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LONG ESSAY (2 × 10 = 20 Marks)

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Q1. Define Hemostasis. List the Stages of Hemostasis. Describe the Intrinsic Mechanism of Clotting. (2+3+5 = 10 marks)

Definition (2 marks)

Stages of Hemostasis (3 marks)

1. Vascular spasm (vasoconstriction) - Immediate reflex contraction of injured vessel wall reducing blood flow.
2. Primary hemostasis (Platelet plug formation) - Platelets adhere to exposed subendothelial collagen (via vWF), become activated, and aggregate to form a loose platelet plug.
3. Secondary hemostasis (Coagulation / Blood clotting) - A cascade of clotting factor reactions converts fibrinogen to fibrin, reinforcing the platelet plug into a stable clot.
4. Fibrinolysis - The clot is eventually dissolved by plasmin once repair is complete.

Intrinsic Mechanism of Clotting (5 marks)

• Factor XII (Hageman factor) is activated to Factor XIIa on contact with collagen.
• High-molecular-weight kininogen (HMWK) and prekallikrein serve as co-factors.

• Factor XIIa activates Factor XI → Factor XIa

• Factor XIa activates Factor IX → Factor IXa
• (Requires Ca²⁺ ions)

• Factor IXa + Factor VIIIa + Ca²⁺ + Phospholipid (platelet surface) form the intrinsic tenase complex
• This complex activates Factor X → Factor Xa

• Factor Xa + Factor Va + Ca²⁺ + Phospholipid form the Prothrombinase complex
• Prothrombinase converts Prothrombin (Factor II) → Thrombin (Factor IIa)
• Thrombin cleaves Fibrinogen → Fibrin monomers
• Fibrin monomers polymerize into a loose fibrin mesh
• Factor XIII (activated by thrombin) cross-links fibrin → stable insoluble fibrin clot

XII → XIIa (contact with collagen)
       ↓
XI → XIa
       ↓ (Ca²⁺)
IX → IXa
       ↓ + VIIIa + Ca²⁺ + PL (Tenase complex)
X → Xa
       ↓ + Va + Ca²⁺ + PL (Prothrombinase)
Prothrombin → Thrombin
       ↓
Fibrinogen → Fibrin monomer → Fibrin polymer (cross-linked by XIIIa)

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Q2. Define Stroke Volume. State the Normal Value. Describe the Factors Regulating Stroke Volume. (1+1+8 = 10 marks)

Definition (1 mark)

Normal Value (1 mark)

• Cardiac Output = SV × Heart Rate = 70 × 72 ≈ 5 L/min

Factors Regulating Stroke Volume (8 marks)

1. Preload (End-Diastolic Volume - EDV)

• The degree of ventricular filling before contraction; reflects initial fiber stretch.
• Governed by Frank-Starling Law: the greater the stretch of myocardial fibers (within physiological limits), the greater the force of contraction and hence the greater the SV.
• Factors increasing preload (increase SV): increased venous return, increased blood volume, leg elevation, exercise (muscle pump), bradycardia (longer diastole = more filling).
• Factors decreasing preload (decrease SV): hemorrhage, dehydration, standing upright, tachycardia.

2. Afterload

• The resistance against which the ventricle must eject blood = aortic impedance / total peripheral resistance (TPR).
• Inverse relationship: Increased afterload → decreased SV (ventricle cannot empty completely).
• Factors increasing afterload (decrease SV): hypertension, aortic stenosis, increased TPR.
• Factors decreasing afterload (increase SV): vasodilators, arterial compliance.

3. Myocardial Contractility (Inotropy)

• The intrinsic strength of contraction of the myocardium, independent of preload/afterload.
• Determined by intracellular Ca²⁺ availability.

