Erythropoiesis & the Erythrogram Flashcards
(55 cards)
What is an erythron? What does it include?
red blood cells and their precursors in the bone marrow
- RBCs in blood vessels and sinuses in the spleen, liver, and bone marrow
- precursor cells in the spleen and bone marrow
What is hemoglobin? How much of an erythrocyte is made up of it?
tetramer of 4 globin chains (2 α and 2 β) linked to a separate heme that binds oxygen
95%
What ion is incorporated into each heme molecule of hemoglobin?
iron in the ferrous state (Fe2+)
MUST be reduced, hemoglobin bound to Fe3+ cannot carry oxygen
What is the function of hemoglobin? How should hemoglobin be in healthy individuals?
transports oxygen from lungs to tissues
100% saturated with oxygen in arterial blood
What is the only way to transport oxygen?
Hgb + Fe2+
Why is iron important for red blood cells?
hemoglobin synthesis depends on iron in the series of enzymatic reactions
What are the 3 major sites of iron distribution in the body?
- erythrocyte hemoglobin - 50-70%
- tissue storage and ferritin - 25-40%
- within other molecules, like myoglobin, cytochromes, and enzymes
What is the major rate-limiting enzyme in hemoglobin synthesis? What is required as a cofactor?
5-aminolevulenic acid synthase (5-ALA)
vitamin B6
What inhibits 5-aminolevulenic acid synthase? What does this cause?
lead
accumulation of heme precursor molecules in erythrocytes
What is porphyria?
rare, hereditary disorder of heme synthesis in cattle, pigs, cats, and humans caused by a deficiency in hemoglobin synthesis enzyme, URO synthase, resulting in porphyrin accumulation with incomplete heme synthesis
What is the major energy source in most species? What 4 metabolic pathways in RBCs use it?
glucose
- glycolysis (Embden-Meyerhoff pathway)
- 2,3-DPG (Rapoport-Leubering) pathway
- pentose phosphate pathway
- methemoglobin reductase pathway
What are the 2 major outcomes of glycolysis? What are the 2 most clinically relevant enzymes?
- generates ATP to maintain membrane function and integrity
- generates NADH to reduce methemoglobin (Fe3+ to Fe2+ + Hgb)
- pyruvate kinase
- phosphofructokinase
What is the purpose of the 2,3-DPG pathway in red blood cells?
aids in the oxygen delivery to tissues when anemia is present
What is the purpose of the pentose phosphate pathway and methemoglobin reductase pathway? What do both these pathways also do?
- generates NADPH, a cofactor for glutathione reductase
- reduces iron from Fe3+ to Fe2+
provide protection against oxidative stress
In what dogs is phosphofructokinase deficiency common? What does this cause? How does it present?
- English Springer Spaniels
- American Cocker Spaniels
shortened RBC lifespan due to impaired ATP production and a decreased 2,3-DPG concentration
alkalemia-induced hemolytic anemia (hyperventilation when stressed/excited)
In what animals is pyruvate kinase deficiency common? What does this cause? How does it present?
- Basenjis
- Chihuahuas
- Beagles
- Dachshunds
- Abyssinians
- Somalis
shortened RBC lifespan and an accumulation of 2,3-DPG with reduced ATP production
bone marrow failure
What is erythropoiesis? How does this begin? What stimulates this process?
erythrocyte production occurring mostly in the bone marrow
blast-forming unit-erythroid (BFU-E) —> committed stem cells (CFU-E) —> rubriblasts (first microscopically recognizable erythroid cell)
erythropoietin from the adult kidney and fetal liver
What is the first cell during erythropoiesis that loses its nucleus?
reticulocyte (polychromatophilic erythrocyte) - commonly produced in response to low RBC circulation
(nucleated erythroid cells should only be in the bone marrow)
What are the 6 major erythrocyte development stages?
- rubriblast
- prorubricyte
- rubricyte - basophilic, polychromatophilic
- metarubricyte - last stage that is nucleated
- reticulocyte - large, basophilic, anucleated
- mature erythrocyte
What is the last mitotic stage in erythrocyte development?
rubricyte
What are the 3 major trends in the cells during erythrocyte development?
- cells produce mRNA for hemoglobin synthesis
- cells undergo mitosis to produce more and smaller cells that have progressively more hemoglobin
- DNA synthesis decreases and fewer mitotic divisions occur
About how long does it take for erythropoietic progenitor cells to become a reticulocyte? How long do reticulocytes circulate before maturing into erythrocytes?
5 days
1-2 days
What nutritional factors affect nucleic acid metabolism and cytoplasmic maturation/hemoglobin formation during erythropoiesis?
NUCLEIC ACID: vitamin B12, folate
CYTOPLASM/HGB: vitamin B6, iron, amino acids, copper
What hormonal and bone marrow factors control erythropoiesis?
HORMONAL: erythropoietin from the adult kidney and fetal liver
BONE MARROW: stem cells, stroma, blood supply
