114 CHOLINE 



in ruptured fatty cysts,"*^^ with the result that red cells are bathed in liver 

 fat. Much of the ceroid that is found in experimental cirrhosis could be 

 explained as the polymerization of unsaturated fats which coat the surface 

 of erythrocytes in hemorrhagic fatty cysts. This explanation is supported 

 not only by direct observation of transition forms between red cells and 

 ceroid aggregates in sections and by the experiments cited above, but also 

 by the fact that, in livers that contain ceroid, hemosiderin is scanty or 

 absent. In cirrhotic livers of rats fed a diet designed to repress ceroid 

 formation, hemosiderin deposits were demonstrated. *'*2 This finding sug- 

 gests that, if red cells become coated with ceroid, their disintegration, with 

 release of histochemically demonstrable iron, is prevented. 



Hemosiderin pigment can usually be demonstrated in cirrhotic livers of 

 human alcoholics. The sequence of pathologic events responsible for this 

 finding may be fundamentally similar to those which produce ceroid in 

 choline-deficient rats, since manipulation of the diet of the latter will 

 diminish ceroid deposition in the animals' livers and favor hemosiderin 

 release."**^ The chain of evidence will not be complete until alcoholics have 

 been encountered in which the converse has occurred — i.e., prevention of 

 hemosiderin formation by coating of red cells with ceroid. Although exam- 

 ples of such prevention have not been reported to date, there are sufficient 

 data at hand to suggest that it is unlikely that the presence of ceroid 

 deposits in experimental cirrhosis indicates any fundamental etiological 

 variant. 



3. Portal versus Non-Portal Cirrhosis 



The classical concept of cirrhosis associated with alcoholism in man is 

 that it is portal in distribution. Orginally this term was also applied to 

 cirrhosis in choline-deficient rats.^^^ It was only after careful and detailed 

 studies by the U. S. Public Health group in Bethesda^^^ that the locus of 

 the initial sites of formation of the trabeculae in these animals was realized 

 to be, in fact, non-portal. This finding has now been independently con- 

 firmed. ^^^' ^^^ It is in line with the lobular distribution of abnormal fat in 

 choline deficiency, which is also initially and primarily non-portal.*^^ Thus 

 portal alcoholic cirrhosis and non-portal experimental cirrhosis appear to 

 differ fundamentally in their cytoarchitecture. 



The initial observers of dietary cirrhosis in rats based their conclusion 

 regarding its portal distribution on careful inspection of microsections of 



*« W. S. Hartroft, Trans. 9th Conf. Liver Injury, New York pp. 109-150 (1950). 



*" P. Gyorgy and H. Goldblatt, /. Exptl. Med. 70, 185-192 (1939). 



4" J. L. Asburn, K. M. Endicott, F. S. Daft, and R. D. Lillie, Am. J. Pathol. 23, 



159-171 (1947). 

 «" L. E. Glynn, H. P. Himsworth, and O. Lindan, Brit. J. Exptl. Pathol. 29, 1-9 



(1948). 



