Hemolytic Anemia

Question 1

How does hereditary spherocytosis cause anemia?

Answer 1

1. RBC membrane disorder due to the weakening of vertical interactions b/w skeleton & lipid membrane of cell
2. RBCs become spherical instead of biconcave
3. Causes ↓ SA:V ratio
4. Easily ruptures in microcirculation & ↓ membrane deformability (causes entrapment in the spleen)
5. Rupturing causes anemia (deficiency of Hb of an individual for their age & sex)
6. Also causes jaundice, sphenomegaly & gall stones
7. Treatment is removal of spleen

Question 2

Glutathione antioxidant system

Answer 2

Question 3

How does primaquine prophylaxis for malaria cause hemolytic anemia?

Answer 3

1. Draw glutathione antioxidant system
2. ROS are formed as a result of reduction of molecular oxygen (during metabolic processes like inflammation; environmentaI factors; damaged bio molecules like DNA, proteins, unsat. lipids)
3. If antioxidant levels ↓, leads to ↑ oxidative stress
4. GSH (glutathione) is one of the main antioxidant systems; it scavenges superoxide radicals (H2O2) by glutathione peroxidase enzyme
5. GSH oxidized to GSSG; must be reduced back which requires NADPH generated by HMP shunt (bc GSH in oxidized form cannot act as antioxidant)
6. 1st step in HMP shunt
7. In some, G6PD is deficient so ↓ NADPH produced; glutathione cannot be maintained in reduced state
8. Free radicals cannot be detoxified so they damage RBC membranes
9. Antimalarials like primaquine are oxidant drugs; when given to patient with ↓ G6PD they can develop hemolytic anemia

Question 4

Explain why the reticulocyte count is increased in hemolytic anemia

Answer 4

1. RBCs are destroyed excessively due to hemolysis. So RBC count ↓
2. Due to this oxygen carrying capacity of blood ↓. Leads to tissue hypoxia
3. Triggers kidney to produce erythropoietin which ↑ RBC production
4. Immature red cells (reticulocytes) are released in large amounts into circulation
5. Hb conc. & RBC count are parameters lowered in hemolytic anemia

Question 5

Explain how the red blood cell membrane is susceptible to damage by ROS

Answer 5

1. ROS are very reactive ions/ compounds of oxygen
2. Free radical ROS: O2- , OH, HO2
   Non free radical ROS: H2O2, O
3. RBC s transport oxygen in the body; contains hb that binds to oxygen when PO2 is ↑ (@lungs) & releases oxygen when when PO2 is ↓ (@tissue)
4. RBCs have no cell organelles so more space for Hb, so RBCs have more oxygen
5. } High possibility of forming ROS in RBC (most common is H2O2)
6. Reacts with lipids in plasma membrane & oxidizes Fe2+ → Fe3+
7. } cell structure is lost & integrity of cell is broken
8. So RBC s are susceptible to attacks from ROS
9. To neutralize, there is HMP shunt which maintains GSH in reduced state to oxidize free radicals (using NADPH)