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Normal Physiology Exam 2025-2026 - Complete Answers

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RENAL PHYSIOLOGY

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Q1. Describe glomerular filtration process. Factors affecting GFR.

• Blood enters the glomerulus via the afferent arteriole and exits via the efferent arteriole
• The filtration barrier consists of three layers:
  1. Glomerular capillary endothelium (fenestrated)
  2. Glomerular basement membrane (GBM) - main barrier to proteins
  3. Podocytes with slit diaphragms (visceral layer of Bowman's capsule)
• Small molecules (water, glucose, urea, ions, amino acids) pass freely; cells and large proteins do NOT
• The filtrate is similar to plasma but essentially protein-free

• Glomerular hydrostatic pressure (PGC): ~60 mmHg - promotes filtration
• Bowman's capsule hydrostatic pressure (PBS): ~18 mmHg - opposes filtration
• Glomerular oncotic pressure (πGC): ~32 mmHg - opposes filtration
• Bowman's capsule oncotic pressure (πBS): ~0 mmHg - promotes filtration
• Net filtration pressure = 60 - 18 - 32 = ~10 mmHg

• Kf (filtration coefficient) = hydraulic conductivity × surface area
• Normal GFR = 125 mL/min (180 L/day)

• Myogenic mechanism
• Tubuloglomerular feedback (macula densa)

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Q2. Describe the mechanism of tubular reabsorption in different parts of the nephron.

• Active transport: requires energy (primary - uses ATP directly; secondary - uses electrochemical gradient)
• Passive transport: osmosis, diffusion, facilitated diffusion

• 100% of glucose and amino acids (Na-glucose cotransporter SGLT2, secondary active)
• 65% of Na⁺ and water (isosmotic reabsorption)
• 65% of Cl⁻, K⁺, HCO₃⁻, Ca²⁺, PO₄³⁻
• Urea passively follows water
• Organic acids and bases secreted here
• Brush border increases surface area

• Descending thin limb: permeable to water only (water exits, concentrates tubular fluid)
• Ascending thin limb: permeable to NaCl (passive)
• Thick ascending limb (TAL): actively reabsorbs NaCl via Na-K-2Cl cotransporter (NKCC2); impermeable to water → dilutes tubular fluid
• ~25% of filtered NaCl reabsorbed here

• Reabsorbs NaCl via Na-Cl cotransporter (NCC)
• Fine regulation of Ca²⁺ (PTH-dependent)
• Impermeable to water (regardless of ADH)

• Principal cells: reabsorb Na⁺ (aldosterone-regulated via ENaC), secrete K⁺
• Intercalated cells: H⁺ secretion (acid-base regulation), HCO₃⁻ reabsorption
• Water permeability controlled by ADH (vasopressin): inserts aquaporin-2 channels
• Without ADH: dilute urine; With ADH: concentrated urine (up to 1200 mOsm/L)

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Q3. Renal Function Tests. Normal Ranges.

• Volume: 1-2 L/day
• Color: pale to dark yellow
• pH: 4.5-8.0 (avg 6.0)
• Specific gravity: 1.001-1.035
• Protein: absent or <150 mg/day
• Glucose: absent (threshold ~180 mg/dL plasma)
• Ketones, blood, bilirubin: absent normally

• Normal: 0.6-1.2 mg/dL (men); 0.5-1.1 mg/dL (women)
• Rises when GFR falls; relatively insensitive until 50% nephron loss

• Normal: 7-20 mg/dL
• BUN:Creatinine ratio: 10:1-20:1

• GFR = (Ucr × V) / Pcr
• Normal: 90-125 mL/min (CKD defined as GFR < 60 for >3 months)

• Normal: 50-1200 mOsm/kg; random ~300-900

• Normal: <150 mg/day
• Nephrotic range: >3.5 g/day

• Varies; useful in differentiating prerenal AKI (<20 mEq/L) from intrinsic (<40 mEq/L)

• Na⁺: 135-145 mEq/L
• K⁺: 3.5-5.0 mEq/L
• Cl⁻: 95-105 mEq/L
• HCO₃⁻: 22-26 mEq/L

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Q4. Explain physiology of micturition reflex.

• Detrusor muscle: smooth muscle of bladder wall (parasympathetic innervation, S2-S4)
• Internal urethral sphincter: smooth muscle (sympathetic, L1-L2 - keeps closed during filling)
• External urethral sphincter: skeletal muscle (somatic, pudendal nerve S2-S4 - voluntary control)

• As bladder fills (capacity ~400-600 mL), stretch receptors in wall signal pelvic nerve afferents to spinal cord
• Sympathetic activation (hypogastric nerve, L1-L2): relaxes detrusor (β₃ adrenoceptors), contracts internal sphincter (α₁)
• Somatic: external sphincter contracted voluntarily/reflexly
• Pontine storage center suppresses voiding

1. Bladder volume reaches threshold (~300-400 mL), afferent signals reach the PMC (pontine micturition center)
2. PMC activates sacral parasympathetic (S2-S4) neurons
3. Parasympathetic (pelvic nerve): releases ACh → muscarinic (M₃) receptors → detrusor contracts
4. Simultaneous inhibition of sympathetic and somatic outflow → internal and external sphincters relax
5. Bladder pressure exceeds urethral resistance → urine flows
6. Spinobulbospinal reflex coordinated by PMC (Barrington's nucleus)

• Cerebral cortex (frontal lobe): voluntary inhibition of voiding
• Hypothalamus: modulates
• Pontine centers: coordinate sphincter relaxation with detrusor contraction

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Q5. Explain functions of the kidney.

1. Excretion of metabolic waste products: urea, creatinine, uric acid, bilirubin metabolites, drug metabolites
2. Regulation of water balance: adjusts urine volume via ADH; maintains total body water
3. Regulation of electrolyte balance: Na⁺, K⁺, Cl⁻, Ca²⁺, Mg²⁺, PO₄³⁻ via selective reabsorption/secretion
4. Regulation of acid-base balance: excretes H⁺, reabsorbs HCO₃⁻, produces new HCO₃⁻; maintains blood pH 7.35-7.45
5. Regulation of blood pressure: via renin-angiotensin-aldosterone system (RAAS); pressure natriuresis
6. Erythropoiesis: produces erythropoietin (EPO) in peritubular fibroblasts → stimulates RBC production in bone marrow
7. Vitamin D activation: converts 25-hydroxyvitamin D → 1,25-dihydroxyvitamin D (calcitriol) via 1α-hydroxylase
8. Gluconeogenesis: the kidney contributes to glucose synthesis (particularly during prolonged fasting)
9. Hormone degradation: degrades low molecular weight hormones (e.g., insulin, PTH)
10. Immune function: produces cytokines; renal tissue expresses pattern recognition receptors

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Q6. Properties and composition of normal urine.

• Urea: 25-35 g (major nitrogenous waste)
• Creatinine: 1-2 g/day
• Uric acid: 0.5-1.0 g/day
• Sodium: 100-250 mEq/day
• Potassium: 25-120 mEq/day
• Chloride: 100-250 mEq/day
• Phosphate: 0.8-2.0 g/day
• Ammonia: 0.3-1.2 g/day
• Water: ~95% of total volume
• Organic acids (hippuric, oxalic acid)
• Hormones and their metabolites

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Q7. Describe the physiology of urine formation.

• ~125 mL/min filtered (180 L/day)
• Ultrafiltrate formed in Bowman's capsule

• PCT: 65% Na⁺, H₂O, all glucose/amino acids, HCO₃⁻
• Loop of Henle: 25% NaCl; creates medullary concentration gradient
• DCT: fine-tunes NaCl, Ca²⁺
• Collecting duct: regulated by ADH (water) and aldosterone (Na⁺/K⁺)
• ~99% of filtrate reabsorbed → 1.5 L/day urine

• Moves substances from peritubular capillaries INTO tubular lumen
• K⁺ secreted in collecting duct (principal cells, aldosterone-regulated)
• H⁺ secreted in PCT and collecting duct (acid-base balance)
• Organic acids and bases (drugs, toxins) - PCT
• NH₄⁺ produced in PCT, secreted throughout

• Medullary interstitium is hypertonic (600-1200 mOsm/kg)
• Created by thick ascending limb (actively pumps NaCl without water)
• Collecting duct, in presence of ADH, becomes water-permeable → water exits → urine concentrated
• Urea recycling contributes to inner medullary hypertonicity
• Vasa recta (countercurrent exchangers) maintain the gradient

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GASTROINTESTINAL PHYSIOLOGY

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Q8. Digestion in the stomach. Digestive and non-digestive functions.

1. Mechanical digestion: peristaltic contractions (3/min) churn food into chyme; pylorus acts as a sieve
2. Protein digestion: pepsinogen activated by HCl → pepsin → cleaves peptide bonds (endopeptidase, works pH <2)
3. Lipase: gastric lipase digests ~30% of triglycerides (lingual + gastric)
4. Intrinsic factor secretion: by parietal cells, essential for vitamin B12 absorption in terminal ileum
5. HCl secretion: creates acidic environment (pH 1-2), activates pepsinogen, kills microorganisms, aids iron absorption

1. Reservoir function: stores up to 1.5-2 L; controlled release of chyme into duodenum
2. Bactericidal action: HCl kills most ingested pathogens
3. Endocrine function: G cells secrete gastrin; D cells secrete somatostatin; ECL cells secrete histamine
4. Mucus protection: mucus-bicarbonate layer protects mucosa
5. Absorption: minimal (alcohol, NSAIDs, lipid-soluble drugs)
6. Hematopoietic: intrinsic factor for B12 absorption → RBC production

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Q9. Digestion in oral cavity. Saliva - amount, composition, properties, physiological role, regulation of salivation.

• Mechanical: teeth mastication → food particle size reduced → increases surface area
• Chemical: salivary amylase (ptyalin) begins starch digestion
• Bolus formation for swallowing (deglutition reflex)

• Amount: 1-1.5 L/day (0.5-2.0 L range)
• pH: 6.0-7.4 (slightly acidic to neutral)
• Composition:
  • Water: ~99%
  • Organic: salivary amylase (ptyalin), lingual lipase, mucin, IgA, lysozyme, lactoferrin, proline-rich proteins
  • Inorganic: Na⁺, K⁺, Cl⁻, HCO₃⁻, Ca²⁺, PO₄³⁻, thiocyanate

• Hypotonic to plasma at rest; more isotonic at high flow
• Viscous (mucin), slightly acidic

1. Moistens food → facilitates chewing and swallowing
2. Solubilizes food chemicals → enables taste
3. Carbohydrate digestion (amylase cleaves α-1,4 glycosidic bonds → maltose, dextrins)
4. Antibacterial (lysozyme, IgA, lactoferrin, peroxidase)
5. Tooth protection (buffers acid, remineralizes enamel with Ca²⁺/PO₄³⁻)
6. Lubricates speech
7. Wound healing (EGF, histatin in saliva)

• Controlled by salivatory nuclei in brainstem (superior and inferior salivatory nuclei)
• Parasympathetic (CN VII - facial, CN IX - glossopharyngeal): major stimulant → profuse, watery saliva via ACh → muscarinic receptors
• Sympathetic (T1-T3): minor effect → scanty, viscous saliva (mucin-rich)
• Stimuli: food in mouth (unconditioned reflex), sight/smell/thought of food (conditioned reflex), nausea stimulates, sympathetic activation inhibits (xerostomia in anxiety)
• Atropine: blocks parasympathetic → dry mouth

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Q10. Gastric juice - composition, properties, physiological role of HCl.

