Synthesis, development, and turnover of Red Blood Cells Flashcards
Hemopoiesis
the process of blood cell formation
Where does hemopoiesis occur? Also specify where in young vs. old animals
- Occurs in the bone marrow within the medullary canals of long bones
- young animals: primary sites in large long bones (tibia and femur)
- Older animals: primary sites are the vertebrate, sternum, and rib bones
Sinusoids
- Small irregularly shaped blood vessel found in bone marrow
- Endothelial cells are not tight, providing holes for mature blood cells to squeeze through and join circulation
Blood cell development
Originate from the pluripotent hemopoietic stem cells
Two lineages:
1. Myeloid progenitors- differentiate in the bone marrow and then travel to target destination
2. Lymphoid progenitors- differentiate in lymph cells when they receive the signal
Myeloid lineage cells
- Erythro MK progenitor
- Rubriblast
- Prorubricyte
- Rubricyte
- Metarubricyte
- Polychromatophilic erythrocyte/Reticulocytes
- Erythrocyte
Lymphoid lineage cells
- Common lymphoid progenitor
- T- lymphoblasts OR B- lymphoblasts
- T-cells OR B-cells
- T-cells become NK cells & B-cells become plasma cells
Erythropoietin (EPO)
Regulates erythropoiesis
Erythropoiesis
production of erythrocytes from hemopoietic stem cell to mature circulating erythrocytes
Rubriblast
- earliest recognizable RBC precursor
- differentiates into prorubricytes
- committed stage for erythrocytes
Prorubricytes
Precursor to rubricytes
Rubricytes
- undergoes a lot of mitosis/differentiation
- first active hemoglobin production
What subcellular structure are highly abundant in rubricytes?
Polyribosomes
- Necessary for making polypeptide chains of hemoglobin
Components of Heme
- Fe2+
- Protoporphyrin IX
Hemoglobin synthesis
- Combine 2 succinyl-CoA + 2 glycine to make a pyrrole
- 4 Pyrrole forms the ring-like structure called protoporphyrin IX
- The protoporphyrin IX combines with Fe2+ to form a heme
- Heme and polypeptide combine to form hemoglobin chain (alpha or beta)
- 2 alpha chains and 2 beta chains form Hemoglobin A
Iron handling and recycling
- Iron needed for hemoglobin is received from the diet
- Fe2+ absorption in the small intestine is extremely slow (reason why eaten lots of iron does not work immediately)
- Fe2+ is bound and transported in the blood as Transferrin- Fe
- Transferrin- Fe binds to receptors in cell membranes of rubricytes in the bone marrow and endocytosed
- Transferrin delivers Fe to mitochondria where heme is synthesized
Change in receptor types as erythropoiesis progresses
- Erythropoietin (EPO) receptors decrease
- Transferrin receptors increases due to demand for iron for hemoglobin production by later precursors of RBCs
Metarubricyte
- Mitosis stops
- Hemoglobinization nears completion (hemoglobin production stopping)
- Nucleus condenses and at end of this stage, the nucleus will be expelled
Polychromatophilic erythrocyte
- Considered an immature RBC
- Staining/“more colour”- due to the presence of residual rRNA from polyribosomes
- Present in small amounts under normal conditions in most species. Except for horses as they never release immature erythrocytes
Reticulocytes
Essentially polychromatophilic cells but stained differently. A more accurate number
Hemolytic anemia
Body destroying RBCs, so body not properly oxygenated so body’s bone marrow will keep making more and more RBCs. Results in an elevated reticulocyte number.
Steady-state process of erythropoiesis
The balance between RBC production and RBC turnover.
- Too much will increase viscosity of blood which would be bad!
Regulated by erythropoietin (mostly made in kidneys 90%)
Pathological conditions leading to abnormal production
- Hypoxia
- Renal diseases
What causes hypoxia?
- Low blood volume
- Anemia
- Low hemoglobin
- Poor blood flow
- Pulmonary disease
Hypoxia’s effect on erythropoietin
Hypoxia and the lack of tissue oxygenation will result in triggering the kidney to increase erythropoietin and make more RBCs
Renal disease’s effect on erythropoietin
Can result in anemia if erythropoietin production is disrupted
Nutrient requirements for erythropoiesis
- Iron for hemoglobin
- Folic acid (Vitamin B9/folate) for DNA synthesis
- Vitamin B12 for DNA synthesis
- Vitamin B6
- Riboflavin, nicotinic acid, pantothenic acid, thiamine, biotin, ascorbic acid
- Copper
- Cobalt
Importance of Vitamin B12 and folate for DNA synthesis
- Both very important in RBC production due to the need for mitotic events in which DNA synthesis is required.
- Folate needed for purine and pyrimidine synthesis
- Vitamin B12 is an important co-factor for methionine synthase enzyme needed for DNA synthesis
- Both also contribute to methyl group production
