492 VITAMIN Bi2 



excessive requirement. Certain apparently unique and, for the most part, 

 poorly understood metabolic phenomena characterize the relationship of 

 the human organism to B12. It is these phenomena which comprise the sub- 

 ject matter for a discussion of the pathologic physiology of B12 deficiency. 



Macrocytic anemias associated with megaloblastosis of the bone marrow 

 have been considered systematically in relation to deficiency of PGA. They 

 will be referred to in this section only in connection with the role of lack 

 of B12 in their pathogenesis. It is a widely held opinion, which is shared by 

 the writer, that megaloblastosis and other marrow changes characteristic of 

 pernicious anemia and related conditions are the direct result of what may 

 be termed PGA metabolic dysfunction. This does not necessarily imply an 

 actual deficiency of PGA, since the enzymatic function of this vitamin is 

 dependent upon its presence in biologically active form, as w^ell as upon 

 the completion of biologic reactions which require the participation of 

 other substances, such as B12. 



Dietary deficiency of B12 might be presumed to occur quite frequently, 

 since sources of the vitamin are limited essentially to foods of animal origin. 

 That clinical evidences of such deficiency are quite rare suggests strongly 

 that at least a major portion of the human requirement of B12 may be sup- 

 plied by intestinal bacterial synthesis. Nevertheless, patients are encoun- 

 tered with macrocytic anemia whose diets have been almost devoid of ani- 

 mal protein and who respond to the parenteral or oral administration of 

 B12. The effectiveness of parenteral therapy'^ "^ might be explained by as- 

 sociated intestinal disturbances with poor absorption of the vitamin, but 

 the clear-cut responses to orally administered doses, such as 5 7 daily,'"'^- 

 indicate that impaired absorption need not be the major cause of nutritional 

 B12 deficiency. It may be postulated that such patients either do not obtain 

 the usual amount of B12 from bacterial sources, perhaps owing to alteration 

 of intestinal flora, or that, because of concomitant nutritional deficiencies, 

 their requirement of the vitamin may be abnormally large. 



3. Pernicious Anemia 



In pernicious anemia the metabolic defect is primarily concerned with 

 failure to assimilate B12 present in the alimentary tract. The demonstration 



' T. D. Spies, R. M. Suarez, G. Garcia Lopez, F. Milanes, R. E. Stone, R. Lopez 



Toca, T. Aramburu, and S. Kartus, J. Am. Med. Assoc. 139, 521 (1949). 

 8 E. Jones, W. J. Darby, and J. R. Totter, Blood 4, 827 (1949). 

 8 J. C. Patel, Brit. Med. J. II, 934 (1948). 

 ^o G. A. Goldsmith, Proc. 3rd Intern. Congr. Haematol. Cambridge, England, 1950, 



Grune & Stratton, New York, p. 11, 1951. 

 11 S. Chaudhuri, Brit. Med. J. II, 825 (1951). 



'2 F. H. Bothell, M. E. Swendseid, S. Miller, and A. A. Cintron-Rivera, Ann. Internal 

 Med. 35, 518 (1951). 



