rectus abdominis, obliques). Lung elasticity depends on elastin fibres; loss in emphysema causes difficulty exhaling.

Gas Exchange & Transport

Alveolar PO2 is 104 mmHg vs deoxygenated blood PO2 of 40 mmHg, creating a steep gradient for O2. Alveolar PCO2 is 40 mmHg vs blood PCO2 of 45 mmHg, driving CO2 diffusion. By equilibrium, pulmonary venous blood has PO2 104 mmHg and PCO2 40 mmHg.

Transport of Oxygen

Oxygen is transported as dissolved (1.5%) and bound to haemoglobin (98.5%). Haemoglobin is a tetramer (α2β2) with four haem groups (Fe2+). Cooperativity gives the oxyhaemoglobin dissociation curve its sigmoid shape. Oxygen capacity is about 20 vol% (15 g/dL Hb × 1.34 mL O2/g). The oxyhaemoglobin dissociation curve illustrates the relationship between PO2 and Hb saturation. At PO2 100 mmHg (alveoli), Hb is 98% saturated. At PO2 40 mmHg (tissues), Hb is 75% saturated, delivering about 5 mL O2 per 100 mL blood. The steep portion of the curve (PO2 20–60 mmHg) allows large O2 unloading with small changes in PO2. Right shift (decreased affinity, promotes O2 unloading to tissues) occurs with: increased temperature (exercise), decreased pH (Bohr effect, from CO2 production and lactic acid), and increased 2,3-bisphosphoglycerate (2,3-BPG, produced by RBCs in response to hypoxia, high altitude, anaemia). Left shift (increased affinity, reduces O2 unloading) occurs with: decreased temperature, increased pH (alkalosis), decreased 2,3-BPG, and carbon monoxide (CO has 200–250 times higher affinity for Hb than O2, shifting the curve left and reducing O2-carrying capacity). Fetal Hb (HbF, γ chains instead of β) has higher O2 affinity than adult Hb (HbA), facilitating O2 transfer across the placenta from maternal to fetal blood. Myoglobin (single polypeptide chain, monomer, found in muscle) has an even higher O2 affinity and a hyperbolic dissociation curve, serving as an O2 reserve in muscle tissue.

The Bohr effect describes the effect of pH and CO2 on Hb-O2 affinity: increased CO2 and H+ decrease Hb-O2 affinity (right shift). This is physiologically important because exercising tissues produce CO2 and lactic acid, promoting O2 unloading exactly where it is needed. The Haldane effect describes the effect of O2 on Hb-CO2 affinity: deoxygenated Hb binds more CO2 (carbaminohemoglobin) and more H+ (because deoxyHb is a weaker acid than oxyHb), facilitating CO2 uptake in tissues. In the lungs, oxygenation of Hb promotes CO2 release (the Haldane effect), while CO2 exhalation increases pH (the Bohr effect), both enhancing O2 loading. Carbon monoxide poisoning: CO binds to Hb with high affinity, reducing O2-carrying capacity and shifting the dissociation curve left, impairing O2 unloading. Treatment: 100% O2 or hyperbaric O2 therapy. Cyanide poisoning: inhibits cytochrome c oxidase (complex IV of the electron transport chain), blocking cellular O2 utilization despite normal O2 delivery.

Transport of Carbon Dioxide

CO2 is transported as dissolved (7%), bicarbonate (70%, catalyzed by carbonic anhydrase in RBCs: CO2 + H2O → H2CO3 → H+ + HCO3−), and carbaminohemoglobin (23%, HbNHCOO−). The chloride shift (HCO3− out of RBC in exchange for Cl−) maintains electroneutrality. The Haldane effect: deoxygenated Hb binds more CO2 and H+. In the lungs, the reverse reactions occur. Respiratory quotient (RQ) = CO2 produced / O2 consumed: 1.0 for carbs, 0.7 for fats, 0.8 for proteins. Hypoxia: deficiency of O2 at the tissue level. Hypoxaemia: low PO2 in arterial blood (normal: 80–100 mmHg). Hypercapnia: elevated PCO2 (> 45 mmHg). Hypocapnia: low PCO2 (< 35 mmHg, from hyperventilation). Chemoreceptors: peripheral (carotid and aortic bodies, sensitive to PO2, PCO2, pH) and central (medullary chemoreceptors, sensitive to PCO2 via changes in CSF pH, responsible for 70–80% of ventilatory drive).

Ventilation-Perfusion Matching & Pulmonary Circulation

Efficient gas exchange requires matching of ventilation (V, air reaching alveoli) and perfusion (Q, blood flow through pulmonary capillaries). The ideal V/Q ratio is about 0.8–1.2 (alveolar ventilation is ~4 L/min, cardiac output is ~5 L/min). In the upright lung, both ventilation and perfusion increase from apex to base, but the gradient is steeper for perfusion. At the apex, V/Q is high (~3.3, “wasted ventilation” or alveolar dead space); at the base, V/Q is low (~0.6, “shunt” effect or physiologic shunt). The lung compensates for V/Q mismatch by hypoxic pulmonary vasoconstriction: low alveolar PO2 causes local vasoconstriction, redirecting blood flow to better-ventilated regions, optimizing V/Q matching. This mechanism is unique to the pulmonary circulation (in systemic circulation, hypoxia causes vasodilation). Pulmonary circulation is a low-pressure, low-resistance system: pulmonary artery pressure is ~25/10 mmHg (mean ~15 mmHg), compared to systemic ~120/80 mmHg. Pulmonary vascular resistance is about 1/10 of systemic resistance. Factors affecting pulmonary vascular resistance: lung volume (lowest at FRC), hypoxia (increases via hypoxic vasoconstriction), acidosis (increases), and recruitment/distension of capillaries (decreases during exercise). Pulmonary oedema: fluid accumulation in the interstitial space and alveoli due to increased pulmonary capillary pressure (e.g., left heart failure) or increased permeability (e.g., ARDS, acute respiratory distress syndrome), impairing gas exchange causing hypoxaemia and crackles on auscultation. Deep vein thrombosis (DVT) can lead to pulmonary embolism (PE): a blood clot lodges in the pulmonary artery, causing V/Q mismatch, hypoxaemia, and potentially right heart strain (cor pulmonale) or death.

Respiratory Volumes & Capacities

Tidal volume (TV) = 500 mL. Inspiratory reserve volume (IRV) = 3000–3300 mL. Expiratory reserve volume (ERV) = 1000–1200 mL. Residual volume (RV) = 1100–1200 mL (cannot be measured by spirometry). Vital capacity (VC = TV + IRV + ERV) = 4500–4800 mL. Total lung capacity (TLC = VC + RV) = 5700–6000 mL. Inspiratory capacity (IC = TV + IRV) = 3500–3800 mL. Functional residual capacity (FRC = ERV + RV) = 2100–2400 mL. Minute ventilation = TV × RR = 6 L/min. Alveolar ventilation = (TV − dead space) × RR = 4.2 L/min.

Volume / Capacity	Abbreviation	Value (mL)	Definition
Tidal Volume	TV	500	Air per normal breath
Inspiratory Reserve Volume	IRV	3000–3300	Additional air forcibly inhaled after normal breath
Expiratory Reserve Volume	ERV	1000–1200	Additional air forcibly exhaled after normal breath
Residual Volume	RV	1100–1200	Air remaining after maximal exhalation
Vital Capacity	VC	4500–4800	TV + IRV + ERV
Total Lung Capacity	TLC	5700–6000	VC + RV
Inspiratory Capacity	IC	3500–3800	TV + IRV
Functional Residual Capacity	FRC	2100–2400	ERV + RV

Disorders of the Respiratory System

Asthma: reversible bronchoconstriction, airway inflammation, triggered by allergens. Emphysema: alveolar wall destruction, loss of elastic fibres, air trapping, barrel chest, increased RV and FRC, caused by smoking. Chronic bronchitis: cough with sputum for ≥ 3 months in 2 consecutive years, mucus gland hypertrophy. Pneumonia: alveolar infection with consolidation (Streptococcus pneumoniae most common). Pulmonary fibrosis: interstitial thickening, reduced compliance. Occupational diseases: silicosis (silica), asbestosis (asbestos), coal worker’s pneumoconiosis.

3. Body Fluids & Circulation

Blood & Its Components

Blood is a connective tissue with plasma (55%) and formed elements (45%). Total blood volume is 5–6 L (70–80 mL/kg). Functions: transport, regulation (pH, temperature, fluid balance), and protection (clotting, immunity).

Plasma

Plasma is 90–92% water with 8–10% solutes. Plasma proteins (7–8 g/dL): albumin (4.5–5 g/dL, maintains colloid osmotic pressure ~25 mmHg), globulins (2.5–3.5 g/dL, immunoglobulins and carrier proteins), fibrinogen (0.3 g/dL, clotting). Serum is plasma without clotting factors. Electrolytes: Na+, K+, Ca2+, Mg2+, Cl−, HCO3−. Plasma oncotic pressure opposes hydrostatic pressure in capillaries.

Formed Elements

Erythrocytes (RBCs, 4.5–5.5 million/mm3) are biconcave discs (7.5 μm) without nucleus, maximizing haemoglobin space (~280 million Hb molecules per RBC). Lifespan is 120 days; removed by macrophages in spleen and liver. Erythropoiesis is stimulated by erythropoietin (EPO) from kidneys. Haemoglobin breaks down into globin (recycled), iron (recycled via transferrin), and haem (converted to biliverdin → bilirubin).

Leukocytes (4000–11000/mm3): neutrophils (40–70%, phagocytes, multilobed nucleus), eosinophils (1–4%, anti-parasitic, allergic), basophils (0.5–1%, release histamine and heparin), lymphocytes (20–40%, B cells for antibodies, T cells for cellular immunity), monocytes (2–8%, differentiate into macrophages). Platelets (1.5–4.5 × 105/mm3, derived from megakaryocytes, lifespan 7–10 days, essential for haemostasis).

Cell Type	Count (per mm3)	Lifespan	Primary Function	Nucleus
Erythrocyte	4.5–5.5 million	120 days	O2 and CO2 transport	Absent
Neutrophil	3000–7000	6–8 hours	Phagocytosis of bacteria	Multilobed
Eosinophil	100–400	8–12 days	Anti-parasitic, allergic	Bilobed
Basophil	20–50	1–2 days	Histamine, heparin release	Bilobed (S-shaped)
Lymphocyte	1500–4000	Days to years	Immune response (B, T)	Large, round
Monocyte	200–800	1–3 days	Macrophage precursor	Kidney-shaped
Platelet	1.5–4.5 lakhs	7–10 days	Haemostasis, clotting	Absent (fragment)

Heart Structure

The heart (300 g) is a four-chambered muscular organ in the mediastinum. The pericardium (fibrous and serous layers with pericardial fluid) encloses it. The heart wall has epicardium, myocardium, and endocardium. Chambers: right atrium (RA), right ventricle (RV), left atrium (LA), left ventricle (LV). Valves: tricuspid (RA→RV, 3 cusps), mitral/bicuspid (LA→LV, 2 cusps), pulmonary (RV→pulmonary trunk), aortic (LV→aorta). Chordae tendineae connect cusps to papillary muscles, preventing prolapse.

Cardiac Conduction System

SA node (natural pacemaker, 70–80/min in RA near superior vena cava). AV node (delays impulse 0.1 sec, in interatrial septum). Bundle of His, right/left bundle branches, Purkinje fibres. Intrinsic rates: SA node 60–100/min, AV node 40–60/min, Purkinje 15–40/min. Cardiac muscle fibres are striated, branched, with intercalated discs (gap junctions) forming a functional syncytium.

