IX. EFFECTS OF DEFICIENCY 203 



difforentiatioii of other hemic elements, the leucocytes and thrombocytes, 

 are also dependent upon adeciuate sujiply of PGA. The inteji;rity of mucosal 

 surfaces may be impaired in VGA deliciency states with secondary infection 

 and ulceration. Glossitis, disturbances in gastrointestinal function, and 

 peripheral neuropathies are sometimes associated with lack of this vitamin. 

 The increase in appetite, strength, and sense of well-being which attends 

 the administration of PGA to a severely deficient patient precedes any 

 appreciable change in peripheral blood values and suggests that the vitamin 

 participates in many metabolic proce::SGS. The predominance of hematologic 

 manifestations is presumably attributable to the continuous production 

 and rapid turnover of the cells of the blood. 



A wide variety of more or less well-defined clinical entities are associated 

 with apparent need for PGA. Although lack of this vitamin may constitute 

 but one facet of a complex dietary deficienc3^ state, many of the disorders 

 in (luestion are wholly correctible by the administration of PGA alone, 

 whereas in others, notably addisonian pernicious anemia, PGA has proved 

 to be an imperfect or secondarj^ form of replacement therapy. 



From what is known and has been discussed earlier regarding the natu- 

 rally occurring forms of PGA, the mode of PGA absorption by the human 

 being, its metabolic function, and its relationship to other nutritional 

 factors, a number of theoretical mechanisms may be postulated by which 

 PGA deficiency states might be presumed to occur. These potential modus 

 operandi include: (1) primary dietary lack of PGA and CF and their con- 

 jugates; (2) incomplete breakdown of conjugates to the free and absorbable 

 forms within the alimentary tract, due, perhaps, to lack of intestinal con- 

 jugases; (3) impaired absorption due to intestinal pathologj'', such as 

 chronic inflammatory disease, hypermotihty, and diminished absorptive 

 surface; (4) non-utilization of PGA after absorption, which may depend 

 upon lack of other nutritional factors such as vitamin B12 , ascorbic acid, 

 or nitrogen and carbon donors, or which may result from the presence of 

 competitive or inhibitor substances such as PGA antimetabolites and an- 

 tagonists. Playing accessory roles which may serve to convert latent or 

 relative PGA deficiency to overt clinical manifestations are situations in 

 which there is an increased demand for the vitamin such as pregnancy and 

 the rapid growth of infancy. 



1. NUTRITION^AL MACROCYTIC AnEMIA 



Hy this designation is meant the presence of macrocytic anemia with 

 megaloblastic bone marrow in persons who ha\'e a history of dietarj^ inade- 

 quacy without gastric, intestinal, or hepatic disease. The specific entities 

 listed below are excluded from this classification. Although the pathogenesis 

 of such anemia would appear obvious, its interpretation is rendered some- 



