2nd Term Final Examination — Complete Answers

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GROUP-A

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Q.1 — Respiratory Unit | Factors Affecting Gas Diffusion | IRDS (1+2+2)

What is a Respiratory Unit?

• Respiratory bronchioles (1st, 2nd, 3rd order)
• Alveolar ducts
• Alveolar sacs
• Alveoli (~300 million alveoli total; total surface area ~70 m²)

Factors Affecting Gas Diffusion Through Respiratory Membrane

IRDS (Infant Respiratory Distress Syndrome)

• Cause: Deficiency of surfactant (dipalmitoyl phosphatidylcholine) in premature infants (<36 weeks gestation). Type II pneumocytes are immature and produce insufficient surfactant.
• Pathophysiology: Without surfactant, surface tension in alveoli is not reduced → alveolar collapse (atelectasis) → reduced lung compliance → hypoxia + hypercapnia
• Features: Tachypnoea, grunting, intercostal retractions, cyanosis
• Treatment: Exogenous surfactant administration, CPAP, glucocorticoids prenatally (betamethasone to mother to mature fetal lungs)

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Q.2 — Spirogram: Lung Volumes & Capacities (2.5+1+1.5)

Spirogram with Normal Values

     ↑ Volume (L)
 6L  |     ____TLC (6L)____
     |    |                |
 4.8L|    | IRV (3L)      |
     |____|               | VC (4.8L)
 3L  |TV  |               |
     | 0.5|____           |
 2.4L|    |ERV (1.2L)     |
     |____|_______________|
 1.2L|    RV (1.2L)       |
     |____________________|→ Time

Note: RV, FRC, and TLC cannot be measured by simple spirometry — require helium dilution or body plethysmography.

How is Residual Volume Measured?

• Helium dilution method: Closed-circuit rebreathing of known [He]; dilution reflects FRC → RV = FRC − ERV
• Nitrogen washout method: Patient breathes 100% O₂; nitrogen washed out is measured
• Body plethysmography (most accurate): Uses Boyle's law; measures thoracic gas volume

Importance of Residual Volume

1. Prevents alveolar collapse between breaths (maintains alveolar patency)
2. Allows continuous gas exchange even during expiration
3. Dilutes incoming inspired air, preventing sudden changes in alveolar gas composition
4. Acts as a buffer to maintain stable PO₂ and PCO₂

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Q.3 — Non-Respiratory Functions of Lungs | Prevention of Lung Collapse (3+2)

Non-Respiratory (Non-Gaseous) Functions of the Lungs

1. Metabolic/Synthetic functions:
   • Synthesis and secretion of surfactant (by type II pneumocytes)
   • Conversion of angiotensin I → angiotensin II (by ACE on pulmonary endothelium)
2. Inactivation/Degradation:
   • Inactivation of bradykinin, serotonin, prostaglandins E₁, E₂, F₂α, norepinephrine
   • Histamine and substance P partly inactivated
3. Filtration: Lung capillaries trap small blood clots (microemboli), preventing entry into systemic circulation
4. Reservoir function: Pulmonary circulation acts as blood reservoir (~500 mL)
5. Immunological defense:
   • Alveolar macrophages phagocytose bacteria and particles
   • IgA secretion in airways
   • Mucociliary escalator removes particulate matter
6. Vocalization: Phonation (voice production)
7. Regulation of acid-base balance: By controlling CO₂ levels
8. Water and heat exchange: Warm and humidify inspired air

Factors that Prevent Lung Collapse (Atelectasis)

1. Surfactant: Reduces surface tension within alveoli (especially small alveoli); obeys LaPlace's law — without surfactant, small alveoli collapse into large ones
2. Collateral ventilation: Pores of Kohn (inter-alveolar) and canals of Lambert (bronchiole-alveolar) allow air redistribution
3. Interdependence of alveoli: Alveoli are structurally interdependent — if one collapses, surrounding tissue exerts radial traction to reopen it
4. Residual volume: Ensures alveoli are never completely emptied
5. Negative intrapleural pressure: Transpulmonary pressure keeps lung expanded against the chest wall

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Q.4 — Chemical Forms of CO₂ | HCO₃⁻ Transport | Chloride Shift (2+2+1)