Cardiac Cycle

The cardiac cycle lasts 0.8 sec (HR 75/min). Atrial systole (0.1 sec): atria contract, filling ventricles with ~20% additional blood. Ventricular systole (0.3 sec): isovolumetric contraction (AV valves close = S1 “lub”), then ejection (semilunar valves open). Ventricular diastole (0.5 sec): isovolumetric relaxation (semilunar valves close = S2 “dub”), then rapid and slow filling. EDV = 120–130 mL, ESV = 50–60 mL, SV = EDV − ESV = ~70 mL. Cardiac output = SV × HR = ~5 L/min. Ejection fraction = SV/EDV = 55–70%. Heart sounds: S1 (AV valve closure, apex), S2 (semilunar valve closure, base), S3 (ventricular filling, normal in children), S4 (atrial contraction against stiff ventricle).

Blood Vessels

Arteries: thick walls with tunica intima, media (smooth muscle, elastic fibres), and adventitia. Elastic arteries (aorta) stretch during systole and recoil during diastole (windkessel effect). Arterioles are resistance vessels regulating peripheral resistance and BP. Capillaries (5–10 μm) are exchange vessels: continuous (muscle, skin), fenestrated (kidneys, intestines), sinusoidal (liver, spleen). Veins are capacitance vessels (65% of blood volume) with one-way valves. Venous return aided by skeletal muscle pump, respiratory pump, and valves.

Portal System

Hepatic portal vein (superior mesenteric + splenic veins) carries blood from GI tract to liver for processing. Hypophyseal portal system connects hypothalamus to anterior pituitary for releasing/inhibiting hormones.

Lymphatic System

The lymphatic system is a network of lymphatic vessels, lymph nodes, and lymphoid organs (spleen, thymus, tonsils, Peyer’s patches). Lymph (derived from interstitial fluid, similar to plasma but with lower protein content) is collected by lymphatic capillaries (with one-way flap valves and anchoring filaments). Lymphatic vessels have valves and smooth muscle, propelling lymph towards the thoracic duct (drains left upper body and lower body, empties into the left subclavian vein) and the right lymphatic duct (drains right upper body, empties into the right subclavian vein). Functions: (1) returns interstitial fluid and proteins to the bloodstream (about 3 L/day, maintaining fluid balance), (2) transports absorbed dietary fats (chylomicrons from intestinal lacteals), (3) immune surveillance (lymph nodes filter lymph, contain B and T lymphocytes, dendritic cells, macrophages). Lymphoedema: swelling due to lymphatic obstruction (e.g., filariasis by Wuchereria bancrofti, surgical lymph node dissection).

Haemostasis & Blood Coagulation

Haemostasis (stopping blood loss from a damaged vessel) involves three stages: (1) vascular spasm (immediate vasoconstriction of damaged vessel, mediated by endothelin, lasts minutes), (2) platelet plug formation (platelet adhesion to exposed collagen via von Willebrand factor, platelet activation releasing ADP, thromboxane A2, serotonin, and platelet aggregation forming a temporary plug), (3) coagulation (conversion of soluble fibrinogen into insoluble fibrin by thrombin, stabilizing the plug). The coagulation cascade has intrinsic (contact activation, all factors in blood, slower) and extrinsic (tissue factor from damaged endothelium, faster) pathways, both converging at factor X → Xa (common pathway).

Coagulation factors are designated by Roman numerals (I–XIII). The cascade: intrinsic pathway (factors XII, XI, IX, VIII) is initiated by contact with negatively charged surfaces; extrinsic pathway (factor VII and tissue factor) is initiated by vascular damage. Both activate factor X (Stuart-Prower factor), which, with factor Va, Ca2+, and platelet phospholipids (prothrombinase complex), converts prothrombin (factor II) to thrombin (factor IIa). Thrombin then converts fibrinogen (factor I) to fibrin (factor Ia) and activates factor XIII (fibrin-stabilizing factor), which cross-links fibrin monomers into a stable mesh. Thrombin also amplifies coagulation by activating factors V, VIII, and XI (positive feedback). Anticoagulants: protein C and S (inactivate factors Va and VIIIa), antithrombin III (inhibits thrombin, factor Xa, and others, potentiated by heparin), tissue factor pathway inhibitor (TFPI). Fibrinolysis: plasminogen is activated to plasmin by tissue plasminogen activator (t-PA), and plasmin digests fibrin into fibrin degradation products (D-dimer). Vitamin K is essential for the hepatic synthesis of factors II, VII, IX, X, protein C, and protein S (warfarin inhibits vitamin K-dependent carboxylation). Haemophilia A: factor VIII deficiency (X-linked recessive, prolonged intrinsic pathway PT and aPTT, normal extrinsic pathway PT). Haemophilia B (Christmas disease): factor IX deficiency. Clotting disorders from vitamin K deficiency: prolonged PT and aPTT. Disseminated intravascular coagulation (DIC): pathological widespread coagulation with consumption of clotting factors and bleeding.

Coagulation Pathway	Initiator	Key Factors	Test
Intrinsic	Contact activation (collagen, glass)	XII, XI, IX, VIII, prekallikrein, HMWK	aPTT (activated partial thromboplastin time)
Extrinsic	Tissue factor (thromboplastin)	VII	PT (prothrombin time)
Common	Factor X activation	X, V, II (prothrombin), I (fibrinogen), XIII	PT and aPTT both prolonged

ECG & Cardiac Arrhythmias

The electrocardiogram (ECG/EKG) records the electrical activity of the heart from the body surface. Standard 12-lead ECG uses 10 electrodes: limb leads (I, II, III, aVR, aVL, aVF) and precordial/chest leads (V1–V6). Lead II (right arm to left leg) is most commonly used for rhythm monitoring. ECG waves and intervals: P wave (atrial depolarization, duration 0.08–0.1 sec, amplitude < 0.25 mV), QRS complex (ventricular depolarization, duration 0.06–0.1 sec, amplitude variable), T wave (ventricular repolarization, 0.16–0.2 sec). The U wave (small deflection after T wave) represents late repolarization of the Purkinje fibres; prominent U waves occur in hypokalemia. Intervals: PR interval (0.12–0.20 sec, from start of P to start of QRS, represents AV conduction time), QT interval (0.35–0.45 sec, from start of QRS to end of T, corrected for heart rate as QTc = QT / √(RR interval in seconds)), ST segment (from J point to start of T wave, normally isoelectric). ECG interpretation: heart rate (300 divided by number of large squares between R waves, or 1500 divided by number of small squares). Rhythm (regular vs irregular). Axis (normal −30° to +90°). Wave morphology (P wave shape, QRS width, ST changes, T wave inversion).

ECG changes in disease: ST elevation myocardial infarction (STEMI): ST elevation ≥ 1 mm in two contiguous leads, with reciprocal ST depression, T wave inversion, and pathological Q waves (marker of completed infarction). Non-STEMI (NSTEMI): ST depression or T wave inversion without ST elevation, elevated troponin. Angina: ST depression during pain, reversible. Pericarditis: diffuse ST elevation with PR depression, concave upward ST shape. Atrial fibrillation: irregularly irregular rhythm, absent P waves, narrow QRS, “irregularly irregular” pulse. Atrial flutter: sawtooth flutter waves (F waves) at 250–350/min with variable AV block (most commonly 2:1). Ventricular tachycardia (VT): wide QRS (> 0.12 sec), rate 100–250/min, can be monomorphic or polymorphic (torsades de pointes). Ventricular fibrillation (VF): chaotic rhythm, no recognizable QRS, cardiac arrest requiring defibrillation. First-degree AV block: PR interval > 0.20 sec (prolonged AV conduction). Second-degree AV block Mobitz type I (Wenckebach): progressive PR prolongation followed by a dropped QRS. Second-degree AV block Mobitz type II: constant PR interval with intermittent dropped QRS (often progresses to complete heart block). Third-degree AV block (complete heart block): complete dissociation of P waves and QRS complexes, atrial rate > ventricular rate (junctional or ventricular escape rhythm). Bundle branch block: wide QRS > 0.12 sec with characteristic morphology in V1 and V6 (RSR′ in V1 for right BBB, deep S in V1 and broad R in V6 for left BBB). Electrolyte effects: hyperkalemia (peaked T waves, widened QRS, sine wave pattern, cardiac arrest), hypokalemia (U waves, ST depression, T wave flattening), hypercalcemia (short QT), hypocalcemia (prolonged QT).

Blood Pressure Regulation & Hypertension

Blood pressure (BP) is determined by cardiac output (CO) and total peripheral resistance (TPR): BP = CO × TPR. Normal BP is < 120/80 mmHg. Systolic BP is the peak arterial pressure during ventricular systole; diastolic BP is the minimum arterial pressure during ventricular diastole. Pulse pressure (systolic − diastolic, normally ~40 mmHg) reflects stroke volume and arterial compliance (widened in aortic regurgitation, atherosclerosis; narrowed in aortic stenosis, shock). Mean arterial pressure (MAP = diastolic + 1/3 pulse pressure, normally ~93 mmHg) is the average pressure driving blood flow to organs. BP is regulated by: (1) short-term (seconds to minutes): baroreceptor reflex (carotid sinus and aortic arch baroreceptors detect stretch, afferent via CN IX and X to the medulla, efferent sympathetic and parasympathetic to adjust HR, contractility, and vessel diameter), chemoreceptor reflex, and atrial stretch receptors; (2) intermediate-term (minutes to hours): RAAS (renin → angiotensin II → aldosterone, vasoconstriction and volume expansion), ADH (vasopressin, water retention and vasoconstriction), and capillary fluid shift (Starling forces); (3) long-term (days to weeks): renal regulation of blood volume (pressure-natriuresis mechanism, where increased BP causes increased Na+ and water excretion, lowering blood volume). Hypertension (persistent BP ≥ 140/90 mmHg) is classified as primary/essential (90–95%, multifactorial: genetic, dietary salt, obesity, stress) or secondary (5–10%, due to renal artery stenosis, CKD, hyperaldosteronism/Conn’s syndrome, phaeochromocytoma, Cushing’s syndrome, coarctation of aorta, sleep apnoea). Complications of hypertension: left ventricular hypertrophy, heart failure, coronary artery disease, stroke (both ischaemic and haemorrhagic), chronic kidney disease, retinopathy, aortic dissection. Treatment: lifestyle modification (salt restriction, exercise, weight loss), antihypertensive drugs (ACE inhibitors, ARBs, calcium channel blockers, diuretics, beta-blockers).

Cardiovascular Disorders

Coronary artery disease (CAD): atherosclerosis of coronary arteries due to plaque formation (lipid core with fibrous cap). Risk factors: smoking, hypertension, hyperlipidaemia, diabetes, obesity, family history, sedentary lifestyle. Acute coronary syndrome (ACS): unstable angina, NSTEMI, STEMI. Diagnosis: ECG, troponin (cardiac-specific, highly sensitive and specific for myocardial injury), CK-MB. Treatment: antiplatelet therapy (aspirin, P2Y12 inhibitors), statins, beta-blockers, ACE inhibitors, revascularization (PCI with stent, CABG). Heart failure: impaired cardiac pump function (systolic: reduced ejection fraction < 40%; diastolic: preserved ejection fraction with impaired filling). Causes: CAD, hypertension, valvular disease, cardiomyopathy, arrhythmias. Symptoms: dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, fatigue, peripheral oedema, raised JVP, lung crackles. Neurohormonal activation in HF: sympathetic activation, RAAS activation, and ADH release (initially compensatory, then maladaptive, causing remodelling). Treatment: diuretics (relieve congestion), ACE inhibitors/ARBs, beta-blockers, spironolactone, SGLT2 inhibitors. Valvular heart disease: aortic stenosis (narrowed valve, LV pressure overload, systolic ejection murmur), aortic regurgitation (leaky valve, volume overload, diastolic murmur), mitral regurgitation (systolic murmur at apex), mitral stenosis (diastolic murmur, opening snap, atrial fibrillation risk). Infective endocarditis: infection of the heart valves (Streptococcus viridans, Staphylococcus aureus), causing vegetations, emboli, fever, and heart murmur. Rheumatic heart disease: autoimmune complication of group A streptococcal pharyngitis (molecular mimicry between M protein and cardiac antigens), causing pancarditis and valvular damage (especially mitral stenosis). Cardiomyopathies: dilated (LV dilation, systolic dysfunction, most common), hypertrophic (LV hypertrophy, diastolic dysfunction, autosomal dominant sarcomere mutations, risk of sudden cardiac death in young athletes), restrictive (stiff ventricular walls, impaired filling). Peripheral arterial disease (PAD): atherosclerosis in leg arteries, causing claudication (leg pain with walking, relieved by rest), critical limb ischaemia (rest pain, ulcers, gangrene). Deep vein thrombosis (DVT): clot formation in deep veins (leg), risk of pulmonary embolism; Virchow’s triad: stasis, hypercoagulability, endothelial injury.