• Amount: 2-3 L/day
• pH: 1.5-2.0 (highly acidic)
• Color: colorless, watery

• H⁺/K⁺-ATPase (proton pump) on apical membrane pumps H⁺ into lumen in exchange for K⁺
• Cl⁻ exits via CFTR channel
• Stimulated by: histamine (H₂ receptors), ACh (M₃), gastrin (CCK-B receptors)
• Inhibited by: somatostatin, secretin, PGE₂, proton pump inhibitors (PPIs)

1. Activates pepsinogen → pepsin (optimal pH 1-2)
2. Denatures proteins → exposes peptide bonds
3. Bactericidal (kills most swallowed organisms)
4. Promotes Fe²⁺ absorption (converts Fe³⁺ → Fe²⁺)
5. Stimulates secretin release from S cells (in duodenum)
6. Inactivates salivary amylase

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Q11. Pancreatic juice - composition, properties, regulation of pancreatic secretion.

• Amount: 1.5-3 L/day
• pH: 7.6-8.2 (alkaline due to HCO₃⁻)
• Clear, colorless, isotonic

• Aqueous component (ductal cells): HCO₃⁻-rich fluid (up to 140 mEq/L) → neutralizes gastric acid in duodenum
• Enzymatic component (acinar cells):

• Trypsinogen → trypsin (activated by enterokinase/enteropeptidase)
• Chymotrypsinogen → chymotrypsin
• Proelastase → elastase
• Procarboxypeptidase A & B → carboxypeptidases

• Pancreatic lipase (with colipase): hydrolyzes triglycerides → fatty acids + monoglycerides
• Phospholipase A₂ (pro-form activated by trypsin)
• Cholesterol esterase

• Secretin (S cells of duodenum, released by acid): stimulates HCO₃⁻-rich juice (aqueous phase)
• CCK (I cells of duodenum, released by fat and protein): stimulates enzyme-rich juice; potentiates secretin
• Vagal (cephalic phase): acetylcholine → enzyme secretion (minor)
• Somatostatin, glucagon, VIP: inhibit
• Gastric inhibitory peptide (GIP): modestly inhibits

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Q12. The role of pancreatic juice for digestion in duodenum.

1. Neutralization of acid: HCO₃⁻ raises duodenal pH from ~2 (chyme) to ~7-8, creating optimal pH for pancreatic enzyme activity and protecting the duodenal mucosa
2. Protein digestion: trypsin + chymotrypsin → oligopeptides; carboxypeptidases → single amino acids; elastase → structural proteins
3. Fat digestion: pancreatic lipase + colipase → fatty acids + monoglycerides; phospholipase A₂ + cholesterol esterase complete fat digestion
4. Carbohydrate digestion: pancreatic amylase → maltose, maltotriose, α-dextrins (from starch)
5. Activation cascade: enterokinase (on duodenal brush border) activates trypsinogen → trypsin, which then activates all other pancreatic zymogens

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Q13. Bile - composition, participation in digestion, functions.

• Produced by hepatocytes: 600-1200 mL/day
• Stored and concentrated in gallbladder (5-10x concentration)

1. Emulsification of fats: bile salts are amphipathic (hydrophilic and hydrophobic); break large fat globules into smaller droplets → increases surface area for lipase action
2. Micelle formation: bile salts form mixed micelles with fatty acids, monoglycerides, fat-soluble vitamins (A, D, E, K) and cholesterol → solubilizes lipids for absorption
3. Activate pancreatic lipase (via colipase)

1. Fat digestion and absorption (as above)
2. Fat-soluble vitamin absorption (A, D, E, K)
3. Cholesterol excretion (only route for eliminating cholesterol)
4. Bilirubin excretion (from heme metabolism)
5. Intestinal motility stimulation
6. Bacteriostatic effect
7. Enterohepatic circulation: 95% of bile salts reabsorbed in terminal ileum → returned to liver; only 5% excreted in feces

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Q14. Digestion in the small intestine.

• Segmentation contractions: mix chyme with digestive secretions
• Peristalsis: propels chyme aborally (3-5 cm/min); ITT (migrating motor complex between meals)

• Carbohydrates: pancreatic amylase → disaccharides; brush border enzymes (sucrase, lactase, maltase, isomaltase) → monosaccharides (glucose, fructose, galactose)
• Proteins: pancreatic proteases → oligopeptides; brush border peptidases (aminopeptidase, dipeptidyl peptidase) → di/tripeptides → absorbed as such or further hydrolyzed
• Fats: pancreatic lipase + bile salts → micelles → absorbed as fatty acids and monoglycerides

• Pancreatic juice (1.5-3 L/day)
• Bile (600-1200 mL/day)
• Succus entericus (intestinal juice, 2-3 L/day): mucus, enterokinase, intestinal enzymes

• Mucosal folds (valvulae conniventes)
• Villi (finger-like projections)
• Microvilli (brush border): total area ~200 m²

• Monosaccharides: Na⁺-glucose cotransporter (SGLT1) at apical; GLUT2 at basolateral
• Amino acids: various Na⁺-dependent cotransporters
• Fatty acids/monoglycerides: diffuse into enterocyte → re-esterified to triglycerides → chylomicrons → lymph (lacteals)
• Water and electrolytes absorbed throughout

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Q15. Digestion, Absorption and Metabolism of Proteins.

• Stomach: pepsin (endopeptidase, pH 1.5-2) → large polypeptides; HCl denatures proteins
• Small intestine:
  • Pancreatic endopeptidases: trypsin, chymotrypsin, elastase → oligopeptides
  • Pancreatic exopeptidases: carboxypeptidases A & B → removes C-terminal amino acids
  • Brush border exopeptidases: aminopeptidases, dipeptidyl peptidase IV → di/tripeptides and amino acids

• Free amino acids: Na⁺-dependent cotransporters (multiple, based on amino acid type) at apical membrane; facilitated diffusion at basolateral
• Di/tripeptides: H⁺-peptide cotransporter (PepT1) → enter enterocyte → hydrolyzed by cytoplasmic peptidases → amino acids enter portal blood
• Portal blood → liver → general circulation

• Anabolism: amino acids used for synthesis of structural proteins, enzymes, hormones, plasma proteins, neurotransmitters
• Catabolism:
  • Transamination: amino group transferred to α-ketoglutarate → glutamate + new α-keto acid (ALT, AST enzymes)
  • Oxidative deamination: glutamate → α-ketoglutarate + NH₄⁺ (glutamate dehydrogenase, in liver)
  • Urea cycle (liver): NH₄⁺ + CO₂ → urea → excreted by kidneys
  • Carbon skeletons: glucogenic (→ glucose via gluconeogenesis) or ketogenic (→ acetyl-CoA → ketone bodies)

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Q16. Digestion, Absorption and Metabolism of Lipids.

• Mouth/Stomach: lingual and gastric lipase → ~30% of TG digested; produces fatty acids that act as surfactants
• Small intestine (main site):
  • Bile salts emulsify fat → large droplets → small droplets (emulsification)
  • Pancreatic lipase + colipase → cleaves ester bonds at sn-1 and sn-3 positions → 2 fatty acids + 2-monoglyceride
  • Phospholipase A₂ → lysophospholipids + fatty acids
  • Cholesterol esterase → free cholesterol + fatty acids
  • Products form mixed micelles with bile salts → transported to brush border

• Micelles deliver fatty acids, monoglycerides, cholesterol, fat-soluble vitamins to enterocyte membrane
• Short- and medium-chain fatty acids (C<12): pass directly into portal blood
• Long-chain fatty acids and monoglycerides: diffuse into enterocyte → re-esterified to TG in smooth ER → packaged with cholesterol, phospholipids, apoproteins (ApoB-48) → chylomicrons
• Chylomicrons enter lacteals → thoracic duct → left subclavian vein

• Chylomicrons delivered to peripheral tissues; TG hydrolyzed by lipoprotein lipase (LPL) → fatty acids for muscle (energy) or adipose (storage)
• Remnants taken up by liver
• Beta-oxidation: fatty acids → acetyl-CoA → TCA cycle → ATP (very energy-dense: 1 palmitate = 129 ATP)
• Lipogenesis: excess acetyl-CoA → fatty acids (liver, adipose); insulin promotes
• Ketogenesis: in fasting/DM, excess acetyl-CoA → ketone bodies (acetoacetate, β-hydroxybutyrate, acetone) in liver

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Q17. Digestion, Absorption and Metabolism of Carbohydrates.

• Oral cavity: salivary α-amylase (ptyalin) cleaves α-1,4 glycosidic bonds → maltose, maltotriose, α-limit dextrins; inactivated by gastric acid
• Stomach: no carbohydrate digestion (salivary amylase inactivated)
• Small intestine (duodenum/jejunum):
  • Pancreatic amylase → maltose, maltotriose, isomaltose, oligosaccharides
  • Brush border disaccharidases:
    • Sucrase → glucose + fructose
    • Lactase → glucose + galactose
    • Maltase → 2 glucose
    • Isomaltase (α-dextrinase) → glucose
  • Dietary fiber: not digested by human enzymes (fermented by colonic bacteria → short-chain fatty acids)

• Glucose and galactose: SGLT1 (Na⁺-glucose cotransporter, secondary active) at apical; GLUT2 at basolateral
• Fructose: GLUT5 (facilitated diffusion) at apical; GLUT2 at basolateral
• Enter portal blood → liver

• Glycolysis (all tissues): glucose → 2 pyruvate (anaerobic → lactate; aerobic → acetyl-CoA)
• Krebs cycle + oxidative phosphorylation: acetyl-CoA → 30-32 ATP/glucose
• Glycogenesis: glucose → glycogen (liver: glycogen phosphorylase; insulin promotes)
• Glycogenolysis: glycogen → glucose (glucagon, epinephrine promote)
• Gluconeogenesis: from lactate, pyruvate, amino acids, glycerol → glucose (liver, kidney; fasting state)
• Pentose phosphate pathway: glucose → NADPH (antioxidant, fatty acid synthesis) + ribose-5-phosphate (nucleotides)

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Q18. Digestion in duodenum. Role of pancreas. Composition and properties of succus entericus.