• Sympathetic stimulation (norepinephrine - β1 receptors → ↑ cAMP → ↑ Ca²⁺)
• Catecholamines (epinephrine)
• Digitalis (inhibits Na⁺/K⁺ ATPase → ↑ intracellular Na⁺ → ↑ Ca²⁺ via Na⁺/Ca²⁺ exchanger)
• Increased heart rate (Bowditch/Treppe effect)
• Hypercalcemia

• Parasympathetic stimulation (mainly atria)
• Hypoxia, acidosis, hypercapnia
• Beta-blockers
• Heart failure
• Myocardial ischemia

4. Heart Rate (Indirect Effect)

• Very high heart rates reduce diastolic filling time → reduce EDV → reduce SV (despite increased contractility from sympathetics).

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SHORT ESSAY (12 × 5 = 60 Marks)

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Q3. Describe Active Transport Mechanism with Examples. (5 marks)

Types:

A. Primary Active Transport

• Energy derived directly from ATP hydrolysis.
• A membrane-bound ATPase (pump) uses ATP to move ions against gradient.

1. Na⁺/K⁺-ATPase pump (Sodium-Potassium pump):
   • Moves 3 Na⁺ OUT and 2 K⁺ IN per ATP hydrolyzed.
   • Maintains resting membrane potential; vital for excitable cells.
   • Ubiquitous in all cells.
2. Ca²⁺-ATPase pump (Calcium pump):
   • Pumps Ca²⁺ out of the cytoplasm into ER (SERCA pump) or out of cell (PMCA).
   • Maintains very low intracellular Ca²⁺ (~10⁻⁷ M).
3. H⁺/K⁺-ATPase (Proton pump):
   • Found in gastric parietal cells.
   • Secretes H⁺ into stomach lumen against concentration gradient.
   • Target of proton pump inhibitors (omeprazole).

B. Secondary Active Transport

• Energy derived indirectly from the concentration gradient of Na⁺ (established by Na⁺/K⁺ ATPase).
• No direct ATP use for transport itself.

1. Co-transport (Symport): Na⁺ and substance move in the same direction.
   • Example: Glucose-Na⁺ co-transport (SGLT) in intestinal and renal tubular epithelium - glucose absorbed with Na⁺.
   • Example: Amino acid-Na⁺ co-transport in gut and kidney.
2. Counter-transport (Antiport): Na⁺ and substance move in opposite directions.
   • Example: Na⁺/Ca²⁺ exchanger (NCX) in cardiac muscle - Na⁺ moves in, Ca²⁺ moves out.
   • Example: Na⁺/H⁺ exchanger (NHE) - Na⁺ in, H⁺ out (acid-base regulation).

Key Characteristics:

• Requires a carrier protein (transporter)
• Shows saturation kinetics (Tm - transport maximum)
• Can be inhibited by metabolic inhibitors (e.g., ouabain inhibits Na⁺/K⁺ ATPase)
• Directional and specific

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Q4. Outline the Steps of Phagocytosis Using Flow Chart. (5 marks)

STEP 1: RECOGNITION & ATTACHMENT
         ↓
  Opsonins (IgG, C3b) coat the particle (bacterium)
  Phagocyte Fc receptors / C3b receptors bind opsonized particle
         ↓
STEP 2: INGESTION (Engulfment)
         ↓
  Pseudopods extend around the particle
  Pseudopods fuse → particle enclosed in a membrane vesicle
  → PHAGOSOME formed (particle inside cell membrane-bound vesicle)
         ↓
STEP 3: PHAGOSOME-LYSOSOME FUSION
         ↓
  Lysosomes (containing digestive enzymes) fuse with phagosome
  → PHAGOLYSOSOME formed
         ↓
STEP 4: KILLING & DIGESTION
         ↓
  ┌─── OXYGEN-DEPENDENT MECHANISMS ───┐
  │  Respiratory burst (NADPH oxidase) │
  │  O₂ → Superoxide (O₂⁻)            │
  │  → H₂O₂ → OH• (hydroxyl radical)  │
  │  Myeloperoxidase: H₂O₂ + Cl⁻      │
  │  → HOCl (hypochlorous acid)        │
  └────────────────────────────────────┘
  ┌─── OXYGEN-INDEPENDENT MECHANISMS ─┐
  │  Lysozyme (cleaves bacterial wall) │
  │  Defensins (membrane disruption)  │
  │  Acid pH (lysosomal enzymes)       │
  │  Lactoferrin (iron chelation)      │
  └────────────────────────────────────┘
         ↓
STEP 5: EXOCYTOSIS (Elimination of Debris)
         ↓
  Residual bodies (undigested material)
  expelled from cell by exocytosis