4. Excretory System

Human Excretory System

The system includes a pair of kidneys, ureters, urinary bladder, and urethra. Kidneys are bean-shaped (10–12 cm, 120–170 g) located retroperitoneally at T12–L3; the right kidney is slightly lower. The kidney is protected by renal fascia, perirenal fat, and fibrous capsule. The renal hilum (medial) transmits renal artery, vein, and ureter. Internally: outer cortex, inner medulla (8–15 renal pyramids), and renal pelvis. Each kidney has about 1–1.5 million nephrons (functional units).

Ureters, Bladder & Urethra

Ureters (25–30 cm) transport urine via peristalsis, entering the bladder obliquely to prevent reflux. The bladder (capacity 400–600 mL) has transitional epithelium (urothelium) and detrusor muscle. Male urethra (18–20 cm, prostatic, membranous, penile) also conducts semen. Female urethra (3–4 cm) opens anterior to vaginal opening.

Nephron Structure

The nephron has the renal corpuscle (glomerulus + Bowman’s capsule) and renal tubule (PCT, loop of Henle, DCT, collecting duct). The glomerular filtration membrane consists of fenestrated endothelium, basement membrane (negatively charged, repels albumin), and podocyte slit diaphragm (nephrin). Cortical nephrons (85%) have short loops; juxtamedullary nephrons (15%) have long loops essential for countercurrent multiplication. The juxtaglomerular apparatus (JGA) includes JG cells (renin secretion), macula densa (senses NaCl), and extraglomerular mesangial cells. JGA regulates the renin-angiotensin-aldosterone system (RAAS).

Urine Formation

Three processes: glomerular filtration, tubular reabsorption, and tubular secretion. GFR = 125 mL/min (180 L/day); urine output is only 1–1.5 L/day (99% reabsorption).

Glomerular Filtration

Driven by glomerular hydrostatic pressure (60 mmHg) opposed by plasma colloid osmotic pressure (32 mmHg) and Bowman’s capsule pressure (18 mmHg). Net filtration pressure = 60 − (32 + 18) = 10 mmHg. Filtration fraction = GFR/renal plasma flow = 20%. Substances < 15 kDa freely filtered; > 70 kDa not filtered. GFR regulated by autoregulation (myogenic response, tubuloglomerular feedback), sympathetic nerves, and hormones (angiotensin II, ANP).

Tubular Reabsorption

PCT reabsorbs 65–70% of filtered Na+, Cl−, water (obligatory via aquaporins), glucose (SGLT2, Tm ~375 mg/min), amino acids, bicarbonate (90%, via Na+/H+ exchange and carbonic anhydrase), phosphate, and urate. The thin descending loop is water-permeable; water moves out passively. The thick ascending loop actively reabsorbs Na+/K+/2Cl− (NKCC2, blocked by furosemide) and is water-impermeable (diluting segment). DCT reabsorbs Na+ and Cl− (NCC, blocked by thiazides). The collecting duct reabsorbs Na+ (ENaC, stimulated by aldosterone) and secretes K+ (ROMK). ADH (vasopressin) inserts aquaporin-2 in the collecting duct for variable water reabsorption. Urea recycling contributes to medullary osmolality.

Segment	Reabsorbs	Secretes	Hormonal Regulation
PCT	Na+, Cl−, HCO3−, water, glucose, amino acids	H+, NH3, organic acids	PTH (phosphate), SGLT2
Thin descending loop	Water	—	—
Thick ascending loop	Na+, K+, Cl−, Ca2+, Mg2+	—	—
DCT	Na+, Cl−, Ca2+	—	PTH (Ca2+), aldosterone
Collecting duct (principal)	Na+, water (with ADH)	K+	Aldosterone (Na+), ADH (water)
Collecting duct (intercalated)	K+, HCO3−	H+	—

Tubular Secretion

PCT secretes H+ (NHE3), organic anions and cations (OAT, OCT). Collecting duct secretes K+ (ROMK) and H+ (H+-ATPase). H+ secretion titrates HCO3− (bicarbonate reclaiming) or is buffered by NH3 (from glutamine) to form NH4+, or by phosphate (titratable acidity). The kidney excretes 40–80 mEq of acid/day.

Countercurrent Mechanism

The loop of Henle acts as a countercurrent multiplier: the thick ascending limb actively transports salts out while remaining water-impermeable, creating a medullary osmotic gradient (up to 1200 mOsm/L). The thin descending limb concentrates tubular fluid by water loss. The vasa recta acts as a countercurrent exchanger, preserving the gradient. Urea recycling (UT-A1, UT-A2, UT-B transporters) contributes 40–50% of medullary osmolality.

Micturition

The bladder fills (first sensation at 200–400 mL) while the detrusor relaxes (β3-adrenergic) and internal sphincter contracts (α1-adrenergic). The micturition reflex is coordinated by the pontine micturition centre. Stretch receptors send afferent signals via pelvic nerves (S2–S4). Efferent parasympathetic signals cause detrusor contraction and internal sphincter relaxation. External sphincter relaxation (pudendal nerve, voluntary) permits voiding. In infants, the reflex is purely spinal.

Regulation of Kidney Function: RAAS & ADH

The renin-angiotensin-aldosterone system (RAAS) is a hormone system that regulates blood pressure, blood volume, and electrolyte balance. When blood pressure falls, renal perfusion decreases, and the juxtaglomerular cells (in the afferent arteriole wall) secrete renin (a proteolytic enzyme). Renin acts on angiotensinogen (a plasma protein produced by the liver, α2-globulin) to form angiotensin I (decapeptide, inactive). Angiotensin-converting enzyme (ACE, present in pulmonary and renal endothelial cells) cleaves angiotensin I to angiotensin II (octapeptide, active). Angiotensin II has multiple actions: (1) potent vasoconstriction (increases TPR and BP), (2) stimulates aldosterone secretion from the adrenal cortex (zona glomerulosa), which increases Na+ and water reabsorption in the collecting duct (expanding blood volume), (3) stimulates ADH release from the posterior pituitary (increases water reabsorption), (4) stimulates thirst (hypothalamus), (5) increases sympathetic outflow, (6) constricts efferent arterioles in the kidney (maintains GFR despite low BP). ACE inhibitors (e.g., captopril, lisinopril) block RAAS and are used for hypertension and heart failure. Angiotensin II receptor blockers (ARBs, e.g., losartan) block AT1 receptors.

Antidiuretic hormone (ADH, vasopressin) is a 9-amino-acid peptide synthesized in the hypothalamus (supraoptic and paraventricular nuclei) and released from the posterior pituitary. Its primary stimulus is increased plasma osmolality (> 280–285 mOsm/L, detected by osmoreceptors in the hypothalamus). Other stimuli: decreased blood volume (> 10% drop, detected by atrial and carotid baroreceptors), angiotensin II, nausea, pain, and stress. ADH acts on V2 receptors in the principal cells of the collecting duct, activating adenylyl cyclase, increasing cAMP, and inserting aquaporin-2 (AQP2) water channels into the apical membrane, increasing water permeability and reabsorption. V1 receptors on vascular smooth muscle cause vasoconstriction (only at high concentrations). ADH deficiency (central or neurogenic diabetes insipidus) causes dilute polyuria and polydipsia; nephrogenic diabetes insipidus results from ADH receptor (V2) or AQP2 mutations (kidney unresponsive to ADH). Atrial natriuretic peptide (ANP) is released from atrial myocytes in response to increased atrial stretch (high blood volume). ANP opposes RAAS: it dilates afferent arterioles, increases GFR, inhibits Na+ reabsorption in the collecting duct, and inhibits renin, aldosterone, and ADH secretion, promoting Na+ and water excretion and lowering blood volume.

Acid-Base Balance by the Kidney

The kidney maintains blood pH within the narrow range of 7.35–7.45 by excreting acid (H+) and reclaiming bicarbonate (HCO3−). The three main mechanisms: (1) HCO3− reclamation in the PCT: filtered HCO3− combines with secreted H+ (via NHE3) to form H2CO3, which is split by carbonic anhydrase (CA-IV, brush border) into CO2 and water; CO2 diffuses into the cell and is rehydrated by CA-II to H2CO3, which dissociates into HCO3− (transported into blood) and H+ (re-secreted). This reclaims 80–90% of filtered HCO3−. (2) Titratable acid excretion: H+ is buffered in the urine by phosphate (HPO42− + H+ → H2PO4−) and other buffers (creatinine, urate). (3) NH3/NH4+ excretion: the PCT metabolizes glutamine to produce NH3 and α-ketoglutarate. NH3 diffuses into the tubular lumen and combines with H+ to form NH4+ (trapped and excreted). This mechanism is upregulated in chronic acidosis (renal ammoniagenesis increases). Metabolic acidosis (low blood pH, low HCO3−) can be caused by diabetic ketoacidosis, lactic acidosis, renal failure, diarrhoea. Metabolic alkalosis (high pH, high HCO3−) can be caused by vomiting, diuretic use, mineralocorticoid excess. Respiratory compensation: hyperventilation (low PCO2) for metabolic acidosis; hypoventilation (high PCO2) for metabolic alkalosis.

Disorders of Excretory System

Renal calculi (calcium oxalate stones, renal colic). Glomerulonephritis (haematuria, proteinuria, hypertension). Uremia: accumulation of urea and creatinine, electrolyte imbalances. Acute renal failure (prerenal, intrinsic, postrenal). CKD (diabetes and hypertension). Dialysis (haemodialysis or peritoneal dialysis) replaces kidney function. Kidney transplantation is definitive for ESRD. Urinary tract infections (UTI): cystitis (bladder infection, dysuria, frequency), pyelonephritis (kidney infection, flank pain, fever). Nephrotic syndrome: massive proteinuria, hypoalbuminemia, oedema, hyperlipidemia. Polycystic kidney disease: autosomal dominant (ADPKD) or recessive, multiple cysts, hypertension, renal failure. Renal artery stenosis: causes secondary hypertension due to increased renin. Fanconi syndrome: generalized PCT dysfunction, causing glycosuria, aminoaciduria, phosphaturia, bicarbonaturia.

5. Nervous System

Structure of Neuron

The neuron is the structural and functional unit of the nervous system, specialized for receiving, conducting, and transmitting electrical signals. A typical neuron has three parts: the cell body (soma or perikaryon), dendrites, and an axon. The cell body contains the nucleus, Nissl granules (rough endoplasmic reticulum), neurofibrils, and other organelles. Dendrites are short, highly branched processes that receive signals from other neurons and conduct them toward the cell body. The axon is a single, long process (up to 1 metre in motor neurons) that conducts nerve impulses away from the cell body to other neurons, muscles, or glands. The axon hillock is the site of action potential initiation (trigger zone).

