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Portal hypertension is , in simple terms , elevated pressure in the portal vein and it occurs when blood flow meets increased resistance in the hepatic sinusoids. The portal vein is formed by the union of the superior mesenteric and splenic veins. The normal portal venous pressure is 5 to 10 mm Hg ( 7 to 14 cm H2O). So, if the pressure of either the hepatic or portal vein is more than 5 mm Hg and the splenic pressure is more than 15 mm Hg, this would be abnormal and would indicate the presence of portal hypertension. Lately, more attention has been focused on this syndrome because its mortality is as high as the mortality of acute myocardial infarction. This essay would highlight the pathophysiology of portal hypertension and discuss its causes, complications and management in brief.(1)(2)(3)
P1-P2 = Q * R where: P1-P2 : pressure gradient The pressure in any vascular system is directly proportional to the flow and resistance in that system. Thus portal hypertension develops either because of increased blood flow or because of an increase in resistance at some point in the portal vein, liver hepatic veins or the heart. A. Increased blood flow in the portal vein: Increased portal venous blood flow is an uncommon cause of portal hypertension, however; since large collaterals are found in patients with high portal pressure, either resistance in the collaterals is higher than believed or there is an abnormally high portal venous inflow which maintains the high pressure in the portal vein and its collaterals. To investigate this, portal venous inflow has been measured using radioactive microspheres in animals with portal hypertension. Within a few days, portal venous inflow increases to greater than normal values because of a fall in splanchnic arteriolar resistance. This increase in portal venous inflow is thought to account for about 40% of the increase in portal pressure. The cause of such an increase is the vasodilatation which is initiated by certain humoral factors produced by the splanchnic organs like nitric oxide (NO).(2)(3) B. Increased resistance: An increase in vascular resistance is the most common cause of portal hypertension. Normally, the liver is a very compliant organ. Hence, intrahepatic resistance decreased with increase in blood inflow. This compensatory mechanism maintains the portal pressure within normal levels. In portal hypertension , this is not seen as the intrahepatic resistance becomes fixed due to fibrosis and mechanical distortion of the liver tree and the hepatic compliance is greatly reduced (see cirrhosis later). The main site of resistance is somewhat controversial. The hepatic sinusoids , terminal hepatic venules and also portal venules have been suggested as possible sites of resistance. In pre-hepatic and post- hepatic portal hypertension, increased resistance is secondary to obstruction of portal venous inflow or hepatic venous outflow. Resistance could be increased by the increased vascular tone seen in cirrhotic livers which could be a deficit of endothelial vasodilators such as NO or an increase in the vasoconstrictors such as prostanoids. Another source of resistance could be the collateral circulation which begins as a consequence of portal hypertension to ease the tension from the portal system. But soon enough, the vascular resistance of this collateral bed outpaces the resistance of the normal liver.(2) C. Hyperdynamic circulation: Chronic elevations in systemic and splanchnic blood flow have been documented as key elements of the hyperdynamic state. Peripheral vasodilatation initiates the development of the decreased systemic vascular resistance and mean arterial pressure, plasma volume expansion (ascites), elevated splanchnic blood flow and elevated cardiac output. The hyperdynamic circulation is mediated in part by vasodilatation , but this alone is not sufficient. Plasma volume expansion has been recognized in portal hypertension for many years. According to the peripheral vasodilatation hypothesis, portal hypertension leads to a relative hypovolaemia induced by the dilation of the systemic and splanchic circulation induced by nitric oxide. This results in underfilling of the systemic vascular space with the consequent decrease in central blood volume. This in turn leads to the activation of the sympathetic nervous system, rennin-angiotensin system and release of anti-diuretic hormone. Mediators from these systems result in sodium and water retention by the kidneys.which results in increased plasma volume or what is known as ascites.(3)
Portal hypertension is classified according to the site of obstruction into prehepatic, intrahepatic and post hepatic. Prehepatic obstruction is due to the blockage of the portal vein before the liver, intrahepatic obstruction is due to distortion of the liver architecture which can be pre-sinusoidal like in schistosomiasis or post-sinusoidal like in cirrhosis while posthepatic is due to venous blockage outside the liver. Here, i’d stress the importance of cirrhosis as the main cause of hypertension.(5) Cirrhosis (intrahepatic obstruction): Cirrhosis results from the necrosis of liver cells followed by fibrosis and
nodule formation. The liver architecture is diffusely abnormal and this
interferes with liver blood flow and function.(5) It causes more than 6000
deaths a year in the UK alone. Alcohol is now the commonest cause in the western
world but HBV infection is the commonest cause worldwide. Regardless of the
nature of the initial insult, the cellular mechanisms underlying hepatic
fibrosis and cirrhosis are common. It has been thought that the
parenchymal cell necrosis may be important in activating hepatic macrophages (kupffer
cells) which would in turn activate the hepatic stellate cells(HSC )in the space
of Disse. The activated HSC proliferate and are activated to a myofibroblast-
