hepatic and biliary disorders
Cirrhosis
Pathophysiology of Cirrhosis
There are 2 primary ingredients: Hepatic fibrosis Regenerating liver cells In response to injury and loss, growth regulators induce hepatocellular hyperplasia (producing regenerating nodules) and arterial growth (angiogenesis). Among the growth regulators are cytokines and hepatic growth factors (eg, epithelial growth factor, hepatocyte growth factor, transforming growth factor-alpha, tumor necrosis factor).Insulin,glucagon, and patterns of intrahepatic blood flow determine how and where nodules develop. Angiogenesis produces new vessels within the fibrous sheath that surrounds nodules. These vessels connect the hepatic artery and portal vein to hepatic venules, restoring the intrahepatic circulatory pathways. Such interconnecting vessels provide relatively low-volume, high-pressure venous drainage that cannot accommodate as much blood volume as normal. As a result, portal vein pressure increases. Such distortions in blood flow contribute to portal hypertension, which increases because the regenerating nodules compress hepatic venules. The progression rate from fibrosis to cirrhosis and the morphology of cirrhosis vary from person to person. Presumably, the reason for such variation is the extent of exposure to the injurious stimulus and the individual’s response. Portal Hypertension is the most common serious complication of cirrhosis, and it, in turn, causes complications, including Overview of Gastrointestinal Bleeding from esophageal, gastric, or rectal varices and portal hypertensive gastropathy Overview of Platelet Disorders None Ascites None Acute kidney injury ( Hepatorenal syndrome ) Pulmonary Hypertension (portopulmonary hypertension) Hepatopulmonary Syndrome (intrapulmonary shunt) Ascites fluid can become infected ( Spontaneous Bacterial Peritonitis (SBP) ). Portopulmonary hypertension can manifest with symptoms of heart failure. Complications of portal hypertension tend to cause significant morbidity and mortality. Cirrhosis can cause other cardiovascular complications. Vasodilation, intrapulmonary right-to-left shunting, and ventilation/perfusion mismatch can result in hypoxia (hepatopulmonary syndrome). Progressive loss of hepatic architecture impairs function, leading to hepatic insufficiency; it manifests as coagulopathy, Acute Kidney Injury (AKI) (hepatorenal syndrome), and Hepatocytes secrete less bile, contributing to cholestasis and Jaundice . Less bile in the intestine causes malabsorption of dietary fat (triglycerides) and fat-soluble vitamins. Malabsorption of Blood disorders are common. Anemia usually results from hypersplenism, chronic GI bleeding, Folate Deficiency (particularly in patients with alcohol use disorder), and Cirrhosis results in decreased production of prothrombotic and antithrombotic factors. Hypersplenism and altered expression of thrombopoietin contribute to thrombocytopenia. Thrombocytopenia and decreased production of clotting factors can make clotting unpredictable, increasing risk of both bleeding and thromboembolic disease (even though international normalized ratio [INR] is usually increased). Overview of Leukopenias is also common; it is mediated by Consider thromboembolic complications in patients with cirrhosis, even if INR is elevated. Hepatocellular Carcinoma frequently complicates cirrhosis from any cause (justifying clinical surveillance). The incidences of hepatocellular carcinoma in cirrhosis from specific etiologies are listed below ( Overview of Chronic Hepatitis : 3 to 8 % per year Overview of Chronic Hepatitis : 3 to 5 % per year Primary Biliary Cholangitis (PBC) : 3 to 5 % per year Metabolic Dysfunction–Associated Liver Disease (MASLD) : 0.3 to 2.6% per year Cirrhosis from other etiologies, eg, Overview of Iron Overload , Cirrhosis is characterized by regenerating nodules and bridging fibrosis. Incompletely formed liver nodules, nodules without fibrosis (nodular regenerative hyperplasia), and congenital hepatic fibrosis (ie, widespread fibrosis without regenerating nodules) are not true cirrhosis. Cirrhosis can be micronodular or macronodular. Micronodular cirrhosis is characterized by uniformly small nodules (<3 mm in diameter) and thick regular bands of connective tissue. Typically, nodules lack lobular organization; terminal (central) hepatic venules and portal triads are distorted. With time, macronodular cirrhosis often develops. The nodules vary in size (3 mm to 5 cm in diameter) and have some relatively normal lobular organization of portal triads and terminal hepatic venules. Broad fibrous bands of varying thickness surround the large nodules. Collapse of the normal hepatic architecture is suggested by the concentration of portal triads within the fibrous scars. Mixed cirrhosis (incomplete septal cirrhosis) combines elements of micronodular and macronodular cirrhosis. Differentiation between these morphologic types of cirrhosis has limited clinical value. 1.Huang DQ, El-Serag HB, Loomba R: Global epidemiology of NAFLD-related HCC: Trends, predictions, risk factors and prevention.Nat Rev Gastroenterol Hepatol8(4):223-238, 2021. doi: 10.1038/s41575-020-00381-6 