Myelinated axons are covered by a myelin sheath formed by Schwann cells (PNS) or oligodendrocytes (CNS). Myelination increases conduction velocity via saltatory conduction at the nodes of Ranvier, where voltage-gated Na+ channels are concentrated. Conduction velocity is proportional to axon diameter and degree of myelination: large myelinated A fibres (50–120 m/s), small unmyelinated C fibres (0.5–2 m/s).

Types of Neurons

Structurally: multipolar (one axon, multiple dendrites, most common in CNS), bipolar (one axon, one dendrite, retina, olfactory epithelium, inner ear), pseudounipolar (single process dividing into two branches, dorsal root ganglia). Functionally: sensory (afferent, receptors to CNS), motor (efferent, CNS to effectors), interneurons (association, connecting sensory and motor, 99% of all neurons).

Central Nervous System

The CNS consists of the brain (cranial cavity) and spinal cord (vertebral canal). Protected by three meninges: dura mater (outer), arachnoid mater (middle, web-like), pia mater (inner, vascular). Subarachnoid space contains cerebrospinal fluid (CSF). The brain is divided into forebrain, midbrain, and hindbrain.

Forebrain

The forebrain includes the cerebrum (85% of brain weight), thalamus, hypothalamus, and limbic system. The cerebrum has two hemispheres connected by the corpus callosum (~200 million fibres). Each hemisphere has four lobes: frontal (motor, executive function, personality), parietal (somatosensory, spatial), temporal (auditory, memory, language comprehension), and occipital (visual). The cerebral cortex (2–4 mm, 6 layers) contains grey matter; inner white matter has myelinated axons. Brodmann areas correspond to specific functions: primary motor cortex (precentral gyrus, area 4), primary somatosensory (postcentral gyrus, areas 1–3), primary visual (calcarine sulcus, area 17), Broca’s area (44–45, motor speech), Wernicke’s area (22, language comprehension).

The thalamus relays sensory information (except olfaction) to the cortex. The hypothalamus regulates temperature, hunger, thirst, sleep-wake cycles, and endocrine function. The limbic system (cingulate gyrus, hippocampus, amygdala) processes emotion, learning, and memory. The basal ganglia (caudate, putamen, globus pallidus, substantia nigra, subthalamic nucleus) regulate motor planning.

Midbrain

The midbrain contains the cerebral aqueduct, superior colliculi (visual reflexes), inferior colliculi (auditory reflexes, startle response), red nucleus (motor coordination), substantia nigra (dopamine; degeneration causes Parkinson’s disease), and cerebral peduncles (motor tracts).

Hindbrain

The hindbrain includes the pons, cerebellum, and medulla oblongata. The pons contains nuclei for cranial nerves V–VIII, pneumotaxic centre (limits inspiration), and apneustic centre (promotes inspiration). The cerebellum (10% of brain mass, 50% of neurons) coordinates voluntary movement, balance, and motor learning; it has the spinocerebellum (posture), cerebrocerebellum (fine movements), and vestibulocerebellum (balance, eye movements). The medulla oblongata (3 cm) contains the cardiac centre, vasomotor centre, respiratory centre, and reflex centres (coughing, sneezing, swallowing, vomiting). The decussation of pyramids (85–90% of corticospinal fibres cross) is located here.

Spinal Cord

The spinal cord (45 cm long) extends from the foramen magnum (C1) to conus medullaris (L1–L2). It has 31 pairs of spinal nerves: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal. Cross-section: central canal (CSF), grey matter (dorsal horn sensory, ventral horn motor, lateral horn autonomic), white matter (ascending and descending tracts). Ascending tracts: dorsal column-medial lemniscus (fine touch, vibration, proprioception), spinothalamic (pain, temperature, crude touch), spinocerebellar. Descending tracts: corticospinal (voluntary movement), rubrospinal (flexor tone), reticulospinal (antigravity reflexes).

Brain Region	Major Structures	Primary Functions
Forebrain	Cerebrum, thalamus, hypothalamus, limbic system, basal ganglia	Cognition, sensation, voluntary movement, emotion, homeostasis
Midbrain	Superior/inferior colliculi, substantia nigra, red nucleus	Visual & auditory reflexes, motor coordination
Pons	Pontine nuclei, respiratory centres	Bridge between cerebrum and cerebellum, respiration
Medulla	Cardiac, vasomotor, respiratory centres; pyramids	Heart rate, BP, breathing, reflexes
Cerebellum	Hemispheres, vermis, flocculonodular lobe	Coordination, balance, motor learning, muscle tone

Peripheral Nervous System

The PNS has 12 pairs of cranial nerves (from the brain) and 31 pairs of spinal nerves (from the spinal cord). Functionally: somatic (voluntary, skeletal muscles) and autonomic (involuntary, smooth/cardiac muscle, glands).

Cranial Nerves

CN I (olfactory, sensory, smell), II (optic, sensory, vision), III (oculomotor, motor, eye movements, pupil), IV (trochlear, motor, superior oblique), V (trigeminal, mixed, face sensation, mastication), VI (abducens, motor, lateral rectus), VII (facial, mixed, facial expression, taste anterior 2/3 tongue), VIII (vestibulocochlear, sensory, hearing, balance), IX (glossopharyngeal, mixed, taste posterior 1/3 tongue, parotid), X (vagus, mixed, parasympathetic to viscera, pharynx/larynx), XI (spinal accessory, motor, trapezius, sternocleidomastoid), XII (hypoglossal, motor, tongue muscles). Mnemonic: “Oh Oh Oh To Touch And Feel Very Green Vegetables So Heavenly!”

Autonomic Nervous System

Sympathetic (thoracolumbar, T1–L2): preganglionic fibres release ACh; postganglionic fibres release norepinephrine (except sweat glands and some blood vessels, which use ACh). Acts on α1, α2, β1, β2, β3 receptors. Adrenal medulla secretes epinephrine (80%) and norepinephrine (20%). Parasympathetic (craniosacral: CN III, VII, IX, X, S2–S4): both pre- and postganglionic fibres release ACh (nicotinic and muscarinic receptors). The enteric nervous system (myenteric and submucosal plexuses) functions independently.

Cerebrospinal Fluid & Blood-Brain Barrier

Cerebrospinal fluid (CSF) is a clear, colourless fluid (about 150 mL total volume in adults, produced at 500–600 mL/day) that fills the ventricles (lateral, third, fourth), central canal of the spinal cord, and subarachnoid space. CSF is produced by the choroid plexus (specialized ependymal cells with tight junctions, in the lateral, third, and fourth ventricles) by ultrafiltration and active secretion. CSF composition: low protein (15–45 mg/dL), low glucose (50–80 mg/dL, about 2/3 of blood glucose), high Na+ and Cl−, few cells (0–5 lymphocytes/mm3). CSF circulates from the lateral ventricles → interventricular foramina (of Monro) → third ventricle → cerebral aqueduct (of Sylvius) → fourth ventricle → median and lateral apertures (of Luschka and Magendie) → subarachnoid space, where it is absorbed into venous blood via the arachnoid granulations (Pacchionian granulations) into the superior sagittal sinus. Functions: (1) mechanical cushioning (the brain floats in CSF, reducing effective weight from 1500 g to about 50 g), (2) chemical buffering, (3) removal of waste (interstitial solutes cleared via the glymphatic system during sleep), (4) transport of hormones and nutrients. Hydrocephalus: excessive CSF accumulation due to impaired absorption or obstruction (e.g., aqueductal stenosis), causing ventricular enlargement and increased intracranial pressure. CSF analysis (lumbar puncture) is used to diagnose meningitis (increased WBCs, protein, decreased glucose in bacterial meningitis), subarachnoid haemorrhage (xanthochromia, increased RBCs), and multiple sclerosis (oligoclonal bands).

The blood-brain barrier (BBB) is a highly selective semipermeable barrier formed by cerebral capillary endothelial cells with tight junctions (claudins, occludins), supported by pericytes and astrocyte foot processes (the neurovascular unit). The BBB prevents the passage of large hydrophilic molecules, most proteins, and many drugs, while allowing small lipophilic molecules (O2, CO2, ethanol), glucose (via GLUT1), amino acids (via specific transporters), and some hormones. The blood-CSF barrier at the choroid plexus is formed by tight junctions between choroid plexus epithelial cells (not the capillary endothelial cells, which are fenestrated). Circumventricular organs (area postrema, subfornical organ, organum vasculosum of the lamina terminalis, median eminence, posterior pituitary) lack an intact BBB, allowing direct sensing of blood-borne substances (e.g., emetic chemoreceptor trigger zone in the area postrema allows detection of circulating toxins).

6. Endocrine System

Endocrine Glands & Their Hormones

The endocrine system consists of ductless glands that secrete hormones directly into the bloodstream. Hormones are chemical messengers classified as peptides/proteins (most pituitary, insulin, glucagon, PTH, calcitonin), steroids (cortisol, aldosterone, sex hormones, vitamin D), amines (T3, T4, catecholamines), and eicosanoids (prostaglandins). Major glands: hypothalamus, pituitary, pineal, thyroid, parathyroids, thymus, adrenals, pancreas, gonads.

Hypothalamus

The hypothalamus (4 g) is the master regulator. It produces releasing and inhibiting hormones for the anterior pituitary: TRH (stimulates TSH), CRH (stimulates ACTH), GnRH (stimulates LH, FSH), GHRH (stimulates GH), GHIH/somatostatin (inhibits GH), PIH/dopamine (inhibits prolactin). It also synthesizes ADH and oxytocin, transported via the hypothalamo-hypophyseal tract to the posterior pituitary. The hypothalamus integrates neural and endocrine signals via the HPA, HPT, and HPG axes.

Pituitary Gland

The pituitary (0.5–0.6 g) is in the sella turcica. Anterior pituitary (adenohypophysis, 80%): GH (somatotropin, 191 amino acids, stimulates growth, lipolysis, increases blood glucose), TSH (stimulates thyroid), ACTH (stimulates adrenal cortex), PRL (milk production), LH (ovulation, testosterone), FSH (follicle development, spermatogenesis). GH is pulsatile, highest during deep sleep; excess in childhood causes gigantism, excess in adulthood causes acromegaly. Posterior pituitary (neurohypophysis): stores and releases ADH (vasopressin, increases water reabsorption in collecting duct via V2 receptors and aquaporin-2) and oxytocin (uterine contraction, milk ejection). ADH deficiency causes diabetes insipidus (polyuria, polydipsia).

Thyroid & Parathyroid

The thyroid (15–25 g) is butterfly-shaped in the neck. Thyroid follicles produce thyroglobulin; iodination forms T4 (90%, less active) and T3 (10%, more active). Functions: increase BMR, promote growth and development (especially foetal brain), increase heart rate. Iodine deficiency causes goitre. Parafollicular cells (C cells) secrete calcitonin (lowers blood Ca2+ by inhibiting osteoclasts and increasing renal Ca2+ excretion). Four parathyroid glands secrete PTH (84 amino acids), which raises blood Ca2+ by stimulating osteoclasts, increasing renal Ca2+ reabsorption, and activating vitamin D (calcitriol) to enhance intestinal Ca2+ absorption. Normal plasma Ca2+: 8.5–10.5 mg/dL.

Adrenal Glands

Adrenal glands (4–5 g each) on top of kidneys. Adrenal cortex (80–90%): zona glomerulosa (mineralocorticoids, aldosterone, regulated by RAAS and K+), zona fasciculata (glucocorticoids, cortisol, regulated by ACTH), zona reticularis (androgens, DHEA). Aldosterone increases Na+ reabsorption and K+ excretion in the collecting duct. Cortisol increases blood glucose (gluconeogenesis, anti-insulin), suppresses immunity (anti-inflammatory), maintains BP, and follows circadian rhythm (highest in early morning). Adrenal medulla secretes epinephrine (80%) and norepinephrine (20%) for fight-or-flight.

