27: Red Cell Metabolism - Schmidt Flashcards
erythrocytes lose nuclei __ entering circulation
before
mRNA disappears 1-2 d after release; no prtn synthesis, no replacement of damage, etc.
old, inelastic RBC are trapped in ___ and phagocytosed by _____
spleen; macrophages
extravascular hemolysis - no RBC lysis in vasculature
hereditary spherocytosis –>
spectrin mutation leads to rounded, short-lived cells
defects of cytoskeleton shorten RBC lifespan
neonatal jaundice, failed phototherapy, blood analysis shows hemolysis –> what might it be?
G6PD deficiency
infant has a problem producing NADPH leading to hemolysis
intravascular v. extravascular hemolysis
intravascular: mechanical disruption, relase of hemoglobin from RBC –> hemoglobinuria
extravascular: normal, removal of stiff RBC, relase of bilirubin from RBC, possible jaundice
4 purposes of RBC metabolism
- keeping iron reduced in Fe2+ form (NADH)
- maintaining K/Ca gradients (ATP)
- keeping prtn SH groups reduced (NADPH)
- maintaining cell shape (ATP)
If RBC metabolism fails (3 things) …
- cells fill with Ca2+
- cells release K+
- lose biconcave shape
Red blood cell eats…
only glucose as an energy source
insulin has no effect on RBCs
look at slide 11
energy clutch and electron sources
what is the purpose of the energy clutch?
keep degrading 1.2bisphosphoglycerate even if no ADP available
2 regulated steps of glycolysis in RBC
- hexokinase
- phosphofructokinase I
acidic pH inhibit glycolysis - less lactate producton
acidic environment –> low 2,3 BP glycerate –>
increased binding affinity of oxygen to RBC
acidosis reduces 2,3BPG production
acidosis reduces 23BPG concentration and improves oxygen saturation
hemolytic crises triggered by:
infection, H2O2 producing drugs, Fava beans
see RBC with a bite taken out of them by a macrophage
G 6PD deficiency
also heinz body
blebbing of outer membrane of the RBC
pyruvate kinase deficiency
tumor cells get energy from..
glycolysis
produce large amounts of lactate
express hypoxia inducible factor 1a to support anaerobic metabolism
what is the cytoskeleton of RBCs like
mesh of spectrin under the PM with glycophorin and/or band/4.2/ankyrin anchoring to the membrane
most common cytoskeletal defect
hereditary spherocytosis
“rounding off of cells”
most commonly an ankyrin mutation but could be others
is glycolysis in RBC insulin dependent?
nope
provides reduction equivalents in the form of NADPH
PPP pentose phosphate pathway
low intraceullar NADPH –>
activates G6PD
pentose products are re-introduced into glycolysis
importance of glutathiione
GSH keeps sulfhydryl groups reduced
provides electrons to convert H2O2 to H20
what converts O2- to H2O2
superoxide dismutase
causes hemolytic anemia for lack of NADPH
G6PD deficiency
PPP defect
causes hemolytic anemia for lack of NADH/ATP
pyruvate kinase deficiency
glycolysis defect
