Question

Explain how hemoglobin is catabolized by the body in both extravascular and intravascular hemolysis.

Explain the effect of the following on RBC survival. Explain your answer.

Explain how EPO regulates RBC production.

Answer 1

Question 1

Intravascular hemolysis occurs due to mechanical trauma inside the vessels, parasites such as falciparum, complement mediated destruction. In intravascular hemolysis, RBC lyses in circulation and hemoglobin is released into circulation. Hemoglobin combines with haptoglobin and this complex is phagocytosed by macrophage in different parts of the body, but especially by the Kupffer cells in liver and macrophage of bone marrow and spleen.Macrophages then release iron from hemoglobin and pass it back to blood,which is carried by transferrin to bone marrow for production of new RBC or to liver and other tissues for storage in the form of ferritin. Globin is degraded to its constituent aminoacids.Since the serum haptoglobin is depleted, hemoglobin oxidizes to methemoglobin. The renal proximal tubular cells reabsorb and catabolise much of the filtered hemoglobin and methemoglobin.But some amount is excreted in urine also.The iron free porphyrin part of hemoglobin is catabolised by the intracellular heme oxygenase enzyme into biliverdin which is rapidly reduced by biliverdin reductase to bilirubin. This bilirubin combine with albumin and is taken to liver,where glucuronidation of bilirubin occurs .This makes bilirubin water soluble.The conjugated bilirubin is secreted in bile to the gut.The glucuronidase enzyme in the gut converts it to urobilinogen.This urobilinogen is excreted in feces.Some of this is reabsorbed in ileum and is taken back to liver and excreted.Some amount is excreted in urine also.

Extravascular hemolysis occurs because of some defect in RBC that makes it less deformablee.Extreme deformability is needed for RBC to pass through the spleen. Hence in extravascular hemolysis, RBC is taken up by cells of reticuloendothelial system such as spleen where it is destroyed and hemoglobin is released and then it is catabolised to produce bilirubin which is excreted by liver and kidneys.

Question 2

Erythropoetin is a hormone produced by kidney.Stimulus for production of this hormone is low oxygen levels in blood.Erythropoeitin stimulates the production of proerythroblasts in the bone marrow. Once these proerythroblasts are produced,erythropoetin will speed up the other steps in erythropoesis,such that adequate number of RBC are produced to carry sufficient oxygen in blood.The level of erythropoetin decrease once normal oxygen levels are reached.