Primal diseases of bone marrow - hemolytic and iron deficiency anemias. Etiology, pathogenesis & pathomorphological characteristics of target organs.
Anemia is a deficiency of RBCs or haemoglobin in the blood. There are different causes (hemorrhagic, hemolysis, decreased RBC production (iron def)) ,and different morphologies (microcytic, macrocytic, normocytic).
Hemolytic anemias are due to premature destruction of RBCs prior to their normal lifespan of 120 days. Destruction can be due to an intrinsic RBC defect, or extrinsic factor.
- Intrinsic hemolytic anemias
- Membrane abnormalities (e.g. spherocytosis)
- Enzyme defects (e.g. glucose 6 phosphate dehydrogenase)
- Disorders of hemoglobin synthesis (e.g. sickle cell anemia)
- Extrinsic hemolytic anemias
- Transfusion reactions
- Autoantibodies (idiopathic, drug associated)
- Mechanical trauma (e.g. defective cardiac valves)
- Infections (e.g. malaria)
Below we will take a look at some examples of hemolytic anemias:
- Hereditary spherocytosis
- AD mutation to membrane skeleton, causes change of RBC shape
- Spherical RBCs are unable to properly pass through splenic cords and are hemolyzed within the spleen
- Treatment is splenectomy - splenomegaly is very common
- Sickle cell anemia
- Most common hemoglobinopathy from Beta-globin gene mutation
- Mutation causes RBC to become sickled when deoxygenated
- Over time RBCs irreversibly sickle causing them to be hemolyzed
- Results in chronic hemolytic anemia and microvascular obstruction and moderate splenomegaly
- Thalassemia
- Mutation to alpha or beta globin chains, common in mediterranean, african and asian regions
- beta-Thalassemia (minor or major) - reduced HbA formation, causing hypochromic and microcytic RBCs, with imbalance of beta and alpha globin chain synthesis, which causes damage to the RBC membranes leading to increased RBC hemolysis and iron overload
- alpha-Thalassemia - depending on number of genes can be asymptomatic, severe (similar symptoms to beta thalassemia), or lethal in utero
- In both cases cells are microcytic and hypochromic
- Glucose-6-Phosphate Dehydrogenase Deficiency
- RBCs lack enough functional G6PD enzyme and are therefore vulnerable to oxidative injury that causes haemolysis. X-linked disease
- Asymptomatic until exposure to environmental factor that produces oxidants (e.g. drugs)
- Paroxysmal nocturnal hemoglobinuria
- Hemolytic anemia that occurs due to acquired somatic mutation in myeloid stem cells
- PIGA gene mutation, causes RBC precursors to be too sensitive to complement-mediated lysis.
- PIGA lies on the X chromosome, but the mutation is acquired, not inherited
- Malaria
Example: a man with G6PD deficiency develops dark urine and jaundice a few days after eating fava beans or taking primaquine, a sulfonamide or nitrofurantoin. The blood smear shows bite cells, and a supravital stain shows Heinz bodies (precipitated, oxidised haemoglobin).
Iron deficiency anemia
- Most frequent cause of anemia
- Iron is transported in the blood bound to transferrin