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Q5. (a) Identify the type of circulatory shock. (b) Describe physiological changes due to blood loss. (1+4 = 5 marks)

(a) Type of Shock (1 mark)

(b) Physiological Changes Due to Blood Loss (4 marks)

1. Baroreceptor Response (within seconds)

• Fall in BP → decreased stretch of aortic arch and carotid sinus baroreceptors
• → Reflex sympathetic activation and parasympathetic withdrawal
• → Tachycardia (↑ HR), vasoconstriction (↑ TPR), ↑ cardiac contractility
• → Attempts to maintain BP and cardiac output

2. Hormonal/Neuroendocrine Response (minutes to hours)

• Renin-Angiotensin-Aldosterone System (RAAS) activated:
  • ↓ renal perfusion → ↑ Renin → ↑ Angiotensin II → vasoconstriction + ↑ Aldosterone → Na⁺ and water retention
• ADH (Vasopressin) released from posterior pituitary → water retention + vasoconstriction
• Catecholamines (epinephrine, norepinephrine) from adrenal medulla → tachycardia, vasoconstriction

3. Fluid Shifts (Transcapillary refill)

• Arteriolar constriction → ↓ capillary hydrostatic pressure
• → Fluid moves from interstitium into capillaries (autotransfusion)
• Helps partially restore blood volume

4. Microcirculatory Changes

• Selective vasoconstriction in skin, gut, kidneys (non-vital organs) → blood redirected to heart and brain
• Pale, cold, clammy skin (cutaneous vasoconstriction)

5. Metabolic Changes

• Hypoperfusion → anaerobic metabolism → lactic acidosis
• Reduced urine output (oliguria) due to ↓ renal perfusion + ↑ ADH/Aldosterone

Clinical Picture:

• Tachycardia, hypotension, narrow pulse pressure
• Pale, cold, clammy skin
• Oliguria, altered sensorium
• Metabolic acidosis

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Q6. Draw a Labelled Diagram of Pacemaker Potential & Show the Effect of Sympathetic Stimulation. (5 marks)

Pacemaker Potential (SA Node Action Potential)

PACEMAKER POTENTIAL (SA NODE)

Membrane
Potential
(mV)
  0 ────────────────────────────────────────────
        /\        /\        /\
       /  \      /  \      /  \
 -40  /    \    /    \    /    \
     /  ↑   \  /      \  /      \
    / Phase4 \/        \/        \
-65 ─threshold (-40mV)──────────────────────────
                    
    |←Phase 4→|←Phase 0→|←Phase 3→|

PHASES:
• Phase 4 (Slow depolarization/Pacemaker potential):
  - Starts at Maximum Diastolic Potential (~−65 mV)
  - Slow inward Na⁺ current (If - "funny current", HCN channels)
  - Slow inward Ca²⁺ current (T-type Ca²⁺ channels)
  - Decreasing outward K⁺ current
  → Membrane depolarizes slowly to threshold (~−40 mV)

• Phase 0 (Upstroke):
  - Threshold reached → L-type Ca²⁺ channels open
  - Rapid Ca²⁺ influx → fast depolarization (no fast Na⁺ channels in SA node)

• Phase 3 (Repolarization):
  - K⁺ channels open → K⁺ efflux → repolarization back to −65 mV

Effect of Sympathetic Stimulation:

