5. Red blood cell formation, regulation of erythropoiesis

You must be able to explain about:
  1. formation of RBC
  2. regulation of RBC production

Red cell formation (erythropoiesis)

- All circulating blood cells are derived from pluripotential hemopoietic stem cells

- The pluripotential cells differentiate to form peripheral blood cells.

- As these cells reproduce, a portion is exactly like the original pluripotent cell.  These cells are retained in the bone marrow to maintain a constant supply.

- The early offspring of the stem cells cannot be recognized as different types of blood cells even though their already have been committed to a particular cell line.  These cells are called committed stem cells.

- Different committed stem cells will produce different colonies of specific types of blood cells.

- In adult red cell formation is in proximal portions of humerus and tibia, the vertebrae, sternum, ribs and the ilia (see illustration)

- In neonates: bone marrow of all bones

 

Formation of haemoglobin

- Synthesis of hemoglobin begins when the RBC is in the proerythroblast stage and continues into the reticular stage, when the cell leaves the bone marrow and passes into the bloodstream.

- During the formation of hemoglobin, the heme molecule combines with a very long polypeptide chain called a globin to form a subunit of hemoglobin called a hemoglobin chain. 

- Four hemoglobin chains bind together loosely to form the entire hemoglobin molecule.

 

Regulation of erythropoiesis

- The total mass of red blood cells in the circulatory system is regulated within very narrow limits

- Any condition that causes the quantity of oxygen that is transported in the tissues to decrease, ordinarily increases the rate of RBC production

- The principal factor that stimulates RBC production is the circulating hormone erythropoietin.

- Vitamin B12 and folic acid (vitamin B9) (both are members of the B vitamin complex): important for the final maturation of RBC.  This is because they are both important for the synthesis of DNA and diminished quantity of DNA leads to failure of nuclear maturation and division.  The RBCs also become larger then normal (megaloblasts) which are fragile and have a short lifespan (they can carry oxygen normally)

how to remember that vit. B difficiency cause blood immaturation?

KEY: CREATE SOME SELF FACTS

Vitamin B refers to vitamin Blood
so, insufficiency of vitamin B9 and B12 causing blood problem (anemia)

Note: lack of intrinsic factor in the GIT causes loss of much of vitamin B12 due to enzyme action in the gut and failure of absorption.

 

Erythropoietin

- Is mainly formed in the kidneys!!! not in bone marrow ok! (80 - 90%)

- Some formation also in the liver (esp. in fetus)

- Decreased tissue oxygenation leads to increase in erythropoietin

- Androgens, thyroid hormones, gluccocorticoids, ACTH and growth hormone all lead to increase in erythropoietin

- Estrogens lead to decreased erythropoietin

KEY: GENERALISATION

anything that causes the development of strong and brutal man can also induce production of blood: ACTH (which can induce glucocorticoid, mineralocorticoid, androgen in adrenal gland), thyroid hormone, Growth hormone.

estrogen the hormone of women do the opposite effect.

KEY: NOTICE

to induce kidney formation of erythropoetin, we can use factors that can induce its superior organ adrenal gland (ACTH)

 

Factors needed for formation of ery:

- Amino acids (globin formation)

- Iron (hypochromic (mikrocytic) anemia)(heme formation)

- Vitamin B12 (DNA maturation)

- Folic acid (vitamin B9) (DNA maturation)

- Vitamin B2 and B6

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