Liver portal hypertension

There is evidence that the long-term use of busulfan with tioguanine increases the risk of nodular regenerative hyperplasia of the liver, portal hypertension and oesophageal varices. 

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... 

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 splanchnic system drains venous blood from the GI tract to the liver. In portal hypertension there is increased resistance to drainage from the originating organ so collateral vessels (varices) develop in the esophagus, stomach, and rectum to compensate for the increased blood volume. Varices divert blood meant for hepatic circulation back to the systemic circulation this has the unintended deleterious effect of decreasing clearance of medications and potential toxins through loss of first-pass metabolism. Varices are weak superficial vessels, and any additional increase in pressure can cause these vessels to rupture and bleed.15... 

FIGURE 19-4. Treatment algorithm for active gastrointestinal bleeding resulting from portal hypertension. (From Schianotd, Bodenheimer HC. Complications of Chronic Liver Disease. In Friedman SL, McQuaid KR, Grendell JH (eds.)... 

Portal hypertension Increased blood pressure within the portal vein that supplies the liver. 

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. 

Kravetz D, Bosch J, Arderiu M, et al. 1989. Hemodynamic effects of blood volume restitution following a hemorrhage in rats with portal hypertension due to cirrhosis of the liver Influence of the extent of portal-systemic shunting. Hepatology 9 808-814. 

Shibayama Y. 1988. On the pathogensis of portal hypertension in cirrhosis of the liver. Liver 8 95-99. 

Surgical correction of portal hypertension in combination with HBO in patients with liver cirrhosis produces a clear clinical effect, and positive changes of the structural and functional status of cellular membranes of microsomes and associated enzymatic complexes of cytochrome P 50 of hepatocytes. 

Azizov KhA (1998) Surgical treatment of the patients with a liver cirrhosis in conditions portal hypertension decompensation with ascite syndrome. MD Thesis (in Russian) Tashkent, Uzbekistan, p 45... 

Amin LI, Anykin T (1988) Influence of surgical treatment of liver cirrhosis with portal hypertension on morphological changes of a liver. In Problems of surgical treatment of patients with hver cirrhosis with portal hypertension. Medicine Publ, Moscow, pp 18-19... 

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. 

Peliosis hepatis has been described in association with contraceptive-induced hepatic tumors and has sometimes developed in isolation, perhaps as a herald of more serious changes to follow, for example cirrhosis and portal hypertension one such case ultimately required an orthotopic liver transplant (219). 

A 70-year-old woman with a 2-year history of primary biliary cirrhosis confirmed by histological and immunological criteria took colestyramine sachets twice daily for 2 months and developed lethargy, confusion, and drowsiness (3). She had signs of chronic liver disease, portal hypertension, and hepatic encephalopathy. Laboratory investigations confirmed a metabolic acidosis (pH 7.15) and hyperchloremia. Multiple cultures failed to reveal sepsis, and a urinary pH of 4.85 together with tests of renal acidification excluded renal tubular acidosis. No other cause was found and she responded to 600 mmol of sodium bicarbonate intravenously over 36 hours. 

CIRRHOSIS A chronic liver disease that is caused by alcohol abuse, toxins, nutritional deficiency, or infection. A main symptom of cirrhosis is portal hypertension. 

Alcoholics with chronic liver disease may have disorders of fluid and electrolyte balance, including ascites, edema, and effusions. These factors may be related to decreased protein synthesis and portal hypertension. Alterations of whole body potassium induced by vomiting and diarrhea, as well as severe secondary aldosteronism, may contribute to muscle weakness and can be worsened by diuretic therapy. Some alcoholic patients develop hypoglycemia, probably as a result of impaired hepatic gluconeogenesis. Some alcoholics also develop ketosis, caused by excessive lipolytic factors, especially increased cortisol and growth hormone. 

Liver cirrhosis is among the top 10 causes of death in the Western world. The disease occurs after chronic damage to hepatic cells, mainly hepatocytes, which can be caused by viral hepatitis, chronic alcohol abuse or toxic injury, biliary disease, and metabolic liver disorders [64], Liver cirrhosis is characterized by an abnormal deposition of connective tissue in the liver, which hampers the normal functions of the liver. Other features of the disease are general tissue damage, chronic inflammation, and the conversion of normal liver architecture into structurally abnormal nodules. Secondary to these anatomical changes are disturbances in the liver function and in the hemodynamics leading to portal hypertension and intrahepatic shunting [39, 64, 103],... 

The patient was a 35-year-old white male with a x-antitrypsin deficiency. He received a combined liver-kidney transplant for cirrhosis complicated by portal hypertension, renal insufficiency secondary to membranoproliferative glomerulonephritis, and combined restrictive and obstructive pulmonary disease at age 18 years. 

This patient illustrates a complicated clinical course of oq-antitrypsin deficiency. Our patient had liver disease that presented during infancy and developed into hepatic cirrhosis. He exhibited most of the complications of cirrhosis, including portal hypertension with ascites, hyperammonemia, malnutrition, and variceal hemorrhage. These complications of cirrhosis are not unique to a,-antitrypsin deficiency, but it is important to note the potential severity of the liver disease associated with this condition. 

Liver disease is managed conventionally, maintaining appropriate nutritional support and managing the complications of portal hypertension and hepatic failure as they occur. We counsel heterozygote parents of a PIZZ... 

A 31-year-old white man with depression, hepatitis C, and cirrhosis of the liver was hospitalized for alcohol detoxification. He had taken methadone 50 mg bd for opium dependence for 6 months. He developed bilateral pedal edema and 27 kg weight gain. There was no ascites, portal hypertension, or congestive heart failure. Most of his laboratory tests were within the reference ranges, except for reduced prothrombin time and platelet count. After stopping alcohol, his methadone dose was reduced to 60 mg/day his edema resolved 15 days later. When the dose of methadone was increased to 70 mg/day there was a progressive increase in the edema. When methadone was withdrawn his edema completely resolved and he lost 8 kg in 2 weeks. 

An enlargement of the spleen can be associated with many conditions, including infections, anaemias, malignancies and liver disease. In portal hypertension the back pressure in the splenic vein causes the spleen to enlarge. 

Any drug that can increase the risk of bleeding must be used with caution or avoided in patients with liver impairment associated with deranged clotting, portal hypertension, varices or low platelets. Examples of such drugs are ... 

Patients with liver impairment, such as cirrhosis with portal hypertension (particularly alcoholic cirrhosis/hepatitis) or acute liver failure, are more susceptible to renal impairment than those without liver impairment. Care should be taken with any drug that is potentially nephrotoxic or could contribute to renal dysfunction in these types of patients. 

Varices indicate that portal vein blood flow has been diverted away from the liver secondary to portal hypertension. This would have a significant impact on first-pass metabolism, increasing the bioavailability of oral drugs that are usually extensively cleared on first pass through the liver, i.e. those with a high extraction ratio (>0.7). 

Most opioids are metabolised in the liver and have a high intrinsic clearance/high first-pass effect. Therefore, when liver metabolism is impaired or when there is decreased blood flow through the liver (e.g. cirrhosis), clearance of opioids may be reduced, resulting in a prolonged duration of action and possible toxicity. Portal hypertension may also increase the oral bioavailability and hence the toxicity risk of opioids, as first-pass metabolism will be reduced. The probability of toxicity occurring is additionally dependent on a number of other patient and drug-related factors. 

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. 

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