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KNRUHS Physiology PYQ Analysis - Blood Chapter

Priority Classification

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🔴 TIER 1 — MOST REPEATED (High Priority, Study First)

1. Erythropoiesis ⭐⭐⭐ (HIGHEST PRIORITY)

• March-21, July-19, Dec-17, July/Aug-14, July-12, July-2000, Aug-1980, April-86, Oct-98, Nov-91
• Asked as: Stages, factors, morphological changes, factors regulating erythropoiesis, effect of Vit B12/iron
• Must prepare: All stages + factors (EPO, iron, B12, folate, androgens) + exam-ready diagram

2. Blood Coagulation / Clotting Mechanism ⭐⭐⭐

• Mar-21, Nov-13, May-07, Oct-1995, Oct-1993, April-84, Oct-1983, Aug-1980, Oct/Nov-18 (intrinsic pathway)
• Asked as: Mechanism of coagulation, clotting factors, intrinsic pathway, cascade amplification, fibrinolytic system
• Must prepare: Intrinsic + Extrinsic + Common pathway + anticoagulants together

3. Anticoagulants ⭐⭐⭐

• Dec-17, July-11, April-03, Feb-01, July-87, Nov-91, April-95, Oct-1998 (heparin/dicoumarol/sodium citrate), Aug-15 (intrinsic + anticoagulants)
• Asked as: Name 3 anticoagulants + mode of action, heparin/dicoumarol/sodium citrate mechanism, Vitamin K antagonist

4. Mismatched / Incompatible Blood Transfusion ⭐⭐⭐

• July-21, Aug-18, Nov-14, Jan-10, April-94, Oct-1984, April-1983
• Asked as: Hazards, effects, consequences, precautions to avoid

5. Platelets (Structure, Count, Functions) ⭐⭐

• Jan-12, Feb-2000 (×2), Oct-1998, April-96, April-95, April-94, July-1991
• Asked as: Functions, morphology + count, enumerate functions + explain one, structure

6. Functions of Plasma Proteins ⭐⭐

• July-19, March/April-05, April-03 (×2), Aug-01, May-1988, Nov-1994, July-1991, April-1995
• Asked as: Functions, isolation, concentration, albumin function, plasma proteins and their functions

7. Rh Factor ⭐⭐

• July-09, May-1999, Oct-1996, July-2000, April-1997, July-1991
• Also embedded in Anticoagulants short Qs (April-03 old)
• Asked as: Rh factor + significance, importance in blood transfusion

8. Blood Groups (ABO + Landsteiner's Laws) ⭐⭐

• July-13, Sep/Oct-07, Feb-09, Oct-04, Oct-1999, May-1988, Oct/Nov-02, Oct-1998
• Asked as: Blood group systems, physiological basis, Landsteiner's laws, determine own blood group

9. Anaemia (Classification + Types) ⭐⭐

• Jan-12, Sep/Oct-07, Feb-2000, May-1999 (long Qs); Nov-20, Jan-11, July-09 (very short Qs)
• Asked as: Anaemia, nutritional deficiency anaemias, classify anaemias, macrocytic/megaloblastic, morphological classification

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🟠 TIER 2 — MOST LIKELY TO BE ASKED IN 2026

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🟢 TIER 3 — LESS LIKELY TO BE ASKED IN 2026

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📊 Quick Reference Summary Table

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🎯 2026 Exam Strategy

1. Erythropoiesis (with diagram)
2. Blood coagulation - both intrinsic & extrinsic pathways
3. Anticoagulants (heparin, warfarin, sodium citrate + mechanisms)
4. Platelets - structure, count, functions
5. Plasma proteins - types, concentrations, functions
6. Blood groups + Rh factor
7. Mismatched blood transfusion - hazards & effects
8. Anaemia - classification (morphological + etiological)
9. Erythropoietin
10. T/B lymphocytes + immunity

• ESR, Eosinophils, Erythroblastosis fetalis, Haemophilia, Anti-coagulants, Lymph, Functions of spleen, Land Steiner's law, Cross matching, WBC functions

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Hazards, Effects & Consequences of Mismatched Blood Transfusion

Definition

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Mechanism (Pathophysiology)

1. Recipient anti-A/anti-B IgM antibodies bind to donor RBC surface antigens
2. Antigen-antibody complex activates the complement cascade (C1 → C3 → C5 → C5b-C9)
3. Membrane Attack Complex (MAC) forms pores in donor RBC membranes
4. Intravascular hemolysis - massive destruction of transfused RBCs
5. Free hemoglobin floods the plasma → hemoglobinemia
6. Complement fragments C3a and C5a activate mast cells → release cytokines (IL-1, IL-6, IL-8, TNF-α)
7. Kallikrein-kinin system activation → bradykinin release → hypotension
8. RBC stroma releases erythrocytin → activates intrinsic coagulation → DIC
9. Free Hb precipitates as acid hematin in distal tubules → acute renal failure

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Classification of Hazards

A. Immunological Reactions

B. Non-Immunological Reactions

• Circulatory overload (TACO)
• Bacterial contamination / septic reaction
• Air embolism
• Hypocalcemia (from citrate in stored blood)
• Hyperkalaemia
• Hypothermia from cold blood

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Effects & Consequences of Acute Hemolytic Reaction

1. Immediate Symptoms (Clinical Features)

Under general anesthesia, fever and pain are masked - the presenting signs are hemoglobinuria, unexplained hypotension, or bleeding diathesis - Miller's Anesthesia, 10e.

