Hepatic Failure Overview

Hepatic Failure

• Portal vein blood circulates through organs, returning to circulatory system
• Blood flow to liver is blocked or slowed in hepatic failure
• Hemorrhoids and splenomegaly can be symptoms of liver failure

Table of Contents

• Assessing liver function (covered in introduction)
• Cirrhosis
• Alcoholic liver disease
• Hepatitis-induced cirrhosis

Cirrhosis

• Injury causes scar tissue and restricts hepatocyte regeneration
• Scar tissue constricts blood flow in hepatic vasculature, causing portal hypertension
• Bile ducts are also constricted, leading to bile stasis
• Main causes of scarring are parenchymal damage, vascular disease, and biliary tract disease

Etiologies of Liver Damage

• Parenchymal damage: alcohol, autoimmune hepatitis, viral hepatitis (hep B and C), nonalcoholic fatty liver disease, obesity, hypertension, and hyperlipidemia
• Vascular disease: right heart failure, hepatic congestion, and clots in hepatic veins
• Biliary tract disease: inflammation of intrahepatic and extrahepatic bile passageways (cholangitis) causing bile backflow

Clinical Manifestations of Cirrhosis

• Compensated cirrhosis is usually asymptomatic, manifesting when the condition decompensates
• Three main complications: portal hypertension, decreased liver function, and hepatocellular carcinoma
• Manifestations include hepatic encephalopathy, esophageal varices, ascites, splenomegaly, and acute kidney injury
• Decreased liver function includes hypoalbuminemia, coagulopathies, ammonia buildup, hyperestrogenism, and hyperbilirubinemia (jaundice)

Portal Hypertension

• Increased pressure in hepatic portal vein causes blood to be diverted
• Development of collateral channels
• Shunting of blood, ammonia, and toxins from the intestines to general circulation
• Leads to splenomegaly, anemia, leukopenia, thrombocytopenia, and bleeding
• Esophageal varices and caput medusae

Portal Hypertension: Portosystemic Shunts

• High pressure in hepatic portal vein causes existing collateral channels to carry blood backwards
• New channels develop between gastric and esophageal veins causing esophageal varices
• Blood bypassing the liver does not get processed into urea, causing hepatic encephalopathy
• Backflow in mesenteric veins causes ascites and splenomegaly

Portosystemic Shunts: Complications

• Internal iliac veins pressure causes hemorrhoids; remnant umbilical veins cause caput medusae
• Rupture of esophageal varices causes hematemesis and melena
• Elevated ammonia levels result in hepatic encephalopathy, manifest by loss of alertness, confusion, anxiety, personality changes, and speech impairment

Portal Hypertension: Ascites

• Blood backs up into the peritoneal cavity filling with fluid
• Hydrostatic pressure increases in mesenteric veins resulting in fluid buildup
• Abdominal distension occurs as fluid builds up in the peritoneal cavity
• Risk of bacterial translocation due to microbes traveling into the peritoneum causing peritonitis

Ascites: Treatment

• Dietary restrictions and diuretics (inhibiting aldosterone-sensitive parts of the nephron, e.g. loop diuretics)
• Bed rest prevents renin system activation
• Paracentesis and volume expanders (albumin) help maintain effective circulating volume

Portal Hypertension: Splenomegaly

• Blood is diverted to the splenic vein, causing the spleen to enlarge
• Sequestration of formed blood elements (e.g., RBCs, platelets, and leukocytes) is known as hypersplenism
• Increased transit time through the spleen leads to removal of formed elements from the blood, resulting in anemia, thrombocytopenia, and leukopenia

Decreased Liver Function

• 80-90% of liver's function is lost causing synthesis, storage, metabolic, and elimination dysregulation
• Main complications include decreased clotting factors, thrombopoietin production, hypoalbuminemia, decreased ammonia clearance, hyperestrogensm, and decreased bilirubin processing

Liver Failure

• Characterized by multiple problems in liver function
• Disorders related to synthesis and storage
• Disorders of metabolic and excretory functions

