THE CIRCULATORY SYSTEM: THE COMMON CARRIER FOR THE BODY 83 



Blood cell formation. Red blood cells live only a short time; there are indica- 

 tions that in man their average life is about 8 weeks. The life span of the white 

 cells is even shorter, estimated at about 4 days, and this does not include the 

 many which die prematurely. Both types of cells must therefore be continually 

 replenished, and this is accomplished by the so-called "blood-forming organs." 



The primary source of the nongranular white cells is lymphoid tissue, which 

 occurs in the lymph nodes, tonsils, and spleen. The granular white cells and the 

 red corpuscles are formed in the red marrow of the bones. Red cell formation is 

 most active within the vertebrae, ribs, sternum, upper ends of the humerus and 

 femur, and in some of the cranial bones. After extensive blood loss or destruction 

 of red corpuscles, the red marrow increases in extent, and in the long bones it 

 may invade the greater part of the shaft, taking the place of the normal yellow 

 marrow. 



In the very young embryo all the red cells are nucleated and are formed by 

 mitosis from parent cells in the epithelial lining (endothelium) of the blood vessels. 

 Later they are produced in several organs, especially the liver. But after birth the 

 formation of red cells is taken over exclusively by the red bone marrow, and all 

 those produced are nonnucleated. Until very recently the nucleated cells were 

 regarded as immature forms of the nonnucleated ones, which were thought to 

 lose the nucleus by degeneration as they matured. But in 1947, August Krogh 

 called attention to the work of a young Danish investigator, Claus Plum, who 

 has radically changed our concepts of erythrocyte formation. By simple and 

 ingenious experiments Plum was able to follow the entire process, and our account 

 is based on his discoveries. 



The blood vessels of bone marrow, like others, are lined with an endothelial 

 layer and consist of arteries, veins, and a rich plexus of interconnected spaces, the 

 sinusoids. At any given time many of the sinusoids are collapsed and closed to the 

 passage of blood. Some of the endothelial cells lining the sinusoids are modified 

 into erythroblasts, or erythrocyte-producing cells. Direct observation of living 

 bone marrow tissue in a small culture chamber showed that the spherical erythro- 

 blast becomes oval, with the nucleus toward the basal end; protoplasm flows 

 toward the opposite (free) end, where suddenly a drop of it is detached to form a 

 small nonnucleate cell. No mitosis is involved in the process. In the rat embryo 

 the maximum rate of erythrocyte formation is just before birth, at which time 

 each erythroblast produces about 260 erythrocytes per day. In the adult rat 

 35 to 100 are produced from each erythroblast per day, and the total daily pro- 

 duction of red cells is about 9 X 10 9 , a truly enormous figure. 



The young erythrocytes are flushed from the sinusoids into the blood stream. 

 They are called reticulocytes, because after special staining they show a network 

 of threads inside the cell. Blood contains a substance which causes the reticu- 

 locytes to "ripen" into mature red corpuscles — a change involving loss of the 

 internal network. Various tissues produce this ripening substance, but the chief 

 source in the pig was found to be the pyloric mucosa and in man the mucosa of 

 the lower part of the stomach. The ripening substance was also discovered to 

 have a marked accelerating effect upon the rate of production of new red cells. 

 The increase in rate of production following injury and loss of blood may be a 

 result of increased concentration of the ripening substance in the blood. 



