Pathophysiology of Portal Hypertension

Dr. Eeman At-Taras Dr. Mohamed Al-Saeid Suliman

Objectives
Review Portal circulation Describe the normal pressure in the hepatic portal vein

List the classifications of portal hypertension

Summarize the mechanistic changes that lead to portal hypertension Discuss the clinical consequences of portal hypertension

Portal system
Superior mesenteric + Splenic vein+ gastric + part from inferior mesentric = Portal vein Portal Vein carries outflow from: 1.) Spleen 2.) Oesophagus 3.) Stomach 4.) Pancreas 5.) Small and large intestine

Hepatic Portal System

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Portal circulation
Portal vein carries 75% of blood to the liver Hepatic vein flow Portal vein flow Hepatic artery flow = 1600 ml/min = 1200 ml/min = 400 ml/min

Hepatic vein pressure = 4 mmHg Portal vein pressure = 7 mmHg Hepatic artery pressure = 100 mmHg

Hepatic Blood Flow

Contains newly absorbed nutrients, drugs, and possibly microbes and toxins from the GI tract

Very low pressure in the hepatic portal vein approx. 5-8 mmHg with only a small gradient across the liver to the hepatic vein which returns the blood to the inferior vena cava

Tortora and Derrickson, 2006

Portocaval anastomosis (portal vein

Collaterals)
The portal venous system has several anastomosis with the systemic venous system. Four collateral pathways Esophageal and gastric venous plexus umbilical vein from the left portal vein to the epigastric venous system retroperitoneal collateral vessels the hemorrhoidal venous plexus In cases of portal hypertension these anastamoses may become engorged, dilated, or varicosed and subsequently
rupture

Portosystemic collateral pathways

Portal Hypertension (PH)

Portal vein pressure above the normal range of 5 to 8 mm Hg Portal vein - Hepatic vein pressure gradient greater than 5 mm Hg

Represents an increase of the hydrostatic pressure within the portal vein or its tributaries

Hepatic Portal Hypertension

Normally, there exists a low-pressure portal venous capillary bed throughout the liver parenchyma Pathological processes such as fibrosis increase the normally low intrahepatic venous pressure resulting in back up of blood into the systemic circulation (bypassing the liver, i.e. Portal-tosystemic shunting) Result: loss of protective and clearance functions of the liver; functional abnormalities in renal salt and water homeostasis and increased risk of GI hemorrhage due to development of engorged blood vessels (esophageal varices)

Portal Hypertension
Portal hypertension results from both: 1.Increased resistance to portal flow (R) 2.Increased portal venous inflow (Q)

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CAUSES OF PORTAL HYPERTENSION

Causes of Portal Hypertension Classification According to Site of Obstruction

1. Prehepatic blockage of the portal vein before the liver; due to portal vein thrombosis or occlusion secondary to congenital portal venous abnormalities 2. Intrahepatic - due architecture, either

distortion

of

the

liver

presinusoidal (e.g. schistosomiasis) postsinusoidal (e.g. cirrhosis); causes include: cirrhosis, alcoholic hepatitis, congenital hepatic fibrosis

Intrahepatic Causes: Cirrhosis

Most common cause Due to progressive liver injury Causes irreversible damage resulting in portosystemic shunting
Increased intrahepatic resistance results from both intrahepatic vasoconstriction and surrounding mechanical factors including collagen deposition and regenerative nodules

Intrahepatic Causes of Portal Hypertension

Non-cirrhotic portal hypertension Unknown etiology arsenic, vinyl chloride and other toxic agents are implicated Presence of mild portal tract fibrosis Lesion does not progress; prognosis is good Schistosomiasis

Parasitic disease caused by trematode flatworms

Confined to endemic areas (Africa, South America) Ova are entrapped in the portal vein Involvement of extensive pipe stem fibrosis

Causes of Portal Hypertension Classification According to Site of Obstruction

3. Posthepatic blockage outside the liver (rare); Budd-Chiari syndrome
Prolonged severe heart failure with tricuspid incompetence and constrictive pericarditis