• Neutralizes acid with HCO₃⁻
• Provides all key digestive enzymes (proteases, lipases, amylase)
• Without pancreatic secretion: severe malabsorption

• Secreted by Lieberkühn crypts (mucous cells) and Brunner's glands (duodenum)
• Amount: 2-3 L/day
• pH: 6.5-7.5
• Composition:
  • Water (~99%)
  • Mucus (protects mucosa)
  • Enterokinase (enteropeptidase): activates trypsinogen → trypsin
  • Brush border enzymes: sucrase, lactase, maltase, aminopeptidases, dipeptidyl peptidase IV, nucleotidases
  • Electrolytes: Na⁺, K⁺, Cl⁻, HCO₃⁻
• Properties: slightly alkaline/neutral, isotonic
• Regulation: distension, chemical irritation (via enteric nervous system); CCK, secretin

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Q19. Basal metabolism. Factors determining basal metabolism. Values of BMR.

• Average adult male: ~1600-1800 kcal/day (~70 W)
• Average adult female: ~1200-1400 kcal/day (~55 W)
• Per unit body surface: ~37-40 kcal/m²/hour
• Per kg body weight: ~1 kcal/kg/hour

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Q20. Absorption in different parts of GIT. Types and mechanisms of absorption.

1. Passive diffusion: concentration gradient, no carrier, no energy; lipid-soluble substances (fatty acids, alcohol, lipid-soluble vitamins, some drugs)
2. Facilitated diffusion: carrier-mediated, down concentration gradient, no energy; fructose (GLUT5), water (aquaporins)
3. Active transport: carrier-mediated, against concentration gradient, requires ATP; glucose, galactose (SGLT1), amino acids, bile salts
4. Secondary active transport (co-transport): Na⁺ electrochemical gradient drives uphill transport; SGLT1 (glucose), amino acid transporters, PepT1 (peptides)
5. Pinocytosis/Endocytosis: macromolecular uptake; vitamin B12-IF complex (ileum), immunoglobulins (neonates)
6. Osmosis: water follows solutes (osmotic gradient)
7. Solvent drag: water movement carries dissolved solutes through tight junctions

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Q21. Role of the liver in digestion.

1. Bile production: hepatocytes synthesize 600-1200 mL bile/day → bile salts, bilirubin, cholesterol, phospholipids, ions; essential for fat emulsification and fat-soluble vitamin absorption
2. Carbohydrate metabolism: glycogen synthesis (postprandial), glycogenolysis and gluconeogenesis (fasting) - maintains blood glucose homeostasis; converts galactose and fructose to glucose
3. Protein metabolism: deaminates amino acids; urea cycle (converts NH₃ → urea); synthesizes plasma proteins (albumin, clotting factors, complement, acute-phase proteins); transamination
4. Lipid metabolism: synthesizes lipoproteins (VLDL); cholesterol synthesis and esterification; fatty acid oxidation; ketogenesis; lecithin synthesis
5. Vitamin storage: stores fat-soluble vitamins (A, D, E, K), B12, folate; activates vitamin D (25-hydroxylation)
6. Iron storage: ferritin stores iron; hepcidin regulates absorption
7. Detoxification: cytochrome P450 enzymes metabolize drugs, toxins, alcohol, hormones; glucuronidation, sulfation
8. First-pass metabolism: orally absorbed drugs pass through portal circulation → liver may significantly metabolize them before reaching systemic circulation
9. Immune function: Kupffer cells (resident macrophages) phagocytose bacteria and debris from portal blood
10. Clotting factors: synthesizes factors I, II, V, VII, VIII, IX, X, XI, XII; requires vitamin K for II, VII, IX, X

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Q22. Functions of GIT hormones.

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Q23. Describe the walls of the gastrointestinal tract and their functions.

• Epithelium: varies by region (simple columnar in most; stratified squamous in esophagus/anus); absorption, secretion, protection
• Lamina propria: connective tissue, capillaries, lymphatics, immune cells (MALT), plasma cells (IgA)
• Muscularis mucosae: thin smooth muscle layer; creates local mucosal folds
• Function: secretion (enzymes, hormones, mucus), absorption, immune defense

• Dense connective tissue with blood vessels, lymphatics, nerve fibers
• Submucosal (Meissner's) plexus: regulates mucosal secretion and blood flow
• Contains Brunner's glands (duodenum) and lymphoid follicles (Peyer's patches - ileum)

• Inner circular layer: constricts lumen; sphincters
• Outer longitudinal layer: shortens tube; peristalsis
• Between them: Myenteric (Auerbach's) plexus: controls motility and coordination
• Functions: peristalsis (propulsion), segmentation (mixing), sphincter control

• Serosa: single layer of mesothelium + connective tissue; covers intraperitoneal organs; reduces friction
• Adventitia: connective tissue only (retroperitoneal organs - esophagus, duodenum 2nd-4th parts, ascending/descending colon, rectum)
• Functions: anchoring, protection, vessels and nerves entry

• Esophagus: skeletal muscle in upper third; stratified squamous epithelium
• Stomach: additional oblique muscle layer; rugae; gastric glands
• Small intestine: villi, microvilli (brush border), plicae circulares; maximizes absorption
• Large intestine: haustra (sacculations), teniae coli (3 longitudinal bands), no villi; absorbs water/electrolytes

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ENDOCRINE PHYSIOLOGY

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Q24. Concept of endocrine glands. Hormones - chemical structure, properties, classification.

1. Secreted in small amounts (nanomolar to picomolar concentrations)
2. High potency (small amounts produce large effects)
3. Act via specific receptors on target cells
4. Regulatory feedback mechanisms control secretion
5. Short half-lives (minutes to hours); degraded by liver/kidneys
6. May have permissive effects (one hormone required for another to work)

• Synthesized as pre-prohormones → prohormones → active hormones
• Examples: insulin, glucagon, PTH, GH, ADH, oxytocin, FSH, LH, TSH, ACTH, GnRH, TRH, somatostatin
• Properties: water-soluble, cannot cross membrane; act via surface receptors; short half-life; stored in secretory vesicles

• Derived from cholesterol
• Examples: cortisol, aldosterone, testosterone, estrogens, progesterone, calcitriol (vitamin D)
• Properties: lipid-soluble, cross cell membrane; act via intracellular receptors; longer half-life; not stored (synthesized on demand)

• Derived from amino acids (tyrosine or tryptophan)
• Catecholamines (from tyrosine): epinephrine, norepinephrine, dopamine → water-soluble, surface receptors
• Thyroid hormones T3, T4 (from tyrosine + iodine): lipid-soluble, nuclear receptors
• Melatonin (from tryptophan): crosses membranes

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Q25. Thyroid iodine-containing hormones (T3 and T4) - biosynthesis, transport, physiological role.

1. Iodide (I⁻) actively transported into follicular cells via Na-I symporter (NIS), driven by Na⁺ gradient
2. Iodide oxidized to active iodine by thyroid peroxidase (TPO) in presence of H₂O₂
3. Tyrosine residues of thyroglobulin (stored in follicular colloid) iodinated:
   • Monoiodotyrosine (MIT): 1 iodine
   • Diiodotyrosine (DIT): 2 iodines
4. Coupling (by TPO): MIT + DIT → T3 (triiodothyronine); DIT + DIT → T4 (thyroxine)
5. Thyroglobulin-T3/T4 stored in colloid
6. On stimulation: pinocytosis of colloid → lysosomes cleave T3/T4 from thyroglobulin → secreted into blood

• 99% bound to plasma proteins:

  • Thyroxine-binding globulin (TBG): 75%
  • Transthyretin (TTR): 15%
  • Albumin: 10%
• Free T3: ~0.3%; Free T4: ~0.03% → biologically active forms
• T4 half-life: ~7 days; T3 half-life: ~1 day

1. Calorigenic effect: increases BMR; increases O₂ consumption in all tissues except brain, testes, uterus, spleen
2. Growth and development: essential for normal growth (synergizes with GH); critical for brain development in fetus and neonates
3. Protein metabolism: low → anabolic; high → protein catabolism
4. Carbohydrate metabolism: increases glucose absorption, glycogenolysis, gluconeogenesis
5. Lipid metabolism: increases lipolysis, cholesterol synthesis AND degradation (net effect: decreases serum cholesterol); increases LDL receptors
6. Cardiovascular: increases heart rate, cardiac output, cardiac contractility; increases sensitivity to catecholamines
7. CNS: maintains normal mental function; essential for myelination
8. Permissive effect: for catecholamines, GH
9. Thermoregulation: produces heat by uncoupling mitochondrial oxidative phosphorylation

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Q26. Hormones of the pancreas and their role in regulation of carbohydrate, protein, and fat metabolism.

• Increases glucose uptake (GLUT4 in muscle, adipose; GLUT2 in liver)
• Promotes glycogenesis (liver and muscle)
• Inhibits glycogenolysis and gluconeogenesis
• Net effect: LOWERS blood glucose

• Promotes amino acid uptake and protein synthesis
• Inhibits protein catabolism
• Net: anabolic

• Stimulates lipogenesis (fatty acid synthesis, TG storage in adipose)
• Inhibits lipolysis and ketogenesis
• Net: promotes fat storage

• Stimulates glycogenolysis (liver) → raises blood glucose
• Stimulates gluconeogenesis

• Stimulates lipolysis → increased fatty acids → β-oxidation
• Stimulates ketogenesis in liver

• Promotes gluconeogenesis from amino acids (increases hepatic uptake)

• Inhibits insulin and glucagon secretion
• Inhibits GI hormones (gastrin, secretin, CCK)
• Slows GI motility and absorption

• Inhibits pancreatic enzyme and HCO₃⁻ secretion
• Inhibits gallbladder contraction

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Q27. Hormones of anterior pituitary (adenohypophysis) and their physiological role.

• GH: GHRH (stimulates), somatostatin (inhibits)
• TSH: TRH (stimulates), T3/T4 feedback (inhibits)
• ACTH: CRH (stimulates), cortisol feedback (inhibits)
• FSH/LH: GnRH (stimulates), sex steroids (feedback)
• Prolactin: dopamine (inhibits, main control), TRH (stimulates)

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Q28. Functions of the Hypothalamus.

• Releases hypophysiotropic hormones into portal vessels:
  • GHRH (→ GH), CRH (→ ACTH), TRH (→ TSH, PRL), GnRH (→ FSH, LH), dopamine (inhibits PRL), somatostatin (inhibits GH, TSH)

• ADH (vasopressin): synthesized in supraoptic nucleus → released from posterior pituitary; controls water reabsorption
• Oxytocin: synthesized in paraventricular nucleus → released from posterior pituitary; uterine contractions, milk ejection

• Posterior/lateral hypothalamus: sympathetic activation ("ergotropic")
• Anterior/medial hypothalamus: parasympathetic ("trophotropic")
• Controls heart rate, BP, GI motility, bladder, sweating

• Anterior hypothalamus: heat loss mechanisms (sweating, vasodilation)
• Posterior hypothalamus: heat conservation (shivering, vasoconstriction)
• Fever: pyrogens raise the "set point"

• Lateral hypothalamus: hunger center (lesion → starvation)
• Ventromedial nucleus: satiety center (lesion → obesity)
• Responds to leptin, ghrelin, glucose levels

• Osmoreceptors detect increased plasma osmolality → stimulate ADH and thirst

• Suprachiasmatic nucleus (SCN): biological clock; regulates sleep-wake, hormone rhythms (cortisol, melatonin)

• Part of limbic system; mediates fear, rage, pleasure, reproductive behavior

• Controls sleep-wake transitions with brainstem

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Q29. Hormonal regulation of calcium and phosphorus metabolism.

