Synthesis, development, and turnover of Red Blood Cells

Question 1

Hemopoiesis

Answer 1

the process of blood cell formation

Question 2

Where does hemopoiesis occur? Also specify where in young vs. old animals

Answer 2

• 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

Question 3

Sinusoids

Answer 3

• 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

Question 4

Blood cell development

Answer 4

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

Question 5

Myeloid lineage cells

Answer 5

1. Erythro MK progenitor
2. Rubriblast
3. Prorubricyte
4. Rubricyte
5. Metarubricyte
6. Polychromatophilic erythrocyte/Reticulocytes
7. Erythrocyte

Question 6

Lymphoid lineage cells

Answer 6

1. Common lymphoid progenitor
2. T- lymphoblasts OR B- lymphoblasts
3. T-cells OR B-cells
4. T-cells become NK cells & B-cells become plasma cells

Question 7

Erythropoietin (EPO)

Answer 7

Regulates erythropoiesis

Question 8

Erythropoiesis

Answer 8

production of erythrocytes from hemopoietic stem cell to mature circulating erythrocytes

Question 9

Rubriblast

Answer 9

• earliest recognizable RBC precursor
• differentiates into prorubricytes
• committed stage for erythrocytes

Question 10

Prorubricytes

Answer 10

Precursor to rubricytes

Question 11

Rubricytes

Answer 11

• undergoes a lot of mitosis/differentiation
• first active hemoglobin production

Question 12

What subcellular structure are highly abundant in rubricytes?

Answer 12

Polyribosomes
- Necessary for making polypeptide chains of hemoglobin

Question 13

Components of Heme

Answer 13

• Fe2+
• Protoporphyrin IX

Question 14

Hemoglobin synthesis

Answer 14

1. Combine 2 succinyl-CoA + 2 glycine to make a pyrrole
2. 4 Pyrrole forms the ring-like structure called protoporphyrin IX
3. The protoporphyrin IX combines with Fe2+ to form a heme
4. Heme and polypeptide combine to form hemoglobin chain (alpha or beta)
5. 2 alpha chains and 2 beta chains form Hemoglobin A

Question 15

Iron handling and recycling

Answer 15

• 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

Question 16

Change in receptor types as erythropoiesis progresses

Answer 16

• Erythropoietin (EPO) receptors decrease
• Transferrin receptors increases due to demand for iron for hemoglobin production by later precursors of RBCs

Question 17

Metarubricyte

Answer 17

• Mitosis stops
• Hemoglobinization nears completion (hemoglobin production stopping)
• Nucleus condenses and at end of this stage, the nucleus will be expelled

Question 18

Polychromatophilic erythrocyte

Answer 18

• 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

Question 19

Reticulocytes

Answer 19

Essentially polychromatophilic cells but stained differently. A more accurate number

Question 20

Hemolytic anemia

Answer 20

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.

Question 21

Steady-state process of erythropoiesis

Answer 21

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%)

Question 22

Pathological conditions leading to abnormal production

Answer 22

• Hypoxia
• Renal diseases

Question 23

What causes hypoxia?

Answer 23

• Low blood volume
• Anemia
• Low hemoglobin
• Poor blood flow
• Pulmonary disease

Question 24

Hypoxia’s effect on erythropoietin

Answer 24

Hypoxia and the lack of tissue oxygenation will result in triggering the kidney to increase erythropoietin and make more RBCs

Question 25

Renal disease’s effect on erythropoietin

Answer 25

Can result in anemia if erythropoietin production is disrupted

Question 26

Nutrient requirements for erythropoiesis

Answer 26

• 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

Question 27

Importance of Vitamin B12 and folate for DNA synthesis

Answer 27

• 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