Pancreas (Islets of Langerhans)

About 1–2 million islets: alpha cells (15–20%, glucagon, raises blood glucose via glycogenolysis and gluconeogenesis), beta cells (60–80%, insulin, lowers blood glucose by promoting uptake via GLUT4, stimulating glycogenesis, lipogenesis, protein synthesis, inhibiting gluconeogenesis), delta cells (5–10%, somatostatin, inhibits insulin and glucagon), F cells (pancreatic polypeptide). Insulin is synthesized as proinsulin (83 aa), cleaved to insulin + C-peptide. C-peptide is a marker of endogenous insulin secretion. Secretion is stimulated by high blood glucose, amino acids, GLP-1, and vagal stimulation; inhibited by somatostatin, epinephrine, and low glucose.

Pineal Gland & Thymus

The pineal gland (pineal body, epiphysis) is a small, pine-cone-shaped endocrine gland located in the epithalamus (dorsal to the midbrain, attached to the roof of the third ventricle). Its primary hormone is melatonin (an amine derived from tryptophan via serotonin). Melatonin secretion follows a circadian rhythm: high during darkness (night), low during light (day), regulated by the suprachiasmatic nucleus (SCN, the body’s master clock) via the retinohypothalamic tract. Melatonin regulates sleep-wake cycles (circadian rhythm), seasonal rhythms (reproduction in some animals), and has antioxidant properties. Melatonin secretion is suppressed by bright light; this explains the role of light exposure in sleep disorders and jet lag. In NEET: melatonin is NOT involved in skin pigmentation (that is melanocyte-stimulating hormone, MSH). The pineal gland also contains calcium concretions (corpora arenacea, “brain sand”) that increase with age and are radiologically visible.

The thymus is a bilobed lymphoid organ located in the superior mediastinum (behind the sternum, between the lungs). It is large in infants (about 20–30 g), reaches maximum size at puberty (30–50 g), and then undergoes involution (atrophy and replacement by adipose tissue) with age. The thymus secretes thymosin, thymopoietin, and thymulin (peptide hormones) that promote the maturation and differentiation of T lymphocytes (T cells) in the thymic cortex and medulla. T cells are essential for cell-mediated immunity: helper T cells (CD4+, activate B cells and macrophages), cytotoxic T cells (CD8+, kill infected or cancerous cells), regulatory T cells (Tregs, suppress excessive immune responses), and memory T cells (provide long-term immunity). The thymus also plays a role in negative selection (elimination of self-reactive T cells) to establish self-tolerance. Thymic aplasia (DiGeorge syndrome, 22q11.2 deletion) results in T cell deficiency and recurrent infections.

Gonads

Ovaries: oestrogens (17β-oestradiol, from developing follicles under FSH, promote female secondary sexual characteristics, endometrial proliferation, bone growth, and have cardioprotective effects) and progesterone (from corpus luteum under LH, prepares endometrium for implantation, maintains pregnancy, raises basal body temperature, and inhibits uterine contractions). The ovarian cycle has two phases: follicular phase (FSH stimulates follicle growth and oestrogen secretion, days 1–14), ovulation (LH surge triggers release of the secondary oocyte, day 14), and luteal phase (LH stimulates corpus luteum to secrete progesterone and oestrogen, days 14–28). If pregnancy does not occur, the corpus luteum degenerates (corpus albicans), progesterone and oestrogen levels fall, triggering menstruation. Testes: testosterone (from Leydig cells under LH, promotes male secondary sexual characteristics, spermatogenesis, libido, muscle mass, bone density, and erythropoiesis). Inhibin (from Sertoli cells in males, granulosa cells in females) inhibits FSH secretion via negative feedback. Sertoli cells also secrete anti-Mullerian hormone (AMH) during foetal development, causing regression of Mullerian ducts (precursors of the female reproductive tract).

Phase	Duration	Dominant Hormone	Ovarian Events	Uterine Events
Follicular	Days 1–14	FSH, Oestrogen	Follicle growth, oestrogen secretion	Menstruation (days 1–5), proliferative phase (days 6–14)
Ovulation	Day 14	LH surge, FSH surge	Secondary oocyte release (ovulation)	—
Luteal	Days 14–28	Progesterone, Oestrogen	Corpus luteum formation, progesterone secretion	Secretory phase (endometrial preparation for implantation)

Gland	Hormone	Chemical Nature	Primary Function
Anterior pituitary	GH, TSH, ACTH, PRL, LH, FSH	Peptides/proteins	Growth, metabolism, reproduction
Posterior pituitary	ADH, Oxytocin	Peptides	Water balance, labour/milk ejection
Thyroid	T3, T4, Calcitonin	Amines (T3/T4), Peptide (calcitonin)	Metabolism, growth, Ca2+ regulation
Parathyroid	PTH	Peptide	Increase blood Ca2+
Adrenal cortex	Cortisol, Aldosterone, Androgens	Steroids	Stress, salt balance, sex hormones
Adrenal medulla	Epinephrine, Norepinephrine	Amines (catecholamines)	Fight-or-flight
Pancreas (beta)	Insulin	Peptide	Lower blood glucose
Pancreas (alpha)	Glucagon	Peptide	Raise blood glucose
Ovaries	Oestrogen, Progesterone	Steroids	Female reproduction
Testes	Testosterone	Steroid	Male reproduction

7. Locomotion & Movement

Types of Movement

Movement occurs at cellular, tissue, organ, and organismal levels. Amoeboid (pseudopodia, e.g., leucocytes, macrophages). Ciliary (cilia, e.g., respiratory epithelium, fallopian tubes). Flagellar (flagella, e.g., sperm). Muscular (by muscle contraction, the most significant for locomotion). Amoeboid movement involves actin polymerization and myosin contraction. Ciliary movement uses dynein arms on microtubules (9+2 axoneme); defects cause Kartagener’s syndrome (chronic respiratory infections, infertility). Muscular movement includes locomotion and other movements (breathing, peristalsis, heartbeat, facial expressions).

Skeletal System

The adult human skeleton has 206 bones (270 at birth, many fuse). Axial skeleton (80): skull (22 bones: 8 cranial + 14 facial), vertebral column (26: 7 cervical, 12 thoracic, 5 lumbar, sacrum, coccyx), sternum, ribs (12 pairs: 7 true, 3 false, 2 floating). Appendicular skeleton (126): pectoral girdle (clavicle, scapula), upper limbs (humerus, radius, ulna, 8 carpals, 5 metacarpals, 14 phalanges), pelvic girdle (2 coxal bones: ilium, ischium, pubis), lower limbs (femur, patella, tibia, fibula, 7 tarsals, 5 metatarsals, 14 phalanges).

The vertebral column has four curvatures: cervical (lordosis, convex anterior), thoracic (kyphosis, concave anterior), lumbar (lordosis), sacral (kyphosis). The sternum has three parts: manubrium, body, xiphoid process. The femur is the longest and strongest bone. The patella is a sesamoid bone. Carpal bones mnemonic: Scaphoid, Lunate, Triquetrum, Pisiform, Trapezium, Trapezoid, Capitate, Hamate (“Some Lovers Try Positions That They Can’t Handle”).

Bone Growth & Remodelling

Bones are classified by shape: long (femur, humerus, phalanges), short (carpals, tarsals), flat (sternum, ribs, skull bones, scapulae), irregular (vertebrae, sacrum, facial bones), and sesamoid (patella, pisiform). Bone tissue contains osteoblasts (bone-forming cells, deposit osteoid matrix mineralized by hydroxyapatite, Ca10(PO4)6(OH)2), osteocytes (mature bone cells in lacunae, maintain matrix, connected by canaliculi), and osteoclasts (large multinucleated cells from monocyte-macrophage lineage, resorb bone via acid and proteolytic enzymes, regulated by RANK-RANKL signalling). Intramembranous ossification: direct bone formation from mesenchyme (flat skull bones, clavicle, mandible). Endochondral ossification: bone replaces cartilage model (long bones), with the epiphyseal growth plate (zones: resting, proliferating, hypertrophic, calcified cartilage). The epiphyseal plate fuses after puberty (oestrogen-driven in both sexes), ending longitudinal growth. PTH increases bone resorption (via osteoclast activation); calcitonin inhibits it. Wolff’s law: bone adapts to mechanical stress. Osteoporosis: decreased bone density, most common in postmenopausal women (oestrogen deficiency), increased fracture risk (hip, wrist, vertebrae). Osteomalacia (adults) and rickets (children): defective mineralization from vitamin D or Ca/P deficiency. Osteomyelitis: bone infection (Staphylococcus aureus most common).

Joints

Joints are classified as fibrous (immovable, e.g., skull sutures, gomphosis of teeth), cartilaginous (slightly movable, e.g., intervertebral discs, pubic symphysis, manubriosternal joint), and synovial (freely movable, most common). Synovial joints have a joint cavity, articular cartilage (hyaline, avascular, nourished by synovial fluid), synovial fluid (ultrafiltrate with hyaluronic acid, lubrication, about 4 mL in knee), joint capsule (fibrous outer layer and synovial membrane), and ligaments. Types: ball-and-socket (multiaxial, 3 degrees of freedom: flexion/extension, abduction/adduction, rotation, e.g., shoulder, hip), hinge (uniaxial, e.g., elbow, knee, ankle), pivot (uniaxial, e.g., atlantoaxial for head rotation, proximal radioulnar), condylar (biaxial, e.g., wrist, metacarpophalangeal), saddle (biaxial, e.g., carpometacarpal of thumb, unique for opposition in humans), gliding (multiaxial limited, e.g., intercarpal, intertarsal, sternoclavicular), ellipsoid (biaxial, e.g., radiocarpal). The knee is the largest and most complex joint (modified hinge, allows some rotation when flexed). It has two menisci (medial C-shaped, lateral O-shaped, fibrocartilage, absorb shock and improve stability) and four major ligaments: ACL (prevents anterior tibial translation), PCL (prevents posterior tibial translation), MCL (resists valgus/abduction stress), LCL (resists varus/adduction stress). Joint disorders: osteoarthritis (degenerative), rheumatoid arthritis (autoimmune), gout (uric acid crystals, big toe, hyperuricemia), dislocation (most common: shoulder anterior dislocation), sprain (ligament injury).

Muscle Contraction

Muscle tissue: skeletal (striated, voluntary), cardiac (striated, involuntary), smooth (non-striated, involuntary). Skeletal muscle fibres are multinucleated, cylindrical cells (10–100 μm diameter, up to 30 cm long) formed by myoblast fusion. Each fibre contains myofibrils with repeating sarcomeres (2.5 μm at rest).

Structure of Sarcomere

The sarcomere extends from Z-disc to Z-disc. A band (anisotropic, dark) contains myosin filaments. I band (isotropic, light) contains only actin filaments. H zone (central A band, only myosin). M line (central, holds myosin filaments). Actin (thin filament) has tropomyosin and troponin complex (T, C, I). Myosin (thick filament) has a head and tail; the head has ATPase activity and actin-binding sites.

