3 - Erythropoiesis and Approach to Anemia Flashcards
gene that enables differentiation into RBCs and megakaryocytes/platelets
GATA-1
how long does it take to make a mature RBC?
28 d
RBC precursors
Pronormoblast Basophilic normoblast Polychromatophilic normoblast Orthochromatic normoblast Reticulocyte Mature RBC
what stimulus is detected by the kidney to induce EPO production and release?
low blood oxygenation
secondary site of EPO production
liver (10%)
type of anemia caused by renal insufficiency
normochromic normocytic
what specifically does EPO do to increase RBC production?
prevents apoptosis of RBC precursors
4 non-EPO stimulators of erythrogenesis
GM-CSF, IL-3, insulin like growth factor, androgens
3 inhibitors of erythrogenesis
IFN gamma, IL1, TNF
what makes Darbepoietin different than other recombinant EPOs?
additional glycosylation site > longer half life
what protein detects low blood oxygenation to stimulate EPO production?
HIFalpha
what protein is responsible for the constitutive release of EPO?
HIFbeta
what disease can interfere with HIFalpha signaling / EPO regulation?
von Hippel Lindau syndrome - it is needed for degradation of HIFalpha when oxygenation is high
EPO receptor is member of what receptor family
cytokine
polycythemia vera
mutation of JAK2 on EPO receptor results in spontaneous dimerization > increased erythropoiesis in absence of EPO
2 families of special cytoskeleton RBC proteins
spectrins, band 3 proteins
what is the function of spectrins
bind to actin and the inside of the membrane, act like a muscle that improves membrane integrity
2,3 DPG stabilizes which form of hemoglobin?
deoxy
if each of these factors increases, what will happen to Hb affinity for oxygen?
pH
Temp
2,3 DPG
inc pH > inc affinity
inc temp > dec affinity
inc 2,3 DPG > dec affinity
what direction does the curve shift if Hb O2 affinity increases?
left
3 types of adult hemoglobins and what subunits they are made up of
A - alpha and beta
A2 - alpha and delta
F - alpha and gamma
nl Hb conc
13-17 g/dL
nl MCV
80-100 fl
nl MCH
27-34 pg
nl MCHC
32-36.4 g/dL
3 categories of anemia
dilutional (ex pregnancy)
proliferative (due to blood loss or hemolysis)
hypoproliferative (decreased production)
nl reticulocyte percentage
1-2%
why do you need a corrected retic count?
when you have a lower HCT, a normal number of retics can result in a high percentage. Corrected for different HCT
sx of anemia
breathlessness, fatigue, pallor, tachycardia, systolic flow murmur
most common cause of hypochromic microcytic anemia
iron deficiency
most common cause of megaloblastic anemia
b12 deficiency
key lab value suggesting hemolytic anemia
high retic count
tx of anemia of chronic renal failure
may need transfusions, usually respond well to exogenous EPO, may require iron supplementation
how high should you aim to get a pt w/ kidney disease’s hemoglobin conc?
~10-11. Less than normal because at normal levels they tend to thrombose
