Results from structural cirrhotic liver changes of increased vasculature fibrosis and regenerative nodules and increased dynamic hepatic vasculature tone from endothelial dysfunction and decreased nitric oxide bioavailability and then cause esophageal varices (Iwakiri Y).
Portal hypertension increases, intrahepatic resistance due to distorted liver architecture with fibrosis and nodules, and then increases in intrahatic vascular tone.
Activation of vasodilators in the splanchnic circulation, most importantly, nitric oxide, leads to progressive splanchnic and systemic vasodilation.
Increased translocation of bacteria and bacterial products due to intestinal dysbiosis, bacterial overgrowth, and altered proteins, also contribute to vasodilatation resulting in the reduction in effective arterial blood volume that activates neurohormonal systems: renin angiotensin-aldosterone, sympathetic and arginine vasopressin systems, leading to sodium and water retention and ascites formation.
In advanced stages of cirrhosis, progressive dilatation leads to more retention of sodium and water, resulting in refractory, ascites and dilutional hyponatremia.
A major complication of cirrhosis.
Direct portal pressure measurement is invasive and requires cannulation of the portal or umbilical veins.
Portal hypertension can be diagnosed by the pressure gradient between the portal vein and the inferior vena cava, defined as the hepatoc venous pressure gradient.
Hepatic venous pressure gradient represents the liver portal perfusion pressure, and it ranges from 1-4 mmHg.
Values greater and 5 mmHg suggests portal hypertension, and values greater than 10 mmHg correspond to clinically significant portal hypertension, at which time clinical complications occur.
Portal hypertension is a result of an increase in resistance or blood flow in the portal venous system and cirrhosis is its most common cause.
The formation of scar tissue and regenerative nodules in the liver leads to an increase in intrahepatic vascular resistance and, therefore, total pressure.
Intrahepatic portal hypertension caused by high vascular resistance at the pre-sinusoidal, post sinusoidal or sinusoidal capillaries.
A normal HVPG (hepatic vein pressure gradient) ranges from 1-4 mmHg and values greater than 10 mmHg are associated with the development of complications such as esophageal varices and ascites.
Variceal bleeding typically occurs when the HVPG is greater than 12 mmHg, and values greater than 20 mmHg within 48 hours of such a bleed are associated with high mortality rates in patients with cirrhosis.
Portal hypertension leads to an increase in the portosystemic collateral flow as it attempts to decompress portal venous system.
The most critically important site of collateral flow is within the mucosa of the proximal stomach and distal esophagus with the development of gastroesophageal varices.
Measurement of the HVPG is performed by an interventional radiologist with a ballooned tip catheter placed in the right main hepatic vein: wedged hepatic venous pressure is obtained through balloon occlusion of the hepatic vein, and free hepatic venous pressure is measured by maintaining the tip of the catheter floating freely approximately 2-4 cm distal to the inferior vena cava.
HPVG is an independent prognostic variable with a 3% increase in mortality risk for each 1 mm of mercury gradient increase.
The main causes of pre-sinusoidal portal hypertension include: nodular regenerative hyperplasia, primary biiary cholangitis, autoimmune cholangiopathy, congenital hepatic fibrosis, schistosomiasis, and polycystic disease.
Cirrhosis is the most common cause of sinusoidal portal hypertension, it also can because by amyloidosis, mastocytosis and Gaucher disease by infiltration disease.
These changes in early stages of cirrhosis related portal hypertension are followed by compensatory splanchnic vasodilatation which, in turn, results in increased portal bloodflow, further activating portal pressure.
Chronic hepatocellular injury promotes activation of perisinusoidal cells, known is hepatic stellate cells, which require a fibrogenic myofibroblast phenotype, resulting in collagen production and sinusoidal construction.
Any process that leads to interference with blood flow or a vascular resistance in the portal venous system can lead to portal hypertension.
Cirrhosis is the most common cause of portal hypertension in Western countries, and all other etiologies accounts for less than 10% of cases.
Portal hypertension causes are classified according to their anatomical location: pre-hepatic, intrahepatic, or posthepatic.
Posthepatic portal hypertension is generally a result of venous outflow impairment with increased vascular resistance to hepatic blood flow and most commonly caused by Budd-Chiari syndrome and right sided heart failure from constrictive pericarditis, restrictive cardiomyopathy, and complex congenital heart diseases.
Isolated portal vein thrombosis may result in pre-hepatic portal hypertension due to impaired blood flow in the portal venous system.
In the absence of cirrhosis portal vein thrombosis can be a consequence of a congenital or acquired prothrombotic state, local complications, pancreatitis, abdominal trauma, or surgery.
Collateral blood vessels between the portal and systemic circulations develop when portal-pressure gradient increases.
Simply defined as abnormal venous pressure elevation in the portal system.
Portal vein pressure normally ranges from 7-12 mmHg at rest and fasting conditions.
With the development of portosystemic collateral circulation, the portal venous blood flow increases secondary to splanchnic vasodilation and increased cardiac output.
Increased portal blood flow then maintains and increases the portal hypertension.
PH is a frequent cause of chylous ascites not related to lymphatic injury.
PH increases shear stress in splanchnic capillaries which increases the release of nitric oxide and results in systemic vasodilatation.
Systemic vasodilatation activates baroreceptors which trigger the renin angiotensin aldosterone system causing retention of salt and water.
Fluid accumulates in the peritoneal space generating low proteins ascites.
Consequences include: ascites, esophageal varices, hepatic encephalopathy, and hepato-renal syndrome leading to substantial morbidly and mortality.
Gastric and esophageal varices are the most important collateral blood vessels formed.
Definitive diagnosis requires the use of invasive methods.
The diagnosis is suggested by the presence of ascites, gastroesophageal varices, splenomegaly, hypersplenism-related thrombocytopenia, portosystemic encephalopathy, and hepatopulmonary syndrome.
One of the above complications, associated with clinical, biochemical, or radiologic features of cirrhosis is sufficient to make a diagnosis.
Cirrhosis accounts for 90% of all causes of portal hypertension, making an invasive assessment of portal pressure a rare requirement for diagnosis.
Treatment achieving a gradient of less than 12 mmHg or a 20% reduction from baseline is associated with a significant decrease in the incidence of complications.
Nonselective beta blockers decrease portal pressure through inhibition of the beta-2-induced splanchnic vasodilation, thereby reducing portal venous inflow.
Nonselective beta blockers decrease portal pressure by inhibition of beta-2 induced splanchnic vasodilation.
Carvedilol promotes a greater reduction in portal pressure compared with other nonselective beta blockers as it has also anti-adrenergic activity.
Angiotensin receptor blockers do not have a significant effect on portal hypertension and are not recommended.
Octreotide does not result in sustained portal pressure reduction and has higher rates of serious adverse affects and is not used as a long-standing regimen.
Weight loss in obese individuals with cirrhosis and portal hypertension may lead to significant reduction in portal pressure.
Endoscopic band ligation, involving the application of rubber bands around the varix may be used for the prevention of variceal bleeding.
Portosystemic shunting procedures are highly effective in reducing portal pressure.