• Source: Chief cells of parathyroid glands (4 glands)
• Stimulus: Low Ca²⁺ → detected by calcium-sensing receptor (CaSR)
• Actions:
  • Bone: stimulates osteoclastic bone resorption → releases Ca²⁺ and PO₄³⁻ into blood
  • Kidney: increases Ca²⁺ reabsorption in DCT; DECREASES PO₄³⁻ reabsorption (phosphaturia); activates 1α-hydroxylase (↑ calcitriol)
  • GI: indirectly increases Ca²⁺ absorption via calcitriol
  • Net: ↑Ca²⁺, ↓PO₄³⁻

• Synthesis: skin (UV → vitamin D₃) → liver (25-hydroxylation) → kidney (1α-hydroxylase → active calcitriol); PTH stimulates 1α-hydroxylase
• Actions:
  • GI: major effect - increases Ca²⁺ and PO₄³⁻ absorption (induces calbindin in enterocytes)
  • Bone: supports bone mineralization; at high doses, stimulates resorption
  • Kidney: mild increase in Ca²⁺ and PO₄³⁻ reabsorption
  • Net: ↑Ca²⁺ and ↑PO₄³⁻

• Source: Parafollicular C cells of thyroid
• Stimulus: HIGH Ca²⁺
• Actions:
  • Bone: inhibits osteoclasts → inhibits bone resorption → lowers serum Ca²⁺
  • Kidney: increases Ca²⁺ and PO₄³⁻ excretion
  • Net: ↓Ca²⁺ and ↓PO₄³⁻
  • Physiological significance in adults is minor; mainly protective after calcium-rich meal

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Q30. Hormones of the adrenal cortex and their role.

• Stimulates gluconeogenesis (liver)
• Decreases glucose uptake in peripheral tissues (anti-insulin)
• Increases blood glucose → "diabetogenic"

• Promotes protein catabolism in muscle, bone, skin → releases amino acids for gluconeogenesis

• Stimulates lipolysis; redistributes fat (central obesity, moon face, buffalo hump in hypercortisolism)

• Inhibits phospholipase A₂ (reduces prostaglandins and leukotrienes via lipocortin/annexin-1)
• Suppresses cytokine production
• Inhibits T-cell proliferation
• Stabilizes mast cell membranes
• Decreases capillary permeability

• Maintains vascular responsiveness to catecholamines
• Stress response (HPA axis activation)
• Permissive effects on many hormones

• Stimulated by: angiotensin II, high K⁺, ACTH (minor)
• Action on kidney collecting duct: binds intracellular mineralocorticoid receptors → induces ENaC (Na⁺ channels) and Na⁺/K⁺-ATPase → Na⁺ reabsorption, K⁺ and H⁺ secretion
• Net effect: Na⁺ and water retention (raises BP); K⁺ loss
• Part of RAAS (renin-angiotensin-aldosterone system)

• DHEA, DHEA-S, androstenedione
• Weak androgens, converted peripherally to testosterone/estradiol
• Important in: pubic/axillary hair development in females; adrenal source of androgens in females

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Q31. Main effects of thyroid hormones. Regulation of thyroid hormone production.

1. Calorigenic/thermogenic: increases BMR and heat production by uncoupling oxidative phosphorylation; increases Na⁺/K⁺-ATPase activity
2. Cardiovascular: increases HR, stroke volume, cardiac output; increases expression of β-adrenergic receptors; decreases systemic vascular resistance
3. Growth: essential for normal bone/tissue growth; synergistic with GH and IGF-1
4. Development: critical for CNS development (fetal/neonatal); myelination, neuronal differentiation; cretinism if deficient
5. Protein metabolism: physiological doses → anabolic; excess → catabolic
6. Carbohydrate: increases intestinal glucose absorption, glycogenolysis, gluconeogenesis
7. Lipid: decreases serum cholesterol (increases LDL receptor expression); increases lipolysis
8. CNS: normal mental function, mood, reflexes
9. GI: increases gut motility (hyperthyroid → diarrhea; hypothyroid → constipation)
10. Permissive: for catecholamines, GH, and other hormone actions
11. Hematopoiesis: stimulates EPO production

• Hypothalamus: TRH (thyrotropin-releasing hormone) → released in response to cold, stress, low T3/T4
• Anterior pituitary: TRH → TSH secretion
• TSH: binds TSH receptor on thyroid follicular cells → increases iodide uptake, TPO activity, thyroglobulin synthesis, T3/T4 release; trophic effect on thyroid
• Negative feedback: T3 (predominantly) inhibits TSH secretion at pituitary AND TRH secretion at hypothalamus
• Other modifiers: glucocorticoids and dopamine inhibit TSH; estrogens increase TBG; iodine excess temporarily inhibits production (Wolff-Chaikoff effect)

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Q32. Hormones of the adrenal medulla (epinephrine and norepinephrine) and their physiological role.

• Adrenal medulla secretes ~80% epinephrine (EPI) + ~20% norepinephrine (NE)

• Hyperglycemia: glycogenolysis (liver) + inhibits insulin secretion (α₂) + stimulates glucagon
• Lipolysis: free fatty acids for energy
• Thermogenesis

• EPI: stronger β effects; "metabolic hormone"; dilates blood vessels in skeletal muscle
• NE: stronger α effects; primarily ↑BP by vasoconstriction; acts mainly as neurotransmitter

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Q33. Hypo- and hyperthyroid states.

• Causes: Hashimoto's thyroiditis (most common), iodine deficiency (worldwide), post-thyroidectomy, post-radioiodine, drugs (lithium, amiodarone)

• Weight gain, fatigue, cold intolerance
• Bradycardia, decreased cardiac output
• Constipation, decreased GI motility
• Dry skin, coarse hair, hair loss, brittle nails
• Myxedema: non-pitting edema (accumulation of glycosaminoglycans)
• Hypercholesterolemia
• Depression, cognitive slowing, psychomotor retardation
• Menstrual irregularities (heavy periods), infertility
• Reflexes: delayed relaxation phase
• Elevated TSH, low free T4

• If untreated: severe intellectual disability, growth retardation, deafness, spastic diplegia
• Neonatal screening (TSH) and early treatment with T4 prevents disability

• Weight loss despite increased appetite
• Tachycardia, palpitations, atrial fibrillation, increased CO
• Heat intolerance, excessive sweating, warm moist skin
• Diarrhea
• Anxiety, irritability, tremor, insomnia
• Exophthalmos (in Graves' disease - TSI activates retroorbital fibroblasts)
• Goiter
• Decreased TSH, elevated free T4 and/or T3
• Thyroid storm: life-threatening hypermetabolic crisis; fever, tachycardia, altered consciousness

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Q34. Mechanism of hormone action - primary and secondary messengers.

• 7 transmembrane domain receptors
• Coupled to G proteins (Gs, Gi, Gq)

• Hormone → receptor → Gs → adenylyl cyclase → ATP → cAMP (second messenger) → PKA (protein kinase A) → phosphorylates enzymes → cellular response
• Examples: glucagon, EPI (β receptors), TSH, ACTH, PTH, ADH (V2), LH, FSH, glucagon
• cAMP degraded by phosphodiesterase (inhibited by caffeine, theophylline)

• Hormone → Gq → phospholipase C → PIP₂ → IP₃ + DAG
• IP₃ → releases Ca²⁺ from ER → Ca²⁺ is second messenger → calmodulin → kinase activation
• DAG → activates protein kinase C (PKC)
• Examples: ADH (V1), oxytocin, TRH, GnRH, EPI (α₁)

• Inhibits adenylyl cyclase → ↓cAMP
• Examples: somatostatin, EPI (α₂), ACh (muscarinic in heart)

• Hormone binds → receptor dimerization → autophosphorylation of tyrosine residues → activates downstream kinases (Ras-MAP kinase, PI3K-Akt pathways)
• Examples: insulin, IGF-1, EGF, PDGF

• Growth hormone, prolactin, cytokines (EPO, interferons)
• Binding → JAK kinases activated → STAT proteins phosphorylated → enter nucleus → gene transcription

• Hormones diffuse across membrane
• Cytoplasmic receptors (steroid hormones): hormone-receptor complex → translocates to nucleus → binds DNA hormone response elements (HREs) → activates/represses gene transcription → new protein synthesis (hours-days response)
• Nuclear receptors (thyroid hormone, calcitriol, retinoic acid): receptor already in nucleus; hormone enters nucleus and binds

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Q35. Posterior pituitary (neurohypophysis) hormones - role and mechanism of action.

• ADH (vasopressin): synthesized in supraoptic nucleus (SON)
• Oxytocin: synthesized in paraventricular nucleus (PVN) Both travel via axonal transport down the hypothalamo-hypophyseal tract to nerve terminals in the posterior pituitary.

• Increased plasma osmolality (main stimulus; detected by SON osmoreceptors; threshold ~285 mOsm/kg)
• Decreased blood volume/pressure (detected by baroreceptors; more powerful but requires >10% volume loss)
• Pain, nausea, stress, nicotine, opioids → stimulate
• Alcohol, cold → inhibit

• V₂ receptors (kidney collecting duct): Gs → ↑cAMP → PKA → inserts aquaporin-2 (AQP2) into apical membrane → water reabsorption from tubular lumen → concentrated urine
• Also induces gene transcription of AQP2 (chronic exposure)

• Concentrates urine (up to 1200 mOsm/L); reduces urine volume
• V₁ receptors (blood vessels): Gq → IP₃/DAG → vasoconstriction → ↑BP (at pharmacological doses)
• V₁b receptors (anterior pituitary): potentiates ACTH release

• Cervical/vaginal stretch → Ferguson reflex → positive feedback release
• Infant suckling → neuroendocrine reflex → milk ejection

1. Parturition: stimulates uterine smooth muscle contractions (myometrium); positive feedback with Ferguson reflex; sensitivity increases at term (more OT receptors)
2. Milk ejection reflex: stimulates myoepithelial cells in mammary glands → milk letdown
3. Bonding/Social behavior: promotes maternal behavior, pair bonding, trust, social recognition
4. Male: stimulates sperm transport (seminiferous tubules)

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Q36. Prostaglandins and their role in the organism.

