Liver Diseases 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
- protoporphorin from heme is converted to unconjugated bilirubin –> carried by albumin to the liver
- Uridine glucuronyl transferase in hepatotcytes conjugates bilirubin
- conjugated bilirubin is transferred to bile canaliculi to form bile –> stored in gall bladder
- bile is released into the small bowel to aid in digestion
- intestinal flora convert conjugated bilirubin to urobilinogen
- urobilinogen is oxidized to stercobilin (makes stool brown) and urobilin (partially reabsorbed into blood and filtered by kidney, making urine yellow)
Causes of jaundice
- Extravascular hemolysis
- Ineffective erythropoiesis
- Physiologic jaundice of the newborn
- Gilbert Syndrome
- Crigler-Najjar syndrome
- Dubin Johnson syndrome
- Biliary tract obstruction
- Viral hepatitis
Extravascular hemolysis or ineffective erythropoiesis
High levels of UCB overwhelm the conjugating ability of the liver
- increased UCB
Clinical features
- Dark urine due to increased unrine urobilinogen –> UCB is not water soluble and thus is absent from urine
- increased risk for pigmented bilirubin gallstones
Physiologic jaundice of the newborn
Newborn liver has transiently low UGT activity
- increased UCB
Clinical features
- UCB is fat soluble and can deposit in the basal ganglia = kernicterus –> leads to neurological deficits and death
Treatment –> phototherapy = makes UCB water soluble
Gilbert syndrome
Mildly low UGT activity
- autosomal recessive
- increased UCB
Clinical features
- jaundice during stress (e.g. severe infection), otherwise not clinically significant
Crigler-Najjar syndrome
Absence of UGT
- increased UCB
Clinical features
- Kernicterus
- usually fatal
Dubin-Johnson Syndrome
Deficiency of bilirubin canalicular transport protein
- autosomal recessive
- increased CB
Clinical features
- liver is dark, otherwise not clinically significant
Rotor syndrome –> similar but lacks liver discoloration
Biliary tract obstruction
Associated with gallstones, pancreatic carcinoma, cholangiocarcinoma, parasites and liver fluke
- increased CB
- decreased urobilinogen
- increased alk 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
Inflammation disrupts hepatocytes and small bile ductules
- increased UCB and CB
Clinical features
- dark urine due to increased urine bilirubin
- urine urobilinogen is normal or decreased
Basic principles of viral hepatitis
Inflammation of liver parenchyma, usually due to hepatitis virus –> other causes include EBV + CMV
- hepatitis virus causes acute hepatitis, which may progress to chronic hepatitis
Acute hepatitis presents as jaundice (mixed CB + UCB) with dark urine (due to CB), fever, malaise, nausea, and elevated liver enzymes (ALT>AST)
- inflammation involves lobules of the liver and portal tracts and is characterized by apoptosis of hepatocytes
- some cases may be asymptomatic with elevated liver enzymes
- symptoms last 6 months
- inflammation predominantly involves portal tract
- risk of progression to cirrhosis
HepA + HepE
Fecal oral transmission
- HAV is commonly acquired by travelers
- HEV is commonly acquired from contaminated water or undercooked seafood
- acute hepatitis –> no chronic state
- Anti-virus IgM marks active infection
- Anti virus IgG is protective, and its presence indicates prior infection or immunization (available for HepA)
- HEV infection in pregnant women is associated with fulminant hepatitis = liver failure with massive liver necrosis
HepB
Parenteral transmission
Results in acute hepatitis –> chronic disease occurs in 20% of cases
HepC
Parenteral tranmission
Results in acute hepatitis, chronic disease occurs in most cases
- HCV-RNA test confirms infection
- decreased RNA levels indicate recovery
- persistence indicates chronic disease
HepD
Dependent on HBV for infection
- superinfection upon existing HBV is more severe than coinfection = infection with HBV and HDV at same time
Cirrhosis
End stage liver damage characterized by disruption of the normal hepatic parenchyma by bands of fibrosis and regenerative nodules of hepatocytes
- fibrosis is mediated by TGF B from stellate cells –> lie beneath the endothelial cells that line the sinusoids
Clinical features of cirrhosis
Portal hypertension leads to
- ascites –> fluid in the peritoneal cavity
- congestive splenomegaly/hypersplenism
- portosystemic shunts –> esophageal varices, hemorrhoids, and caput medusae
- hepatorenal syndrome = rapidly developing renal failure secondary to cirrhosis
