THE HEPATIC CIRCULATION 



I429 



of protein, possibly carbohydrates, but not fat, is 

 followed by the development of hepatic hyperemia 

 in man (54, 152, 200, 240). Reininger & Sapirstein 

 (240) have found that hepatic blood flow increases 

 in rats after a protein meal, in proportion to the rise 

 in cardiac output and blood flow to other tissues 

 that occurs at the same time. Similar changes in 

 systemic and hepatic circulation have been de- 

 tected in man during febrile reactions to pyrogenic 

 agents (46, 152, 170) in association with increased 

 total oxygen consumption. Liver temperature rises 

 after protein feeding and during fever (152), pre- 

 sumably as a result of augmented hepatocellular 

 metabolism. When hepatic oxygen consumption is 

 increased by thyrotoxicosis, EHBF does not change 

 appreciably (218). According to Bondy and others 

 (38) uncontrolled human diabetes is not associated 

 with a significant change in EHBF, although Lips- 

 comb & Crandall ( 1 97) have observed high values 

 in diabetic dogs. A definite increment in EHBF has 

 been observed in dogs also during hyperglycemia 

 produced by glucagon administration and hypogly- 

 cemia produced by insulin (112, 276, 279). Epi- 

 nephrine release may be involved in the latter and 

 must, indeed, be weighed in the evaluation of hepatic 

 hyperemia, whatever its cause. Sympathoadrenal 

 activation is an unlikely participant, however, in the 

 action of /-hydrazinophthalazine which has been 

 found (207) to elicit a pattern of circulatory and 

 metabolic adjustments, in every respect like that 

 produced by pyrogen, except that body temperature 

 does not rise. If the expansion in splanchnic blood 

 volume during the action of hydralazine in dogs is 

 typical of the hepatic hyperemic reaction in general, 

 it may be concluded that vascular smooth muscle is 

 uniformly affected with simultaneous arteriolar and 

 venous dilatation. Moreover, the tendency for ar- 

 terial pressure to fall to low levels in these conditions 

 may be the result of interference with venous return 

 by "splanchnic pooling." Hyperemic responses de- 

 serve careful study not only for the light that may be 

 cast upon normal hepatosplanchnic interrelation- 

 ships but also for better understanding of derange- 

 ments in integration that may be involved in the 

 production of hepatic disorders. 



Throughout the foregoing discussion attention 

 has been directed chiefly to the local and systemic 

 factors that may determine hepatic blood flow in 

 health and disease. Admittedly the account is sketchy 



owing to inadequacies of the author and the space 

 available. An effort has been made to cover in some 

 detail the elements of hepatic and splanchnic hemo- 

 dynamics. The role of the preportal systems in the 

 spleen, gastrointestinal tract, and pancreas have 

 been alluded to frequently but it has been difficult to 

 give these factors the weight they deserve, chiefly 

 because the evidence available is so fragmentary and 

 questionable. As noted at the outset, methodology- 

 must take first rank as a cause for uncertainty. Dif- 

 ficulty in generalization arises also from dependence 

 upon data drawn from but one, or too few, experi- 

 mental animal species; from acute responses tram- 

 meled by unphysiologic conditions of anesthesia, 

 restraint, and surgery; and, finally, from portions, 

 rather than the totality of any reaction. Emphasis 

 has been placed upon correlation of structure and 

 function. For this reason, among others, the arteriolar 

 resistances have been stressed as determinants of 

 flow and pressure gradients. The volume of blood 

 contained within the vasculature has been assigned 

 chiefly to the large veins and translocations or re- 

 arrangement of content ascribed, therefore, to 

 alterations in venous smooth muscle function and 

 inlet-outlet balance. Neither of these inferences is 

 invalidated by the possibility touched upon at several 

 points, that extravascular influences may dominate 

 more slowly developing changes. Tissue turgor, fibro- 

 sis, extravascular cellular or fluid infiltration, and 

 distortion by compression or traction may affect 

 vascular path lengths and numbers, as well as cross 

 sections, with a corresponding effect upon resistance 

 and volume capacity. Much remains to be learned 

 about the dynamics of flow in sinusoidal capillaries 

 and it is possible that conventional explanations 

 will ultimately prove inadequate. The hepatic vascu- 

 lature and the splanchnic reservoir proximal to it 

 participate in systemic circulatory reactions, but the 

 evidence suggests that maintenance of hepatocellular 

 function has priority and that homeostatic adjust- 

 ments operate solely to produce a state that does not 

 actively impair over-all compensation, without adding 

 much to it. Perhaps the shift of blood from the 

 splanchnic bed is helpful but the data cannot be con- 

 strued to favor conclusively an active rather than a 

 passive role. The liver is undoubtedly essential to 

 metabolic activity, but the role of the hepatic 

 circulation in metabolic homeostasis remains to be 

 elucidated. In this direction, hepatic circulatory 

 physiology may stand upon the threshold to signifi- 

 cant discoveries. 