Chemical Forms of CO₂ in Blood

How CO₂ is Transported as HCO₃⁻ in Blood

1. CO₂ diffuses from tissues into RBCs
2. Inside RBCs, carbonic anhydrase (CA) catalyzes: CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻
3. HCO₃⁻ accumulates inside RBC → diffuses out into plasma via HCO₃⁻/Cl⁻ exchanger (Band 3 protein)
4. H⁺ is buffered by haemoglobin (Hb + H⁺ → HHb)
5. In the lungs, the reaction reverses: HCO₃⁻ re-enters RBC, reforms CO₂, which is exhaled

Chloride Shift (Hamburger Phenomenon)

• As HCO₃⁻ leaves the RBC at tissue level, Cl⁻ enters the RBC in exchange (via Band 3 protein) to maintain electrical neutrality
• This is the chloride shift (or Hamburger shift)
• Reverse occurs in lungs: Cl⁻ leaves RBC as HCO₃⁻ re-enters

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Q.5 — Local Nervous System of GIT | BER (1+2.5+1.5)

Name of the Local Nervous System of GIT

Parts and Functions of ENS

• Contains ~100 million neurons (more than spinal cord)
• Contains sensory neurons, interneurons, and motor neurons
• Neurotransmitters: ACh (excitatory), NO and VIP (inhibitory), substance P, serotonin (5-HT)
• Can function independently of CNS (via intrinsic reflex arcs)
• Modulated by sympathetic (inhibitory) and parasympathetic (excitatory) divisions

What is BER (Basic Electrical Rhythm)?

• BER = Slow waves / pacemaker potentials generated by Interstitial Cells of Cajal (ICC)
• ICC are located in the myenteric plexus region; act as the "pacemaker" of the gut
• BER sets the maximum frequency of contractions in each GI segment:
  • Stomach: ~3/min
  • Duodenum: ~12/min
  • Ileum: ~8–9/min
  • Colon: ~6/min
• BER itself does not cause contraction; it only sets the timing. Actual contraction occurs when action potentials are superimposed on BER peaks (triggered by hormones/neural input)

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Q.6 — Clinical SAQ: Exercise and Oxy-Hb Dissociation Curve (1+2.5+1.5)

Scenario: 22-yr-old student runs to catch a bus → rapid breathing, sweating, ↑ muscle temperature, ↑ CO₂ production

(a) Direction of Shift of Oxy-Hb Dissociation Curve

(b) Why Does This Rightward Shift Occur During Exercise?

(c) Physiological Advantage of This Rightward Shift

• The P₅₀ increases (O₂ released at higher PO₂)
• More O₂ is unloaded to exercising muscles per unit of blood flow
• At tissue PO₂ of 40 mmHg, O₂ saturation drops from ~75% (resting) to ~50% during exercise → 2–3× more O₂ delivered to metabolically active muscles
• This precisely matches O₂ supply to increased metabolic demand — an elegant homeostatic mechanism

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SEQ — Q.7 (GROUP-A): GI Movements + Peristalsis (2+3+5)

Types of GI Movements in Different Parts of GIT

Types of Movements of Small Intestine

1. Segmentation (Rhythmic Segmentation):
   • Most common movement of small intestine
   • Ring-like contractions at multiple points simultaneously
   • Chyme is divided and re-divided → thorough mixing with digestive enzymes
   • Does NOT propel chyme significantly; primarily a mixing movement
2. Peristalsis:
   • Wave of contraction preceded by relaxation moving aborally
   • Propels chyme towards the ileocaecal valve
3. Migrating Motor Complex (MMC):
   • Occurs during fasting (interdigestive period)
   • Starts in stomach, sweeps to terminal ileum every ~90 min
   • "Housekeeper" function — clears undigested residue

Peristalsis (Detailed)

1. Stimulus: Distension of gut wall by bolus
2. Stretch activates sensory neurons in the ENS
3. Oral side: Ascending excitation → ACh released → circular muscle contracts + longitudinal muscle relaxes
4. Anal side: Descending inhibition → VIP/NO released → circular muscle relaxes + longitudinal muscle contracts
5. Net result: bolus is propelled forward

