Q.2 Clinical Case Scenario - Answers

i) Likely Diagnosis (4 marks)

ii) Relating Symptoms to the Underlying Pathophysiology (3 marks)

1. Polyuria and Polydipsia

• Hyperglycemia raises blood glucose above the renal threshold (~10 mmol/L / 180 mg/dL)
• The kidney cannot fully reabsorb the excess filtered glucose - this causes glucosuria
• Glucose in the tubular lumen exerts osmotic pressure, drawing water into the urine - osmotic diuresis - causing polyuria
• Polyuria leads to dehydration and hyperosmolality, stimulating the thirst center in the hypothalamus - causing polydipsia
• (Harper's Illustrated Biochemistry, 32nd Ed)

2. Polyphagia (Increased Appetite)

• Despite high blood glucose, cells (especially muscle and fat) are starved of glucose because insulin is needed to facilitate GLUT4-mediated glucose uptake
• The brain and hypothalamus perceive "starvation," stimulating hunger signals - leading to polyphagia
• This is the paradox of diabetes: high blood glucose + cellular glucose starvation = increased hunger

3. Weight Loss

• Despite polyphagia, caloric energy is literally "spilled" into the urine as glucose
• Additionally, in the absence of adequate insulin signaling: lipolysis increases (fat breakdown) and protein catabolism accelerates (muscle wasting) to generate alternative fuel - contributing to weight loss

4. Weakness

• Reduced glucose uptake by muscle cells (due to insulin resistance) means less ATP production, causing generalized fatigue and muscular weakness
• Electrolyte shifts from osmotic diuresis (loss of Na⁺, K⁺) also contribute

5. Glucosuria but NO Ketonuria

• In T2DM, residual insulin secretion is sufficient to suppress lipolysis and ketogenesis in the liver
• Therefore, urine contains glucose but not ketone bodies (in contrast to Type 1 DM or DKA)

6. Fungal Infection (Candidiasis) and Non-Healing Wounds

• High glucose in skin secretions and urine creates a rich medium for Candida albicans growth - explains the genital/waist fungal infection
• Hyperglycemia impairs neutrophil function (chemotaxis, phagocytosis) and T-cell immunity, reducing the ability to fight infections
• Non-healing wounds result from microvascular disease (thickened basement membranes, reduced blood flow) and neuropathy (reduced sensation allowing wounds to worsen unnoticed)

Insulin Resistance + Relative ↓ Insulin
            ↓
     Hyperglycemia
    /      |       \
Polyuria  Glucosuria  Cellular glucose starvation
Polydipsia           → Polyphagia
Weight loss          → Weakness
    \
     Fungal growth + Impaired immunity
     → Fungal infections, Non-healing wounds

Clinical Case Scenario - Iron Deficiency Anemia in Pregnancy

The Case Summary

• 32-year-old female, 28 weeks pregnant (3rd trimester)
• Complaints: dizziness, palpitation, breathlessness on exertion, easy fatigability
• Examination: pale, malnourished, spoon-shaped nails (koilonychia), pitting edema over ankles
• Investigations: Hb = 8 gm%, RBC count = 3.4 million/cu.mm

a) Likely Findings on Blood Smear (3 marks)

1. Microcytic Red Cells (small RBCs)

• Red cells are smaller than normal (MCV < 80 fL)
• In IDA, insufficient iron means less haemoglobin is synthesised per cell, so cells continue dividing until they are abnormally small

2. Hypochromic Red Cells (pale RBCs)

• The zone of central pallor is enlarged - normally it is 1/3 of the cell diameter; in IDA it takes up most of the cell
• Only a narrow peripheral rim of haemoglobin is visible around a large pale centre
• This is directly due to low haemoglobin content per cell

3. Pencil Cells (Elliptocytes / Cigar-shaped cells)

• Small, elongated, pencil-shaped red cells are characteristically seen in IDA
• These represent poikilocytosis (abnormal shapes) specific to iron deficiency

4. Anisocytosis and Poikilocytosis

• Anisocytosis = variation in cell size (mix of small and occasional normal-sized cells)
• Poikilocytosis = variation in cell shape (tear drops, elongated forms)

5. Normal/Hypersegmented Neutrophils

• A single hypersegmented neutrophil (5+ lobes) may be seen if there is a co-existing folate deficiency (common in pregnancy - dimorphic picture)

6. Low Platelet Count / Thrombocytosis

• Mild reactive thrombocytosis (elevated platelets) may be present due to chronic blood loss or iron depletion

Why this Patient has Iron Deficiency Anemia - Pathophysiology Link

• The fetus and placenta have a high demand for iron for haemoglobin synthesis and organ development
• Blood volume expands ~40-50% in pregnancy ("physiological haemodilution"), increasing iron requirement
• This patient is also malnourished, compounding dietary iron deficiency
• As a result: iron stores are depleted → impaired haem synthesis → hypochromic microcytic anaemia