like cells. As a result of such an activation, collagen ( type 1 and 11) is laid
down in the space of Disse causing the endothelial cells to lose their fenestrae
and this is called capillarisation. Because of so, the portal vein can no longer
take the blood to the hepatocytes and this creates the porto hepatic anastamosis
which plays an important role in elevating the portal pressure. Besides, the
expanding regenerating nodules make the picture worse by further obstructing the
hepatic veins which also increases the portal pressure.(2)(4)(6) How does cirrhosis result in Portal hypertension?: 1. The porto hepatic shunt decrease the blood supply to the liver. Normally, 100% of the portal venous blood flow can be recovered from the hepatic veins, whereas in cirrhosis only 13% is obtained. The remainder enters collateral channel . By doing so, the intestinal blood toxins escape the liver filter and serve their toxic impacts elsewhere( see complications).(4)(6) 2. liver Fibrosis and regenerative nodules increase the portal pressure. Such a rise in the portal pressure would cause the blood to back up through the collateral channels into spleen causing splenomegaly, into the left gastric vein causing esophageal and gastric varices, paraumblical vein to abdominal wall causing caputus medusa, into the hemorrhoids veins causing rectal varices and hemorroids.(2)(1) 3. The trauma that caused cirrhosis creates an arterio-venous anastamoses in fibrous septa which increases the pressure in the portal vein increasing therefore the back pressure and the collateral circulation.(6)
Ascites: which is a result of lots of causes. First of all, the damaged liver can’t produce albumin in the vascular system. So, the hypoproteinemia or the reduced oncotic pressure would induce edema or ascites formation because the filtration through the capillary wall caused by the hydrostatic pressure is increased and reabsorption of fluid is impaired. Secondly and more importantly, ascites is thought to be the result of sodium retention. Sodium retention is brought by the peripheral arterial vasodilator by NO. Such dilation would reduce the blood volume effectively which would activate the sympathetic nervous system and the rennin-angiotensin system thus promoting salt and water retention. Faulty inactivation of an antidiuretic that is released from the posterior pituitary has been claimed as a cause of water retention. Faulty inactivation of aldestrone in the cirrhotic liver may also explain the salt retention correlated with ascites.(5)(6) Renal failure: the mechanism is similar to ascites. The initiating factor is thought to be extreme peripheral vasodilatation possibly by NO which would lead to hypovolemia and thus plasma rennin, aldosterone, noradrenaline and vasopressin increase leading to vasoconstriction of the renal vasculature which would create a high resistance that would direct the blood away from the renal tubules.(5) Encephalopathy: in portal hypertension, the blood bypasses the liver via the collaterals and the toxic metabolites pass directly to the brain to produce the Encephalopathy. Examples of such toxic metabolites are ammonia, free fatty acids and mercaptans. (5) Esophageal varices: bleeding from the esophageal varices cause massive hematemesis that might cause hypovolemic shock and this is an emergency. It is the result of the back pressure in the collateral circulation Caput medusa : they are dilated abdominal veins caused by the back pressure of blood in the umbilical vein. Hepatic insufficiency due to diversion of blood by extrahepatic portal collaterlals and intrahepatic portahepatic venous anastomoses. Hemorrhage tendency which is caused by a defect in the hepatic formation of coagulation factor VII. Testicular atrophy, gynecomastia, pectoral and axillary alopecia and palmar erythema caused by the active estrogen that escapes inactivation in the in the liver Leukopenia , thrombocytopenia and anemia are the resultants of the enlargement of the spleen.(6)
- There is no definitive treatment for portal hypertension. All what portal hypertension therapy tries to do is to treat or reduce the impact of the complications of this syndrome. - in 1800, splenoctomy was the primary therapy for portal hypertension because they noticed that enlarged spleen often seen in patients with cirrhosis led to increased portal venous flow. However, nowadays splenectomy is rarely indicated for hypersplenism resulting from portal hypertension. - Acute variceal bleeding: resuscitation is essential , fluid replacement should be in the form of colloid or packed cells since saline may exacerbate ascites. Moreover, balloon tamponade may be useful to control variceal haemorrhage as well as certain vasoactive drugs like Terlipressin which is a vasopressin analogue. - Ascites: Bed rest, sodium restriction and diuretics (aldosterone antagonist) control ascites. Give antibiotics( cefotaxime) if the ascites get infected with E.coli. - Coagulopathy: is corrected by fresh frozen plasma, cryoprecipitate or platelet infusions. - Hepatorenal syndrome: there is limited therapeutic options of HRS. It is important to correct any intravascular hypovolaemia while monitoring central venous pressure to treat any percipitating infection and to withdraw potentially nephrotoxic medications such as non steroidal anti inflammatory drugs, aminoglycosides and diuretics. Liver transplantation is the only treatment to improve the outcome for patients with HRS. - Surgical by pass procedures include porto systemic anastamosis, splenorenal shunt and mesocaval shunt. Porto caval shunt or mesocaval shunt decreases pressure within the liver as well as reduces ascites.(7)(8)
1. Robert Berkow,etal. The Merck Manual of Diagnosis and Therapy. 6 th ed.
Rahway: Merck Research Laborat
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Introduction