Every second 2.5 million RBC's are destroyed. Although this represents only 0.00001% of the total 25 trillion cells, these cells must be replaced if homeostasis is to be maintained.

Production of New RBC's - Erythropoiesis (takes 4 days)

1. Hemocytoblasts - Stem cells in the bone marrow from which all blood cells form.

2. Proerythroblasts - are produced by the division and differentiation of stem cells.

3. Basophilic (early) erythroblasts - During this stage in erythropoiesis hemoglobin synthesis begins.

4. Intermediate erythroblasts - At this time, we see the accumulation of hemoglobin due to its continued synthesis.

5. Late erythroblasts - During this stage the nucleus is extruded from the cell.

6. Reticulocyte - These cells exhibit a net-like appearance or reticulum in their cytoplasm when stained. A small number of reticulocytes (only 1 to 3% of the circulating red cells) are found in the circulation.

7. Mature erythrocytes - At this final stage of maturation there is a loss of ribosomes. These cells enter the circulation.

Factors Stimulating RBC Production - The common denominator is blood hypoxia due to a reduced oxygen carrying capacity.

1. Hemorrhage

2. Damage to bone marrow

3. Exposure to high altitude

4. Exercise

5. Hemolytic disease

6. Low hemoglobin levels

Basic Mechanism of RBC Production

1. Hypoxia in blood (also low Bp) specifically stimulates the juxtaglomerular apparatus within the nephron of the Kidney to produce and release erythropoietin.

2. Erythropoietin stimulates the red marrow of the bones to form increased numbers of proerythroblasts. It also shortens the time period for the maturation of erythrocytes.

3. The increase in red blood cell production leads to an increased oxygen carrying capacity of the blood. This increased capacity reduces the stress of hypoxia and, in turn, produces a negative feedback contol on red blood cell production.

Aging of RBC's

A typical mature erythrocyte lives for about 12O days in the circulation. Since these cells lack a nucleus, they cannot divide or synthesize new cellular components. As a result, the cells degenerate due to aging or damage.

Breakdown of RBC's

Old damaged RBC's are removed from the circulation in the following ways:

1. 90% are removed from the circulation by the phagocytic activities of macrophages in the liver, spleen and lymph nodes.

2. 10% of the old cells hemolyze in the circulation. The fragments of these cells are then engulfed by macrophages.

3. The chemical components of the RBC are broken down within vacuoles of the macrophages due to the action of lysosomal enzymes. The hemoglobin of these cells is degraded into:

a. Globin which is further digested down to amino acids. These amino acids can then be utilized by the phagocytes for protein synthesis or released into the blood.

b. Heme molecules go through a series of changes. The macrophages convert heme into biliverdin and then bilirubin. Bilirubin is released into the blood where it forms a complex with blood albumin (bound bilirubin). In the liver cells (hepatocytes) the bound bilirubin reacts with glucuronic acid to form conjugated bilirubin. Most of the conjugated bilirubin is secreted into the small intestine with the bile. In the large bowel, bacteria convert bilirubin into the yellow-brown pigment (urobilinogen) that gives feces its characteristic color. Some of this pigment re-enters the blood from the colon and is removed by the kidney into the urine (characteristic color).

c. Iron is removed from heme molecules in the phagocytes. The macrophages can store iron or release it to the blood. In the plasma, it binds to the protein transferrin and is carried to the bone marrow where the iron can be used to synthesize new hemoglobin. Excess iron can be stored in the bone marrow and liver. Some iron is lost in the bile. For this reason, we must take in some iron with our food.

Jaundice - is a yellowish staining of the integument and sclera of the eyeball due to an accumulation of bile pigments. The chief causes of jaundice are:

1. An increased rate of RBC breakdown. This may be due to a hemolytic blood disease, e.g., sickle cell anemia or erythro-blastosis fetalis.

2. Obstruction in the biliary system. Blockage of the bile ducts due to the formation of gall stones.

3. Liver damage. Hepatitis, cirrhosis and liver cancer will all exhibit jaundice.