XI. PATHOLOGY 491 



lesions that could at'coiint for death were found in the internal organs, and 

 autopsies and histological studies did not reveal the cause of death. Hema- 

 tological examinations showed various abnormalities, especially leucopenia 

 and granulocytopenia, which were closely correlated with mortality, but 

 there was no evidence of infection, and death could not be attributed directly 

 to the leucopenia. Hemoglobin levels and red blood cell counts were also 

 lowered. Injections of vitamin B12 usually brought about rapid improve- 

 ment and restored the blood picture to normal. In some instances the 

 injection of 0.5 mg. of folic acid twice w'eekly resulted in improvement. 

 Perhaps folic acid had a sparing effect upon the residual amounts of vitamin 

 Hi 2 in the tissues. 



C. HUMAN BEINGS 

 FRANK H. BETHELL 



1. Introduction 



The pathologic manifestations of vitamin B12 deficiency in man are so 

 interrelated with those of pteroylglutamic acid deficiency that, for the most 

 part, no clear separation of the two can be made. This is particularly true 

 of hemopoietic disturbances resulting in megaloblastic anemia, which repre- 

 sent the most common and clinicallj^ the most important evidences of 

 deficiency of either B12 or PGA. However, like PGA, B12 is concerned with 

 metabolic processes involving tissues other than the hemopoietic system, 

 and through such functions, distinctions may be made between certain 

 manifestations of lack of B12 and those of PGA. Thus, there is considerable 

 evidence that B12 is concerned with growth of children, and the role of B12 

 deficiency in producing the neurologic lesions of pernicious anemia seems 

 to be well established. Whether other neuropathies characterized by sen- 

 sory disturbances which have been benefited by large doses of B12 are at- 

 tributable to a lack of the vitamin or to a defect in its metabolism is still 

 an unsettled question. 



2. Mechanisms 



The usual mechanisms w^hich may be concerned in the production of 

 most vitamin deficient states are applicable to vitamin B12. These may be 

 summarized as: limited sources of supply available to the organism; in- 

 terference with or impairment of absorption; destructive or inhibiting 

 influences; metabolic derangements affecting its conservation, storage, or 

 utilization; imbalance between the substance in question and other me- 

 tabolites upon which its function depends; and situations giving rise to 



* H. J. Borson, D. Singman, S. Lepkovsky, M. K. Dimick, V. Gase, and R. Perry, 



Am. J. Physiol. 162, 714 (1950). 