• Coordinated by myenteric plexus
• Enhanced by parasympathetic (vagus/pelvic nerves)
• Inhibited by sympathetic stimulation
• Serotonin (5-HT₄ receptors) plays a key role in initiating peristalsis

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SEQ — OR: Respiratory Centers + Chemical Regulation of Respiration (3+2+5)

Respiratory Centers (Labeled Diagram)

PONS
┌─────────────────────────────────┐
│  PONTINE RESPIRATORY GROUP      │
│  ┌──────────────┐               │
│  │ Pneumotaxic  │ (NTS, Kölliker│
│  │ Center       │  -Fuse nucleus)│
│  └──────────────┘               │
│  ┌──────────────┐               │
│  │ Apneustic    │               │
│  │ Center       │               │
│  └──────────────┘               │
└─────────────────────────────────┘
MEDULLA
┌─────────────────────────────────┐
│  ┌──────────────┐               │
│  │ DRG (Dorsal  │ — Inspiratory │
│  │ Resp. Group) │   neurons (I) │
│  └──────────────┘               │
│  ┌──────────────┐               │
│  │ VRG (Ventral │ — Insp + Exp  │
│  │ Resp. Group) │   (forced)    │
│  └──────────────┘               │
│  ┌──────────────┐               │
│  │Pre-Bötzinger │ — Rhythm      │
│  │Complex       │   generator   │
│  └──────────────┘               │
└─────────────────────────────────┘

Functions

Effects of a Lesion Between Pons and Medulla

• Apneustic breathing: Prolonged, gasping inspirations with brief expirations
• Because the apneustic center is released from pneumotaxic inhibition → prolonged inspiratory bursts
• If lesion is below the pons but above the medulla: irregular, ataxic breathing

Chemical Regulation of Respiration

• Located on ventrolateral surface of medulla
• Respond to ↑ PCO₂ → CO₂ crosses BBB → carbonic acid → ↑ [H⁺] in CSF → stimulates increased ventilation
• Most powerful stimulus for respiration in normal conditions
• Do NOT respond to hypoxia directly

• Carotid bodies (IX nerve) — more important; Aortic bodies (X nerve)
• Respond to: ↓ PO₂ (<60 mmHg), ↑ PCO₂, ↑ H⁺ (↓ pH), ↑ temperature, ↑ K⁺
• Hypoxia is the primary stimulus for peripheral chemoreceptors
• In COPD patients with chronic CO₂ retention: respiratory drive is maintained by hypoxic drive (peripheral chemoreceptors)

• ↑ CO₂ or ↓ pH → ↑ respiratory rate and depth (hyperventilation) → CO₂ blown off → pH restored
• ↓ PO₂ → stimulates peripheral chemoreceptors → ↑ ventilation

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GROUP-B

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Q.1 — Diagram of Nephron | Juxtaglomerular Apparatus (2+3)

Typical Nephron (Labeled)

                    AFFERENT ARTERIOLE
                           ↓
BOWMAN'S CAPSULE → [Glomerulus] ← Efferent arteriole
         ↓                              ↓
  Proximal Convoluted           Peritubular capillaries
     Tubule (PCT)               Vasa recta
         ↓
   Loop of Henle
   ┌─────────────────┐
   │ Thick descending │
   │ Thin descending  │
   │ Thin ascending   │
   │ Thick ascending  │
   └─────────────────┘
         ↓
  Distal Convoluted
     Tubule (DCT)
         ↓
  Collecting Duct
         ↓
    Renal Pelvis → Ureter

Components of Juxtaglomerular Apparatus (JGA) and Functions

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Q.2 — GFR: Definition, Calculation, Factors Decreasing GFR (1+2+2)

Definition of GFR

• Normal value: 125 mL/min (≈180 L/day) in an adult male
• Clinically estimated by creatinine clearance (~120 mL/min)