Sliding Filament Theory

Contraction occurs when myosin heads bind to actin, forming cross-bridges, and pull actin filaments toward the M line, shortening the sarcomere (A band remains constant, I band and H zone shorten). Steps: (1) Action potential at the neuromuscular junction releases ACh from the motor end plate. (2) ACh binds to nicotinic receptors, depolarizing the sarcolemma. (3) Depolarization travels along T-tubules, causing Ca2+ release from the sarcoplasmic reticulum (via ryanodine receptors). (4) Ca2+ binds to troponin C, causing tropomyosin to shift and expose myosin-binding sites on actin. (5) Myosin heads (with bound ATP) hydrolyse ATP to ADP + Pi, change conformation (cocked), and bind to actin. (6) Power stroke: myosin heads pivot, releasing ADP + Pi, pulling actin inward. (7) ATP binds to myosin heads, causing detachment. (8) ATP hydrolysis recocks the myosin head for the next cycle. (9) The cycle repeats as long as Ca2+ and ATP are available. (10) Relaxation: Ca2+ is pumped back into the sarcoplasmic reticulum (Ca2+ ATPase), tropomyosin re-covers binding sites.

Rigor mortis occurs after death when ATP is depleted: myosin heads bind to actin but cannot detach, causing muscle stiffness. Energy for contraction: ATP is used for cross-bridge detachment (myosin ATPase) and Ca2+ reuptake (Ca2+ ATPase). Creatine phosphate buffers ATP levels. Oxygen debt (excess post-exercise oxygen consumption, EPOC) is the extra O2 needed to convert lactic acid to glycogen, replenish ATP and creatine phosphate, and restore O2 stores.

Muscle Tone & Types of Muscle Fibres

Muscle tone is the resting tension maintained by low-level involuntary contraction of a small number of motor units (alternating to prevent fatigue). Tone is maintained by the stretch reflex (gamma motor neuron system) and is absent in lower motor neuron lesions (flaccid paralysis, hyporeflexia, atrophy) but increased in upper motor neuron lesions (spasticity, hyperreflexia, clonus, Babinski sign). Skeletal muscle fibres are classified by myosin ATPase isoform: Type I (slow oxidative, red, high myoglobin, many mitochondria, fatigue-resistant, for posture and endurance), Type IIa (fast oxidative-glycolytic, intermediate), and Type IIb/IIx (fast glycolytic, white, low myoglobin, few mitochondria, fatigable, for sprinting and power). Motor unit: a single alpha motor neuron and all the fibres it innervates (10 fibres in extraocular muscles for fine control, 2000 in quadriceps for force). Henneman’s size principle: motor units are recruited in order of size (Type I → IIa → IIb) as force increases. Fatigue: depletion of ATP and creatine phosphate, lactic acid accumulation, ionic imbalances. Oxygen debt (EPOC): extra O2 consumed after exercise to convert lactic acid to glycogen (Cori cycle in liver), replenish ATP and creatine phosphate, restore myoglobin O2, and clear CO2. The Cori cycle: lactate from muscle is transported to the liver, converted to glucose via gluconeogenesis, and returned to muscle as blood glucose.

Feature	Skeletal Muscle	Cardiac Muscle	Smooth Muscle
Striations	Present	Present	Absent
Control	Voluntary (somatic)	Involuntary (autonomic)	Involuntary (autonomic)
Nuclei	Multinucleated (peripheral)	Single (central)	Single (central)
Intercalated discs	Absent	Present	Absent
Gap junctions	Absent	Present (syncytium)	Present (single unit)
Calcium source	SR (mostly)	SR + extracellular	SR + extracellular
Speed of contraction	Fast	Moderate	Slow
T-tubules	At A-I junction	At Z-discs	Caveolae instead
Fatigue	Rapid	Resistant	Very resistant

8. Neural Control & Coordination

Synaptic Transmission

A synapse is a junction between two neurons or between a neuron and an effector. Synapses are classified as electrical (gap junctions, direct ion flow, bidirectional, very fast, found in cardiac and smooth muscle, some CNS regions) and chemical (most common, unidirectional, involves neurotransmitters, slower but modifiable). A typical chemical synapse has a presynaptic terminal (synaptic bouton), synaptic cleft (20–30 nm), and postsynaptic membrane with receptors. When the action potential reaches the presynaptic terminal, voltage-gated Ca2+ channels open, Ca2+ influx triggers synaptic vesicle fusion with the presynaptic membrane (via SNARE proteins: synaptobrevin, syntaxin, SNAP-25), and neurotransmitter is released by exocytosis.

Neurotransmitters

Major neurotransmitters: acetylcholine (ACh, at neuromuscular junctions, autonomic ganglia, CNS, degraded by acetylcholinesterase), noradrenaline/norepinephrine (CNS and sympathetic postganglionic), dopamine (substantia nigra to striatum, reward, movement; deficiency in Parkinson’s disease), serotonin/5-HT (mood, sleep, appetite), GABA (gamma-aminobutyric acid, main inhibitory neurotransmitter in CNS), glutamate (main excitatory neurotransmitter in CNS), glycine (inhibitory in spinal cord), histamine (arousal), substance P (pain), endorphins (endogenous opioids, pain relief), nitric oxide (NO, unconventional gasotransmitter, diffuses directly across membranes).

Neurotransmitters act on ionotropic receptors (ligand-gated ion channels, fast response, e.g., nicotinic ACh receptors, GABA-A receptors, AMPA glutamate receptors) and metabotropic receptors (G-protein-coupled receptors, slow response, second messengers, e.g., muscarinic ACh receptors, GABA-B receptors, dopamine receptors). EPSPs (excitatory postsynaptic potentials) are depolarizations that bring the neuron closer to threshold; IPSPs (inhibitory postsynaptic potentials) are hyperpolarizations that move the neuron away from threshold. Summation of EPSPs and IPSPs (spatial and temporal) at the axon hillock determines whether an action potential is generated.

Reflex Arc

A reflex is a rapid, involuntary, stereotyped response to a stimulus. The reflex arc consists of: (1) receptor (senses the stimulus), (2) sensory (afferent) neuron (transmits impulse to CNS), (3) integration centre (usually spinal cord grey matter, single synapse for monosynaptic reflexes, multiple for polysynaptic), (4) motor (efferent) neuron (transmits impulse to effector), (5) effector (muscle or gland that responds). Examples: patellar reflex (monosynaptic, spinal L2–L4, stretch of quadriceps tendon causes knee jerk), withdrawal reflex (polysynaptic, pain stimulus causes flexor contraction and extensor inhibition via reciprocal inhibition), crossed extensor reflex (withdrawal of one limb with extension of the opposite limb for support), corneal reflex (blink in response to corneal touch via CN V and VII), pupillary light reflex (direct and consensual constriction via CN II and III).

Sense Organs

Eye (Visual System)

The eye is a spherical organ (about 24 mm diameter) with three layers: fibrous (sclera + cornea), vascular (choroid, ciliary body, iris), and neural (retina). The cornea (avascular, transparent, most refractive power, ~40 dioptres) is nourished by aqueous humour. The iris (coloured, smooth muscle: dilator pupillae sympathetic, sphincter pupillae parasympathetic) regulates pupil size. The lens (biconvex, transparent, crystalline proteins, accommodated by ciliary muscle: contraction makes lens more convex for near vision, relaxation flattens lens for far vision). Aqueous humour (produced by ciliary epithelium, fills anterior and posterior chambers, drained via the canal of Schlemm at the iridocorneal angle; impaired drainage causes glaucoma). Vitreous humour (gel, fills the posterior cavity).

The retina has photoreceptors (rods and cones): rods (120 million, rhodopsin pigment, scotopic/low-light vision, no colour, high sensitivity), cones (6 million, photopic/bright-light vision, three types: red/L, green/M, blue/S, each with different photopsin pigments). The fovea centralis has the highest density of cones and the highest visual acuity. The optic disc is the blind spot (no photoreceptors, where the optic nerve exits). Phototransduction: light activates rhodopsin (11-cis retinal → all-trans retinal), activating transducin (G-protein), which activates phosphodiesterase, cGMP breakdown, closure of Na+ channels (dark current stops), hyperpolarization of photoreceptor, reduced glutamate release, signalling to bipolar cells and ganglion cells, whose axons form the optic nerve. The optic nerves from both eyes cross at the optic chiasm (nasal fibres cross, temporal fibres stay ipsilateral) and project to the lateral geniculate nucleus (thalamus) and then to the primary visual cortex (area 17 in the occipital lobe).

The pupillary light reflex: light shone in one eye causes both pupils to constrict (direct and consensual response). The afferent limb is CN II (optic nerve); the efferent limb is CN III (oculomotor nerve, parasympathetic fibres to sphincter pupillae). Absence of the direct reflex with an intact consensual reflex indicates an afferent defect (e.g., optic nerve lesion, Marcus Gunn pupil/relative afferent pupillary defect/RAPD). The accommodation reflex (near response): when looking from far to near, three changes occur: (1) medial rectus muscles contract (convergence), (2) ciliary muscle contracts (lens becomes more convex, increases refractive power), (3) sphincter pupillae contracts (miosis/pupil constriction). Presbyopia: age-related loss of lens elasticity, causing difficulty with near vision (corrected with reading glasses or bifocals). Myopia (nearsightedness): image focuses in front of the retina (eyeball too long or lens too strong), corrected with concave (diverging) lenses. Hyperopia (farsightedness): image focuses behind the retina (eyeball too short), corrected with convex (converging) lenses. Astigmatism: irregular corneal curvature causing blurred vision, corrected with cylindrical lenses. Cataract: lens opacification (clouding), most common with aging, treated by surgical lens replacement. Glaucoma: increased intraocular pressure due to impaired drainage of aqueous humour, causing optic nerve damage and visual field loss. Colour blindness: most common is X-linked red-green deficiency (lack of L or M cone photopsin). Strabismus: misalignment of the eyes (crossed eyes/esotropia or wall-eyed/exotropia), can cause amblyopia (lazy eye) if untreated in childhood. Binocular vision: the overlapping fields of view of both eyes provide depth perception (stereopsis); this depends on the integration of slightly different images from each eye in the visual cortex.

Ear (Auditory & Vestibular System)

The ear is divided into external (pinna, external auditory canal, tympanic membrane), middle (malleus, incus, stapes, Eustachian tube connecting to nasopharynx), and inner ear (cochlea for hearing, vestibule and semicircular canals for balance). Sound waves vibrate the tympanic membrane, the three ossicles amplify vibration (mechanical advantage ~22:1 due to lever action and area ratio), and the stapes pushes the oval window, creating pressure waves in the perilymph of the scala vestibuli. The waves travel through the cochlea, displace the basilar membrane (frequency mapping: high frequencies at the base, low frequencies at the apex), and cause shearing of hair cell stereocilia against the tectorial membrane. Hair cell depolarization opens voltage-gated Ca2+ channels, triggering neurotransmitter release (glutamate) onto the cochlear nerve (CN VIII). The organ of Corti contains inner hair cells (about 3500, primary sensory cells) and outer hair cells (about 12,000, electromotile, amplify and tune the response). Hearing range in humans: 20 Hz to 20,000 Hz (most sensitive at 1000–3000 Hz).

The vestibular system detects balance and head position. The semicircular canals (anterior, posterior, lateral) detect rotational acceleration via crista ampullaris (hair cells in ampulla). The utricle and saccule detect linear acceleration and head tilt via the macula (otolithic membrane with otoconia/otoliths). Hair cell mechanotransduction: stereocilia deflection towards the kinocilium causes depolarization; away causes hyperpolarization.

Nose, Tongue & Skin

Olfaction (smell): olfactory epithelium in the nasal roof contains olfactory receptor neurons (about 10–20 million, each expressing one of ~350 functional olfactory receptor types). Odorants bind to GPCRs, activating adenylyl cyclase, increasing cAMP, opening cyclic nucleotide-gated (CNG) cation channels, causing depolarization. Axons of olfactory receptor neurons project through the cribriform plate of the ethmoid bone to the olfactory bulb (glomeruli) and then to the olfactory cortex, amygdala, and hippocampus. Olfaction is the only sensory system that does NOT relay through the thalamus before reaching the cortex.

