H&M Chp 2 Flashcards
Cell lineage of erythropoiesis
stem cell–>CFUgemm–> BFUe–>CFUe–> erythrocyte precursor
What is the first recognizable erythrocyte precursor found in the bone marrow?
pronormoblast
What do pronormoblasts look like?
large cell, dark blue cytoplasm, central nucleus with nucleoli, slightly clumped chromatin
Pronormoblasts give rise to ___ mature red cells.
16
Are nucleated red cells/normoblasts found in peripheral blood?
No- unless erythropoiesis is occuring in extramedullary erythropoiesis or some marrow diseases
Of normoblasts, reticulocytes, RBC, which contain nuclear DNA?
normoblast only
Of normoblasts, reticulocytes, RBC, which contain RNA in cytoplasm?
normoblast and reticulocyte
Of normoblasts, reticulocytes, RBC, which are found in the bone marrow?
all 3
Of normoblasts, reticulocytes, RBC, which are found in peripheral blood?
reticulocytes and RBC
As normoblasts give rise to progessively smaller cells, they contain progressively more ____ and progessively less _____.
hemoglobin; RNA and protein synthetic apparatus
What happens to the nucleus and chromatin as normoblasts are dividing?
becomes more condensed, nucleus is excluded from late normoblasts forming reticulocytes
Describe reticulocytes
slightly larger than RBC, 1-2 days in marrow and circulate for 1-2 days before losing all RNA and becoming RBC
Describe the structure of erythropoietin.
heavily glycosylated, 165 aa, 34 kDa
90% of erythropoietin is produced by ____. 10% is produced by _____.
peritubular interstitial cells of kidney; liver and other places
Are there preformed stores of erythropoietin?
no
What is the stimulus for production of erythropoietin?
oxygen tension in tissues of the kidney. Hypoxia–> HIFa and b–> erythropoietin production
The erythropoietin gene contains a ____ at its 3’ end.
Hif response element
Erythropoietin production ____ in anemia. Why?
increases- O2 delivery to kidney is affected
What is the function of GATA-1 and FOG-1
These are stimulated by erythropoietin. They enhance expression of erythroid-specific genes and anti-apoptotic genes of the transferring receptor
What is the main indication for erythropoietin therapy?
end stage renal disease
What metals are required for effective erythropoiesis?
iron and cobalt
What vitamins are required for effective erythropoiesis
B12, folate, C, E, B, thiamin, riboflavin
What hormones are required for effective erythropoiesis?
androgens, thyroxine
Describe Hb A
dominant Hb after 3-6 monthes of age. alpha2beta2 polypeptide chains. Each chain has its own heme group
Describe the chains that make up Hb F
alpha2 gamma 2
Describe the chains that make up Hb A2
alpha-2-delta-2
Heme synthesis occurs largely in the ____.
mitochondria
What is the 1st step of heme synthesis?
glycine+ succinyl coA= porphobilinogen. enzyme: rate limiting aminoaevulinic acid (ALA)
coenzyme: B6, which is stim. by erythropoietin
What 2 things ultimately come together to form heme?
Fe and protoporphyrin
What 2 things come together to form hemoglobin?
heme (from mitochondria) and globin (a2b2 from ribosomes)
What do the B chains do when O2 is unloaded?
they are pulled apart, permitting entry of 2,3 DPG resulting in a lower affinity for O2
What chain contacts stabilize hemoglobin?
A1B1, A2B2
What causes the O2 hemoglobin dissociation curve to shift to the right?
high concentrations of H (lower pH), CO2, DPG, Hb S
What causes the O2 hemoglobin dissociation curve to shift to the left?
Hb F,
_____ is a clinical state where circulating hemoglobin presents with Fe3 instead of Fe2
methaemoglobinaemia
Hemoglobin is broken down by ____.
macrophages
When are erythropoietin levels high? Low?
High: tumor secreting erythropoietin causing polycythaemia, low in severe renal disease or polycythaemia vera
Side effects of erythropoietin therapy?
rise in blood pressure, thrombosis, local injection reactions
What is often needed to maximize erythropoietin therapy?
oral/parenteral iron
The P50 of normal blood is ____
26.6 mmHg
Inherited defects of RBC membrane proteins can cause _____
spherocytosis and elliptocytosis
