Ok, let us finish our last discussion on hemolytic anemia. Today we gonna talk on G6PD deficiency.
Ok, why deficiency in Glucose-6-Phosphate Dehydrogenase specifically leads to hemolytic anemia. Before we go into deep, let us do some simple Biochemistry recap.
All cells inside the body are vulnerable towards reactive oxidant including the red cell itself. So, how does red cell protect itself against the oxidant?
Red cell contains glutathione (GSH) which is a very powerful antioxidant used to inactivate the reactive endogenous and exogenous oxidants.
After inactivating oxidants, GSH (active form) turns into GSSH (inactive form). In order to reactivate the GSSH back to GSH, it needs an enzyme called Glutathione reductase. Glutathione reductase itself needs sufficient amount of NADPH. The level of NADPH is kept sufficient by G6PD.
Why? In the Pentose Phosphate Pathway (PPP), G6PD will produce NADPH when converting Glucose-6-Phosphate into 6-Phosphogluconate. Tada!! Now we get it clear! Without G6PD, glutathione couldn’t be reactivated; therefore red cells couldn’t protect themselves from reactive oxidants. So, the red cells die!!!! (hemolysis)
Ok, now let us go to the etiology of the disease.
G6PD deficiency is due to X-linked inheritance of mutant gene.
This is why, G6PD deficiency is commonly seen in boys rather than girls.
Hemolysis is only prominent after 2-3 days exposure towards oxidants. This is because it takes about 2-3 days for glutathione to be completely depleted as there is no reactivation of glutathione happen.
Below are the predisposing factors that will lead to hemolysis in G6PD deficiency patients
1) Drug induced
+Antimalarial drugs, primaquine and chloroquine
+ Large doses of aspirin
2) Infection induced
+ Viral hepatitis
3) Food induced
+ Fava beans
When there is a presence of oxidant in the body, glutathione will neutralize it. But if the oxidant attacks are persisted, glutathione level will deplete and it couldn’t be reactivated since G6PD is deficient.
Oxidant/free radicals will attack sulfhydryl group of the globin chain. Once it attacks, sulfhydryl group of the globin chain will form precipitate which is called as the Heinz body. Heinz body is a dark matter within red cells
Heinz body formation will lead to these consequent events:-
1) Heinz body will bind to the cell membrane and it will disintegrate the cell membrane. Eventually red cells will undergo intravascular hemolysis.
2) Heinz body is recognized by the splenic macrophage as a foreign body; therefore it engulfs part at the red cell containing the Heinz bodies. This will lead to the formation of BITE CELL. Bite cell has lost its membrane integrity and eventually it will form a spherocytes. Spherocytes will undergo extravascular hemolysis in the reticuloendothelial system.
Those are pretty much about G6PD deficiency. Soon, we are going to discuss on iron deficiency and megaloblastic anemia.
Until then, thanks guys!!