How GFR is Calculated

GFR = (U × V) / P

GFR = Inulin clearance = (U_in × V) / P_in

4 Factors that Decrease GFR

1. ↓ Glomerular capillary hydrostatic pressure (PGC): due to ↓ BP, vasoconstriction of afferent arteriole (e.g., sympathetic stimulation, NSAIDs)
2. ↑ Bowman's capsule pressure (PBS): urinary obstruction (stones, BPH) → back pressure → opposes filtration
3. ↑ Plasma oncotic pressure (πGC): severe dehydration, hyperproteinemia → opposes filtration
4. ↓ Filtration coefficient (Kf): glomerulonephritis, diabetic nephropathy → thickening/scarring of glomerular membrane

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Q.3 — Substances Completely Reabsorbed | Sodium Reabsorption (1+4)

4 Substances Completely Reabsorbed from Renal Tubules

1. Glucose — reabsorbed entirely in PCT (until Tm is exceeded ~180 mg/dL plasma glucose)
2. Amino acids — completely reabsorbed in PCT via Na⁺-amino acid cotransporters
3. Bicarbonate (HCO₃⁻) — ~85% reabsorbed in PCT; remainder in DCT and collecting duct
4. Small proteins/peptides — endocytosed by PCT cells and degraded

Sodium Reabsorption Through Renal Tubules

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Q.4 — Prerequisites for Concentrated Urine | Countercurrent Mechanism (1+4)

Pre-requisites for Concentrated Urine Formation

1. Hyperosmotic medullary interstitium: High osmolality gradient from cortex to inner medulla (300–1200 mOsm/kg)
2. Presence of ADH (Vasopressin): Makes collecting duct permeable to water via aquaporin-2 (AQP2) insertion
3. Intact countercurrent system (loop of Henle + vasa recta)
4. Urea recycling: Urea accumulates in inner medulla and contributes ~50% of medullary hypertonicity

How Countercurrent Mechanism Forms Concentrated Urine

1. Descending limb: Permeable to water, impermeable to NaCl → water moves out osmotically into hypertonic medullary interstitium → tubular fluid becomes increasingly concentrated as it descends
2. Ascending limb (thick): Impermeable to water; actively transports Na⁺, K⁺, Cl⁻ (NKCC2) → NaCl pumped into interstitium without water → tubular fluid becomes dilute (~100 mOsm at DCT)
3. Net effect: Creates a gradient of hypertonicity in medullary interstitium (300 mOsm at cortex → 1200 mOsm at papilla)

• ADH (released in response to ↑ plasma osmolality or ↓ blood volume) → V2 receptors → cAMP → AQP2 insertion → collecting duct permeable to water
• Water moves out of collecting duct into hypertonic interstitium → urine concentrated to up to 1200 mOsm

• U-shaped capillaries that parallel the loop of Henle
• Blood flows into medulla and back — exchanges solutes and water passively
• Preserves the medullary concentration gradient (prevents washout)

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Q.5 — Renal Clearance | Facultative Water Reabsorption (2+3)

Renal Clearance

C = (U × V) / P

Facultative Water Reabsorption in Renal Tubule

• Obligatory water reabsorption (~65–70%): Occurs in PCT — water follows Na⁺ and solutes osmotically; independent of body needs; not regulated by ADH
• Facultative water reabsorption (~5–10%): Occurs in distal tubule and collecting duct; regulated by ADH; depends on body's water needs

1. ↑ Plasma osmolality → hypothalamic osmoreceptors → ↑ ADH secretion from posterior pituitary
2. ADH binds V2 receptors on principal cells of collecting duct → ↑ cAMP → PKA activation → phosphorylation of AQP2 → insertion of AQP2 into luminal membrane
3. Water moves from tubular lumen → cell → interstitium (via AQP3/4 on basolateral side)
4. Water retained → diluted plasma → feedback inhibition of ADH
5. Without ADH: Collecting duct remains impermeable to water → dilute urine produced (e.g., diabetes insipidus)

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Q.6 — Clinical SAQ: Syphilis + Bladder Dysfunction (1+1+3)

Scenario: 48-yr-old male, untreated syphilis → unable to fully empty bladder, overflow dribbling, loss of bladder sensation

(a) Type of Bladder Dysfunction

• Tertiary syphilis damages dorsal column and dorsal roots of sacral spinal cord (tabes dorsalis)
• Specifically damages the afferent (sensory) limb of the micturition reflex

(b) Micturition Centers and Component Primarily Affected

• Loss of bladder fullness sensation → patient doesn't feel urge to void → bladder overfills
• Detrusor muscle becomes atonic (overstretched)

