Tissue oxygenation regulates RBC production. If the amount of oxygen transported to the tissues decreases,
the rate of RBC production increases.
The Feedback Mechanism: Tissue hypoxia (abnormally low oxygen level) triggers the kidneys to increase
production of erythropoietin. This hormone stimulates bone marrow to produce stem cells and speeds the
passage of newly formed RBCs through the various generations. Bone marrow continues producing RBCs as
long as tissue hypoxia is present or until tissue is adequately oxygenated. Feedback signals to bone marrow
diminish production of erythropoietin to the level needed to maintain the normal production of RBCs.
RBC production can be judged by counting reticulocytes in the blood and by ferrokinetics, that is, the amount
and traffic of iron in the blood.
If bone marrow produces many RBCs rapidly, immature cells are released into the blood. The number of
reticulocytes can increase to as high as 30%-50% of total circulating RBCs. Erythroblasts (NRBCs – nucleated
red blood cells) may also appear in the circulating blood.
Maturation of RBCs depends on the presence of two substances – vitamin B12 (cyanocobalamin) and folic acid
(another member of the vitamin B complex). Both are needed for cell synthesis of DNA (deoxyribonucleic acid,
the genetic material that controls heredity). Both are obtainable from a normal diet and must pass through the
gastrointestinal (GI) tract.
Lack of one or both of these substances inhibits RBC production and causes blood cells forming in the bone
marrow to enlarge. Called megaloblasts (literally, large immature cells) in the forming stage and macrocytes
(large cells) as adult RBCs, these abnormal cells are irregular in shape, have flimsy membranes, and often
contain excess hemoglobin. Macrocytes carry oxygen but have a very short life.
Poor absorption of vitamin B12 is due to lack of secretion of intrinsic factor by the gastric mucosa. Intrinsic
factor must be present for absorption and utilization of vitamin B12. Folic acid deficiency may be due to lack of
vitamin C. These absorption and deficiency problems can arise in alcoholics, geriatric patients, and in pregnant
or lactating women.