NORMAL (solid line) vs SYMPATHETIC STIMULATION (dashed line):

     0 mV ─────────────────────────
           /\    /\    /\   / \  /\  (faster rate)
          /  \  /  \  /  \ /    \/  
    -40 ─────threshold──────────────
         ↑↑↑ Steeper slope ↑↑↑
         
    -65 ─────────────────────────────
         |←shorter→|
         
Sympathetic effect:
• Norepinephrine binds β1 adrenergic receptors
• ↑ cAMP → ↑ If (HCN channel activity)
• → STEEPER slope of Phase 4 (faster depolarization)
• → Threshold reached MORE QUICKLY
• → INCREASED heart rate (POSITIVE CHRONOTROPY)
• Also: ↑ conduction velocity (positive dromotropy)
• Also: ↑ contractility (positive inotropy)

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Q7. Name 2 Gastrointestinal Hormones and Describe Their Functions. (5 marks)

1. Gastrin

• Stimulates gastric acid (HCl) secretion by parietal cells (via CCK-B/gastrin receptors)
• Stimulates pepsinogen secretion by chief cells
• Stimulates intrinsic factor secretion
• Promotes gastric mucosal growth (trophic effect)
• Increases gastric motility
• Weakly stimulates pancreatic enzyme secretion

2. Secretin

• Stimulates pancreatic bicarbonate (HCO₃⁻) secretion (primary action) → neutralizes gastric acid in duodenum
• Stimulates bile secretion from liver (choleretic effect - increases bile volume and bicarbonate content)
• Inhibits gastric acid secretion (antagonizes gastrin)
• Inhibits gastric emptying
• Stimulates pepsin secretion from chief cells
• Weakly stimulates pancreatic enzyme secretion

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Q8. Describe Enterohepatic Circulation. Mention Its Importance. (5 marks)

Enterohepatic Circulation

Circuit (Step-by-step):

LIVER
  ↓ Bile acids synthesized from cholesterol
  ↓ Conjugated with glycine or taurine → bile salts
  ↓ Secreted into bile → stored in gallbladder
  ↓
DUODENUM
  ↓ Released into duodenum (on eating)
  ↓ Bile salts emulsify dietary fats
  ↓ Facilitate micelle formation and fat absorption
  ↓
TERMINAL ILEUM (main site)
  ↓ Active reabsorption of ~95% of bile salts
  ↓ (Sodium-bile acid cotransporter, IBAT/ASBT)
  ↓ Some passive absorption in jejunum/colon
  ↓
PORTAL VEIN
  ↓ Bile salts return to liver via portal blood
  ↓
LIVER → Re-secreted into bile → cycle repeats
  ↓ (~5% lost in feces → replaced by new synthesis)

Importance:

1. Conservation of bile acids - Only ~5% (0.3-0.5 g/day) is lost in feces; the rest is recycled, saving the liver from synthesizing large quantities daily.
2. Fat digestion and absorption - Ensures adequate bile salt concentration in the intestinal lumen to form micelles for dietary fat, fat-soluble vitamins (A, D, E, K) and cholesterol absorption.
3. Cholesterol homeostasis - Bile acid synthesis is a major route of cholesterol excretion; enterohepatic circulation regulates hepatic cholesterol metabolism. Bile acid sequestrants (cholestyramine) interrupt this cycle, forcing ↑ cholesterol catabolism → ↓ LDL cholesterol.
4. Regulation of bile acid synthesis - Bile acids returning to the liver exert feedback inhibition on the rate-limiting enzyme CYP7A1 (cholesterol 7α-hydroxylase), preventing excessive synthesis.
5. Drug/toxin metabolism - Some drugs (e.g., morphine glucuronide) undergo enterohepatic recycling, prolonging their half-life.

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Q9. Mention the Differences Between Obligatory and Facultative Reabsorption of Water. (5 marks)

Summary:

• Obligatory = compulsory, always happening, not regulated - reclaims the vast majority of water.
• Facultative = optional, regulated by ADH - accounts for the final concentration/dilution of urine.

