B VITAMIN DEFICIENCY STATES 415 



Addisonian pernicious anemia is a spontaneously occurring macrocytic 

 anemia further characterized by a permanent, histamine-refractory 

 achlorhydria, hyperplastic megaloblastic bone marrow, glossitis, and 

 frequent neurological manifestations ranging from peripheral neuritis to 

 degenerative lesions of the spinal cord. It is frequently accompanied by 

 depigmentation of the hair, increased urinary urobilin, and increased 

 plasma iron and bilirubin. There are generally high blood and urinary 

 levels of phenolic compounds. 114 Tyrosine seems to increase the efficacy 

 of some liver extracts, and it is readily apparent that there is a close 

 interrelationship between folic acid, ascorbic acid, and tyrosine metab- 

 olism; 115, 116 but the precise manner in which folic acid influences the 

 ascorbic acid-controlled oxidation of tyrosine is at present obscure. Im- 

 paired absorption of tyrosine has been made the basis of a "tolerance 

 test" in which, after a 4-gm oral dose, the blood levels reach a peak only 

 after three hours, as contrasted with one hour in healthy persons. Per- 

 nicious anemia patients differ from those with cirrhosis in that the blood 

 tyrosive level is markedly elevated. 117 ' 118 During remissions there is occa- 

 sionally a transitory edema of unexplained etiology, 119 and a few perni- 

 cious anemia patients exhibit cardiac symptoms. 120 



The cause of pernicious anemia is unknown, but it has generally been 

 considered to be an acquired metabolic defect that results in an impair- 

 ment of erythrocyte maturation. Liver has long been known to sustain 

 patients with the disease, but its continued consumption is necessary, and 

 highly potent concentrates of the antipernicious anemia factor have been 

 used parenterally for some time. As previously mentioned, achlorhydria 

 is an invariable accompaniment of this disease, and it has been found 

 that the gastric juice from normal persons when incubated with beef 

 steak produces a curative substance, but the gastric juice from patients 

 does not. The active principle is produced by the mucosa of the pyloric 

 and cardiac regions of the stomach, and the commencement of the 

 duodenum, and desiccated defatted hog stomach may be used thera- 

 peutically as an alternative to liver. Ternberg and Eakin have recently 

 shown 120a that the active principle in gastric juice, long designated as 

 the "intrinsic factor," is in reality a protein which combines with vitamin 

 B 12 (extrinsic factor) to form a complex which is resistant to the destruc- 

 tive changes wrought upon vitamin Bi 2 itself by the digestive processes 

 (p. 342) . In pernicious anemia, the intrinsic factor is absent, and conse- 

 quently a "conditioned" vitamin B i2 deficiency results even in the pres- 

 ence of an adequate nutritional supply, since the vitamin consumed is 

 destroyed before it can be absorbed. 121 " 123 It has been suggested that 

 these interrelationships favor the substitution of the term erythrotin for 

 vitamin B 12 , apoerythein for intrinsic factor, and erythein for the complex. 



