Pathoma Liver Flashcards
jaundice
*yellow discoloration of the skin
*earliest sign is scleral icterus (yellow discoloration of the sclera)
*due to increased serum bilirubin, usually > 2.5 mg/dL
*arises with disturbances in bilirubin metabolism
normal bilirubin metabolism
- RBCs are consumed by macrophages of the reticuloendothelial system
- protoporphyrin (from heme) is converted to unconjugated bilirubin (UCB)
- albumin carries UCB to the liver
- uridine glucuronyl transferase (UGT) in hepatocytes conjugates bilirubin
- conjugated bilirubin (CB) is transferred to bile canaliculi to form bile, which is stored in the gallbladder
- bile is released into the small bowel to aid in digestion
- intestinal flora convert CB to urobilinogen, which is oxidized to stercobilin (makes stool brown) and urobilin (partially reabsorbed into blood and filtered by kidney, making urine yellow)
causes of jaundice - overview
*extravascular hemolysis or ineffective erythropoiesis
*physiologic jaundice of the newborn
*Gilbert syndrome
*Crigler-Najjar syndrome
*Dubin-Johnson syndrome
*biliary tract obstruction (obstructive jaundice)
*viral hepatitis
extravascular hemolysis / ineffective erythropoiesis & jaundice
*etiology: high levels of UCB overwhelm the conjugating ability of the liver
*lab findings: increased UNCONJUGATED bilirubin
*clinical features:
-dark urine due to increased urine urobilinogen (UCB is not water soluble and, thus, is absent from urine)
-increased risk for pigmented bilirubin gallstones
physiologic jaundice of the newborn
*etiology: newborn liver has transiently low uridine glucuronyl transferase (UGT) activity
*lab findings: increased UNCONJUGATED bilirubin
*clinical features:
-UCB is fat soluble and can deposit in the basal ganglia (kernicterus) leading to neurological deficits and death
-tx is phototherapy (makes UCB water soluble)
Gilbert syndrome & jaundice
*etiology: mildly low uridine glucuronyl transferase (UGT) activity; autosomal recessive
*lab findings: increased UCB
*clinical features:
-jaundice during stress (e.g. severe infection)
-otherwise, not clinically significant
Crigler-Najjar syndrome & jaundice
*etiology: ABSENCE of uridine glucuronyl transferase (UGT)
*lab findings: increased UCB
*clinical features:
-kernicterus
-usually fatal
Dubin-Johnson syndrome & jaundice
*etiology: deficiency of bilirubin canalicular transport protein; autosomal recessive
*lab findings: increased CONJUGATED bilirubin (CB)
*clinical features:
-LIVER IS DARK/black; otherwise, not clinically significant
-Rotor syndrome is similar, but lacks liver discoloration
biliary tract obstruction & obstructive jaundice
*etiology: associated with gallstones, pancreatic carcinoma, cholangiocarcinoma, parasites, and liver fluke (anything that blocks the biliary tract)
*lab findings: increased CONJUGATED bilirubin; decreased urobilinogen; increased alkaline phosphatase
*clinical features:
-dark urine (due to bilirubinuria) and pale stool
-pruritis due to increased plasma bile acids
-hypercholesterolemia with xanthomas
-steatorrhea with malabsorption of fat-soluble vitamins
viral hepatitis & jaundice
*etiology: inflammation disrupts hepatocytes and small bile ductules
*lab findings: increase in both conjugated and unconjugated bilirubin
*clinical features:
-dark urine due to increased urine bilirubin
-urine urobilinogen is normal or decreased
viral hepatitis
*inflammation of liver parenchyma
*usually due to hepatitis virus; other causes include EBV and CMV
*hepatitis virus causes acute hepatitis, which may progress to chronic hepatitis
acute hepatitis - clinical presentation
*jaundice (mixed conjugated & unconjugated bilirubin) with dark urine (due to CB)
*fever
*malaise
*nausea
*elevated liver enzymes (ALT > AST)
*sx last < 6 months
note - inflammation involves lobules of the liver and portal tracts and is characterized by apoptosis of hepatocytes
chronic hepatitis - clinical presentation
*symptoms last > 6 months
*inflammation predominantly involves portal tract
*risk of progression to cirrhosis
Hepatitis A (HAV) & Hepatitis E (HEV) - transmission