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Q10. State the Normal Renal Threshold for Glucose. Describe Glucose Reabsorption by the Tubules. (2+3 = 5 marks... wait, marked as 3+2 = 5 marks)

Normal Renal Threshold for Glucose (2 marks)

• Normal renal threshold for glucose = 180 mg/dL (10 mmol/L)
• This is the plasma glucose concentration at which glucose first appears in the urine (glycosuria).
• Below this level, all filtered glucose is reabsorbed.
• Transport maximum (Tm) for glucose = 375 mg/min in men (~320 mg/min in women)
  • This is the maximum rate at which tubules can reabsorb glucose.

Glucose Reabsorption by the Tubules (3 marks)

TUBULAR LUMEN          TUBULAR CELL          PERITUBULAR CAPILLARY

                    Na⁺/K⁺-ATPase (basolateral)
                    3Na⁺ OUT, 2K⁺ IN → low intracellular Na⁺
                    
Glucose + 2Na⁺ ──→ [SGLT2 / SGLT1] ──→ Glucose accumulates
(luminal side)     Co-transporter       inside cell
                   (Secondary           
                    Active Transport)         ↓ GLUT2
                                        Glucose ──→ Blood
                                        (facilitated diffusion)

• SGLT2 (high capacity, low affinity): Located in early PCT (S1 segment) - reabsorbs ~90% of filtered glucose
• SGLT1 (low capacity, high affinity): Located in late PCT (S3 segment) - reabsorbs remaining ~10%
• GLUT2 (basolateral): Facilitates glucose exit from cell into blood (facilitated diffusion, no energy)

• At plasma glucose < 180 mg/dL: all glucose reabsorbed, none in urine
• At plasma glucose > 180 mg/dL (renal threshold): transporters start saturating → glycosuria begins
• At plasma glucose > 300 mg/dL (Tm): transporters fully saturated → glucose in urine increases proportionally

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Q11. Describe the Factors Affecting Compliance. Name Two Conditions Where Compliance is Altered. (3+2 = 5 marks)

Definition

• C = ΔV / ΔP (normal = ~200 mL/cmH₂O)

Factors Affecting Lung Compliance (3 marks)

1. Surface Tension

• Air-water interface at alveolar surface generates surface tension that opposes lung expansion.
• Surfactant (dipalmitoyl phosphatidylcholine - DPPC) produced by Type II pneumocytes reduces surface tension → increases compliance.
• Without surfactant → ↓ compliance → alveolar collapse (atelectasis).
• (Laplace's Law: P = 2T/r) - surfactant is more effective in small alveoli, preventing collapse.

2. Elastic Recoil of Lung Tissue

• Lung parenchyma contains collagen (resists expansion) and elastin (allows stretch and recoil).
• Increased elastin/collagen cross-linking (e.g., fibrosis) → ↓ compliance.
• Destruction of elastic tissue (e.g., emphysema) → ↑ compliance.

3. Lung Volume

• Compliance is lower at high lung volumes (near-full inflation - elastic limit reached) and lower at very low volumes (surfactant depleted, alveolar collapse).
• Maximum compliance at normal tidal breathing range.

4. Age

• Compliance increases with age (loss of elastic recoil) but may reduce in extreme old age.

5. Blood Volume in Lungs

• Pulmonary congestion (↑ blood/fluid in lungs) → ↓ compliance.

6. Body Position

• Supine position → ↓ compliance compared to upright.

Two Conditions Where Compliance is Altered (2 marks)

• Pulmonary Fibrosis: Excess collagen deposition replaces elastic tissue → lungs become stiff, cannot expand easily → restrictive lung disease. Patient breathes fast and shallow. ↑ work of breathing.
• Infant Respiratory Distress Syndrome (IRDS/NRDS): Premature infants lack surfactant → high surface tension → alveolar collapse → ↓ compliance → severe respiratory distress.
• Others: Pulmonary edema, pneumonia, ARDS.

