INTI~ODI:CTION.No adequate account of the histopathology of experimental fatsoluble (vitamin) A deficiency has hitherto been published, and no conception of the pathogenesis of the striking gross effects observed in this condition has been possible.Few pathological studies have been made, and the majority of these have resulted in wholly negative results and, therefore, erroneous conclusions as to the sequence of events and importance of infections.Analysis of the following papers in most instances reveals as cause for failure either improperly composed diet or insufficient duration of the experiments. A number of workers have assumed that the eye and its glands alone deserved study--organs which we have found to exhibit much less striking lesions than the respiratory and genitourinary tracts and certain glands. In light of the pathology described in this paper it is no longer tenable to characterize the condition of fatsoluble A deficiency by names referring to the eye pathology; i.e., xerophthalmia--keratomalacia. Atrophy of many glands, arrest of growth, emaciation, and replacement of many different epithelia by stratified keratinizing epithelium actually characterize fat-soluble A avitaminosis. The specific pathology is the widespread keratinization.Emmett and Alien 1 in a comparison of changes due to vitamin A and ]3 deficiency respectively in the rat report "no special outstanding pathological findings," in the absence of fat-soluble A, in contrast to atrophies and hypertrophies found in B deficiency. The duration of their experiments was not given.Stephenson and Clark 2 failed to find a distinctive pathology in keratomalacia in rats. TISSUE CHANGES AFTER VITAMIN A DEFICIENCYTsuji, 3 although his thesis was the effect of complete vitamin deficiency upon the thyroid, noted only atrophy of organs which he regarded as secondary to atrophy of the thyroid.Davis and Outhouse 4 studied only the kidneys, spleen, heart, lungs, pancreas, liver, and testes. As they report that the testes were normal in most of their cases, it is certain that either their diet was not deficient in fat-soluble (vitamin) A or that the duration of the experiments was too short.Cramer, Drew, and Mottram ~ in a study of the effects of vitamin deficiency in rats upon the function of lymphocytes and lymphoid tissue found no pathology in fat-soluble A deficiency. The duration of their experiments is not given.Wason 6 found no lesions in any organ other than the eyes. She regarded the changes in the cornea as secondary to bacterial invasion.Meyerstein ~ failed to find any characteristic pathology in either vitamin A or vitamin B deficiency in rats.Outstanding papers dealing with the pathology are those of Mori s and Lambert and Yudkin. 9a°Mori's paper was published from the department of Chemical Hygiene in the School of Hygiene and Public Health of Johns Hopkins University so that, presumably, his animals were upon diets approvedby McCollum. The composition of the diet employed is not stated, nor are protocols given. Information in regard to...

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The earliest demonstrable effect of vitamin A deficiency in rats t and guinea pigs 2 is upon epithelial structures.The sequences are atrophy of the epithelium concerned and the substitution for it of a stratified keratinizing epithelium identical in appearances in all locations and arising from focal proliferation of basal cells. Since replacement by keratinizing epithelium in many organs has also been found in human infants, 8 in the monkey Macacus rhesus, 4 in the albino mouse, 5 and gross changes point to the same phenomenon in swine, 6 in dogs, ~ in rabbits, s in calves 9 and in the domestic fowl, l°-n 1

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