• Phospholipase A₂ (activated by mechanical stress, hormones, cytokines) liberates AA from membrane phospholipids
• COX-1 (constitutive) and COX-2 (inducible) convert AA → PGG₂ → PGH₂
• Tissue-specific isomerases produce: PGE₂, PGI₂ (prostacyclin), PGD₂, PGF₂α, TXA₂ (thromboxane)
• NSAIDs (aspirin, ibuprofen) inhibit COX → reduce prostaglandin synthesis

1. Inflammation: PGE₂ and PGI₂ → vasodilation, increased vascular permeability; PGE₂ → sensitizes pain receptors (hyperalgesia, allodynia)
2. Fever: PGE₂ (from hypothalamic COX-2 induced by pyrogens/IL-1, IL-6, TNF) → raises hypothalamic set point
3. Pain: PGE₂ sensitizes nociceptors; COX inhibitors reduce pain
4. Gastric protection: PGE₂ and PGI₂ → increase mucus and HCO₃⁻ secretion; decrease acid secretion; increase mucosal blood flow; NSAIDs (especially non-selective) remove this protection → ulcers
5. Renal function: PGE₂ and PGI₂ → afferent arteriolar vasodilation → maintain GFR in volume-depleted states; NSAIDs block this → acute kidney injury in at-risk patients
6. Uterus: PGF₂α → myometrial contraction; PGE₂ → uterine contraction and cervical ripening; used in obstetrics to induce labor or treat PPH; dysmenorrhea from excess PGF₂α
7. Platelet aggregation: TXA₂ (from platelets) → vasoconstriction and platelet aggregation; PGI₂ (from endothelium) → vasodilation and inhibits aggregation (opposing effects)
8. Bronchi: TXA₂ → bronchoconstriction; PGE₂ → bronchodilation or bronchoconstriction (receptor-dependent); overproduction in asthma
9. Vascular tone: PGI₂ → vasodilation; TXA₂ → vasoconstriction

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NERVOUS SYSTEM

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Q37. Structure and classification of synapses. Mechanism of excitation in electrical and chemical synapses. Ionic mechanisms of postsynaptic potentials.

1. Chemical synapses: most common; use neurotransmitters; unidirectional; with synaptic delay (~0.3-0.5 ms)
2. Electrical synapses (gap junctions): direct ionic flow between cells via connexin channels; bidirectional; no delay; rare in adult CNS (cardiac muscle, smooth muscle, some CNS glial/neuronal junctions)

• Axodendritic (most common), axosomatic, axoaxonic, dendrodendritic

• Excitatory (EPSP), inhibitory (IPSP)

• Presynaptic terminal: contains synaptic vesicles, mitochondria, voltage-gated Ca²⁺ channels
• Synaptic cleft: ~20-40 nm wide
• Postsynaptic membrane: ligand-gated ion channels (ionotropic) or G-protein coupled receptors (metabotropic)

1. Action potential arrives at presynaptic terminal
2. Depolarization opens voltage-gated Ca²⁺ channels → Ca²⁺ influx
3. Ca²⁺ triggers vesicle fusion with presynaptic membrane (SNARE proteins) → exocytosis of neurotransmitter
4. NT diffuses across cleft, binds postsynaptic receptors
5. Ion channels open → postsynaptic potential
6. NT removed: reuptake (transporters), enzymatic degradation (AChE, MAO), diffusion

• Gap junctions: connexon channels connect cytoplasm of adjacent cells
• Current flows directly → faster than chemical synapses
• Bidirectional; synchronize populations of neurons

• Ionotropic receptors open channels permeable to Na⁺ and K⁺ (e.g., AMPA, nAChR)
• Reversal potential ~0 mV → net inward current → local depolarization
• Spatial and temporal summation of EPSPs → reach threshold → action potential at axon hillock

• Cl⁻ influx (GABA-A, glycine receptors): membrane potential moves toward E_Cl (~-70 mV) → hyperpolarization
• K⁺ efflux (GABA-B, metabotropic): membrane hyperpolarizes toward E_K (~-90 mV)
• Result: harder to generate action potential (inhibition)

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Q38. Reflex activity of the nervous system. Classification of reflexes.

1. Receptor (sensory receptor)
2. Afferent (sensory) nerve
3. Reflex center (in spinal cord or brain)
4. Efferent (motor) nerve
5. Effector (muscle or gland)

• Unconditioned (innate): genetically programmed; permanent; withdrawal reflex, swallowing, coughing, knee jerk
• Conditioned (acquired): learned; requires cortex; Pavlovian conditioning

• Defensive (cough, sneeze, blink)
• Alimentary (salivation, swallowing, gastric secretion)
• Sexual
• Orienting (head turning toward stimulus)

• Exteroceptive (stimuli from outside body)
• Interoceptive (from viscera - autonomic reflexes)
• Proprioceptive (from muscles, tendons, joints - muscle stretch reflex)

• Somatic (skeletal muscle)
• Autonomic/Visceral (smooth muscle, cardiac muscle, glands)

• Monosynaptic: stretch (myotatic) reflex - only 1 synapse (Ia afferent → α-motor neuron); fastest
• Polysynaptic: involve interneurons; withdrawal reflex, crossed-extensor reflex

• Spinal reflexes (center in spinal cord)
• Bulbar (brainstem): gag, swallowing, vomiting
• Cerebellar, mesencephalic, cortical (voluntary)

• Phasic (brief) vs. tonic (sustained)

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Q39. Spinal cord - reflex activity and conduction functions. Role in musculoskeletal and autonomic regulation.

1. Stretch reflex (myotatic): monosynaptic; Ia afferents (muscle spindle) → α-motor neurons → muscle contracts; antagonist inhibited (reciprocal inhibition via Ia inhibitory interneurons); maintains muscle tone and posture; knee jerk (L3-L4), biceps (C5-C6)
2. Golgi tendon organ reflex (inverse myotatic/autogenic inhibition): Ib afferents from GTO → inhibitory interneurons → inhibit α-motor neuron → muscle relaxation when tension too high; protective
3. Flexion (withdrawal) reflex: nociceptive stimulus → polysynaptic reflex → flexors contract (withdraw limb); crossed-extensor reflex: contralateral extensors contract to maintain balance
4. Clasp-knife reflex: hyperextension → sudden relaxation of spastic muscle (velocity-sensitive component of GTO/spindle)

• Micturition, defecation, sexual function (S2-S4)
• Vasoconstriction, sweating (T1-L2 sympathetic)

• Dorsal columns (DCML): fine touch, vibration, proprioception, 2-point discrimination (ipsilateral)
• Anterolateral system (spinothalamic): pain, temperature (contralateral; decussates 1-2 levels above entry)
• Spinocerebellar tracts: unconscious proprioception to cerebellum

• Corticospinal (pyramidal): voluntary fine motor (lateral CST - decussates in medulla; anterior CST)
• Rubrospinal, vestibulospinal, reticulospinal: posture, muscle tone, reflex modulation

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Q40. Structure of the spinal cord, its parts. Functions.

• Elongated cylindrical structure, ~45 cm long
• Two enlargements: cervical (C5-T1, for upper limb) and lumbosacral (L2-S3, for lower limb)
• Conus medullaris: tapered end at L1-L2
• Cauda equina: spinal nerve roots below conus

• Dorsal horns (posterior): receive sensory (afferent) input; contains interneurons and neurons for pain/temperature (Rexed laminae I-VI)
• Ventral horns (anterior): contain α-motor neurons (large), γ-motor neurons (small); control skeletal muscles
• Lateral horns (T1-L2, S2-S4): preganglionic autonomic neurons (sympathetic at T1-L2; parasympathetic at S2-S4)

• Dorsal funiculus: dorsal columns (DCML pathway)
• Lateral funiculus: lateral corticospinal tract, spinothalamic, spinocerebellar
• Ventral funiculus: anterior corticospinal, reticulospinal, vestibulospinal

1. Conduction: relay sensory info to brain; relay motor commands from brain to muscles
2. Segmental reflexes: stretch, withdrawal, autonomic (micturition, defecation)
3. Integration: interneurons coordinate simple motor programs
4. Autonomic control: sympathetic (T1-L2) and parasympathetic (S2-S4) preganglionic neurons

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Q41. Describe divisions of the nervous system.

• Brain (cerebrum, cerebellum, brainstem)
• Spinal cord

• Cranial nerves (12 pairs)
• Spinal nerves (31 pairs)
• Peripheral ganglia
• Enteric nervous system (ENS - "gut brain")

• Voluntary control of skeletal muscle
• Sensory: touch, pain, temperature, proprioception from skin, muscles, joints
• Motor: single neuron from CNS to muscle (no synapse in periphery)

• Involuntary control of smooth muscle, cardiac muscle, glands
• Two-neuron chain: preganglionic → ganglion → postganglionic → effector
• Divisions:
  • Sympathetic: fight-or-flight (T1-L2 origin; chain ganglia)
  • Parasympathetic: rest-and-digest (cranial nerves III, VII, IX, X and S2-S4)
  • Enteric: intrinsic nervous system of GI tract (myenteric and submucosal plexuses); can function autonomously

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Q42. Structure and functions of the retina.

1. Retinal pigment epithelium (RPE): phagocytoses shed photoreceptor outer segments, vitamin A recycling, blood-retinal barrier
2. Photoreceptors (outer segments, then inner segments)
3. Outer nuclear layer (photoreceptor nuclei)
4. Outer plexiform layer (synapses between photoreceptors and bipolar cells)
5. Inner nuclear layer (bipolar cells, horizontal cells, amacrine cells, Müller cells)
6. Inner plexiform layer (synapses bipolar→ganglion)
7. Ganglion cell layer
8. Nerve fiber layer (axons of ganglion cells → optic nerve)

• Peripheral retina; absent from fovea
• Scotopic vision (low light, night)
• Pigment: rhodopsin (opsin + 11-cis-retinal, derived from vitamin A)
• No color discrimination; high sensitivity

• Concentrated in fovea centralis (highest visual acuity)
• Photopic vision (daylight, color)
• Three types: S (blue, 420 nm), M (green, 530 nm), L (red, 560 nm)
• Lower sensitivity but higher acuity

1. Light → 11-cis-retinal isomerizes to all-trans-retinal → activates opsin → rhodopsin
2. Rhodopsin activates transducin (G-protein)
3. Transducin activates PDE (phosphodiesterase) → cGMP degraded → cGMP-gated cation channels CLOSE
4. Dark current (Na⁺ influx) stops → photoreceptor hyperpolarizes (-70 mV in dark → -80 mV in light)
5. Less glutamate released → bipolar cell activated/inhibited depending on type
6. Signal processed by bipolar → ganglion → optic nerve (CN II) → LGN of thalamus → V1 (occipital cortex)

• Fovea centralis: only cones; highest acuity; no overlying cells (direct photon access)
• Optic disc (blind spot): no photoreceptors; exit point of optic nerve; normally not perceived
• Macula lutea: yellow pigment (lutein, zeaxanthin), protects against UV

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Q43. Medulla oblongata and pons - role in regulation of autonomic functions.

