Cirrhosis portal hypertension

This patient has a massively raised ALT, indicating considerable hepato-cyte damage. All functions of the liver are likely to be affected, including reduced secretory and excretory function, demonstrated in this case by a raised bilirubin reduced synthetic function, shown by the raised INR (albumin is imaffected at this time due to its long half life) reduced metabolic function, indicated by accumulation of ammonia and other toxins leading to encephalopathy. Blood flow through the liver is likely to be unaffected, as there is no cirrhosis/portal hypertension. As with all other functions of the liver, this patient s ability to metabolise drugs is likely to be severely affected. Renal function is also impaired secondary to paracetamol toxicity. 

Fischer, J. E., Hepatic coma in cirrhosis, portal hypertension, and following portacaval shunt. Its etiologies and the current status of its treatment, Arch. Surg., 108, 325, 1974. 

Hepatobiliary disease occurs due to bile duct obstruction from abnormal bile composition and flow. Hepatomegaly, splenomegaly, and cholecystitis may be present. Hepatic steatosis may also be present due to effects of malnutrition. The progression from cholestasis (impaired bile flow) to portal fibrosis and to focal and multilobar cirrhosis, esophageal varices, and portal hypertension takes several years. Many patients are compensated and asymptomatic but maybe susceptible to acute decompensation in the event of extrinsic hepatic insult from viruses, medications, or other factors.7... 

Describe the epidemiology and social impact of portal hypertension and cirrhosis. 

O Portal hypertension is the precipitating factor for the complications of cirrhotic liver disease—ascites, spontaneous bacterial peritonitis (SBP), variceal bleeding, and hepatic encephalopathy. Lowering portal pressure can reduce the complications of cirrhosis and decrease morbidity and mortality. 

Cirrhosis is the progressive replacement of normal hepatic cells by fibrous scar tissue. This scarring is accompanied by the loss of viable hepatocytes, which are the functional cells of the liver. Progressive cirrhosis is irreversible and leads to portal hypertension that is in turn responsible for many of the complications of advanced liver disease. These consequences include (but are not limited to) spontaneous bacterial peritonitis (SBP), hepatic encephalopathy, and variceal bleeding.1... 

FIGURE 19-1. The portal venous system. (From Timm EJ, Stragand JJ. Portal hypertension and cirrhosis. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 694, with permission.)... 

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. 

Sinusoidal damage from cirrhosis is the most common cause of portal hypertension. The sinusoids are porous vessels within the liver that surround radiating rows of hepatocytes, the basic functional cells of the liver (Fig. 19-2). Progressive destruction of hepatocytes and an increase in fibroblasts and connective tissue surrounding the hepatocytes culminate in cirrhosis. Fibrosis and regenerative nodules of scar tissue... 

The pathophysiologic mechanisms of portal hypertension and of cirrhosis itself are entwined with the mechanisms of ascites (Fig. 19-3). Cirrhotic changes and the subsequent decrease in synthetic function lead to a decrease in production of albumin (hypoalbuminemia). Albumin is the major intravascular protein involved in maintaining oncotic pressure in the vascular system low serum albumin levels and increased capillary permeability allow fluid to leak from the vascular space into body tissues. This can result in peripheral edema, ascites, and fluid in the pulmonary system. The obstruction of hepatic sinusoids and... 

Clinical Presentation of Cirrhosis and Complications of Portal Hypertension... 

Drug therapy for portal hypertension and cirrhosis can alleviate symptoms and prevent complications but it cannot reverse cirrhosis. Drug therapy is available to treat the complications of ascites, varices, spontaneous bacterial peritonitis, hepatic encephalopathy, and coagulation abnormalities. 

Garcia-Tsao G Current management of the complications of cirrhosis and portal hypertension Variceal hemorrhage, ascites, and spontaneous bacterial peritonitis. Gastroenterology 2001 120 726-748. 

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. 

The most important sequelae of portal hypertension are the development of varices and alternative routes of blood flow. Patients with cirrhosis are at risk for varices when portal pressures exceed the vena cava pressure by greater than or equal to 12 mm Hg. 

All patients with cirrhosis and portal hypertension should be considered for endoscopic screening, and patients with large varices should receive primary prophylaxis with /J-adrenergic blockers. 

See Chap. 39, Portal Hypertension and Cirrhosis, authored by Julie M. Sease, Edward G. Timm, and James J. Stragand, for a more detailed discussion of this topic. 

Approximately 20% of patients with chronic HBV infection develop complications of decompensated cirrhosis, including hepatic insufficiency and portal hypertension. HBV is a risk factor for development of hepatocellular carcinoma. 

Sookoian, S. etal., A1166C angiotensin II type 1 receptor gene polymorphism may predict hemodynamic response to losartan in patients with cirrhosis and portal hypertension, Am. J. Gastroenterol., 100, 636, 2005. 

Hepatic function impairment Exercise caution when administering saquinavir to patients with hepatic insufficiency. Exacerbation of chronic liver dysfunction, including portal hypertension, in patients with underlying hepatitis B or C, cirrhosis or other underlying liver abnormalities have been reported. 

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