VII. EFFECTS OF DEFICIENCY 539 



body type of reactions leading to the t'onniitioii of larj^e, pigment-laden 

 giant ( ells whit-h eventually dominate the picture. Tocopheri^l therapy 

 arrests the process but in most locations brings about no more than a lim- 

 ited reduction in pigment and very little change in other cellular reactions. 

 Similar alterations of adipose tissue have been observed in the mouse,-* 

 hamster,-' pig,'^'' ^^- and mink;^^, 133 [^ jg ^f interest that the naturally oc- 

 curring "yellow fat disease" or "steatitis" of mink, frequently causing seri- 

 ous losses of kits prior to the pelting season, fits into this picture. In all 

 instances a dietary intake of highly unsaturated fats and inadequacy of 

 \'itamin E have been involved. The most satisfactory explanation for the 

 histopathologic reactions described above is that unsaturated dietary fats 

 incorporated into adipose tissue cells which lack sufficient tocopherol as 

 an antioxidant to stabilize them, or to counteract peroxides which accumu- 

 late in the tissues, undergo polymerization or combine with cell proteins, 

 or both, to form acid-fast pigment which provokes giant cell reactions and 

 perhaps a certain amount of cell necrosis. 



b. Liver 



Certain histopathologic changes in the liver have been observed in a 

 few species, but, in most instances, lack of vitamin E is merely one of several 

 factors involved. In chicks there has been reported a phenomenon of "ery- 

 thropagocytosis," in which the liver shows brownish discoloration and, 

 microscopically, enlargement of hepatic cells, AAddening of sinusoids, and 

 much hemosiderin in hepatic and Kupffer cells; there is also hyperplasia of 

 myeloid tissue. '^^ Its occurrence only when ferric chloride-treated diets are 

 supplemented with halibut liver oil raises questions as to its specificity. 



After prolonged vitamin E depletion in mice (14 months or more) 

 Menschik et alP- ^^^ have noted progressive accumulation of coarse "lipo- 

 proteic" globules, swelling, and nuclear pycnosis in hepatic cells; they also 

 describe sinusoidal dilation, extravasation of erythrocytes or obvious hemor- 

 rhage, hemosiderin in Kupffer cells, and disorganization of the parenchj^ma. 

 llistochemically, the lipoproteic globules are composed of a mixture of un- 

 saturated fatty acids, phospholipids, and cholesterol, probably combined 

 with protein, resembling the "ceroid" of nutritional cirrhosis referred to 

 before and suggesting abnormal metabolic changes in liver fat. 



In nutritional cirrhosis (diffuse hepatic fibrosis) of rats fed diets low in 

 lipotropic factors (methionene, choline) there is an extensive fatty infiltra- 

 tion of the liver followed by a progressive deposition of fibrous tissue in the 



"' K. L. Robinson and W. E. Coey, Nature 168, 997 (1951). 

 '32 J. R. Gorham, N. Boe, and G. A. Baker, Cornell Vet. 41, 332 (1951). 

 1" J. R. Gorham, G. A. Baker, and N. Boe, Vet. Med. 46, 100 (1951). 

 '3^ Z. Menschik and T. J. Szczesniak, Anat. Record 103, 349 (1949). 