(c) Why Overflow Dribbling Occurs

• Afferent sensory loss → no urge to void → bladder fills beyond normal capacity → becomes overdistended
• Intravesical pressure eventually exceeds urethral sphincter resistance
• Urine leaks passively and continuously in small amounts = overflow incontinence/dribbling
• The detrusor is unable to generate a sustained contraction to empty the bladder → large post-void residual
• This is the classic presentation of tabes dorsalis causing a sensory (afferent) neurogenic bladder

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SEQ — Q.7 (GROUP-B): Renal Function Tests (10 marks)

Renal Function Tests (RFTs)

A. Tests of Glomerular Function

B. Tests of Tubular Function

C. Tests of Renal Blood Flow

D. Urinalysis

E. Imaging

• USG kidneys: Size, echogenicity, obstruction, cysts
• CT scan / IVP: Structural abnormalities, calculi
• Renal biopsy: Definitive histological diagnosis

F. Staging of CKD by GFR

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SEQ — OR: How the Kidney Maintains Homeostasis (10 marks)

Kidney and Homeostasis

1. Regulation of Water Balance (Osmolality)

• Mechanism: Varies urine volume from 400 mL to 20 L/day
• ↑ Plasma osmolality → ↑ ADH → ↑ water reabsorption in collecting duct → concentrated urine
• ↓ Plasma osmolality → ↓ ADH → dilute urine
• Maintains plasma osmolality at 280–295 mOsm/kg

2. Regulation of Electrolytes

• Sodium: Regulated by aldosterone (RAAS), ANP, ADH
• Potassium: Secretion in collecting duct regulated by aldosterone; prevents hyper/hypokalaemia
• Calcium: 1α-hydroxylation of 25-OH-vitamin D₃ → active vitamin D → ↑ Ca²⁺ absorption from gut; PTH increases Ca²⁺ reabsorption
• Phosphate: Regulated by FGF-23 and PTH

3. Regulation of Acid-Base Balance

• Kidneys secrete H⁺ in the form of: titratable acids (H₂PO₄⁻) and ammonium (NH₄⁺)
• Reabsorb HCO₃⁻ (85% in PCT, remainder in DCT/CD)
• Generate new HCO₃⁻ via ammoniagenesis
• Correct metabolic acidosis (↑ H⁺ secretion, ↑ HCO₃⁻ production) and alkalosis (↓ HCO₃⁻ reabsorption)

4. Regulation of Blood Pressure

• RAAS: ↓ BP → renin → angiotensin II → aldosterone → Na⁺/water retention → ↑ BP
• ANP: ↑ BP/volume → ANP from atria → ↑ GFR, ↓ Na⁺ reabsorption → ↓ BP
• Pressure natriuresis: ↑ BP → ↑ Na⁺ and water excretion → normalizes BP
• Kidneys produce vasodilatory prostaglandins (PGE₂, PGI₂) and kallikrein-kinin system

5. Erythropoiesis

• Peritubular fibroblasts (in response to hypoxia) secrete erythropoietin (EPO)
• EPO stimulates RBC production in bone marrow
• Loss of this function → anaemia of CKD

6. Vitamin D Activation

• Kidney performs the final step: 25-OH-D₃ → 1,25(OH)₂-D₃ (calcitriol) by 1α-hydroxylase
• Calcitriol → ↑ intestinal Ca²⁺ and PO₄³⁻ absorption; ↑ bone mineralization
• Loss → renal osteodystrophy

7. Gluconeogenesis

• During prolonged fasting, kidneys contribute ~20% of total gluconeogenesis (using glutamine)

8. Excretion of Metabolic Waste Products

• Urea, creatinine, uric acid, bilirubin metabolites, drugs and toxins
• Failure → uraemia (urea encephalopathy, pericarditis, platelet dysfunction)

9. Regulation of ECF Volume and Composition

• Daily the kidney filters 180 L and precisely reabsorbs 99% — maintaining ECF volume, composition, and tonicity within narrow limits

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Summary of All Answers

GROUP-A (Respiratory Physiology + GIT)

GROUP-B (Renal Physiology)