• Emphysema: Destruction of alveolar walls and elastic tissue by proteases → ↑ compliance → loss of elastic recoil → air trapping, barrel chest. Expiration becomes active (effort-dependent). Obstructive pattern.

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Q12. List the Various Types of Hypoxia. Describe Causes and Features of Each Type. (5 marks)

Types of Hypoxia (4 main types - Barcroft's classification):

1. Hypoxic Hypoxia (Hypoxemic Hypoxia)

• High altitude (low atmospheric PO₂)
• Hypoventilation (COPD, respiratory muscle paralysis, opioid overdose)
• Diffusion impairment (pulmonary fibrosis, pulmonary edema)
• V/Q mismatch (pneumonia, atelectasis, pulmonary embolism)
• Right-to-left cardiac shunt (Tetralogy of Fallot)

• ↓ PaO₂, ↓ O₂ saturation
• Cyanosis (central)
• Responds to supplemental O₂ (except shunts)
• Hyperventilation (stimulation of peripheral chemoreceptors)

2. Anemic Hypoxia (Hemic Hypoxia)

• Anemia (↓ hemoglobin quantity)
• Carbon monoxide poisoning (CO binds Hb with 250× affinity vs O₂ → carboxyhemoglobin)
• Methemoglobinemia (Fe²⁺ oxidized to Fe³⁺ - cannot carry O₂)
• Hemoglobin abnormalities (HbS)

• PaO₂ is normal
• Reduced O₂ content of blood
• No cyanosis in CO poisoning (cherry-red color of CO poisoning)
• Does NOT respond to supplemental O₂ in CO poisoning
• Fatigue, weakness, pallor (in anemia)

3. Stagnant Hypoxia (Circulatory/Ischemic Hypoxia)

• Heart failure (low cardiac output)
• Circulatory shock (hemorrhagic, cardiogenic)
• Local ischemia (thrombosis, embolism, vasospasm)
• Increased blood viscosity

• PaO₂ and O₂ content are normal
• Tissues extract more O₂ → wide arteriovenous O₂ difference
• Venous PO₂ is very low
• Cyanosis may be present (peripheral - due to deoxygenated blood in sluggish capillaries)
• Cold extremities, reduced urine output

4. Histotoxic Hypoxia

• Cyanide poisoning (CN⁻ inhibits cytochrome c oxidase - Complex IV of ETC)
• Carbon monoxide (also inhibits cytochrome oxidase)
• Hydrogen sulfide poisoning

• PaO₂, O₂ saturation, O₂ content, and blood flow are ALL normal
• Venous PO₂ is high (tissues cannot extract O₂)
• Cells produce lactate (anaerobic metabolism despite O₂ availability)
• Cyanide: bitter almond breath, rapid death without treatment
• Does NOT respond to supplemental O₂ alone

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Q13. Describe the Mechanism of Acclimatization at High Altitude. (5 marks)

Immediate Responses (seconds to minutes):

1. Hyperventilation (most important early response):
   • ↓ PaO₂ → stimulates peripheral chemoreceptors (carotid and aortic bodies)
   • → ↑ respiratory rate and depth → washes out CO₂ → respiratory alkalosis
   • Initially limited by alkalosis suppressing central respiratory drive
   • Alkalosis stimulates bicarbonate secretion in urine (renal compensation) → respiratory drive is sustained

Short-term Responses (hours to days):

1. Renal compensation for respiratory alkalosis:
   • Kidneys excrete HCO₃⁻ → normalizes blood pH
   • Allows continued hyperventilation without inhibition
   • CSF pH also normalizes → central chemoreceptors allow continued hyperventilation
2. Increased cardiac output:
   • ↑ Heart rate (sympathetic activation)
   • ↑ SV initially → increased O₂ delivery
   • Returns to normal over days

