A patient with microangiopathic haemolytic anaemia has elevated LDH, low haptoglobin and haemoglobinuria. The haemoglobinuria indicates which pathological level of haemolysis?
- A Predominantly extravascular haemolysis in the reticuloendothelial system
- B Haemolysis localised to the bone marrow during ineffective erythropoiesis
- C Hepatic destruction of aged erythrocytes releasing Hb into portal circulation
- D Predominantly intravascular haemolysis, with free Hb exceeding haptoglobin binding capacity and renal tubular reabsorption capacity ✓
Explanation
Free haemoglobin released into plasma (intravascular haemolysis) is rapidly bound by haptoglobin; the Hb-haptoglobin complex is cleared by hepatic macrophages. When haemolysis overwhelms haptoglobin capacity, free Hb appears in plasma (haemoglobinaemia), filtered at the glomerulus. Proximal tubule cells reabsorb Hb up to a threshold; beyond that, free Hb appears in urine (haemoglobinuria). This dark urine is characteristic of severe intravascular haemolysis (TTP-HUS, paroxysmal nocturnal haemoglobinuria, G6PD crisis, mismatched transfusion). Extravascular haemolysis (spleen/liver macrophages) does not produce significant haemoglobinaemia or haemoglobinuria.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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