Portal Hypertension Pathophysiology

Portal vascular resistance is increased in chronic liver disease
When the liver is injured, stellate cells are activated and transformed into myofibroblasts which contract under the influence of mediators such as endothelin and prostaglandins This results in abnormal blood flow patterns and increased resistance to blood flow

Additionally, the balance is shifted towards fibrogenesis

The increased resistance leads to portal hypertension and opening of portosystemic anastomoses (portal venous pressures >10 mmHg)

Consequences of Portal-toSystemic Shunting

Hepatic Encephalopathy Increased risk of massive GI tract bleeding (varices and coagulopathy) Malabsorption of fat and fat soluble vitamins (due to decreased bile flow) Ascites Drug sensitivity Hyperestrogenemia Hyperglycemia

CLINICAL FEATURES

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Clinical Consequences of Portal Hypertension

Hepatic encephalopathy
Worsening brain function (e.g. confusion, altered state of consciousness, coma) due to build up of noxious/toxic substances in the blood Occurs with cirrhosis and fulminant hepatic failure Toxins pass directly to the brain
Toxins include ammonia (major factor- produced by breakdown of protein by intestinal bacteria), mercaptans, fatty acids, false neurotransmitter (octopamine)

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Hepatic encephalopathy
Ammonia generated in the intestines from nitrogenous compounds in the diet is taken directly into the systemic circulation rather than being metabolized in the liver. This causes disturbances in neurotransmitter trafficking.

Clinical Consequences of Portal Hypertension - Ascites

Presence of excess fluid in the peritoneal cavity; can range from very mild to extremely fatal (as in the case of hepatorenal syndrome) Secondary to renal sodium and water retention that occur as a result of peripheral arterial vasodilation and consequent reduction in effective blood volume Portal hypertension exerts a local hydrostatic pressure which leads to increased hepatic and splanchnic production of lymph and transudation of fluid into the peritoneal cavity Low serum albumin (due to poor liver function) reduces plasma oncotic pressure

Pathophysiology of Ascites Formation and Hepatorenal Syndrome

Splanchnic arterial vasodilation causes hypovolemia which is compensated for by increased cardiac output (hyperdynamic circulation) With progression of disease there is deterioration of circulatory function Consequent stimulation of RAS system, sympathetic NS and secretion of antidiuretic hormone
Sanyal et al., 2008

Result: Sodium retention

Clinical Consequences of Portal Hypertension

Esophageal varices
Dilated submucosal veins in the lower esophagus and upper stomach One third of patients who develop varices will bleed (especially with large varices due to severe liver disease) Management
prevention of bleeding and rebleeding Non-selective beta blockade (sufficient to reduce pulse rate by 25%) Endoscopic treament Transjuglar portosystemic stent shunts (divert blood away from the liver)

Esophageal varices

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Pathophysiology of Variceal Bleeding

Sanyal et al., 2008 (Gastroenterology)

Clinical Consequences of Portal Hypertension

Splenomegaly Results from the increased back flow of blood from the hepatic vein
Spleen size increases to > 400 mg Caput medusa Rectal varices Hepatorenal syndrome

Summary
Functions of the liver are numerous and include detoxication of noxious substances and drugs, protein and lipid metabolism, storage of glycogen and vitamins, production of bile, etc; portal hypertension undermines the functions of the liver as it results in portosystemic shunting of blood Hepatic portal vein pressure is affected by both blood flow and resistance to flow; portal hypertension occurs when the pressure in the hepatic portal vein rises above the normal 5-8mmHg Causes of portal hypertension can be classified into: prehepatic, intrahepatic (most commonly cirrhosis) and posthepatic Portal hypertension can lead to several complications including esophageal varices, hepatic encephalopathy, ascites and hepatorenal syndrome as well as splenomegaly

References
McPhee and Ganong (2006). Pathophysiology of Disease: An Introduction to Clinical Medicine. Chapter 14 Kumar and Clark (2005). Clinical Medicine; 6th edition. Chapter 24. Rocky, D. Hepatology. Vol 25(1): 1997.

Sanyal et al. (2008). Gastroenterology Vol. 134(6): 1715-1728

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