Portal pressure

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. 

The aim of pharmacologic treatment in portal hypertension is to decrease portal pressure and reduce the effects of sympathetic activation. 

As previously discussed, increased portal pressure triggers the release of nitric oxide to directly vasodilate the splanchnic arterial bed and decrease portal pressure. Unfortunately, nitric oxide also dilates the systemic arterial system, causing a decrease in blood pressure and a decrease in renal perfusion by lowering the effective intravascular volume. The kidney reacts by activating the renin-angiotensin-aldosterone system, which increases plasma renin activity, aldosterone production, and sodium retention. This increase in intravascular volume furthers the imbalance of intravascular oncotic pressure, allowing even more fluid to escape to the extravascular spaces. 

Vasodilation and decreased arterial pressure are also detected centrally. The sympathetic nervous system is activated to increase blood pressure, which in turn increases portal pressure. Unchecked, these combined effects enable the cycle of portal pressure and ascites to continue, setting up a self-perpetuating loop of ascites formation. 

Patients with ascites or known varices must be assumed to have portal hypertension and are treated as such, even if direct measurements of portal pressure have not been made.29... 

Doses should be titrated as tolerated with the goal of decreasing heart rate by 25% or to approximately 55 to 60 beats/minute.11,36 Heart rate is not an accurate marker for portal pressure reduction, but it is the accepted surrogate marker for effectiveness because there are no other acceptable alternatives. 

Nitrates have been suggested in patients who do not achieve therapeutic goals (heart rate reduction) with P-blocker therapy alone. Trials to evaluate the effects of nitrates (e.g., isosorbide mononitrate) on portal pressure, both alone and in combination with P-blockers, show enhanced reduction of portal pressure however, there is an increase in mortality when nitrates are used alone. Adverse effects are significantly higher in patients treated with the combination of non-selective P-blockers and nitrates as opposed to P-blocker monotherapy.42,43 Unfortunately,... 

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. 

Prevention of complications, achieving adequate lowering of portal pressure with medical therapy using /i-adrenergic blocker therapy, or supporting abstinence from alcohol. 

The mainstay of primary prophylaxis is the use of nonselective / -adrenergic blocking agents such as propranolol or nadolol. These agents reduce portal pressure by reducing portal venous inflow via two mechanisms decrease in cardiac output, and decrease in splanchnic blood flow. They prevent bleeding, and there is a trend toward reduced mortality. 

There is insufficient evidence to recommend nitrates in addition to ji-adrenergic blockers to further lower portal pressure. 

For patients who fail to achieve sufficient reductions in portal pressure with /3-blocker therapy alone, combination therapy with isosorbide mononitrate may more effectively lower portal pressures. 

Endoscopy, vasoactive drug endoscopy, CBC CBC, evidence of heart rate and portal pressure Acute control acute bleed. 

Coagulation rotherapy, volume resuscitation, pharmacologic prophylaxis Blood products (PPF, plate- CBC, prothrombin ation, reduce portal pressures Normalize PT, maintairV... 

Sodium retention and hypo albumin aemi a are constant features. The former appears consequent on disturbed blood volume distribution, withslanch-nic dilatation and reduced effective central arterial blood volume leads to sodium retention. Hypoalbu-minaemia associated with reduced hepatic albumin synthesis, and raised portal pressure associated with obstruction to flow, as well as active sodium retention all predispose to ascites. Hypoalbuminaemia is associated with reduced hepatic synthesis. 

Several drugs are available that reduce portal pressures. These may be used in the short term for the treatment of active variceal hemorrhage or long term to reduce the risk of hemorrhage. 

Romero G, Kravetz D, Argonz J, Bildozola M, Suarez A, Terg R. Terlipressin is more effective in decreasing variceal pressure than portal pressure in cirrhotic patients. J Hepatol 2000 32(3) 419-25. 

A. Mallat, Hepatic stellate cells and intrahepatic modulation of portal pressure,... 

Systemic vasodilatation, the severity of liver disease and portal pressure contribute to the abnormalities of sodium handling in cirrhosis. 

Schneider AW, Kalk JF, Klein CP. Effect of losartan, and angiotensin II receptor antagonist, on portal pressure in cirrhosis. Hepatology 1999 29 334-9. 

Hepatic portal hypertension and oesophageal var-iceal bleeding reduction of portal pressure (see p. 656). 

Portal pressure is a function of resistance in the portal venous system and ih.e flow of blood through it. In cirrhosis, portal venous resistance is increased, and inflow of blood is increased by splanchnic vasodilatation and elevation of cardiac output. Variceal bleeding is increasingly likely as the pressure gradient between the portal and systemic venous systems rises beyond 12 mmHg. 

Management involves measures directed at the varices and also to reduce portal pressure by pharmacological methods and blood shunting procedures. 

Direct treatment of varices by endoscopy is preferred. Band ligation, in which the varices are strangulated by application of small elastic bands has fewer complications than sclerotherapy, which involves injecting sclerosant into and around the varices but may lead to oesophagitis, stricture or embolisation of sclerosant. Either technique can control bleeding in about 90% of patients, and rebleeding is reduced if this direct treatment is combined with reduction of portal pressure (see below). 

Reduction of portal pressure. Vasopressin (anti-duiretic hormone, see p. 711), in addition to its action on the renal collecting ducts (through receptors), constricts smooth muscle (Vj receptors) in the cardiovascular system (hence its name), and particularly in splanchnic blood vessels, so reducing blood flow in the portal venous system. Unfortunately, coronary vasoconstriction can also occur, and treatment has to be withdrawn from 20% of patients because of myocardial ischaemia. Glyceryl trinitrate (transdermally, sublingually, or intravenously) reduces the cardiac risk and, advantageously, further reduces portal venous resistance and pressure. 

Somatostatin and its synthetic analogue octreotide reduce portal pressure by decreasing splanchnic blood flow. Octreotide has the advantage of a longer duration of action so that it can be given as a bolus injection rather than the constant intravenous infusion needed for administration of somatostatin. Its can be used as an alternative to terlipressin, having similar efficacy and indications for use. 

A persistent pressure elevation of > 12 mmHg in the portal vein circulation, dilation of the portal vein to >13 mm or an increase in the portal pressure gradient of > 7 mmHg (difference between the pressure of the portal vein and that of the inferior vena cava) is termed portal hypertension. At pressure values of more than 20 mmHg, collaterals generally develop. Portal hypertension is regarded as a systemic disease which affects a number of organ systems. 

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