Gustation (taste): taste buds (about 10,000, mostly on tongue papillae: circumvallate, fungiform, foliate) contain taste receptor cells with microvilli (taste pores). Five basic tastes: sweet (sugars, artificial sweeteners, T1R2/T1R3 GPCRs), salty (Na+ ions, ENaC channel), sour (H+ ions, PKD2L1 channel), bitter (many compounds, T2R GPCRs, ~25 receptors), umami/savoury (glutamate/MSG, T1R1/T1R3 GPCRs). Each taste bud has cells for all five modalities. Cranial nerves VII (facial, anterior 2/3 of tongue), IX (glossopharyngeal, posterior 1/3), and X (vagus, epiglottis and pharynx) carry taste signals to the nucleus of the solitary tract in the medulla, then to the thalamus and gustatory cortex. Cutaneous sensation (skin): mechanoreceptors (Meissner’s corpuscles for light touch, Pacinian corpuscles for vibration/deep pressure, Merkel’s discs for sustained touch, Ruffini endings for stretch), thermoreceptors (cold and warm), nociceptors (pain), and proprioceptors (muscle spindles, Golgi tendon organs, joint receptors).

Sense Organ	Receptor Type	Stimulus	Cranial Nerve	Primary Cortex
Eye	Rods (rhodopsin), Cones (photopsins)	Light (380–760 nm)	CN II (Optic)	Occipital lobe (area 17)
Ear (hearing)	Hair cells in organ of Corti	Sound (20 Hz–20 kHz)	CN VIII (Vestibulocochlear)	Temporal lobe (areas 41, 42)
Ear (balance)	Hair cells in crista & macula	Acceleration, head tilt	CN VIII	Cerebellum, brainstem
Nose	Olfactory receptor neurons	Odorant molecules	CN I (Olfactory)	Olfactory cortex (no thalamic relay)
Tongue	Taste receptor cells in taste buds	Chemicals (5 basic tastes)	CN VII, IX, X	Gustatory cortex (insula)
Skin	Mechano-, thermo-, nociceptors	Touch, pressure, temperature, pain	Spinal nerves (dermatomes)	Somatosensory cortex (postcentral gyrus)

Memory, Sleep & Higher Brain Functions

Memory is the process of encoding, storing, and retrieving information. The hippocampus (in the medial temporal lobe) is essential for forming new declarative memories (facts, events); damage (e.g., Alzheimer’s disease, bilateral hippocampal damage) causes anterograde amnesia (inability to form new memories). The amygdala encodes emotional memories (especially fear conditioning). The prefrontal cortex is involved in working memory, executive function, and decision-making. The cerebellum and basal ganglia are involved in procedural memories (skills, habits). Memory types: sensory memory (milliseconds to seconds), short-term/working memory (seconds to minutes, limited capacity about 7 ± 2 items), long-term memory (lifelong, unlimited capacity), subdivided into explicit/declarative (episodic for events, semantic for facts) and implicit/non-declarative (procedural, conditioning, priming). Long-term potentiation (LTP) in the hippocampus is the cellular basis of learning and memory: high-frequency stimulation of synapses strengthens connections via NMDA receptor activation, Ca2+ influx, and insertion of more AMPA receptors. Sleep is divided into non-REM (NREM, stages N1–N3, about 75% of total sleep time) and REM (rapid eye movement, about 25%, associated with vivid dreaming, muscle atonia, and desynchronized EEG). NREM sleep (especially slow-wave sleep, N3, delta waves 0.5–4 Hz) is important for memory consolidation (declarative memory), growth hormone release, and tissue repair. REM sleep (theta and beta waves, similar to awake EEG) is important for emotional regulation and procedural memory consolidation. The sleep-wake cycle is regulated by the SCN (circadian clock, located in the hypothalamus), which projects to the pineal gland (melatonin secretion, high at night, low during the day). The ascending reticular activating system (ARAS, in the brainstem: locus coeruleus, raphe nuclei, cholinergic nuclei in the pons and midbrain) maintains wakefulness. Adenosine accumulates during wakefulness and promotes sleep (caffeine is an adenosine receptor antagonist, promoting wakefulness). The ventrolateral preoptic nucleus (VLPO) in the hypothalamus promotes NREM sleep by inhibiting the ARAS (the “flip-flop” switch model of sleep-wake transitions).

EEG & Brain Rhythms

The electroencephalogram (EEG) records cortical electrical activity. Brain waves: delta (0.5–4 Hz, deep sleep, N3), theta (4–8 Hz, light sleep, drowsiness, N1–N2), alpha (8–13 Hz, relaxed wakefulness, eyes closed, occipital predominance), beta (13–30 Hz, alert wakefulness, active thinking, frontal predominance), gamma (> 30 Hz, high-level cognitive processing, sensory binding). EEG is used to diagnose epilepsy (spike-and-wave discharges in absence seizures, generalized spikes in tonic-clonic seizures), sleep disorders (polysomnography), and brain death (isoelectric EEG, no electrical activity over 30 minutes). The default mode network (DMN) is active during rest and mind-wandering, involving the medial prefrontal cortex, posterior cingulate cortex, and angular gyrus; it is suppressed during focused tasks and shows altered connectivity in depression and Alzheimer’s disease. Neuroplasticity: the brain’s ability to reorganize structure and function in response to experience, learning, and injury. Neurogenesis (birth of new neurons) occurs in the subgranular zone of the dentate gyrus (hippocampus) and the subventricular zone (olfactory bulb) throughout life. Brain-derived neurotrophic factor (BDNF) promotes neuronal survival, growth, and synaptic plasticity, and is increased by exercise and enriched environments. Stroke (cerebrovascular accident, CVA): ischaemic (thrombotic or embolic, about 80%) or haemorrhagic (about 20%), causing focal neurological deficits (hemiplegia, aphasia, neglect, visual field defects). Transient ischaemic attack (TIA): temporary focal neurological deficit lasting < 24 hours, warning sign of impending stroke. Alzheimer’s disease: progressive neurodegenerative disorder with amyloid-beta plaques, neurofibrillary tangles (hyperphosphorylated tau), and loss of cholinergic neurons in the basal forebrain (nucleus basalis of Meynert), leading to memory loss, cognitive decline, and personality changes. Parkinson’s disease: loss of dopaminergic neurons in the substantia nigra pars compacta, causing resting tremor (pill-rolling), bradykinesia, rigidity, and postural instability; treated with L-DOPA/carbidopa, dopamine agonists, and deep brain stimulation. Multiple sclerosis: autoimmune demyelination of CNS axons, causing optic neuritis, weakness, sensory loss, and ataxia, with relapsing-remitting or progressive course.

9. Chemical Coordination & Integration

Hormones & Their Classification

Chemical coordination is mediated by hormones, which are classified by chemical nature into peptides/proteins (insulin, glucagon, GH, TSH, ACTH, PTH, calcitonin, ADH, oxytocin), steroids (cortisol, aldosterone, testosterone, oestradiol, progesterone, vitamin D/calcitriol), amines (thyroid hormones T3/T4 from tyrosine, catecholamines epinephrine/norepinephrine from tyrosine, melatonin from tryptophan), and eicosanoids (prostaglandins, thromboxanes, leukotrienes from arachidonic acid). Peptide hormones are water-soluble, cannot cross the plasma membrane, and act via membrane receptors (GPCRs or enzyme-linked receptors) with second messengers (cAMP, IP3/DAG, Ca2+, cGMP). Steroid hormones are lipid-soluble, diffuse across the membrane, bind to intracellular receptors (cytoplasmic or nuclear), and act as transcription factors modulating gene expression (slow, hours to days). Thyroid hormones are amine-derived but lipid-soluble and act via nuclear receptors (similar to steroids).

Mechanism of Hormone Action

Peptide hormone mechanism (e.g., glucagon, ADH via V2, PTH, ACTH, calcitonin): (1) hormone binds to a G-protein-coupled receptor (GPCR) on the target cell membrane, (2) the activated receptor causes a conformational change in the associated G-protein (Gs, Gi, or Gq), (3) Gs activates adenylyl cyclase, converting ATP to cyclic AMP (cAMP, the second messenger), which activates protein kinase A (PKA), which phosphorylates specific target proteins, leading to cellular responses; Gi inhibits adenylyl cyclase, decreasing cAMP; (4) Gq activates phospholipase C (PLC), which cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3, releases Ca2+ from the endoplasmic reticulum, activating calmodulin-dependent kinases) and diacylglycerol (DAG, activates protein kinase C/PKC); (5) the response is terminated by phosphodiesterases (degrade cAMP) and phosphatases (dephosphorylate target proteins). Examples: glucagon binds to Gs-coupled receptors on hepatocytes, increasing cAMP, activating PKA, which phosphorylates and activates glycogen phosphorylase (glycogenolysis) and inhibits glycogen synthase (inhibits glycogenesis), raising blood glucose. ADH (V2 receptor) in the collecting duct: Gs → cAMP → PKA → phosphorylation and insertion of aquaporin-2 water channels.

Steroid hormone mechanism (e.g., cortisol, aldosterone, oestrogen, testosterone, progesterone, vitamin D/calcitriol): (1) steroid hormone diffuses across the plasma membrane (lipid-soluble), (2) binds to a specific intracellular receptor (cytoplasmic or nuclear), (3) hormone-receptor complex translocates to the nucleus (if cytoplasmic), (4) the complex binds as a dimer to specific DNA sequences called hormone response elements (HREs) in the promoter regions of target genes, (5) coactivators or corepressors are recruited to modify chromatin structure and regulate transcription, (6) mRNA is transcribed, exported to the cytoplasm, and translated into proteins that mediate the physiological response. The response is slower (hours to days) but longer-lasting than peptide hormone responses. Thyroid hormones (T3 and T4) are tyrosine-derived amines that are lipid-soluble and act via nuclear receptors (thyroid hormone receptors, TRs, bound to DNA as heterodimers with retinoid X receptor/RXR). T3 (more active) binds to TR, recruiting coactivators, increasing transcription of genes involved in metabolism (Na+/K+ ATPase, myosin heavy chain, uncoupling proteins).

Growth factor/cytokine mechanism (e.g., insulin, insulin-like growth factor/IGF-1, epidermal growth factor/EGF, erythropoietin/EPO): hormone binds to a receptor tyrosine kinase (RTK), which dimerizes and autophosphorylates tyrosine residues on its intracellular domain. Phosphorylated tyrosines serve as docking sites for adaptor proteins (e.g., IRS proteins for insulin, Grb2 for EGF). Insulin signalling: insulin binds to the α subunits of the insulin receptor (a preformed dimer), causing autophosphorylation of β subunits, activating IRS-1/IRS-2, which activate PI3K-Akt pathway (phosphorylates AS160, causing GLUT4 translocation to the membrane for glucose uptake; activates glycogen synthase for glycogenesis; activates mTOR for protein synthesis; inhibits FOXO transcription factors to suppress gluconeogenesis) and the MAPK/ERK pathway (cell growth, proliferation, gene expression). Insulin resistance in type 2 diabetes involves impaired IRS-1/PI3K signalling. Growth hormone binds to the GH receptor (a class I cytokine receptor), activating JAK2-STAT5 signalling, leading to increased IGF-1 production in the liver, which mediates many of GH’s growth-promoting effects. Receptor guanylyl cyclase (e.g., ANP receptor): hormone binding activates guanylyl cyclase, producing cGMP as the second messenger, activating protein kinase G (PKG), causing vasodilation and natriuresis. NO (nitric oxide) is a gasotransmitter that diffuses into cells, activates soluble guanylyl cyclase, producing cGMP, causing vascular smooth muscle relaxation (vasodilation); Viagra (sildenafil) inhibits PDE5, which degrades cGMP, potentiating NO-induced vasodilation.