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2. Acute Renal Failure (Most Serious Consequence)

• Free Hb saturates plasma haptoglobin (capacity ~100 mg Hb/100 mL plasma)
• Excess free Hb reaches kidneys → in acidic urine, precipitates as acid hematin in distal convoluted tubules
• Mechanical tubular obstruction → oliguria/anuria
• Additionally, renal vasoconstriction from nitric oxide scavenging by free Hb reduces renal blood flow → acute tubular necrosis (ATN)
• Result: Acute Kidney Injury (AKI)

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3. Disseminated Intravascular Coagulation (DIC)

• Lysed RBC stroma releases erythrocytin (thromboplastin-like substance)
• Activates the intrinsic clotting pathway
• Consumption of clotting factors I (fibrinogen), II, V, VIII, and platelets
• Simultaneously, fibrinolysis is activated
• Net result: paradoxical bleeding despite widespread clotting

• Prolonged PT and PTT
• Decreased fibrinogen
• Decreased platelet count
• Elevated FDPs (Fibrin Degradation Products)
• Positive D-dimer

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4. Shock (Circulatory Collapse)

• Complement activation → C3a, C5a → mast cell degranulation → histamine + serotonin release → vasodilation
• Kallikrein-kinin activation → bradykinin → marked hypotension
• Combined with haemorrhage from DIC → cardiogenic + distributive shock
• Death may result from anaphylaxis, renal failure, electrolyte imbalance, or circulatory overload

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5. Jaundice (Prehepatic / Haemolytic)

• Massive intravascular haemolysis → large amounts of unconjugated bilirubin released
• Liver temporarily overwhelmed → unconjugated hyperbilirubinemia
• Scleral icterus, jaundice appear within hours
• Urine shows urobilinogen, urobilin, and red cell casts

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6. Delayed Hemolytic Reaction (3-10 days later)

• Occurs with minor antigen incompatibilities (Kidd, Duffy, Kell systems)
• Recipient has low-titre IgG antibodies from prior sensitization (pregnancy/previous transfusion)
• Complement activation stops at C3b → opsonization → extravascular hemolysis in the RES (spleen, liver)
• Milder presentation: anaemia, jaundice, fever, positive DAT
• NO hemoglobinuria (as haemolysis is extravascular)

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Investigations After Suspected Mismatched Transfusion

1. Stop the transfusion immediately
2. Haematological: Hb, PCV, haptoglobin (decreased), LDH (elevated), peripheral smear (spherocytes)
3. Urine: Hemoglobinuria, urobilinogen, red cell casts
4. Serology: Direct Antiglobulin Test / Coombs test (positive), cross-match repeat
5. Coagulation: PT, aPTT, fibrinogen, platelet count (for DIC)
6. Serum bilirubin: Unconjugated fraction raised
7. Bacteriological: Culture of residual donor blood (to rule out bacterial contamination)

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Management (Immediate Steps)

1. Stop transfusion immediately
2. Maintain urine output ≥75-100 mL/hour (IV fluids + mannitol → furosemide if needed)
3. Alkalinize urine (IV sodium bicarbonate - prevents acid hematin precipitation)
4. Treat hypotension with IV fluids/vasopressors
5. Manage DIC - FFP, platelets, cryoprecipitate
6. Send blood and urine samples to blood bank
7. Return unused blood to blood bank for repeat crossmatch
8. Monitor for ARDS, hepatic failure

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Causes of Death in Incompatible Transfusion

• Anaphylactic shock (immediate)
• Acute renal failure (hours to days)
• DIC with uncontrollable haemorrhage
• Electrolyte imbalance (hyperkalaemia, hypocalcaemia)
• Circulatory overload

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Precautions to Prevent Mismatched Transfusion

1. ABO and Rh grouping of both donor and recipient
2. Cross-matching before every transfusion (major + minor crossmatch)
3. Check patient identity with two identifiers before administration
4. Verify blood bag label against lab report
5. Watch for similarly named patients in the ward (most common clerical error)
6. Blood must be checked by two trained personnel
7. Use barcode scanning systems in modern settings
8. Start transfusion slowly (first 50 mL over 15 min under observation)
9. Screen for irregular antibodies (indirect Coombs test) in recipients with previous transfusions or pregnancies

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Anemia - Definition, Classification & Features (15 Marks)

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Definition

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Classification of Anemia

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SYSTEM 1 - ETIOLOGICAL / PATHOPHYSIOLOGICAL Classification

