Liver Disease

What is the blood supply to the liver?

Hepatic artery and portal vein.

Hepatocyte

Liver cells.

Describe enterohepatic circulation

Bile is released from the liver and stored/concentrated in the gall bladder. Gall bladder empties bile into duodenum. Bile emulsifies fats and allows them to be absorbed by lymphatics.

- Recycling of bile acids between the liver and small intestine.

What do statins do?

Reduce cholesterol in the blood by modifying cholesterol uptake in the liver.

What are the major functions of the liver?

Detoxification (bilirubin, ammonia, drugs/toxins, hormones), lipid metabolism, carbohydrate metabolism, protein synthesis, conjugation/excretion of bilirubin, synthesis/excretion of bile acids.

What toxic accumulations occur due to liver disease?

Ammonia, bilirubin, drugs/toxins, and endogenous hormones (especially estrogen).

What blood abnormalities occur with liver disease?

Low plasma albumin → edema; deficiency of coagulation factors → bleeding.

What GI consequence occurs due to lack of bile acids?

Inability to absorb intestinal fat.

What are common causes of liver disease progression?

Viral hepatitis, alcoholism, and gallstone obstruction.

What is the final endpoint for many liver diseases?

Cirrhosis: a scarred liver.

What is the most important consequence of cirrhosis?

Portal hypertension, which can be associated with liver failure or severe hemorrhage.

What is the outcome of cirrhosis of the liver

People will die of hemorrhage.

How can gallstones impact the liver?

Stones formed in the gallbladder may pass and obstruct the bile duct

What are the major patterns of liver injury?

Inflammation (hepatitis), degeneration (hydropic or fatty liver), necrosis (infarcts or Councilman bodies, which are when the cells die), autoimmune/toxic injury, and fibrosis (cirrhosis).

Fibrosis of the liver

Cirrhosis.

Steatosis

A fatty liver.

How susceptible are the liver cells to damage?

Liver cells take a lot of damage before they are killed.

Steatosis leads to _______________

Cirrhosis.

What liver enzymes increase with liver disease?

Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT).

What protein abnormalities occur with liver disease?

High levels of bilirubin, low albumin, and low coagulation factor production.

What coagulation test abnormalities occur?

Prolonged prothrombin and partial thromboplastin time.

What are three major functional patterns of liver injury?

Jaundice, cholestasis, and hepatic failure.

Cholestasis

Bile isn't moving, causing jaundice and pruritus to be deposited.

Jaundice

Excess bilirubin in the blood

Icterus

Yellow discoloration of the skin and sclera.

What are the three types of jaundice?

Prehepatic, hepatic, posthepatic

Describe prehepatic jaundice

Hemolytic anemia. Killed off too many RBCs.

Describe hepatic jaundice

Hyperbilirubinemia (too much bilirubin), unconjugated (not water soluble) bilirubin deposited in the brain (kernicterus)

Kernicterus

Bilirubin in the brain.

Describe posthepatic jaundice

The bile duct is blocked, so bile and bilirubin build up

What percentage of liver function must be lost for failure?

About 90%.

Key clinical features of liver failure?

Jaundice, ascites, hypoalbuminemia, hypoglycemia, hyperammonemia, fetor hepaticus (bad breath).

Hormonal effects of liver failure due to estrogen buildup?

Palmar erythema (red hands), gynecomastia (breast tissue), balding, testicular atrophy.

Neurologic and renal complications from liver failure?

Hepatic encephalopathy and hepatorenal syndrome.

What is cirrhosis?

End-stage liver disease with patterned fibrosis and scarring.

What are common causes of cirrhosis?

Alcoholism and viral hepatitis (~66% of cases).

Two anatomic types of cirrhosis?

Portal cirrhosis and biliary cirrhosis.

What are the complications of portal cirrhosis?

Portal triads are repeatedly damaged, regenerated, and eventually scarred. Portal hypertension → ascites, splenomegaly, esophageal varices. Usually caused by alcoholism or viral infections.

What is biliary cirrhosis?

Chronic inflammation of bile ducts.

Clinical features of cirrhosis?

Fatigue, weight loss, anorexia, sudden jaundice, death from liver failure, variceal hemorrhage, or hepatocellular carcinoma. High risk for liver cancer.

What is acute viral hepatitis?

Inflammation of the liver. Incubation, prejaundice phase, jaundice phase.

What is chronic viral hepatitis?

Can be due to autoimmune or alcoholisim

What is fulminant hepatic failure?

Clinical syndrome of sudden and severely impaired liver function in a previously healthy person.

Features of hepatitis A

Usually unaware they have it.

Features of hepatitis B

Leads to chronic hepatitis. sexually transmitted or IV drug users will get it from sharing needles.

Features of hepatitis C

Very risky for developing liver cancer (hepatocellular carcinoma. This is curable, but there is no prevention. Takes upwards to 20 years for cirrhosis to develop.

Who most commonly develops autoimmune hepatitis?

Young women; associated with lupus, RA, thyroiditis. Treatment is immunosuppressive therapy.

What are types of toxic liver injury?

Dose-dependent (acetaminophen suicide from a high dose which can cause liver damage), and idiosyncratic reactions.

What percent of alcoholics develop cirrhosis?

16%, affects women more then men.

Describe the progression of alcoholic liver disease

Steatosis → alcoholic hepatitis → cirrhosis.

Is steatosis reversible?

Yes, this usually occurs after binge drinking.

After years of steatosis, what can appear suddenly after years?

Hepatitis. This is not always reversible with complete cessation of drinking.

Alcoholic cirrhosis is ____________

Irreversible.

What do gallstones cause in the intrahepatic ducts?

Inflammation and biliary colic.

What is primary biliary cirrhosis?

Autoimmune destruction of bile ducts; cured only by transplant.

What is primary sclerosing cholangitis?

Scaring of the bile ducts. Inflammation of the bile ducts often leads to biliary cirrhosis. Often seen in men with ulcerative colitis.

What causes portal or hepatic vein occlusion?

Thrombosis often occurs after abdominal injury (surgery or pancreatitis). Hepatic vein occlusion is rarer but more serious.

What causes chronic passive congestion?

R-sided HF.

Are liver infarcts serious?

Usually not, due to dual blood supply and the regenerative capability of the liver tissue.

Common benign liver tumors?

Cavernous hemangiomas, liver cell adenomas.

What viruses increase hepatocellular carcinoma risk 200×?

HBV and HCV. Very high mortality following cachexia or bleeding due to low clotting factors.

Features of hepatocellular carcinoma?

Highly invasive, metastatic, high mortality.

What is cholangiocarcinoma?

Malignancy of bile duct epithelium; associated with primary sclerosing cholangitis and schistosomiasis.

What is the primary purpose of the gallbladder?

Store and concentrate bile

What are most gallbladder diseases associated with?

Gallstones.

What is cholelithiasis?

Gallstones, including common bile duct stones (choledocholithiasis).

Who is at risk for cholesterol stones?

Older adults, women > men, obese individuals, certain ethnicities, oral contraceptive use.

What are pigment stones made of?

Bilirubin and non-cholesterol substances.

What is cholecystitis?

Inflammation of the gallbladder, usually from stones.

What is a common procedure to treat gallbladder disease?

Cholecystectomy.

What is an adenocarcinoma of the gallbladder?

Tumor of the gallbladder

What is the most common cause of extrahepatic bile duct disease?

Obstruction (stones, pancreatic cancer, surgical scarring).

What is ascending cholangitis?

Blockage ascending up the tract causes liver infection.