ICL 3.2: Structural & Enzymatic Disorders Flashcards
what are the most common proteins in RBC cell membranes?
- ankyrin
- spectrin
- band 3
how is hereditary spherocytosis inherited?
autosomal dominant
what population is mostly effected by hereditary spherocytosis?
caucasian
northern european
what is hereditary spherocytosis?
spectrin or ankyrin deficiency!!
membrane loss leads to spherocytes
these misshapen RBCs are destroyed in the spleen = extravascular hemolysis
what are the clinical symptoms of hereditary spherocytosis?
anemia
jaundice
splenomegaly
gallstones
what test is done for hereditary spherocytosis?
- osmotic fragility test
RBCs are more likely to lyse in a hypotonic solution
incubate for 24 hours first before testing or you can get 25% false negative
- auto-hemolysis test
incubate cells in their own plasma for 48 hours, normally 5% lyse but in HS 10-50% will lyse
how do you treat hereditary spherocytosis?
splenectomy
no spleen = no spherocytes being removed!
better for adults though, kids need their spleen
you have to give them encapsulated organism vaccines though now that they don’t have a spleen
what is hereditary elliptocytosis?
inherited blood disorder in which an abnormally large number of RBCs are oval or elliptical shaped
leaves to chronic hemolysis of weird RBCs
how do you treat hereditary elliptocytosis?
remove the spleen lol
what is hereditary stomatocytosis?
autosomal dominant
lack of protein 7.2 (stomatin)
outside of the RBC shape looks fine but the inside of the cell looks like a white line
leads to hemolysis of RBCs
how do you treat hereditary stomatocytosis?
don’t do a splenectomy!
usually causes more clots for some reason
what is hereditary pyropoikilocytosis?
HPP is autosomal recessive
unstable spectrin causes unstable membrane cytoskeleton
both spectrum genes from mom and dad are abnormal so every cell in the blood smear is abnormal!!
what is PNH?
paroxysmal nocturnal hemoglobinuria
rare, acquired genetic clonal stem cell defect
PIG-A gene mutation results in lack of membrane CD55 and CD59
if anchor protein isn’t made, there’s holes in the RBC and the RBC gets lysed
causes C-mediated intravascular lysis of ALL cells (WBC, RBC, platelets)
what mutation causes PNH?
PIG-A gene mutation leading to deficiency of glycosylphosphatidylinositol anchor protein in RBC
what is haptoglobin?
it’s a suicide molecule
it gives itself up to get rid of all the toxic molecules coming out of a cell when it gets hemolyzed
what are the signs of PNH?
chronic hemolysis
anemia, jaundice, gallstones
venous thrombosis
clinical triad: hemolysis, pancytopenia, thrombosis
what tests can be done to test for PNH?
- Ham test: put RBCs in acidic solution to see if they hemolyze
- cytometric analysis
what is a cytometric analysis and how is it used to diagnose PNH?
tests to see if CD55 and CD59 are present
normal cells have CD59 and CD55 present at the same time
go look at the figure in your notes
what’s the treatment for PNH?
Soliris antibody
completely stops PNH
what’s the inheritance of G6PD deficiency?
x-linked recessive
males are more likely to have it
what are the classes of G6PD deficiency?
class I-V
what is class I G6PD deficiency?
sever enzyme deficiency, <1% normal enzyme activity
chronic hemolysis
what is class II G6PD deficiency?
<10% enzyme activity
intermittent hemolysis
drug induced
what is class III G6PD deficiency?
mild to
10-60% enzyme activity
moderate enzyme deficiency
intermittent hemolysis
what is what is class IV G6PD deficiency?
very mild enzyme deficiency
60-90% enzyme activity
no clinical problem
what is class V G6PD deficiency?
very mild enzyme deficiency
> 110% enzyme activity
no clinical problems
what can cause G6PD deficiency?
- drugs: antimalarials, sulfonamides, nitrofurantoin, antipyretics, analgesics
- herbal medicines
- moth balls
- insecticides & fungicides
- fava beans
- food coloring with aniline dyes
- potential oxidant agents during certain illness
what does pyruvate kinase deficiency cause?
without pyruvate kinase in the glycolysis pathway, PEP can’t be turned into pyruvate to make ATP
in RBCs this is the only way they can make energy because they don’t have mitochondria!
so without pyruvate kinase, there’s RBC hemolysis