                        ┌─────────────────────┐
                        │        ANEMIA        │
                        └──────────┬──────────┘
              ┌──────────────────┼───────────────────┐
              ▼                  ▼                   ▼
    ┌──────────────┐   ┌──────────────────┐  ┌──────────────────┐
    │  BLOOD LOSS  │   │ INCREASED RBC    │  │ DECREASED RBC    │
    │              │   │ DESTRUCTION      │  │ PRODUCTION       │
    │  (Hemorrhagic│   │ (Hemolytic       │  │ (Hypoprolifera-  │
    │   Anemia)    │   │  Anemia)         │  │  tive Anemia)    │
    └──────┬───────┘   └────────┬─────────┘  └──────────┬───────┘
           │                    │                        │
    ┌──────┴──────┐     ┌───────┴──────┐       ┌────────┴────────┐
    │   ACUTE     │     │  INTRINSIC   │       │  EXTRINSIC      │
    │  Blood Loss │     │  (within RBC)│       │  (outside RBC)  │
    │  - Trauma   │     └───────┬──────┘       └────────┬────────┘
    │  - Surgery  │             │                        │
    └─────────────┘     ┌───────┼──────────┐    ┌───────┼───────────┐
    ┌──────────────┐    ▼       ▼           ▼    ▼       ▼           ▼
    │  CHRONIC     │  Mem-   Enzyme     Hb    Immune  Non-immune   
    │  Blood Loss  │  brane  defects    defects
    │  - GI bleed  │  defects          
    │  - Menorrhagia│
    └──────────────┘

A. Blood Loss Anemia

• Trauma, surgery, ruptured aneurysm
• Normocytic normochromic initially
• Reticulocytes increase after 3-5 days

• GI tract lesions (ulcer, carcinoma)
• Gynecological: menorrhagia, fibroids
• Eventually leads to iron deficiency → microcytic hypochromic

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B. Hemolytic Anemia (Increased RBC Destruction)

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C. Decreased Production (Hypoproliferative / Dyserythropoietic)

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SYSTEM 2 - MORPHOLOGICAL Classification (Based on RBC Size - MCV)

                        ┌──────────────────────┐
                        │        ANEMIA         │
                        └──────────┬───────────┘
         ┌────────────────────────┼────────────────────────┐
         ▼                        ▼                        ▼
┌──────────────────┐   ┌──────────────────┐   ┌──────────────────┐
│    MICROCYTIC     │   │    NORMOCYTIC    │   │    MACROCYTIC    │
│    HYPOCHROMIC   │   │   NORMOCHROMIC   │   │                  │
│  MCV < 80 fL     │   │  MCV 80-100 fL   │   │  MCV > 100 fL    │
│  MCH < 27 pg     │   │  MCH 27-33 pg    │   │                  │
└────────┬─────────┘   └────────┬─────────┘   └────────┬─────────┘
         │                       │                      │
  ┌──────┴───────┐       ┌───────┴───────┐     ┌────────┴────────┐
  │ TAILS        │       │               │     │  MEGALOBLASTIC  │
  │ Iron def.    │   Acute blood loss     │  B12 deficiency      │
  │ Thalassemia  │   Hemolytic anemia     │  Folate deficiency   │
  │ Sideroblastic│   Aplastic anemia      │  MDS                 │
  │ Anemia of    │   Renal disease        │  Chemotherapy        │
  │ chronic dis. │   Hypothyroidism       ├─────────────────────┤
  └──────────────┘   Mixed deficiency     │  NON-MEGALOBLASTIC  │
                     └───────────────┘    │  Liver disease       │
                                          │  Alcoholism          │
                                          │  Hypothyroidism      │
                                          │  Reticulocytosis     │
                                          └─────────────────────┘

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SYSTEM 3 - Based on Bone Marrow Response (Reticulocyte Count)

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Quick Comparison Table - Key Anemias

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Clinical Features of Anemia (General)

• Fatigue, weakness, exertional dyspnea
• Palpitations, headache, dizziness
• Tinnitus, fainting
• Reduced exercise tolerance

• Pallor (conjunctival, palmar, sublingual)
• Tachycardia, wide pulse pressure
• Systolic flow murmur (hyperdynamic circulation)
• Ankle edema in severe cases
• Specific signs: koilonychia (iron def.), glossitis (B12), jaundice (hemolytic)

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Summary Flowchart (Exam-Ready)

ANEMIA
│
├── BY ETIOLOGY
│   ├── Blood Loss → Acute / Chronic
│   ├── Hemolytic → Intrinsic (membrane, enzyme, Hb defects)
│   │              → Extrinsic (immune, microangiopathic, infection)
│   └── Decreased Production → Nutritional / Marrow failure / EPO deficiency
│
├── BY MORPHOLOGY (MCV)
│   ├── Microcytic (<80 fL) → Fe def., Thalassemia, Sideroblastic, ACD
│   ├── Normocytic (80-100) → Blood loss, Hemolytic, Aplastic, Renal
│   └── Macrocytic (>100)  → Megaloblastic (B12, Folate) / Non-megaloblastic (Liver, Alcohol)
│
└── BY BONE MARROW RESPONSE
    ├── Hyperregenerative (Retics ↑) → Hemolysis, Blood loss
    └── Hyporegenerative (Retics ↓) → Iron def., Aplastic, B12 def.

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