Pathology · Anemias (Hemolytic, Microcytic, Macrocytic, Hemoglobinopathies)

In hereditary spherocytosis due to ankyrin deficiency, the primary structural consequence is:

  • A Loss of spectrin-actin cytoskeleton anchorage to the lipid bilayer, causing membrane vesiculation and loss of surface area
  • B Deficiency of band 3 leading to chloride-bicarbonate exchanger dysfunction
  • C Absent GPI anchor formation with complement-mediated lysis
  • D Deficient 4.2 protein causing increased cation permeability
Correct answer: A. Loss of spectrin-actin cytoskeleton anchorage to the lipid bilayer, causing membrane vesiculation and loss of surface area

Explanation

Ankyrin links β-spectrin to band 3 (anion exchanger); its deficiency disconnects the spectrin-actin cytoskeletal lattice from the lipid bilayer. The unsupported lipid bilayer vesiculates over time, progressively reducing RBC surface-to-volume ratio and producing spherocytes. These rigid, non-deformable cells are trapped and destroyed in the splenic sinusoids (extravascular hemolysis). GPI anchor deficiency characterizes PNH. Increased cation permeability with 4.2 deficiency is a lesser mechanism. Band 3 deficiency also causes spherocytosis but the primary mechanism of ankyrin deficiency is skeletal uncoupling.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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