Cirrhosis hepatic blood flow

HRT (oral and transdermal) should not be initiated or continued in patients with decompensated cirrhosis. The hepatocyte damage is irreversible and can only worsen over time. The significant reduction in metabolic capacity and reduction in hepatic blood flow will lead to drug accumulation, with consequent increased risk of hepatotoxicity. There is also the potential to worsen the cholestatic picture in this patient, who is already profoundly jaundiced. 

E Congestive heart failure. Lidocaine is cleared by liver metabolism. Any condition that deaeases liver metabolism or liver blood flow may increase lidocaine levels. If a patient has CHF, advanced age, shock, or liver cirrhosis, a lower infusion rate should be considered. Diabetes, atrial flutter, tachycardia, and sodium levels are unlikely to affect hepatic blood flow or lidocaine clearance. 

B43. Bradley, S. E., MacPherson, A. I., Gammeltofti, A., and Blakemore, A. H., Effect of portacaval anastomosis on hepatic oxygen extraction and estimated hepatic blood flow in patients with cirrhosis. J. Clin. Invest. 30, 630-634 (1951). 

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. 

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. 

Occasionally toxic compounds can directly damage the hepatic sinusoids and capillaries. One such toxic compound is monocrotaline, a naturally occurring pyrrolozidine alkaloid, found in certain plants (Heliotropium, Senecio, and Crotolaria species). Monocrotaline (Fig. 7.7) is metabolized to a reactive metabolite, which is directly cytotoxic to the sinusoidal and endothelial cells, causing damage and occlusion of the lumen. The blood flow in the liver is therefore reduced and ischemic damage to the hepatocytes ensues. Centrilobular necrosis results, and the venous return to the liver is blocked. Hence, this is known as veno-occlusive disease and results in extensive alteration in hepatic vasculature and function. Chronic exposure causes cirrhosis. 

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. 

Hepatic fibrosis is seen with chronic exposure to hepatoxicants that cause increasing damage to hepatocytes and is part of the wound healing response. Chronic fibrosis leads to severe disruption of the liver architecture by the deposition of extracellular matrix (ECM). Advanced fibrosis disrupts the proper blood flow and results in scarring of the liver that can lead to irreversible liver damage known as cirrhosis. Chronic exposure to the hepatoxins CCI4, monocrotaline, and alcohol are examples of compounds that cause excessive fibrosis. 

Biopsy results, where available, are invaluable. They may have been taken to help diagnose a disease or to give an indication of its progression. Either way, they enable you to differentiate between a mild hepatitis with an ALT of 100 and cirrhosis with a similar transaminase level. This is very helpful in determining whether or not hepatocyte function is likely to be impaired. It may also demonstrate poor biliary canaliculi or portal tracts which may result in defective bile or blood flow. 

Ultrasound, particularly Doppler ultrasound, provides an indication of blood flow through the liver and whether that flow is reversed. This is another way of identifying whether first-pass metabolism is likely to be affected by collateral blood flow bypassing the liver. The scan may also show whether the liver is large and inflamed (hepatitis) or small and knobbly (cirrhosis). 

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. 

Acipimox is only partly metabolised and should be safe in this patient. Niacin undergoes extensive first-pass metabolism, which would be reduced due to the decrease in liver blood flow caused by the patient s cirrhosis. Niacin (nicotinic acid) has been reported to cause transient elevations in transaminases at high doses. Hepatitis and fibrosis have also been reported with niacin, usually with the SR once-daily formulation. 

Complex changes in blood flow occur with liver disease. Resistance to hepatic portal blood flow rises in cirrhosis, and portasystemic and intrahepatic shimts reduce drug delivery to hepatocytes. The pattern of change caused by disease relates to the manner in which the healthy liver treats a drug and there are two general classes ... 

Arterial bruit A systolic rushing sound synchronized with the heart beat indicates increased arterial blood flow. This often barely audible sound is easier to discern if one listens for arterial bruit and feels the patient s pulse at the same time. It is sometimes heard where aneurysm or stenosis is present in large arteries (e.g. coeliac artery, hepatic artery) as well as in arteriovenous malformations, highly vascularized liver tumours, pronounced acute alcohol hepatitis, 1-2 days after liver biopsy resulting from temporary arteriovenous fistula, or in twisted arteries in cirrhosis. It is seldom found in healthy persons. (10, 13, 44)... 

Following the administration of 100-200 MBq Tc-sulphur colloid intravenously, liver cirrhosis is characterized by a reduction in the uptake of radioactivity in the liver and an increased uptake by the spleen and bone marrow. Colloidal uptake in the liver is thus a valuable parameter for assessing any functional loss of the hepatic RES and for evaluating the residual parenchyma which is still functioning. It should be noted that the phagocytic capacity of the hepatic RES is closely related to the sinusoidal blood flow, the reduction of which is a result of the development of collaterals in the area of the hepatic... 

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