[428 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



move rapidly from the gut into the portal venous 

 blood and are carried directly to the liver. Since the 

 bulk of the blood bathing the parenchymal cells 

 comes from the portal vein, and since the sinusoidal 

 walls are completely permeable to large molecules 

 (209), the extracellular tissue fluid of the hepatic 

 parenchyma must vary much more widely in com- 

 position, osmolarity, and acidity than interstitial 

 fluid elsewhere in the body. Cellular function is 

 undoubtedly influenced by the milieu interieur as a 

 whole as well as by certain active ingredients in it. 

 The gastrointestinal tract may be said to control the 

 chemical environment of liver cells not only by its 

 absorptive activity but also by its oxygen consump- 

 tion, for the liver must be content with the leavings of 

 the gut. Owing to the difficulty of sampling portal 

 venous blood, little is known about the fluctuations 

 in the chemical composition of portal venous blood 

 and their impact upon hepatocellular function. Much 

 more, but still too little, is known about the manner 

 in which portal venous pressures may be affected by 

 the interplay between hepatic and splanchnic re- 

 sistances. 



The behavior of portal venous blood flow and pres- 

 sure under normal conditions has been discussed at 

 length above and the pattern of partition will be 

 covered in another chapter. Since there is a lack of 

 data on the distribution of flow and pressures through- 

 out the total hepatosplanchnic vasculature, the rela- 

 tive importance of pre- and postportal vein resistances 

 cannot be clearly defined. The fact that portal venous 

 inflow usually accounts for some two-thirds to three- 

 quarters of the hepatic venous outflow points to domi- 

 nance by the preportal resistances (35, 37, 115, 

 132, 204, 255). The rise in portal venous pressure 

 during the action of epinephrine may be ascribed 

 therefore largely to mesenteric (subsuming under 

 this term the total preportal bed) vasodilation, the 

 fall with norepinephrine to mesenteric vasoconstric- 

 tion. Vasopressin (103, 142, 308) has also been 

 found to be a most effective agent in lowering portal 

 venous pressure in man and dogs by contraction of 

 the mesenteric arterioles in association with a reduc- 

 tion in hepatic blood flow. The resulting rearrange- 

 ment of pressure gradients may result in a fall in 

 sinusoidal pressure, so that the much weaker hepatic 

 arteriolar constriction may be effectively countered 

 by the rise in arteriosinusoidal pressure difference 

 and hepatic arterial inflow actually increased (171). 

 There is relatively little evidence of an actively 

 maintained balance between arterial and portal 



venous flow to the liver, although the arrangement of 

 resistances noted above does lead to an apparent 

 reciprocity when one or the other inflow is predomi- 

 nantly affected (36, 158). Ligation of the portal vein 

 is thus immediately followed by an increase in hepatic 

 arterial inflow, up to 100 per cent above control, and 

 hepatic arterial ligation has a similar effect upon 

 portal venous flow, but the increment fails to restore 

 total flow to the control level (158, 254). Perhaps 

 subsequent changes in tissue function set in train 

 delayed corrective adjustments that assure adequate 

 perfusion, but local mechanisms to provide immedi- 

 ately for reciprocity seem to be lacking. Indeed, 

 portal venous pressure may be persistently reduced 

 after hepatic arterial ligation so that an increment in 

 portal inflow fails to make up the deficit in perfusion. 

 A similar phenomenon has been encountered in 

 patients with cirrhosis (52) where parenchymal 

 cellular damage and extensive fibrosis have grossly 

 deformed the architecture of the liver and its vascula- 

 ture. The blood flow through the cirrhotic liver is 

 significantly reduced by attenuation of the total 

 vascular bed and by compression and distortion of 

 the hepatic venous outflow tract. The resultant ele- 

 vation in sinusoidal and portal venous pressure is 

 often combined with a fall in plasma albumin con- 

 centration. Portal venous hypertension appears to 

 be the primary event responsible for increased move- 

 ment of fluid across capillary and sinusoidal walls 

 and for the formation of ascites. Secondary cir- 

 culatory, humoral, and renal changes are also essen- 

 tial features [see (16) and (196) for a recent examina- 

 tion of this problem]. The portal venous pressure 

 may be markedly diminished by portacaval anasto- 

 mosis, in association with a significant fall in hepatic 

 blood flow that tends to persist without any evi- 

 dence of hepatic arteriolar dilatation. Hepatic venous 

 oxygen concentration is well below normal in cir- 

 rhotic patients and it falls still lower after establishment 

 of a portacaval shunt, indicating further that hepatic 

 arterial and portal venous inflows are not neces- 

 sarily correlated. The relative independence of the two 

 vascular supplies may indeed contribute in the patho- 

 genesis and perpetuation of cirrhosis (289). 



Under normal resting conditions the gastroin- 

 testinal vasculature could conceivably determine 

 hepatic function through its domination of sub- 

 strate supply, but, in fact, the hepatic blood supply 

 appears to be adjusted to the metabolic requirements 

 of the body as a whole. Digestion and absorption, 

 as such, do not affect hepatic blood flow. Ingestion 