*fecal-oral transmission
-HAV is commonly acquired by travelers
-HEV is commonly acquired from contaminated water or undercooked seafood
Hepatitis A (HAV) & Hepatitis E (HEV) - additional info
*acute hepatitis; NO chronic state
*anti-virus IgM marks active infection
*anti-virus IgG is protective (its presence indicates prior infection or immunization - HAV)
*HEV infection in pregnant women is associated with FULMINANT HEPATITIS (liver failure with massive liver necrosis)
Hepatitis B (HBV) - transmission
*parenteral transmission (childbirth, unprotected intercourse, IV drug abuse)
Hepatitis B (HBV) - additional info
*results in acute hepatitis
*chronic disease occurs in 20% of cases
acute hepatitis B (HBV) labs
HBsAG: + (first serologic marker to rise)
HBeAG and HBV DNA: +
HBcAB: IgM
HBsAB: -
what is the key marker of infection in Hep B
HBsAG (hep B surface antigen)
-first serologic marker to rise in acute infection
-negative in resolved infections
-positive presence > 6 months defines chronic state
window phase of hepatitis B (HBV) labs
HBsAG: -
HBeAG and HBV DNA: -
HBcAB: IgM
HBsAB: -
resolved phase of hepatitis B (HBV) labs
HBsAG: -
HBeAG and HBV DNA: -
HBcAB: IgG
HBsAB: IgG (protective)
chronic phase of hepatitis B (HBV) labs
HBsAG: + (presence > 6 months defines chronic state)
HBeAG and HBV DNA: +/-; presence of HBeEg or HBV DNA indicates infectivity
HBcAB: IgG
HBsAB: -
labs for someone immunized against hepatitis B (HBV)
HBsAG: -
HBeAG and HBV DNA: -
HBcAB: -
HBsAB: IgG (protective)
Hepatitis C (HCV) - transmission
*parenteral transmission (IV drug use, unprotected intercourse, needle stick)
*risk from transfusion is almost nonexistent now, due to screening of the blood supply
Hepatitis C (HCV) - additional info
*results in acute hepatitis; chronic disease occurs in most cases
*HCV-RNA test confirms infection:
-decreased RNA levels indicate recovery
-persistence indicates chronic disease
Hepatitis D (HDV) - info
*dependent on HBV for infection
*SUPERINFECTION upon existing HBV is more severe than coinfection (infection with HBV & HDV at the same time)
cirrhosis
*end-stage liver damage
*characterized by disruption of normal hepatic parenchyma by bands of fibrosis and regenerative nodules of hepatocytes
*fibrosis is mediated by TGF-beta from stellate cells, which lie beneath the endothelial cells that line the sinusoids
cirrhosis - clinical features
- portal hypertension leads to:
-ascites (fluid in the peritoneal cavity)
-congestive splenomegaly/hepatomegaly
-portosystemic shunts (esophageal varices, hemorrhoids, and caput medusae)
-hepatorenal syndrome - decreased detoxification leads to:
-mental status changes, asterixis, and coma (due to increased ammonia)
-gynecomastia, spider angiomata, and palmar erythema (due to hyperestrinism)
-jaundice - decreased protein synthesis leads to:
-hypoalbuminema with edema
-coagulopathy (due to decreased synthesis of clotting factors)
alcohol-related liver disease
*damage to hepatic parenchyma due to consumption of alcohol
*most common cause of liver disease in the West
*3 common complications:
-fatty liver
-alcoholic hepatitis
-cirrhosis
alcohol-related liver disease & fatty liver
*fatty liver is the accumulation of fat in hepatocytes
*results in a heavy, greasy liver
*resolves with abstinence from alcohol
alcohol-related liver disease & alcoholic hepatitis
*chemical injury to hepatocytes
*generally seen with binge drinking
*acetylaldehyde (metabolite of alcohol) mediates damage
*characterized by swelling of hepatocytes with formation of Mallory bodies (damaged cytokeratin filaments), necrosis, and acute inflammation
*presents with PAINFUL hepatomegaly and elevated liver enzymes (AST > ALT)
*may result in death
alcohol-related liver disease & cirrhosis
*cirrhosis is a complication of long-term, chronic alcohol-induced liver damage
*occurs in 10-20% of alcoholics
non-alcoholic fatty liver disease
*fatty change, hepatitis, and/or cirrhosis that develops without exposure to alcohol or other known insult
*associated with obesity
*diagnosis of exclusion
*ALT > AST