• Cardiac center: cardio-acceleratory (sympathetic) and cardioinhibitory (vagal, parasympathetic) areas → regulate HR and cardiac contractility; receive input from baroreceptors (aortic arch, carotid sinus via CN IX, X)
• Vasomotor center: regulates vascular tone (sympathetic vasoconstriction); controls blood pressure

• Dorsal respiratory group (DRG): inspiratory neurons; receives input from peripheral chemoreceptors (IX, X)
• Ventral respiratory group (VRG): controls forced expiration and inspiration; Pre-Bötzinger complex generates respiratory rhythm

• Vomiting center (area postrema): chemoreceptor trigger zone (CTZ); responds to emetogenic drugs, toxins
• Swallowing center: coordinates pharyngeal and esophageal phase of deglutition
• Cough and sneezing centers
• Hiccup center
• CN IX (glossopharyngeal) and CN X (vagus) nuclei: nucleus ambiguus (motor for IX, X, XI - pharynx, larynx); nucleus tractus solitarius (NTS - taste, visceral sensation)

• Pneumotaxic center (Pontine respiratory group): limits inspiration, promotes expiration; regulates breathing rhythm
• Apneustic center: promotes sustained inspiration; inhibited by pneumotaxic center

• Trigeminal nuclei (V): face sensation, mastication
• Abducens nucleus (VI): lateral eye movement
• Facial nucleus (VII): facial expression, lacrimal/salivary secretion
• Vestibulocochlear (VIII) nuclei: balance and hearing

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Q44. Function of Synapse (Excitatory and Inhibitory).

• Transmits electrical signals from one neuron to another (or to effector cells)
• Allows integration, amplification, and modulation of signals
• Site of pharmacological action of many drugs

• Neurotransmitters: glutamate (major excitatory NT in CNS), acetylcholine (NMJ), aspartate
• Opens Na⁺/K⁺ channels (ionotropic: AMPA, NMDA) → net inward current → membrane depolarizes toward 0 mV
• Produces EPSP (Excitatory Postsynaptic Potential): local graded depolarization
• Summation: temporal (rapid sequential stimuli) and spatial (multiple inputs) → trigger action potential at axon hillock when threshold (~-55 mV) is reached
• Role: transmit information, activate motor neurons, relay sensory signals, facilitate learning (LTP via NMDA)

• Neurotransmitters: GABA (main CNS inhibitory NT), glycine (spinal cord/brainstem)
• GABA-A: opens Cl⁻ channels → Cl⁻ influx → IPSP (hyperpolarization toward -70 mV)
• GABA-B: opens K⁺ channels → K⁺ efflux → hyperpolarization
• Glycine: opens Cl⁻ channels → IPSP
• Role: prevents over-excitation (prevents epilepsy), provides precise timing, creates surround inhibition, coordinate antagonist muscles, maintain normal rhythms
• Tetanus toxin (blocks glycine release), strychnine (blocks glycine receptors) → convulsions
• Benzodiazepines, barbiturates → enhance GABA-A → sedation, anxiolysis

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Q45. Effects of sympathetic and parasympathetic stimulation on different visceral functions.

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Q46. Classification of neurotransmitters and their functions.

• Glutamate: major excitatory NT in CNS; AMPA, NMDA, kainate, mGluR receptors; synaptic plasticity, learning
• GABA (γ-aminobutyric acid): major inhibitory NT; GABA-A (Cl⁻), GABA-B (K⁺); prevents over-excitation
• Glycine: inhibitory NT in spinal cord and brainstem; Cl⁻ channels; motor coordination, reflex inhibition

• Dopamine: reward, motivation, motor control (substantia nigra → striatum); prolactin inhibition; pathways: nigrostriatal, mesolimbic, mesocortical, tuberoinfundibular; Parkinson's (↓DA in nigrostriatal); schizophrenia (↑DA)
• Serotonin (5-HT): mood, sleep, appetite, GI motility; from raphe nuclei; depression (↓5-HT); SSRIs restore
• Norepinephrine (NE): arousal, attention, fight-or-flight; from locus coeruleus; sympathetic postganglionic
• Epinephrine: minor CNS role; major hormone from adrenal medulla
• Histamine: wakefulness, appetite; from tuberomammillary nucleus; allergic responses (H₁)

• NMJ (nAChR: nicotinic), ganglia, CNS, parasympathetic effectors (M)
• Functions: voluntary movement, memory (hippocampus), REM sleep; Alzheimer's disease (↓ACh)

• Endorphins, enkephalins, dynorphins (opioids): pain modulation, reward; μ, δ, κ receptors
• Substance P: pain transmission; released by nociceptors
• Neuropeptide Y (NPY): appetite stimulation, vasoconstriction
• VIP: vasodilation, GI secretion
• Somatostatin: inhibitory modulator
• CRH, TRH, GnRH (hypothalamic peptides)

• ATP/ADP: fast signaling (P2X, P2Y receptors); pain, autonomic
• Adenosine: inhibitory; sleep promotion; caffeine blocks adenosine receptors

• NO (nitric oxide): retrograde messenger; vasodilation; LTP; non-conventional NT (not in vesicles)
• CO (carbon monoxide): similar to NO

• 2-AG, AEA (anandamide): retrograde inhibitory; suppress presynaptic NT release; CB1 (CNS), CB2 (immune)

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Q47. Physiology of the cerebellum. Role in movement regulation. Afferent inputs and descending pathways.

• Two hemispheres + vermis (midline)
• Three lobes: flocculonodular (vestibulocerebellum), anterior (spinocerebellum), posterior (cerebrocerebellum)
• Cortex: 3 layers (molecular, Purkinje, granular); Purkinje cells are the sole output of cerebellar cortex (inhibitory, GABA)
• Deep nuclei: dentate (largest), interposed (globose + emboliform), fastigial → output to thalamus and brainstem

1. Coordination of voluntary movements: timing, accuracy, smoothness; lesion → ataxia, dysmetria (past-pointing), dysdiadochokinesia
2. Muscle tone regulation: maintains appropriate muscle tone via γ-motor neurons; lesion → hypotonia
3. Balance and posture: via flocculonodular lobe; receives vestibular input; lesion → truncal ataxia, gait disturbance
4. Motor learning: adaptation of motor programs (e.g., learning to ride a bike); climbing fiber-parallel fiber coincidence detection
5. Error correction: compares intended vs actual movement; sends corrective signals; "predictor" model

• Mossy fibers (via inferior, middle, superior cerebellar peduncles):
  • Spinocerebellar tracts (dorsal and ventral): unconscious proprioception from muscle spindles, GTOs, joint receptors → spinocerebellum
  • Pontocerebellar fibers (from pontine nuclei, which receive from motor cortex): cerebrocerebellar loop
  • Vestibulocerebellar fibers: vestibular apparatus → flocculonodular lobe
  • Reticulocerebellar, trigeminocerebellar, olivocerebellar
• Climbing fibers (from inferior olivary nucleus, 1:1 with Purkinje cells): error signals, motor learning → powerful activation of Purkinje cells

• Purkinje cells (GABA, inhibitory) → deep nuclei (tonically active, excitatory)
• Deep nuclei → via superior cerebellar peduncle:
  • Dentate nucleus → thalamus (VL) → motor cortex → corticospinal tract (voluntary movement)
  • Interposed nuclei → red nucleus → rubrospinal tract
  • Fastigial nucleus → brainstem (vestibular nuclei, reticular formation) → vestibulospinal and reticulospinal tracts (posture, balance)

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Q48. Functions of the Thalamus.

• All sensory information (except smell) passes through thalamic nuclei before reaching cortex
• VPL (ventroposterolateral): body somatosensation (pain, temperature, touch, proprioception) via spinothalamic and DCML → somatosensory cortex (S1)
• VPM (ventroposteromedial): face sensation (CN V) + taste
• LGN (lateral geniculate nucleus): visual relay → V1 (occipital cortex)
• MGN (medial geniculate nucleus): auditory relay → A1 (temporal cortex)
• VA/VL (ventroanterior/ventrolateral): motor relay (from cerebellum, basal ganglia → motor cortex)

• VL: cerebellum → VL → motor cortex; VA: basal ganglia → VA → prefrontal/premotor cortex
• Critical for coordinating motor output

• Intralaminar and reticular nuclei receive input from ascending reticular activating system (ARAS)
• Regulate cortical arousal, sleep-wake transitions
• Thalamic oscillations (sleep spindles) during NREM sleep generated by thalamo-cortical loops

• Thalamic reticular nucleus (TRN): inhibitory shell; controls which signals reach cortex
• Acts as a "gatekeeper" - filters irrelevant stimuli

• Anterior thalamic nuclei: part of Papez circuit; medial dorsal (MD) nucleus: prefrontal, involved in working memory; thalamic infarcts → amnesia

• Intralaminar nuclei receive pain signals; diffuse projection to cortex → affective component of pain

• MD nucleus → prefrontal cortex; pulvinar → parietal/temporal cortex; involved in language, attention

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Q49. Morpho-functional characteristics of the cerebral cortex. Main regions.

• ~2.5 mm thick; 6 layers (neocortex, most of cortex):
  1. Molecular (plexiform): mainly fibers and horizontal cells
  2. External granular: small pyramidal and granule cells; input
  3. External pyramidal: medium pyramidal cells; output to other cortical areas
  4. Internal granular: granule cells; main thalamocortical input (sensory cortex most prominent here)
  5. Internal pyramidal (ganglionic): large pyramidal cells (Betz cells in M1); output to subcortical
  6. Multiform (fusiform): mixed cells; output to thalamus and brainstem
• Surface area: ~2000-2500 cm² (folded into gyri and sulci)
• ~86 billion neurons

• S1 (primary somatosensory cortex): postcentral gyrus (parietal lobe, Brodmann areas 3a, 3b, 1, 2); receives VPL/VPM input; somatotopic map (homunculus - hands and face disproportionately large)
• V1 (primary visual cortex): calcarine sulcus, occipital lobe (BA17); retinotopic map; binocular columns, orientation columns
• A1 (primary auditory cortex): Heschl's gyri, superior temporal gyrus (BA41/42); tonotopic map
• Gustatory cortex: anterior insula/operculum
• Vestibular cortex: posterior insula, parietal cortex

• M1 (primary motor cortex): precentral gyrus, frontal lobe (BA4); somatotopic motor homunculus; large Betz cells → corticospinal tract; controls voluntary fine motor movements
• Supplementary motor area (SMA): medial frontal (BA6); planning of complex movements
• Premotor cortex: lateral frontal (BA6); selection of movements, mirror neurons

• Prefrontal cortex: executive function, working memory, decision-making, personality, attention (lesion → frontal lobe syndrome: poor judgment, disinhibition)
• Parietal association cortex (BA5,7): multisensory integration, spatial awareness; neglect syndrome
• Temporal association cortex (BA20-22): object recognition ("ventral stream - what"), memory
• Wernicke's area (BA22, posterior superior temporal gyrus, dominant hemisphere): language comprehension; Wernicke's aphasia: fluent but meaningless speech
• Broca's area (BA44-45, inferior frontal gyrus, dominant hemisphere): speech production; Broca's aphasia: non-fluent, telegraphic speech with intact comprehension

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Q50. Types of sensory receptors. Mechanisms of signal transformation.

