140 . VITAMINS A AND CAROTENES 



tions of the deficiency disease. It might be added, however, that there 

 exists no morphologic alteration of tissue which alone can be considered 

 strictly pathognomonic of vitamin A deficiency. Where the clinician is 

 content merely to prescribe an increased intake of vitamin A, and to at- 

 tribute any observed remission of symptoms to this therapeutic measure, 

 an uncertain and often contradictory body of evidence accumulates. Un- 

 fortunately the latter type of evidence is often too prevalent in the clinical 

 literature. 



5. Vitamin A and Epithelia 



The most striking histopathologic manifestation of vitamin A depletion, 

 as observed in a variety of experimental animals and in man, is the inability 

 to maintain the morphologic integrity of various specialized epithelia. Epi- 

 thelia which are normally stratified and keratinized, such as the epidermis 

 proper, are thought to undergo excessive keratinization of the superficial 

 layers (hyperkeratosis). In epithelia which undergo only periodic keratini- 

 zation, such as the vaginal epithelium of rodents during estrus, a state of 

 continuous cornification results. In epithelia of the stratified squamous 

 type covering mucous surfaces such as those of the cornea and conjunctivae, 

 and in transitional epithelia such as are found in the renal pelvis and 

 bladder, the superficial cells are replaced by layers of keratinized cells. 

 The columnar or cuboidal cells lining ducts of glands often become flattened 

 and cornified. More highly differentiated epithelia, such as the pseudo- 

 stratified columnar ciliated of the respiratory tract (nares, paranasal sinuses, 

 larynx, trachea, and bronchi), respond to vitamin A depletion by atrophj'' 

 of the superficial cell layers which are replaced by a stratified keratinized 

 type of epithelium. The germinal epithelium of the testes and the enamel 

 organ of the tooth become atrophic but not keratinized. Mucous and muco- 

 serous glands related to the involved mucous surfaces become hypofunc- 

 tional and atrophic. Certain glands, especially those of ectodermal origin 

 (sebaceous, sweat, lacrimal) may exhibit diminished functional activity; 

 actual atrophy of the gland parenchyma may occur. It is often difficult to 

 determine whether this atrophy represents a direct effect or is secondary 

 to duct blockage by keratinized cells, a process frequently observed in 

 ducts of glands in which alterations of parenchymal structiu'e are not 

 observed. 



The general picture is one of a deop-seated disturbance in basal cells of 

 various types of epithelia which are unal)le to differentiate in the manner 

 normally typical for each location and can give rise only to cells with 

 potentialities for producing a stratified keratinized type of epithelium. 

 There is thus a change from one type of epithelium to another, or a meta- 

 plasia, always directed toward a stratified keratinized layer; hence the term 