hemochromatosis - overview
*excess body iron leading to deposition in tissues (hemosiderosis) and organ damage (hemochromatosis)
*tissue damage is mediated by generation of FREE RADICALS
primary hemochromatosis - etiology
*due to autosomal recessive defect in iron absorption
*due to mutation in HFE gene, usually C282Y mutation
note - secondary hemochromatosis is from chronic transfusions
hemochromatosis - clinical presentation
*presents in late adulthood
*classic triad = cirrhosis, secondary diabetes mellitus, & bronze skin
*other findings: dilated cardiomyopathy, cardiac arrhythmias, and gonadal dysfunction (due to testicular atrophy)
*increased risk of hepatocellular carcinoma
hemochromatosis - lab findings
*increased ferritin
*decreased TIBC
*increased serum iron
*increased percent saturation
hemochromatosis - biopsy
*liver biopsy reveals accumulation of brown pigment in hepatocytes
*Prussian blue stain distinguishes iron (blue) from lipofuscin
*lipofuscin in a brown pigment that is a by-product from the turnover of peroxidized lipids; commonly present in hepatocytes
hemochromatosis - treatment
phlebotomy (remove red cells, decreasing the iron load)
Wilson disease - etiology
*autosomal recessive defect (ATP7B gene) in ATP-mediated hepatocyte copper transport
*results in lack of copper transport into bile and lack of copper incorporation into ceruloplasmin
*copper builds up in hepatocytes, leaks int serum, and deposits in tissues
*copper-mediated production of hydroxyl free radicals leads to tissue damage
Wilson disease - clinical presentation
*presents in childhood with:
-cirrhosis
-neurologic manifestations (behavioral changes, dementia, chorea, and Parkinsonian sx due to deposition of copper in basal ganglia)
-Kayser-Fleisher rings in cornea
*increased risk of hepatocellular carcinoma
*labs show increased urinary copper, decreased serum ceruloplasmin, and increased copper on liver biopsy
*tx = D-penicillamine (chelates copper)
primary biliary cholangitis
*autoimmune granulomatous destruction of intrahepatic bile ducts
*classically arises in women (avg age of 40)
*associated with other autoimmune diseases
*etiology unknown; ANTIMITOCHONDRIAL ANTIBODY is present
*presents with features of obstructive jaundice
*cirrhosis is a late complication
*tx with ursodeoxycholic acid
primary sclerosing cholangitis
*inflammation and fibrosis of intrahepatic and extrahepatic bile ducts
*periductal fibrosis with an “onion-skin” appearance
*uninvolved regions are dilated, resulting in a “beaded” appearance on contrast imaging
*etiology unknown, but associated with ulcerative colitis; p-ANCA is often positive
*presents with obstructive jaundice (cirrhosis is a late complication)
*increased risk for cholangiocarcinoma
Reye syndrome
*fulminant liver failure and encephalopathy in children with viral illness who take ASPIRIN
*likely related to mitochondrial damage of hepatocytes
*presents with hypoglycemia, elevated liver enzymes, and nausea with vomiting
*may progress to coma & death
hepatic adenoma
*benign tumor of hepatocytes
*associated with oral contraceptive use; regresses upon cessation of drug
*risk of rupture, and intraperitoneal hemorrhage, especially during pregnancy (tumors are subcapsular and grow with exposure to estrogen)
hepatocellular carcinoma - risk factors
*chronic hepatitis (e.g. HBV and HCV)
*cirrhosis (alcohol, non-alcoholic fatty liver disease, etc)
*aflatoxins derived from Aspergillus (induce p53 mutations)
hepatocellular carcinoma
*malignant tumor of hepatocytes
*often detected late because symptoms are masked by cirrhosis; poor prognosis
*serum tumor marker = alpha-fetoprotein
hepatocellular carcinoma & Budd-Chiari
*increased risk for Budd-Chiari syndrome:
-liver infarction secondary to hepatic vein obstruction
-presents with painful hepatomegaly and ascites
metastasis to liver
*more common than primary tumors
*most common sources include colon, pancreas, lung, and breast carcinomas
*results in multiple nodules in the liver
*clinically may be detected as hepatomegaly with a nodular free edge of the liver
