Anemia means deficiency of red cells or hemoglobin in the circulating blood. The deficiency may be qualitative, quantitative or both. Since various factors contribute to the formation, maturation, release and ultimate destruction of the fed cells, it is well-nigh important to recapitulate our knowledge about the cytology and physiology of red cells, in the marrow and in the circulation, in normal health.
The red cells, and for that matter, all the circulating cells in the blood, are derived from undifferentiated mesenchymal cells. The earliest precursor of the erythrocytes is a haemocytoblast which matures and passes through the different stages of pro-erythroblast, early, intermediate and normoblast. These are all nucleated cells, and the late normoblast loses its nucleus to become a reticulocyte. Intracellular reticulin structures, demonstrated by supra-vital staining, characterize a reticulocyte. This develops into a functionally active erythrocyte or red blood cell.
At birth, the entire bone marrow is active in blood formation. A few months later, fat cells begin to appear and gradually this process advances in centers of long bones, until at puberty when most of the marrow of the long bones becomes converted into fatty tissue without any active blood formation. Thus, in the normal adult, the areas of active blood formation are only the bone marrow of ribs, vertebrate, sternum, skull, os innominatum, and the proximal ends of the humerus and femur.
Erythropoiesis occurs in the cellular portions of the bone marrow. Red cells normally develop from nucleated precursors which are differentiated from the endothelium of the inter sinusoidal capillaries, the activity of erythropoiesis being maximum in collapsed capillaries or in those where blood flow is slow. When maturation of the red cells is sufficiently advanced they are released into the circulation by temporary opening of orifices of the intersinusoidal capillaries into the following blood of the sinusoids.
The effect of increased blood loss is to reverse the normal prepubertal fatty innovation of marrow, by causing the disappearance of the fat cells at the margin of the marrow cavity adjacent to the cellular portion of the marrow, which extends peripherally in the long bones. During active blood regeneration, further enlargement of the marrow cavities may occur by actual resorption of cortical bone. This invasion of the cortex causes the appearance of “hairs on end” in X-ray picture of the skull. When even more blood formation is needed, extamedullary foci of haematopoiesis may appear in the spleen, lymph, nodes and the liver.
Thus in all cases of anemia, expect those due to toxic damage to the bone marrow, the marrow shows compensatory hyperplasia. Microscopically, the hyperplastic marrow is found to contain a great excess of erythroblastic cells. Two kinds of eryperplasia may occur:-
(1) Normoblastic hyperplasia – where the erythroblasts and erythrocytes are of normal size.
(2) Megaloblastic hyperplasia – where the erythroblasts are abnormally large and mature into abnormally large erythrocytes (the megaloblast and the megalocyte or macrocyte). In both normoblastic and megaloblastic hyperplasia, haemoglobinization of the immature cells is hastened, so that early erythroblasts with still immature nuclei contain abundant haemoglobin and have eosinophilic cytoplasm
In normal health, RBC and haemoglobin levels are maintained by a balance between their production in bone marrow and destruction by the normal lytic systems of the body after the normal wear and tear of circulation for 120 days, the average life span of a red cell. The daily rate of production and destruction of RBC must be equal in normal health, and approximate 1/120th part of circulating RBC , i.e, about 50ml. blood. Hence it follows that, to maintain the number of red cells in constant level, in health, 2’6×10 11 new RBC and 64g of haemoglobin must be formed daily simultaneously with the daily destruction of RBC liberating approximately 21mg. of iron, 250mg. of protophyrin and 6’2g. of globin. The protoporphyrin part is excreted and is responsible for the formation of the bile pigments, viz ,bilirubin in plasma and urobilinogen in urine and stool. The iron and globin are retained in the body and utilize for the formation of new red cells.
anemia due to any cause would signify a disruption in the balance between the production of RBC in bone marrow and its destruction in the body so that the latter outstrips the former. In some cases, the production rate remains normal but the destruction rate of red cells is abnormally high as in haemorrhage or haemolysis. Again in some other cases the destruction rate of RBC remains normal but the rate of production of RBC is less than normal as in inadequate supply of haemopoietic material to the bone marrow, or in disturbance of bone marrow function caused by injurious actions of various toxic, physical or chemical agents.
The anemias can, therefore, be conveniently divided into four major groups