Question

2. Describe the biochemical reason why deoxygenated hemoglobin S polymerizes? Apart from polymerization, what are the causes of the clinical manifestations in sickle cell disease?

Answer 1

Deoxygenated hemoglobin has more acidic pH than oxygenated hemoglobin.The acidic pH and dehydration favours the polymerization of Hemoglobin S.Hemoglobin S also has sticky ends which help in attaching the HbS end to end forming polymers.

Apart from the polymerization ; there are various crises in sickle cell disease.

1)Aplastic crisis-Because of the less life span of sickle shaped RBCs ;the bone marrow is producing new RBCs rapidly.During parvovirus B19 infection; the bone marrow is supressed.This leads to aplastic crisis.

2)Sequesteration crisis--The sickle shaped RBCs get sequestrated in the spleen leading to decreased RBC count in the peripheral blood.

3)Occlusive crisis -The sickle shaped RBCs polymerize and block the microvasculature of the bone.This leads to severe bone pain.When it occurs in the pulmonary circulation ; it causes chest pain.