265b congenital anemia Flashcards
RBC membrane proteins that are important - integral and peripheral?
integral - band 3
peripheral - spectrin and ankyrin
ankyrin fxn
link spectrin t0 band 3
spectrin
a and b subunits that self associate - supports lipid bilayer as a scaffold
band 3
Cl and HCO3 exchange in bilayer
hereditary spherocytosis (HS) - cause?
Defect in proteins interacting with RBC membrane skeleton and plasma membrane (e.g., ankyrin, band 3, protein 4.2, spectrin).
hereditary spherocytosis (HS) - findings?
hemolysis –> anemia, jaundice
Splenomegaly
aplastic crisis (parvovirus B19 infection).
hereditary spherocytosis (HS) - labs?
osmotic fragility test+.
Eosin-5-maleimide binding test useful for screening.
^MCHC, reticulocytosis, ^RCDW
Normal to decreased MCV with abundance of cells; masks microcytia.
hereditary spherocytosis (HS) - Rx?
splenectomy, transfusions
hereditary spherocytosis (HS) - RBC appearance?
Less membrane causes small and round RBCs with no central pallor (^ MCHC, ^ red cell distribution width) –> premature removal of RBCs by spleen. (AKA spherocytes)
hereditary spherocytosis (HS) - findings?
hemolysis –> anemia, jaundice
Splenomegaly
aplastic crisis (parvovirus B19 infection).
RBC metabolism
no nuclei/mito
uses 2 pathways
1) pentose phosphate pathway to make NADPH using G6PD
2) Glycolysis to make ATP - pyruvate kinase is major rate limiting step
hereditary spherocytosis (HS) - Rx?
splenectomy
glycolysis in RBCs
Glucose –> G6P via hexokinase then F6P
F6P –> F1,6P via PFK I then to PEP
PEP –> pyruvate via PK (generates ATP)
pyruvate –> lactate
Hereditary elliptocytosis - rbc appearance? cause?
elliptocyte due to spectrin deficiency
RBC metabolism
no nuclei/mito
uses 2
1) pentose phosphate pathway to make NADPH using G6PD
2) Glycolysis to make ATP - pyruvate kinase is major rate limiting step
G6PD deficiency - findings? RBC smear appearance?
abdominal/back pain, hemoglobinuria a few days after oxidant stress –> coca-cola urine + jaundice, fever
Labs: blood smear shows RBCs with Heinz bodies (Hg is denatured and precipitates in RBCs) and bite cells.
“Stress makes me eat bites of fava beans with Heinz ketchup.”
glycolysis in RBCs
Glucose –> G6P via hexokinase then F6P
F6P –> F1,6P via PFK I then to PEP
PEP –> pyruvate via PK (generates ATP)
pyruvate –> lactate
G6PD deficiency - inheritance?
X-linked recessive
G6PD deficiency - pathogenesis?
Defect in G6PD –> reduced glutathione –> ^ RBC susceptibility to oxidant stress.
Hemolytic anemia following oxidant stress (classic causes: sulfa drugs, antimalarials, infections, fava beans).
G6PD deficiency - findings?
Back pain, hemoglobinuria a few days after oxidant stress.
Labs: blood smear shows RBCs with Heinz bodies and bite cells.
“Stress makes me eat bites of fava beans with Heinz ketchup.”
pyruvate kinase deficiency - genetics?
AR
pyruvate kinase deficiency - pathogenesis?
Defect in pyruvate kinase–> decreased ATP –> rigid RBCs.
pyruvate kinase deficiency - findings?
hemolytic anemia in a newborn –> hyperbilirubinemia
anemia, jaundice (but no increase in hemolysis?)
increased 2,3 DPG –> right shift of O2 curve