Receptor Type	Hormone Examples	Second Messenger / Mechanism	Speed of Response
GPCR (Gs)	Glucagon, ADH (V2), PTH, ACTH, TSH, FSH, LH, β-adrenergic	cAMP → PKA	Fast (seconds to minutes)
GPCR (Gq)	ADH (V1), GnRH, TRH, α1-adrenergic, angiotensin II	IP3 → Ca2+, DAG → PKC	Fast (seconds to minutes)
GPCR (Gi)	Somatostatin, α2-adrenergic	cAMP decrease	Fast (seconds to minutes)
Receptor tyrosine kinase	Insulin, IGF-1, EGF, PDGF	PI3K-Akt, MAPK/ERK	Moderate (minutes)
Receptor guanylyl cyclase	ANP, BNP	cGMP → PKG	Fast (seconds)
Nuclear receptor	Cortisol, oestrogen, testosterone, T3/T4, vitamin D	Gene transcription regulation	Slow (hours to days)
Cytokine receptor (JAK-STAT)	GH, prolactin, EPO, leptin	JAK2 → STAT → gene transcription	Moderate (minutes to hours)

Feedback Mechanisms

Hormone secretion is regulated by feedback loops to maintain homeostasis. Negative feedback (more than 95% of hormonal regulation): the product of a pathway inhibits its own production, maintaining stability. Examples: (1) Thyroid hormones (T3, T4) inhibit TRH and TSH secretion via negative feedback at the hypothalamus and pituitary—when T3/T4 are high, TRH and TSH decrease, reducing further thyroid stimulation. (2) Cortisol inhibits CRH and ACTH via negative feedback at the hypothalamus and pituitary. (3) Blood glucose: high glucose stimulates insulin (lowers glucose); low glucose stimulates glucagon (raises glucose). (4) PTH: low blood Ca2+ stimulates PTH; high Ca2+ inhibits PTH. (5) Blood pressure: baroreceptor reflex provides rapid negative feedback (high BP reduces sympathetic outflow, lowering HR and TPR). Positive feedback (amplifying, about 2–3% of hormonal regulation): the product enhances its own production, creating a self-amplifying loop that continues until a specific event terminates it. Examples: (1) Oxytocin during labour (cervical stretch stimulates more oxytocin release from the posterior pituitary, causing stronger uterine contractions, which cause more cervical stretch, until the baby is delivered). (2) LH surge before ovulation: rising oestrogen from the dominant follicle switches from negative to positive feedback at the pituitary, stimulating a massive LH surge, which triggers ovulation. (3) Blood clotting cascade: thrombin activates factor XI, V, and VIII (positive feedback), rapidly amplifying clot formation. (4) Sodium channel opening during action potentials: initial depolarization opens more voltage-gated Na+ channels, causing rapid upstroke until Na+ channels inactivate. The key NEET distinction: negative feedback maintains stability (set point); positive feedback amplifies change and must be terminated by an external event.

Circadian Rhythms in Hormone Secretion

Many hormones exhibit circadian (24-hour) rhythms driven by the suprachiasmatic nucleus (SCN) of the hypothalamus. Cortisol peaks in the early morning (6–8 AM, helps prepare the body for waking), declines throughout the day, and is lowest at midnight. Growth hormone is secreted in pulses, with the largest pulse occurring during slow-wave sleep (N3). Melatonin is high at night and low during the day (promotes sleep). Testosterone peaks in the early morning. TSH peaks in the late evening and early night. Leptin peaks at night (satiety during sleep). Circadian disruption (shift work, jet lag, sleep deprivation) alters hormone rhythms and is associated with metabolic disorders, depression, and increased cancer risk. The pineal melatonin rhythm is entrained by light via the retinohypothalamic tract (RHT) from the retina to the SCN, and from the SCN to the pineal gland via a polysynaptic pathway (SCN → paraventricular nucleus → preganglionic sympathetic in spinal cord → superior cervical ganglion → pineal). Light exposure at night suppresses melatonin secretion and phase-shifts the circadian clock.

Hypothalamic-Pituitary Axis

The HPT axis: Hypothalamus → TRH → Anterior pituitary → TSH → Thyroid → T3/T4 → negative feedback on TRH and TSH. The HPA axis: Hypothalamus → CRH → Anterior pituitary → ACTH → Adrenal cortex → Cortisol → negative feedback on CRH and ACTH. The HPG axis: Hypothalamus → GnRH → Anterior pituitary → LH + FSH → Gonads → Sex steroids + inhibin → negative feedback on GnRH, LH, FSH. The GH axis: Hypothalamus → GHRH (+), GHIH/Somatostatin (−) → Anterior pituitary → GH → Liver → IGF-1 → negative feedback on GHRH and GH.

Hormonal Disorders

Growth disorders: gigantism (GH excess in children), acromegaly (GH excess in adults, enlarged hands, feet, jaw, coarse facial features), dwarfism (GH deficiency in children, normal proportions). Pituitary disorders: diabetes insipidus (ADH deficiency, polyuria, polydipsia, dilute urine, treated with desmopressin), SIADH (ADH excess, water retention, hyponatremia). Thyroid disorders: hyperthyroidism/Graves’ disease (excess T3/T4, exophthalmos, goitre, tachycardia, weight loss, heat intolerance), hypothyroidism (deficiency, myxoedema in adults, cretinism in children, weight gain, cold intolerance, bradycardia), goitre (iodine deficiency, TSH stimulation causes thyroid enlargement). Parathyroid: hyperparathyroidism (excess PTH, hypercalcaemia, kidney stones, bone resorption), hypoparathyroidism (PTH deficiency, hypocalcaemia, tetany, Chvostek and Trousseau signs). Adrenal: Cushing’s syndrome (excess cortisol, moon face, buffalo hump, striae, hyperglycaemia, osteoporosis), Addison’s disease (cortisol and aldosterone deficiency, hyperpigmentation, hypotension, hyponatremia, hyperkalemia, weight loss), Conn’s syndrome (aldosterone excess, hypertension, hypokalemia). Pancreatic: diabetes mellitus type 1 (autoimmune destruction of beta cells, absolute insulin deficiency, presents in childhood/young adulthood, ketosis-prone), type 2 (insulin resistance with relative insulin deficiency, obesity-related, adult-onset, ketosis-resistant). Diabetes mellitus features: hyperglycaemia, glucosuria, polyuria, polydipsia, polyphagia, weight loss. Chronic complications: retinopathy, nephropathy, neuropathy, cardiovascular disease.

Disorder	Hormone Imbalance	Key Features
Gigantism	GH excess (childhood)	Excessive linear growth
Acromegaly	GH excess (adult)	Enlarged hands, feet, jaw
Cushing’s syndrome	Cortisol excess	Moon face, buffalo hump, hyperglycaemia
Addison’s disease	Cortisol + aldosterone deficiency	Hyperpigmentation, hypotension, hyperkalemia
Graves’ disease	Thyroid hormone excess	Exophthalmos, goitre, tachycardia, weight loss
Myxoedema	Thyroid hormone deficiency (adult)	Weight gain, cold intolerance, bradycardia
Cretinism	Thyroid hormone deficiency (child)	Mental retardation, stunted growth
Diabetes mellitus type 1	Insulin deficiency	Hyperglycaemia, ketosis, young onset
Diabetes mellitus type 2	Insulin resistance	Hyperglycaemia, obesity, adult onset
Diabetes insipidus	ADH deficiency	Polyuria, polydipsia, dilute urine

Integration of Systems

The endocrine, nervous, and immune systems form an integrated regulatory network. The neuroendocrine system (hypothalamus-pituitary axis) links neural activity to hormonal secretion. The sympathetic-adrenal-medullary (SAM) axis mediates the acute stress response (catecholamines). The HPA axis mediates the chronic stress response (cortisol). The renin-angiotensin-aldosterone system (RAAS) integrates renal, cardiovascular, and endocrine function for blood pressure regulation. The endocrine system regulates metabolic integration: insulin and glucagon control fuel homeostasis; thyroid hormones set the metabolic rate; growth hormone and IGF-1 regulate growth; cortisol modulates metabolism, immunity, and stress responses; sex hormones coordinate reproductive function. Calcium homeostasis is regulated by PTH, calcitonin, and vitamin D. Blood glucose homeostasis integrates the pancreas (insulin, glucagon), liver (glycogen storage, gluconeogenesis), muscle (GLUT4, glycogen), adipose tissue (lipogenesis, lipolysis), and the brain (obligate glucose consumer, about 120 g/day). The body’s response to exercise integrates increased sympathetic outflow, catecholamine and cortisol release, increased ventilation and cardiac output, and fuel mobilization (glycogenolysis, lipolysis, gluconeogenesis).

Practice Questions (10 MCQs for NEET)

The following questions are designed to test your understanding of key concepts across all 9 sections of Human Physiology. Attempt each question before checking the solution. These are modelled on the pattern of previous NEET Biology papers, covering all systems from digestion to chemical coordination.

Quick Reference: Key Numeric Values for NEET

The following table summarizes important numeric values frequently tested in NEET Biology Human Physiology questions. Memorizing these will help you solve numerical problems quickly and accurately.

Parameter	Normal Value	Relevant System
Total blood volume	5–6 L (70–80 mL/kg)	Circulation
Cardiac output at rest	5–5.5 L/min	Circulation
Stroke volume	70 mL (EDV 120–130 mL, ESV 50–60 mL)	Circulation
Heart rate at rest	70–80 bpm	Circulation
Ejection fraction	55–70%	Circulation
Systolic / Diastolic BP	120/80 mmHg	Circulation
Mean arterial pressure	~93 mmHg	Circulation
RBC count (male/female)	5.5 / 5.0 million/mm3	Circulation
WBC count	4000–11000 /mm3	Circulation
Platelet count	1.5–4.5 lakhs/mm3	Circulation
Hb concentration	14–16 g/dL (male), 12–14 g/dL (female)	Circulation
Blood pH	7.35–7.45	Circulation / Excretion
Plasma protein concentration	7–8 g/dL	Circulation
Oncotic pressure	25 mmHg	Circulation
Tidal volume	500 mL	Respiration
Vital capacity	4500–4800 mL	Respiration
Total lung capacity	5700–6000 mL	Respiration
Residual volume	1100–1200 mL	Respiration
Anatomical dead space	150 mL	Respiration
Alveolar PO2 / PCO2	104 / 40 mmHg	Respiration
Respiratory rate at rest	12–16 breaths/min	Respiration
GFR	125 mL/min (180 L/day)	Excretion
Urine output per day	1–1.5 L/day	Excretion
Number of nephrons per kidney	1–1.5 million	Excretion
Medullary osmolality (tip)	~1200 mOsm/L	Excretion
Serum creatinine	0.6–1.2 mg/dL	Excretion
Blood glucose (fasting)	70–100 mg/dL	Endocrine
Renal threshold for glucose	~180 mg/dL	Endocrine / Excretion
Serum Ca2+	8.5–10.5 mg/dL	Endocrine
Saliva per day	1–1.5 L/day	Digestion
Gastric juice per day	2–3 L/day	Digestion
Pancreatic juice per day	1.5–2 L/day	Digestion
Bile per day	600–1000 mL/day	Digestion
Length of small intestine	~6 m	Digestion
Length of large intestine	~1.5 m	Digestion
Number of bones (adult)	206	Locomotion
Number of spinal nerves	31 pairs	Nervous System
Cranial nerves	12 pairs	Nervous System
CSF volume	~150 mL	Nervous System
CSF production rate	500–600 mL/day	Nervous System
SaO2 (arterial O2 saturation)	95–98%	Respiration
Oxygen carrying capacity of blood	~20 mL O2/100 mL blood (20 vol%)	Respiration