Flashcards in Hematology Deck (373)
What are the sites of fetal hematopoiesis?
0-2 mos: yolk sac
2-7 mos: liver and spleen
5-9 mos: bone marrow
How do sites of hematopoiesis differ between infants and adults?
Infants: marrow in all bones
Adult: more limited: *vertebrae and pelvis*, ribs, sternum, skull, sacrum, proximal ends of femur
In bone marrow, how many cells are stem cells?
1 in 20x10^6 (20 million)
Beyond this: sign of potential leukemia
What are molecular markers for hematopoietic stem cells (HSCs)?
HSC: CD34+ and CD38-
Once committed to differentiation, become CD38+, but lack lineage specific markers.
What transcription factors regulate the survival of HSCs in bone marrow?
What transcription factors commit cells to the myeloid lineage in early hematopoiesis?
What transcription factors commit cells to erythropoietic and megakaryopoietic lineages?
Where are Erythropoietin and Thrombopoietin produced?
EPO: 90% in kidney
3 roles of growth factors in hematopoiesis
1. control of cell cycle
2. gene activation
3. inhibition of apoptosis
What is BCL-2?
Production stimulated by growth factor
Inhibits release of cytochrome C from mitochondria
3 families of adhesion molecules
Immunoglobin superfamily: antigen dependent surface receptors (TCR, etc) and antigen independent surface adhesion molecules
Selectins: leukocyte and platelet adhesion to endothelium
Integrins: cell adhesion to ECM
What is CFU-GEMM?
first step of erythropoiesis: commitment of pluripotent stem cells to non-lymphoid lineage
CFU-GEMM: Colony Forming Unit - Granulocyte, Erythrocyte, Megakaryocyte, Macrophage
What is BFU-E?
Erythrocyte Burst Forming Unit - first committed erythroid progenitor
divides -> CFU-E
Is there RNA in the cytoplasm of an RBC?
What is erythropoietin? Where is it produced?
Glycosylated polypeptide (165 AA)
90% produced by peritubular interstitial cells of kidney
10% in liver and elsewhere
What factors in the kidney stimulate erythropoietin production?
HIF-2a and B
What type of anemia results following kidney damage (failure, removal, etc.)
Because of reduced production rather than Hb or structure problem.
What is normal adult hemoglobin and what are its subunits?
consists of 2a and 2B
What forms of Hb are normally found in adult blood?
HbA (a2B2): dominant
HbF (a2Y2): fetal
Where are the components of hemoglobin synthesized?
All in RBC precursor cells
protoporphyrin: in mitochondria
Fe2+: transported by Transferrin -> mito -> + protoporphyrin -> haem
What is the P50 of hemoglobin under normal conditions? How does it change?
P50: partial pressure of O2 at which Hb is 50% sat.
normal blood: 26.6
increased affinity: falls
decreased affinity (ex. 2,3-DPG): rises
4 factors that move Hb O2 dissociation curve to the right
Move to right (low O2 affinity)
factors that move Hb O2 dissociation curve to the left
Move to left (high affinity)
What is methemoglobinemia? Causes?
Circulating Hb w/ Fe3+ rather than 2+ (patients often cyanotic)
Hereditary HbM: AA substitution affecting heme pocket
Hereditary deficiency of methemoglobin reductase
Toxic: drug or toxin induced oxidation of Fe2+ in Hb.
How do RBCs produce energy?
ATP and NADH: Embden-Meyerhof pathway (glycolytic)
NADPH: Hexose Monophosphate Shunt (PPP)
Important proteins in RBC membrane structure.
Band 3 (Cl- / HCO3- exchanger): binds ankyrin which binds protein 4.2 which together bind alpha spectrin
Glycophorin binds protein 4.1 and actin which bind spectrin
What is the relationship between anemia and 2,3-DPG?
2,3-DPG usually rises in setting of anemia -> rightward shift of Hb / O2 dissociation curve: Hb gives O2 to tissues more readily.
With what Hb concentration do symptoms of anemia usually become apparent?
What are the criteria for microcytic, hypochromic anemia, and what are the causes?
Iron deficiency, thalassemia, anemia of chronic disease (some), lead poisoning, sideroblastic anemia