Chapter 21: Cirrhosis and Portal Hypertension

INTRODUCTION

• Chronic liver injury causes damage to normal liver tissue, resulting in development of regenerative nodules surrounded by dense fibrotic material, which are diagnostic hallmarks of cirrhosis.

PATHOPHYSIOLOGY

• The distorted architecture of the cirrhotic liver impedes portal blood flow, interferes with hepatocyte perfusion, and disrupts hepatic synthetic functions such as the production of albumin. Clinical consequences of cirrhosis include increased intrahepatic resistance leading to portal hypertension, varices, and variceal bleeding; ascites; infection; hepatic encephalopathy (HE); and hepatocellular carcinoma.

• Primary causes of cirrhosis in developed countries include hepatitis C, excessive alcohol intake, and nonalcoholic fatty liver disease (Table 21-1).

• Cirrhosis causes changes to the splanchnic vasculature and circulation. Splanchnic vasodilation and the formation of new blood vessels contribute to increased splanchnic blood flow, formation of gastroesophageal varices, and variceal bleeding. Additionally, splanchnic vasodilation leads to hypoperfusion of the renal system, which causes activation of the renin–angiotensin–aldosterone system and, subsequently, significant fluid retention. The pathophysiologic abnormalities that cause it often result in ascites, portal hypertension and esophageal varices, HE, and coagulation disorders.

• Portal hypertension is noted by elevated pressure gradient between the portal and central venous pressure and is characterized by hypervolemia, increased cardiac index, hypotension, and decreased systemic vascular resistance.

• Ascites is the pathologic accumulation of fluid within the peritoneal cavity. It is one of the earliest and most common presentations of cirrhosis.

Portal Hypertension and Varices

• The most important sequelae of portal hypertension are the development of varices and alternative routes of blood flow resulting in acute variceal bleeding. Portal hypertension is defined by the presence of a gradient of >5 mm Hg (0.7 kPa) between the portal and central venous pressures.

• Progression to bleeding can be predicted by Child–Pugh score, size of varices, and the presence of red wale markings on the varices. First variceal hemorrhage occurs at an annual rate of about 15% and carries a mortality of 7%–15%.

Hepatic Encephalopathy

• HE is a functional disturbance of the brain caused by liver insufficiency or portal systemic shunting that presents on a wide spectrum of symptom severity ranging from subclinical alterations to coma.

• The symptoms of HE are thought to result from an accumulation of gut-derived nitrogenous substances in the systemic circulation as a consequence of decreased hepatic functioning and shunting through portosystemic collaterals bypassing the liver. These substances then enter the central nervous system (CNS) and result in alterations of neurotransmission that affect consciousness and behavior.

• Altered ammonia, glutamate, benzodiazepine receptor agonists, ...