Portal hypertension hepatic blood flow

Portacaval anastomosis decreases BSP disposal (Bl, B42, L3). There was a fall in the hepatic blood flow in all 12 patients who imderwent portacaval anastomoses for portal hypertension, but the BSP extraction ratio was increased (B42). Formation of Eck fistulae in dogs reduces BSP clearance (S27). Portacaval transposition does not affect the hepatic blood flow or the extraction ratio (S35). 

Portal hypertension is a consequence of increased resistance to blood flow through the portal vein. Increased resistance is usually due to restructuring of intrahepatic tissue (sinusoidal damage) but may also be caused by presinusoidal damage such as portal vein occlusion from trauma, malignancy, or thrombosis. A third (and the least common) mechanism is outflow obstruction of the hepatic vein. This latter damage is posthepatic, and normal liver structure is maintained. This chapter will focus on portal hypertension caused by intrahepatic damage from cirrhosis. 

The resulting resistance to blood flow results in portal hypertension and the development of varices and ascites. Hepatocyte loss and intrahepatic shunting of blood results in diminished metabolic and synthetic function, which leads to hepatic encephalopathy (HE) and coagulopathy. 

Cirrhosis results in elevation of portal blood pressure because of fibrotic changes within the hepatic sinusoids, changes in the levels of vasodilatory and vasoconstrictor mediators, and an increase in blood flow to the splanchnic vasculature. The pathophysiologic abnormalities that cause it result in the commonly encountered problems of ascites, portal hypertension and esophageal varices, HE, and coagulation disorders. 

Portal hypertension most commonly occurs as a consequence of chronic liver disease. Portal hypertension Is caused by Increased blood flow within the portal venous system and increased resistance to portal flow within the liver. Splanchnic blood flow is increased in patients with cirrhosis due to low arteriolar resistance that is mediated by increased circulating vasodilators and decreased vascular sensitivity to vasoconstrictors. Intrahepatic vascular resistance is increased in cirrhosis due to fixed fibrosis within the spaces of Disse and hepatic veins as well as reversible vasoconstriction of hepatic sinusoids and venules. Among the consequences of portal hypertension are ascites, hepatic encephalopathy, and the development of portosystemic collaterals—especially gastric or esophageal varices. Varices can rupture, leading to massive upper gastrointestinal bleeding. 

In compensated cirrhosis, sodium retention can occur in the absence of vasodilatation and effective hypovolaemia. Sinusoidal portal hypertension can reduce renal blood flow even in the absence of haemodynamic changes in the systemic circulation, suggesting the existence of a hepatorenal reflex. Portal hypertension increases the hydrostatic pressure within the hepatic sinusoids and favours transudation of fluid into the peritoneal cavity. 

Most opioids are metabolised in the liver and many (exceptions include tramadol) undergo a high first-pass effect [50], Because of this, clearance is highly dependent on liver blood flow, rather than the capability of hep-atocyte enzymes. If liver blood flow is reduced, as in hepatic cirrhosis with portal hypertension for example, the metabolism of most opioids would be expected to decrease, with a subsequent increase in oral bioavailability and risk of accumulation. 

The first-pass effect may be reduced in cirrhosis and portal hypertension owing to reduced blood flow through the liver. Additionally, in cirrhosis and acute hepatitis the number of functional hepatocytes may be reduced. Drugs with a high first-pass extraction ratio and a narrow therapeutic window, such as the statins, are more likely to be toxic in patients with liver dysfunction [20]. In liver disease, an increase in the percentage of drug reaching the systemic circulation is an important factor in statin toxicity. 

Gnpt R., Sawant, R, Parameshwar, R.V., Lele, V.R., Kulhalli, P.M., Mahajanl, S.S. Gastric mucosal blood flow and hepatic perfusion index in patients with portal hypertensive gastropathy. Gastroenterol. Hepatol. 1998 13 921-926... 

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