Decreased detoxification results in
- mental status changes, asterixis, and eventual come due to increased serum ammonia –> metabolic, so reversible
- gynecomastia, spider angiomata, and palmar erythema due to hyperestrinism
- jaundice
Decreased protein synthesis leads to
- hypoalbuminemia with edema
- coagulopathy due to decreased synthesis of clotting factors –> degree of deficiency is followed by PT
Alcohol related liver disease
Damage to hepatic parenchyma due to consumption of alcohol
- most common cause of liver disease in the west
Fatty liver = accumulation of fat in hepatocytes –> results in a heavy, greasy liver; resolves with abstinence
Alcoholic hepatitis results from chemical injury to hepatocytes –> generally seen with binge drinking
- acetaldehyde mediates damage = metabolite of alcohol
- 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
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 develop without exposure to alcohol or other known insult
- associated with obesity
- diagnosis of exclusion
- ALT > AST
Hemochromatosis
Excess body iron leading to deposition in tissues (hemosiderosis) and organ damage (hemochromatosis)
- tissue damage is mediated by generation of free radicals
Due to autosomal recessive defect in iron absorption (primary) or chronic transfusions (secondary)
- primary hemochromatosis is due to mutations in the HFE gene, usually C282Y –> cysteine is replaced by tyrosine at amino acid 282
Clinical features and tx of hemochromatosis
Presents in late adulthood
- classic triad = cirrhosis, secondary diabetes mellitus and bronze skin
- other findings = dilated cardiomyopathy, cardiac arrhythmias and gonadal dysfunction due to testicular atrophy
Increased risk of hepatocellular carcinoma
Tx –> phlebotomy
Diagnosis of hemochromatosis
Labs show increased ferritin, decreased TIBC, increased serum iron and increased % sat (iron overloaded state)
Liver biopsy reveals accumulation of brown pigment in hepatocytes
- prussian blue stain distinguishes iron (blue) from lipofuscin –> brown pigment that is a by product from the turnover (“wear and tear”) of peroxidized lipids –> commonly present in hepatocytes
Wilson disease
Autosomal recessive defect in ATP-mediated hepatocyte copper transport in ATP7B gene
- results in lack of copper transport into bile and lack of copper incorporation into ceruloplasmin
- copper builds up in hepatocytes, leaks into serum, and deposits in tissues
- copper mediated production of hydroxyl free radicals leads to tissue damage
Clinical features, labs and tx of Wilsons disease
Presents in childhood with…
- cirrhosis
- neurologic manifestations –> behavioral changes, dementia, chorea, and parkinsonian symptoms due to deposition of copper in basal ganglia
- kayser-fleisher rings in the 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 cirrhosis
Autoimmune granulomatous destruction of intrahepatic bile ducts
- classically arises in women (avg age 40 years)
- associated with other autoimmune diseases
Etiology is unknown
- antimitochondrial antibody is present
Presents with features of obstructive jaundice
- cirrhosis is a late complication
Primary sclerosing cholangitis
Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts
- periductal fibrosis with an onion skin appearance
- uninvolved regions are dilated –> results in a “beaded” appearance on contrast imaging
Etiology is unknown, but associated with ulcerative collitis
- p-ANCA 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
- nausea with vomiting
- may progress to coma and death
Hepatic adenoma
Benign tumor of hepatocytes
Associated with oral contraceptive use –> regresses upon cessation of drug
Risk of rupture and intraperitoneal bleeding, especially during pregnancy
- tumors are subcapsular and grow with exposure to estrogen
Hepatocellular carcinoma
Malignant tumor of hepatocytes
Risk factors
- chronic hepatitis
- cirrhosis –> alcohol, nonalcoholic fatty liver disease, hemochromatosis, wilson disease, and A1AT deficiency
- aflatoxins –> derived from aspergillus (induce p53 mutations)
Increased risk for budd-chiari syndrome
- liver infarction secondary to hepatic vein obstruction
- presents with painful hepatomegaly and ascites
Tumors are often detected late because symptoms are masked by cirrhosis –> poor prognosis
Serum tumor marker is alpha fetoprotein
Metastasis to liver
More common than primary liver 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
