PATHOLOGICAL METABOLISM OF THE BLOOD 555 



fragmentation plays a more important part in normal blood destruction 

 than does phagocytosis. They have found that normal blood regularly con- 

 tains small numbers of fragmentation forms, microcytes and poikilocytes, 

 and that accumulations of them are regularly present in the spleen, but are 

 found only inconstantly in other organs. 



That fragmentation also plays an important role in blood destruction 

 under pathological conditions appears from their observations that' micro- 

 cytes and poikilocytes are observed in animals with severe anemia due to 

 hemorrhage. These fragmentation forms, it would appear, are not put 

 forth as such by the bone-marrow, according to our former conception, 

 but are portions of yo.ung cells fragmented while circulating because being 

 formed to meet the emergency they are in large part unable to with- 

 stand the wear and tear of function. They are fragmented, while still 

 circulating, to a fine hemoglobin-containing dust. The cell fragments 

 are rapidly removed from the blood. Their occurrence in large numbers 

 in the spleen both of normal and anemic animals suggests that this organ 

 exercises some important function in connection with these forms. 



It is not probable that a hemolytic process, in the ordinary sense, 

 plays an important part in normal blood destruction. Kous and Robertson 

 in their search of the organs and circulating blood of their animals could 

 find neither shadows of red blood-cells nor hemolyzing corpuscles any- 

 where. And, as is well known, free hemoglobin is almost never found in 

 the normal circulating blood. Destruction of erythrocytes by hemolysis, 

 however, certainly occurs in those pathological conditions where con- 

 siderable quantities of free hemoglobin can be demonstrated in the blood- 

 plasma and where hemoglobin passes into the urine. 



The Regeneration of Red Blood-Cells. Perhaps the most certain evi- 

 dence of blood destruction is to be found in the constant activity of the 

 bone-marrow in the production of new cells. Under normal conditions, 

 the bone^marrow produces just a sufficient number of erythrocytes to 

 replace those destroyed in the wear and tear of the body's existence, so 

 that the total number of red blood-cells in the body varies but slightly. 

 Any loss or destruction of erythrocytes calls forth a stimulation of the 

 erythrogenetic function of the narrow proportional to the loss or destruc- 

 tion of blood, with a consequent tendency to return to the normal count. 

 That the converse is also true follows from the experiments of Robertson 

 (c) on plethoric animals. He was able to show that the supplying of fresh 

 blood-cells by transfusion results, at least temporarily, in a lessening 

 of marrow activity as determined by a fall in the percentage of reticulated 

 blood-corpuscles. Bone-marrow activity, however, will compensate only 

 so long and so far as it is functionally capable. When, for any reason, 

 excessive loss of blood or increased blood destruction leads to exhaustion 

 of vhe marrow, compensation fails and anemia results. 



The nature of the stimulus to blood regeneration has been the subject 