• Mechanoreceptors: touch, pressure, vibration, sound, proprioception
• Thermoreceptors: warm (>30°C) and cold (<20°C) temperatures
• Nociceptors: pain (mechanical, thermal, chemical stimuli)
• Photoreceptors: light (rods, cones in retina)
• Chemoreceptors: taste, smell, blood O₂/CO₂/pH (carotid/aortic bodies)
• Osmoreceptors: plasma osmolality (hypothalamus)
• Baroreceptors: blood pressure (carotid sinus, aortic arch)
• Proprioceptors: muscle spindles (Ia, II), Golgi tendon organs (Ib), joint receptors

• Exteroceptors: external environment (skin, retina, cochlea)
• Interoceptors: internal (visceral, baroreceptors, chemoreceptors)
• Proprioceptors: body position and movement

• Free nerve endings: pain, temperature, itch (Aδ and C fibers)
• Encapsulated (special structural receptors):
  • Meissner's corpuscles: light touch, 2-point discrimination (fingertips)
  • Pacinian corpuscles: vibration, pressure
  • Ruffini endings: skin stretch, sustained pressure
  • Merkel's discs: fine touch, edges
  • Muscle spindles (intrafusal fibers): stretch
  • Golgi tendon organs: tension

1. Stimulus acts on receptor membrane (mechanical deformation, chemical binding, temperature, light)
2. Receptor potential generated (generator potential):
   • Specific ion channels open (mechanically gated, ligand-gated, TRP channels for heat/cold)
   • Graded potential (not all-or-none) proportional to stimulus intensity
   • E.g., Pacinian corpuscle: deformation → opens Na⁺/K⁺ channels → depolarization
3. Encoding: if receptor potential reaches threshold at spike initiation zone → action potentials generated
   • Frequency of APs encodes stimulus intensity (rate coding)
   • Timing, location, and identity of receptor pathway encode other qualities
4. Adaptation:
   • Rapidly adapting (RA): respond to change in stimulus (onset/offset); e.g., Pacinian (vibration, touch onset), Meissner's
   • Slowly adapting (SA): respond throughout sustained stimulus; e.g., Merkel's, Ruffini, muscle spindles (for sustained stretch), nociceptors
5. Signal transmission: afferent nerve fiber → spinal cord → thalamus → cortex for conscious perception

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Q51. Main functions of the limbic system.

• Hippocampus: essential for formation of new declarative (explicit) memories (episodic and semantic); consolidation from short-term to long-term; bilateral hippocampal damage → anterograde amnesia (HM case)
• Spatial memory and navigation (place cells)

• Amygdala: center for emotional processing, especially fear and anxiety; associates stimuli with emotional significance (fear conditioning); projects to hypothalamus and brainstem for autonomic fear response (tachycardia, sweating, freeze)
• Cingulate gyrus: emotional experience, emotional response to pain, attention

• Nucleus accumbens (ventral striatum) and septal nuclei: reward circuitry; dopamine from VTA → nucleus accumbens → pleasure; basis of addiction

• Hypothalamus (functionally part of limbic system): emotion → autonomic responses (fight-or-flight, visceral changes with emotion)

• Olfactory cortex (piriform cortex) is directly connected to limbic structures (only sense with direct limbic access without thalamic relay) → explains strong emotional/memory responses to smell

• Limbic input to hypothalamus modulates endocrine responses to stress (HPA axis via CRH), reproductive behavior (GnRH)

• Amygdala: social cognition, recognition of facial expressions; damage → failure to recognize fear in faces

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Q52. Autonomic (Vegetative) Nervous System - morpho-functional characteristics.

• Controls involuntary functions: smooth muscle, cardiac muscle, glands
• Two-neuron efferent chain: preganglionic (myelinated B fiber) in CNS → ganglion → postganglionic (unmyelinated C fiber) → effector
• Regulated by hypothalamus, limbic system, brainstem

• Origin: intermediolateral cell column, T1-L2 (thoracolumbar)
• Preganglionic: short; synapse in paravertebral chain ganglia (bilateral) or prevertebral ganglia (celiac, superior/inferior mesenteric)
• Postganglionic: long; NT = norepinephrine (adrenergic); except sweat glands (ACh)
• Preganglionic NT: ACh → nicotinic receptors in ganglia
• Adrenal medulla: modified sympathetic ganglion; preganglionic fibers → chromaffin cells → epinephrine + NE into blood
• Divergent system: 1 preganglionic → 20+ postganglionic → mass response

• Origin: craniosacral - cranial nerves (III, VII, IX, X) and sacral cord (S2-S4)
• CN III (Edinger-Westphal): pupil constriction, lens accommodation
• CN VII: lacrimal, submandibular, sublingual glands
• CN IX: parotid gland
• CN X (vagus): heart, lungs, GI tract to splenic flexure (~75% of parasympathetic output)
• S2-S4 (pelvic splanchnics): distal colon, rectum, bladder, genitalia
• Preganglionic: long; Postganglionic: very short (ganglia near or within organ)
• NT preganglionic and postganglionic: ACh → muscarinic receptors on effectors
• Discrete, localized responses

• "Second brain": ~100 million neurons in GI wall
• Myenteric plexus (Auerbach's): between circular and longitudinal muscle → controls motility
• Submucosal plexus (Meissner's): controls secretion and blood flow
• Can function independently of CNS; modified by sympathetic (inhibits) and parasympathetic (stimulates)

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Q53. Function of Synapse (Excitatory and Inhibitory).

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Q54. Functions of the Hypothalamus.

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REPRODUCTIVE SYSTEM

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Q55. Describe the ovarian cycle.

1. Menstruation (days 1-5): progesterone and estrogen drop → endometrial shedding; concurrent with early follicular phase
2. Follicular recruitment: FSH (from anterior pituitary) rises → recruits cohort of primordial follicles → primary → secondary → tertiary (antral) follicles
3. Follicular development: granulosa cells proliferate; theca cells synthesize androgens → aromatized to estradiol by granulosa cells (FSH-induced aromatase)
4. Selection of dominant follicle (days 8-10): one follicle becomes dominant (secretes most estrogen, responds best to FSH); others undergo atresia
5. LH surge (day 13-14): rising estradiol (above threshold >200 pg/mL for >50 hrs) triggers positive feedback on pituitary → massive LH surge → triggers ovulation and luteinization

• LH surge → proteolytic enzymes, prostaglandins → follicle wall ruptures → oocyte (in metaphase II) released with cumulus oophorus
• Oocyte travels to fallopian tube; completes meiosis II only if fertilized

1. Corpus luteum formation: ruptured follicle collapses → granulosa-lutein cells and theca-lutein cells (luteinized by LH) → corpus luteum
2. Progesterone and estradiol secretion: progesterone peaks around day 21; prepares endometrium for implantation (secretory phase)
3. Negative feedback: progesterone + estrogen suppress FSH and LH → no new follicles mature
4. Corpus luteum regression (luteolysis): if no fertilization/implantation → CL degenerates by day 25-26 → drop in P4 and E2 → endometrium sheds (menstruation) → FSH rises again → new cycle begins
5. If fertilized: hCG (from trophoblast) rescues corpus luteum → maintains progesterone for first trimester until placenta takes over

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Q56. Androgens and their physiological role.

• Testosterone: major male androgen (Leydig cells of testes); also produced in small amounts by ovaries and adrenal cortex
• Dihydrotestosterone (DHT): converted from testosterone by 5α-reductase; more potent (stronger AR binding); active in prostate, skin, external genitalia
• DHEA/DHEA-S and androstenedione: weak androgens from adrenal cortex; converted peripherally

1. Fetal: testosterone → virilization of male external genitalia (Wolffian duct → epididymis, vas deferens, seminal vesicles); DHT → development of external genitalia (prostate, scrotum, penis)
2. Pubertal/Secondary sex characteristics: facial, body, pubic/axillary hair growth; voice deepening (laryngeal growth); penile and testicular growth; sebum production (acne)
3. Spermatogenesis: testosterone essential for spermatogenesis (paracrine, via Sertoli cells)
4. Libido: maintains sexual drive in both males and females
5. Erythropoiesis: stimulates EPO production and direct marrow stimulation → more RBCs (men have higher Hgb than women)
6. Anabolic effects: protein synthesis → muscle mass and strength; bone mineralization; nitrogen retention; closure of epiphyses at puberty
7. Metabolic: promotes lean body mass, reduces fat

• Androgens (adrenal DHEA primarily): pubic and axillary hair growth
• Converted to estrogen in adipose, skin (aromatase)
• Libido
• Bone density

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Q57. Estrogens and their physiological role.

• Estradiol (E2): most potent; main reproductive-age form; ovaries (granulosa cells)
• Estrone (E1): menopause (adipose tissue conversion)
• Estriol (E3): main pregnancy estrogen (placenta)

1. Female sexual development (secondary sex characteristics):
   • Breast development (ductal growth, fat deposition)
   • Female fat distribution (hips, thighs, buttocks)
   • Pubic/axillary hair (with androgens)
   • External genitalia development and maturation
   • Vaginal epithelium cornification and lubrication
2. Reproductive cycle:
   • Endometrial proliferation (proliferative phase - days 5-14)
   • Increases LH receptor on granulosa cells
   • Positive feedback → LH surge → ovulation (see Q55)
   • Negative feedback on FSH/LH (when E2 < threshold)
   • Stimulates cervical mucus to become thin, watery, sperm-friendly
3. Bone:
   • Inhibit osteoclasts → prevent bone resorption → maintain bone density
   • Estrogen deficiency (menopause) → ↑osteoclast activity → osteoporosis
4. Cardiovascular:
   • ↑HDL, ↓LDL cholesterol → cardioprotective
   • Vasodilation (↑NO production)
   • Explains lower CVD incidence in premenopausal women vs men
5. Liver: increases synthesis of coagulation factors, SHBG, TBG, HDL; explains ↑DVT risk with exogenous estrogens
6. CNS: mood regulation (serotonin modulation); neuroprotective; memory; menopause → mood changes, hot flashes (GnRH pulsatility without feedback), vaginal dryness
7. Epiphyseal closure: estrogen at puberty in both sexes closes growth plates

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Q58. Hormone of corpus luteum - progesterone and its physiological role.