Liver Function

• Impaired clotting factor production leads to GI bleeds, intracranial hemorrhages, and nosebleeds
• Blood loss is exacerbated by low platelet count
• Hypoalbuminemia exacerbates ascites and edema because of colloid pressure disruption
• Fewer hepatocytes convert ammonia into urea, causing ammonia buildup

Liver Failure: Endocrine Disorders

• The liver normally metabolizes estrogens keeping them in circulation long-term.
• High levels of estrogens cause testicular atrophy and gynecomastia in males, menstrual irregularities, infertility, and reduced libido in females
• Impaired bilirubin conjugation leads to bile acid reduction and malabsorption of fats and fat-soluble vitamins (e.g., K). This accumulates in the sclera and skin (cholestasis), resulting in jaundice.

Liver Failure: Treatment

• Eliminating alcohol if alcohol-related
• Providing sufficient carbohydrates to prevent protein breakdown
• Managing ammonia production by controlling protein intake
• Preventing infections
• Liver transplantation can treat end-stage liver disease

Alcoholic Liver Disease

• Alcohol is metabolized by the liver through alcohol dehydrogenase
• Conversion process produces Acetaldehyde, NADH is a product
• Excess NADH is problematic disrupting normal metabolite production/breakdown
• Excess NADH inhibits: Fatty Acid Oxidation, Gluconeogenesis, and Ketogenesis
• This causes an excess build-up of fats and reduced production of glucose

Alcoholic Liver Disease: Alcohol Consumption

• Amount of alcohol intake needed varies based on body size, age, sex, and ethnicity
• Conservative estimates suggest 80g/day for 10-12 years.
• Fat accumulation and inflammation can resolve if alcohol consumption decreases, but scarring remains
• Alcoholic Liver Disease occurs in three stages: fatty liver, alcoholic hepatitis, and cirrhosis

Fatty Liver

• Increased lipogenesis leads to fat (steatosis) accumulation in hepatocytes.
• Liver size increases, becoming yellow
• Progression's cause is unclear, but likely relates to alcohol consumption amount, diet and hormones
• Fatty liver is usually reversible

Alcoholic Hepatitis

• Characterized by liver inflammation and cell damage
• Necrosis of liver cells occurs, along with presence of inflammation, and fibrotic tissue
• Severity increases if alcohol intake is increased
• High mortality rate (about 10%), persistent drinking leads to cirrhosis in 1-2 years

Alcoholic Cirrhosis

• End-stage of alcoholic liver disease
• Characterized by uniform nodules in the liver due to liver's regenerative capacity
• Nodules compress hepatic veins and bile ducts, causing complications such as cholestasis, and portal hypertension (leads to portosystemic shunts)

Hepatitis-Induced Cirrhosis

• Hepatitis generally refers to liver inflammation
• Many viruses (e.g., Epstein-Barr virus, herpesviruses, enteroviruses, and hepatitis A, B, C, D, and E) cause systematic liver inflammation
• Hepatitis occurs through direct hepatocyte injury and the body's immune response to viral antigens
• Inability to remove virus early may lead to chronic hepatitis and ability to transmit virus.
• Hepatitis A, D, and E do not frequently result in chronic liver disease
• Viral hepatitis syndromes include, asymptomatic infection, acute hepatitis with or without progression to liver failure, carrier state with or without chronic hepatitis, chronic hepatitis with or without progression to cirrhosis

Hepatitis B

• Double-stranded DNA virus
• Transmitted through blood and serum contact, sexual contact, and intravenous drug use
• Includes acute and chronic forms of hepatitis, cirrhosis, fulminant hepatitis, and carrier state
• Immunization provides long-term protection. Treatment includes interferons and antiviral agents, liver transplantations also

Hepatitis C

• Single-stranded RNA virus
• Transmitted through blood or serum contact, e.g. drug use
• Frequently results in Chronic hepatitis, cirrhosis, and hepatocellular cancer,
• Absence of vaccine; treatment includes interferons, nucleoside agents, and liver transplantations