604 XIII. HEMOGLOBIN AND PORPHYRIN SYNTHESIS 



2.1. Development of the Red Cell 



In normal adult man erythrocytes are formed only in the red bone marrow. 

 In periods of abnormal strain on the hemopoietic system, in certain anemias, 

 foci of erythrocyte formation arise in liver, spleen, and lymph nodes (c/., e.g., 

 1112,2065). 



Embryonically red blood cells are first formed in small blood islands in 

 the yolk sac and possibly also in the body stalk, chorion, and embryo itself. 

 These ultimately coalesce to form the circulatory system, and the primitive 

 red cells multiply intravascularly. Next, hemopoiesis begins in the liver 

 and, later still, to a small extent in the spleen and in other parts of the 

 embryo {1005; cf. also Needham, 2017, pp. 590,599). In this period intra- 

 vascular cell division stops. The red cells arise from mesodermic cells of 

 undifferentiated potentialities; these hemocytoblasts develop into megalo- 

 blasts (nucleated) and later into megalocytes (nonnucleated), except in some 

 species (cat, rabbit), where normoblastic formation is found during intra- 

 vascular red cell formation (1888) . In the period of hepatic red cell formation 

 the smaller normoblasts begin to replace the megaloblasts. In the bone 

 marrow of the normal adult, the normoblasts and normocytes are the only 

 hemoglobin-containing cells found, while only normocytes are found in the 

 circulating blood. The earlier idea that the megaloblast is a precursor of the 

 normoblast in the development of the red cell in the adult has been aban- 

 doned {1385). In some pathologic conditions, such as pernicious anemia, a 

 reversion to the embryonic mode of red cell formation occurs, with megalo- 

 blasts and megalocytes in the bone marrow and circulating blood. 



While in birds the cells retain their nucleus, the nucleus of the mammalian 

 cell disintegrates before the cell is released from the intrasinusoidal capillaries 

 of the bone marrow into the circulating blood. Only in pathologic conditions 

 with hastened hemopoiesis are nucleated red cells found in the blood. Nor- 

 mally the cell enters the circulation as a reticulocyte. This no longer contains 

 a nucleus, but a network of basophilic nature and unknown chemical struc- 

 ture is present, which is stained by brilliant cresyl blue. Reticulocytes 

 number less than 1% of the erythrocytes of the circulating blood under 

 normal conditions, but in periods of accelerated hemopoiesis the percentage 

 may rise to 100. 



The relationship of the various cell forms is briefly summarized below: 



UndiflFerentiated cell 



Nucleated • 



i 

 -Hemocytoblast" 



i 



Normoblast Megaloblast 



i " 1 



f Reticulocyte 



Nonnucleated i i i 



[ Normocyte Megalocyte 



The maturation of reticulocytes proceeds in the circulating blood {1023, 

 1198,1224,1523,2249) in the course of 24-96 hours. Recent observations of 