• Corpus luteum (luteal phase): main source in reproductive age
• Placenta (from 8-10 weeks; takes over from CL at ~10 weeks)
• Adrenal cortex (small amounts)
• Testes (small amounts)

1. Endometrium (secretory phase, days 15-28): converts proliferative endometrium → secretory (glands produce glycogen-rich secretions) → prepares for implantation of blastocyst; "decidualization"
2. Maintains pregnancy:
   • Prevents premature myometrial contractions (uterine quiescence)
   • Maintains decidua
   • Suppresses maternal immune response to fetus (immunotolerance)
   • Maintains CL via hCG (early); placenta takes over progesterone production at 10 weeks
3. Cervical mucus: causes thick, viscous, impenetrable mucus → blocks sperm entry after ovulation and during pregnancy
4. Breast: stimulates lobular-alveolar development (proliferation of secretory acini in preparation for lactation); works with estrogen
5. Temperature: raises basal body temperature by 0.3-0.5°C after ovulation (thermogenic effect via hypothalamus) → used in natural family planning
6. CNS: has anxiolytic and sedative effects (GABA-A receptor allosteric modulator via metabolite allopregnanolone); premenstrual syndrome associated with progesterone withdrawal
7. Negative feedback: suppresses LH and FSH in luteal phase (with estrogen) → prevents new follicle development; basis of combined oral contraceptive pill action
8. Respiration: stimulates respiratory drive (mild hyperventilation in pregnancy)

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Q59. Explain Spermatogenesis.

• Type A spermatogonia (stem cells) on basement membrane of seminiferous tubule
• Type A → mitosis → Type A (self-renewal) AND Type B spermatogonia
• Type B spermatogonia → primary spermatocytes (diploid, 46 chromosomes, 2n)

• Meiosis I (reductional): primary spermatocyte (diploid) → 2 secondary spermatocytes (haploid, 23 chromosomes, 2n DNA content per cell)
• Meiosis II (equational): each secondary spermatocyte → 2 spermatids (haploid, 23 chromosomes, n DNA)
• One primary spermatocyte → 4 spermatids

• No further division; morphological transformation
• Formation of acrosome (from Golgi; contains enzymes for zona pellucida penetration: acrosin, hyaluronidase)
• Nucleus condenses (nuclear DNA compacted with protamines)
• Flagellum (tail) develops from centriole → motility
• Mitochondria arrange around mid-piece → ATP for motility
• Excess cytoplasm shed as residual body (phagocytosed by Sertoli cells)
• Result: mature spermatozoon: head (nucleus + acrosome), mid-piece (mitochondria), tail (flagellum)

• Sertoli cells: blood-testis barrier (tight junctions), nourish spermatogenic cells, secrete inhibin (inhibits FSH), androgen-binding protein (ABP), activin; respond to FSH
• Leydig cells: in interstitium; secrete testosterone (stimulated by LH); testosterone essential for spermatogenesis locally
• FSH: acts on Sertoli cells → supports spermatogenesis
• LH: acts on Leydig cells → testosterone
• Testosterone: acts paracrine via Sertoli cells → spermatogenesis

• Volume: 1.5-5 mL semen/ejaculation
• Count: ≥15 million/mL (WHO 2021)
• Motility: ≥40% motile
• Morphology: ≥4% normal (Kruger strict criteria)

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Q60. Ovarian Hormones and Functions.

• Source: granulosa cells (follicular phase, stimulated by FSH)
• See Q57 for full physiological role
• Summary: female sexual development, endometrial proliferation, positive feedback for LH surge, bone protection, cardiovascular benefits, CNS effects

• Source: corpus luteum (luteal phase, stimulated by LH); granulosa-lutein cells
• See Q58 for full physiological role
• Summary: prepares endometrium for implantation, maintains pregnancy, thermogenic, anti-estrogenic effects on cervical mucus, breast lobular development, negative feedback

• Source: theca cells (stimulated by LH)
• Mostly converted to estrogens by granulosa cells (aromatase)
• Excess → hyperandrogenism (PCOS: anovulation, hirsutism, acne)

• Source: granulosa cells
• Function: specifically inhibits FSH secretion (negative feedback to anterior pituitary)
• Inhibin B: dominant in follicular phase; Inhibin A: dominant in luteal phase

• Source: granulosa cells
• Function: stimulates FSH secretion; promotes FSH receptor expression on granulosa cells; locally promotes folliculogenesis

• Source: granulosa cells of small antral follicles
• Function: inhibits primordial follicle recruitment; inhibits FSH-stimulated follicular growth (intraovarian regulation)
• Marker of ovarian reserve (measured clinically to assess fertility/IVF prognosis)

• Source: corpus luteum (mainly in pregnancy)
• Function: relaxes pelvic ligaments and pubic symphysis; cervical ripening; inhibits uterine contractions

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Quick Index

RENAL (Q1-7)

• Q1 - Glomerular filtration, Starling forces, GFR (normal 125 mL/min), factors affecting GFR
• Q2 - Tubular reabsorption: PCT (65%), Loop of Henle (25%), DCT, Collecting duct (ADH/aldosterone)
• Q3 - Renal function tests with normal ranges (creatinine, BUN, GFR, urinalysis)
• Q4 - Micturition reflex: detrusor, sphincters, PMC, spinal coordination
• Q5 - 10 kidney functions: excretion, water/electrolyte/acid-base balance, BP, EPO, vitamin D, gluconeogenesis
• Q6 - Urine composition and physical properties
• Q7 - Urine formation: filtration → reabsorption → secretion → countercurrent concentration

GIT (Q8-23)

• Q8 - Gastric digestion; digestive and non-digestive functions
• Q9 - Oral digestion, saliva (1-1.5 L/day, composition, role, regulation via CN VII/IX)
• Q10 - Gastric juice (2-3 L/day, pH 1.5-2); HCl functions (activates pepsin, bactericidal, Fe²⁺ absorption)
• Q11 - Pancreatic juice (1.5-3 L/day, pH 7.6-8.2); regulation by secretin and CCK
• Q12 - Role of pancreas in duodenal digestion: neutralization + all enzyme classes
• Q13 - Bile composition, emulsification, micelle formation, enterohepatic circulation
• Q14 - Small intestinal digestion and absorption; structural adaptations
• Q15-17 - Digestion, absorption, and metabolism of proteins, lipids, carbohydrates
• Q18 - Duodenal digestion; succus entericus composition
• Q19 - BMR: values, factors (thyroid hormones are the main regulator)
• Q20 - Absorption mechanisms: passive diffusion, facilitated diffusion, active transport, pinocytosis
• Q21 - Liver in digestion: bile, protein/carbohydrate/fat metabolism, detoxification
• Q22 - GIT hormones table: gastrin, secretin, CCK, GIP, motilin, somatostatin, GLP-1, PYY
• Q23 - GI wall layers: mucosa, submucosa, muscularis externa, serosa/adventitia

ENDOCRINE (Q24-36)

• Q24 - Endocrine glands, hormone properties, classification (peptide, steroid, amine)
• Q25 - T3/T4 biosynthesis (NIS → TPO → coupling), transport (TBG), physiological role
• Q26 - Pancreatic hormones: insulin (anabolic, lowers glucose), glucagon (catabolic, raises glucose), somatostatin
• Q27 - Anterior pituitary: GH, TSH, ACTH, FSH, LH, Prolactin
• Q28 - Hypothalamus: pituitary control, ADH/oxytocin synthesis, temperature, hunger, thirst, circadian clock
• Q29 - Ca²⁺/PO₄ regulation: PTH (↑Ca², ↓PO₄), calcitriol (↑both), calcitonin (↓both)
• Q30 - Adrenal cortex: cortisol (glucocorticoid), aldosterone (mineralocorticoid), adrenal androgens
• Q31 - Thyroid hormone effects and HPT axis (TRH → TSH → T3/T4 → negative feedback)
• Q32 - Epinephrine/NE: synthesis, fight-or-flight effects, metabolic effects, receptor pharmacology
• Q33 - Hypothyroidism (weight gain, bradycardia, myxedema) vs. hyperthyroidism (weight loss, tachycardia, exophthalmos)
• Q34 - Hormone mechanisms: GPCRs (cAMP, IP₃/DAG), tyrosine kinase, JAK-STAT, nuclear receptors
• Q35 - ADH (V2: AQP2 → concentrated urine; V1: vasoconstriction) and Oxytocin (labor, milk ejection, bonding)
• Q36 - Prostaglandins: synthesis via COX, roles in inflammation, fever, pain, gastric protection, platelet function

NERVOUS SYSTEM (Q37-54)

• Q37 - Synapse structure, chemical vs. electrical, EPSP (Na⁺/K⁺ channels) vs. IPSP (Cl⁻/K⁺ channels)
• Q38 - Reflex arc, classification: unconditioned/conditioned, monosynaptic/polysynaptic, somatic/autonomic
• Q39 - Spinal cord reflexes (stretch, withdrawal), ascending/descending tracts
• Q40 - Spinal cord anatomy: gray matter (dorsal/ventral/lateral horns), white matter funiculi
• Q41 - CNS/PNS; somatic vs. autonomic (sympathetic, parasympathetic, enteric)
• Q42 - Retina layers, rods vs. cones, phototransduction (cGMP → channel closure → hyperpolarization)
• Q43 - Medulla (cardiovascular, respiratory, vomiting, swallowing centers) and pons (pneumotaxic, CN V-VIII)
• Q44/53 - Excitatory synapses (glutamate, depolarization) vs. inhibitory (GABA/glycine, hyperpolarization)
• Q45 - Sympathetic vs. parasympathetic effects table on all organ systems
• Q46 - Neurotransmitter classification: amino acids, monoamines, ACh, neuropeptides, purines, gaseous
• Q47 - Cerebellum: coordination, tone, balance, motor learning; mossy/climbing fiber inputs; dentate → thalamus → cortex output
• Q48 - Thalamus: sensory relay (VPL, VPM, LGN, MGN), motor relay (VL), consciousness, attention, memory
• Q49 - Cerebral cortex layers, somatosensory (S1), motor (M1), visual (V1), auditory (A1), Wernicke's, Broca's areas
• Q50 - Sensory receptor types, transduction: receptor potential → AP encoding → adaptation (RA vs. SA)
• Q51 - Limbic system: memory (hippocampus), emotion (amygdala), reward, autonomic, olfaction, social behavior
• Q52 - ANS morpho-functional: sympathetic (thoracolumbar, NE), parasympathetic (craniosacral, ACh), enteric

REPRODUCTIVE (Q55-60)

• Q55 - Ovarian cycle: follicular phase (FSH, estrogen rise, LH surge) → ovulation (day 14) → luteal phase (CL, progesterone)
• Q56 - Androgens: testosterone, DHT (5α-reductase); roles in development, spermatogenesis, anabolism, libido, erythropoiesis
• Q57 - Estrogens: estradiol, bone protection, endometrial proliferation, CVD protection, CNS effects
• Q58 - Progesterone: secretory endometrium, uterine quiescence, cervical mucus, thermogenic, anxiolytic
• Q59 - Spermatogenesis: spermatogonia → meiosis → spermiogenesis (acrosome, flagellum) → spermiation; FSH/LH/testosterone control
• Q60 - Ovarian hormones: estrogens, progesterone, androgens, inhibin (↓FSH), activin (↑FSH), AMH (ovarian reserve), relaxin