426 VITAMIN K GROUP 



vents its absorption. 2*' Whether the hypoprothrombinemia and bleeding 

 reported to occur in animals receiving large doses of vitamin A" is second- 

 ary to reduced vitamin K synthesis or absorption, or to an alteration of 

 hepatic function, is not clear; addition of a vitamin K analog to the diet 

 of the hypervitaminotic A animal prevents the clotting changes without, 

 however, any alteration in the vitamin A concentration in the liver. *^ The 

 status of quinine^^ and certain rare earths^^ is likewise uncertain; hypo- 

 prothrombinemia, which is corrected by vitamin K, has been observed 

 following their administration. Quick^^ has questioned the quinine effect 

 on clotting. 



(3) Diversion of Intestinal Lymph. In the rat a profound incoagulability 

 of the blood may be produced by withdrawal of intestinal or thoracic duct 

 lymph ;^' correction with parenteral vitamin K is prompt. ^^ The pathway 

 for vitamin K absorption would thus seem to be via the intestinal lympha- 

 tics, through the thoracic duct, to the vascular tree. The possibility of a 

 vitamin K deficiency in prolonged loss of lymph resulting from thoracic 

 duct avulsion might be considered; actually, hematuria often does accom- 

 pany lymphatic chyluria. 



d. Hepatic Utilization of Vitamin K 



(1) Liver Damage. It has long been known that severe liver damage ^^ or 

 hepatectomy^^ leads to a prolongation of the clotting time of whole blood. 

 With the development of methods for estimating plasma prothrombin it 

 was discovered that a lack of prothrombin in the blood was a prominent 

 part of these clotting changes.*'^ Furthermore, administration of vitamin K 

 to man or animals with liver damage has proved ineffectual in correcting 



" R. F. Light, R. P. Alscher, and C. N. Frey, Science 100, 225 (1944). 



58 S. E. Walker, E. Eylenburg, and T. Moore, Biochem. J. 41, 575 (1947). 



59 L. A. Pirk and R. Engelberg, J. Am. Med. Assoc. 128, 1093 (1945). 



so E. Vincke and E. Schmidt, Hoppe-Seyler's Z. physiol. Chem. 273, 39 (1942). 



«i A. J. Quick, J. Lab. Clin. Med. 31, 79 (1946). 



^2 C. A. Owen, Jr., Studies on the Conversion of Prothrombin to Thrombin; Effect 

 of Conversion Variations on Prothrombin Tests. Thesis, Graduate School, Uni- 

 versity of Minnesota, 1950. 



63 J. D. Mann, F. D. Mann, and J. L. Bollman, Am. J. Physiol. 158, 311 (1949). 



"^ M. Doyon, Compt. rend. soc. biol. 58, 30 (1905) ; M. Doyon, A. Morel, and N. Kareff, 

 ibid. 58, 493 (1905). 



"M. Doyon and N. Kareff, Compt. rend. soc. biol. 56, 612 (1904); P. Nolf, Arch, 

 intern, phijsiol. 3, 1 (1905-1906). 



«" H. P. Smith, E. D. Warner, and K. M. Brinkhous, J. Exptl. Med. 66, 801 (1937); 

 E. D. Warner, ibid. 68, 831 (1938) ; W. D. Andrus, J. W. Lord, Jr., and R. A. Moore, 

 Surgery 6, 899 (1939); K. M. Brinkhous and E. D. Warner, Proc. Soc. Exptl. Biol. 

 Med. 44, 609 (1940) ; J. L. Bollman, H. R. Butt, and A. M. Snell, J. Am. Med. Assoc. 

 115, 1087 (1940); B. Uvnas, Acta Physiol. Scand. 3, 97 (1941); D. J. Ingle, J. E. 

 Nezamis, and M. C. Prestrud, Am. J. Physiol. 161, 199 (1950). 



