Flashcards in Pathology of Anemia 1 Deck (18)
RBCs destroyed within vascular compartment resulting in
-free hemoglobin forms complexes with haptoglobin (levels usually become low) and is removed by the liver
RBCs are destroyed by macrophages (normal RBC catabolism but exaggerated)
-does not result in significant hemoglobinemia or hemoglobinuria
-can result in splenomegaly
-more common than intravascular hemolysis
-Intrinsic defect in RBC membrane
-RBCs are spheroidal-->destroyed by spleen
-Autosomal dominant in 75%
-deficiency in any membrane skeletal protein but most common in spectrin
-spectrin content varies-correlates with severity of disease
Autosomal dominant form: ankyrin gene mutation
Autosomal recessive: mutation in alpha spectrin gene
-loss of membrane fragments-->reduction in surface to volume ratio-->sphere
What happens in hereditary spherocytosis if the spleen is removed?
-spherocytes persist but anemia is improved
-spleen macrophages are what kills the RBCs because they can not squeeze through the splenic sinus fast enough because they are not biconcave
What do hereditary spherocytes look like on a blood smear?
spheroidal red cells
no central zone of pallor
What are the clinical features of hereditary spherocytosis?
-jaundice-increased bilirubin from RBC metabolism
-largely asymptomatic in 20-30%-mild hemolysis with compensatory erythropoiesis
-chronic mild to moderate hemolytic anemia
-aplastic crisis may occur
What are findings that help diagnose hereditary spherocytosis?
-Increased MCHC(mean cell hemoglobin concentration)
-Increased osmotic fragility
How is G6PD deficiency inherited?
-considerable polymorphisms exist, more than 250 variants
Are there normally symptoms in G6PD deficiency?
no unless red cells are subject to oxidant injury following exposure to offending drugs or toxins
-drugs: antimalarials, sulfonamides, nitrofurantoin
-infections: generation of oxidant free radicals in macrophages
What does G6PD do? What happens without it
convert NADP to NADPH which is need to reduce GSSG to GSH
GSH relieves oxidative stress in RBCs
1. without G6PD-not enough NADPH is available to regenerate glutathione
2. H202 accumulates-oxidizing sulfhydryl groups of globin chains
3. hemoglobin denatures
-->forming Heinz bodies
4. Heinz bodies attach to RBC membrane
5. causes membrane damage and decreases deformability
What does the membrane damage and decreased deformability lead to?
1. intravascular hemolysis-from membrane damage
2. Macrophages in splenic cords bite the Heinz bodies-->spherocytes
3. extravascular hemolysis-red blood cells trapped in the spleen-spherocytes-can't move fast enough?
What happens in drug induced hemolysis with G6PD deficiency?
-acute with variable severity
-intravascular hemolysis, characterized by hemoglobinemia, hemoglobinuria and decreased hematocrit, typically develops after two to three days
How does sickle cell disease occur?
-point mutation-valine instead of glutamic acid-6th position of b-globin-->HgbS
-deoxygenation-->HbS molecules aggregate and polymerize (gelation or crystallization)
-red cell becomes distorted into sickle shape
What is the sickling of the red blood cells influenced by?
1. amount of HbS and its interaction with other hemoglobin chains in the RBC
2. The mean corpuscular hemoglobin concentration (increases in sickle cell disease>?)
3. Fall in pH
What are the 2 major clinical consequences of sickling?
1. chronic hemolytic anemia
a. intravascular hemolysis-increased mechanical fragility of severely damaged RBCs
b. extravascular hemolysis- rigid sickle RBC becoming SEQUESTERED in the spleen
2. occlusion of small blood vessels
What happens to the spleen in sickle cell disease?
-children may have moderate splenomegaly caused by the red pulp congestion
-over time, hypoxic tissue damage occurs and the spleen becomes small and fibrotic-->auto or functional splenectomy
What are the clinical results of having sickle cell?
1. widespread microvascular obstriction from the rigid red cells and other abnormalities may result in ischemic damage
2. intermittent sudden episodes are called vaso
occlusive, or painful crisis
3. aplastic crisis may occur occasionally
4. increased susceptibility to infections