Long-term Responses (days to weeks):

1. Erythropoiesis (↑ Red cell production):
   • Hypoxia → HIF-1α (Hypoxia Inducible Factor) → stimulates kidneys to produce Erythropoietin (EPO)
   • EPO → stimulates bone marrow → ↑ RBC production and ↑ hematocrit
   • Increases oxygen-carrying capacity of blood
   • Begins in 2-3 days, maximal in 2-3 months
2. 2,3-DPG increase:
   • Hypoxia → RBCs produce more 2,3-diphosphoglycerate (2,3-DPG)
   • 2,3-DPG binds to Hb → right shift of O₂-dissociation curve → Hb releases O₂ more readily to tissues
   • Occurs within 24-48 hours
3. Increased pulmonary ventilation (sustained):
   • Maintained hyperventilation → keeps PaO₂ as high as possible
4. Cellular adaptations:
   • Increased mitochondrial density
   • Increased myoglobin concentration (O₂ storage/transport within cells)
   • Increased vascularization (↑ capillary density in tissues)
   • More efficient oxidative enzymes
5. Pulmonary vasoconstriction:
   • Hypoxic pulmonary vasoconstriction (HPV) redirects blood from poorly ventilated to better ventilated areas; however, generalized HPV at altitude can cause pulmonary hypertension.

Summary Table:

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Q14. Describe the Factors Affecting Airway Resistance. (5 marks)

• R = ΔP / Flow (Hagen-Poiseuille Law: R = 8ηl / πr⁴)
• Normal total airway resistance ≈ 1-2 cmH₂O/L/sec
• Major site of resistance: Medium bronchi (2nd-7th generation) - NOT the trachea (too wide) or small airways (too many in parallel)

Factors Affecting Airway Resistance:

1. Radius of Airway (Most Important Factor)

• R ∝ 1/r⁴ (Poiseuille's law) - doubling the radius reduces resistance 16-fold!
• Factors that decrease radius → increase resistance:
  • Bronchoconstriction (asthma, anaphylaxis)
  • Mucosal edema (infection, inflammation)
  • Mucus hypersecretion (COPD, bronchitis)
  • Foreign body, tumor

2. Lung Volume

• At high lung volumes: airways are pulled open (radial traction by lung parenchyma) → ↓ resistance
• At low lung volumes: airways narrow → ↑ resistance → small airway closure (closing capacity)
• This explains why COPD patients breathe at high lung volumes (barrel chest) to keep airways open

3. Bronchomotor Tone (Autonomic Nervous System)

4. Viscosity and Density of Air (η)

• R ∝ η (viscosity)
• Breathing helium-oxygen mixture (Heliox) reduces gas density → reduces turbulence → reduces resistance in upper airway obstruction
• Breathing 100% O₂ vs air has minimal effect on viscosity

5. Type of Airflow

• Laminar flow (Reynolds number < 2000): R depends on viscosity; R = 8ηl/πr⁴
• Turbulent flow (Re > 4000): R depends on gas density, not just viscosity; requires higher ΔP
• Turbulence occurs at high flow rates, branch points, irregular surfaces (mucus, tumors)

6. Dynamic Compression of Airways (During Forced Expiration)

• During forced expiration, pleural pressure becomes positive → compresses airways from outside → dynamic airway collapse
• This is the mechanism of air trapping in emphysema

7. Secretions / Mucus in Airways

• Excess mucus (bronchitis) narrows lumen → ↑ resistance

8. Position / Body

• Supine position slightly increases resistance compared to upright (gravity effects)

• Asthma: Bronchoconstriction + mucosal edema + mucus → ↑ resistance → expiratory wheeze
• COPD (Emphysema): Loss of radial traction + airway collapse → ↑ resistance during expiration
• Treatment: Bronchodilators (β2 agonists - salbutamol; anticholinergics - ipratropium) reduce airway resistance

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