Liver/Pancreatic Diseases Flashcards
Jaundice of the newborn
Newborn liver has transiently low Uridine glucuronyl transferase activity
Increased unconjugated bilirubin
Can deposti in basal ganglia leading to neurological deficits and death
Treatment is phototherapy (makes UCB more water soluble)
Gilbert syndrome
Mildly low uridine glucoronyl transferase
Decreased bilirubin uptake by hepatocytes
Increased Unconjugated bilirubin
Asymptomatic or mild jaundice
Increases during stress
Crigler Najjar Syndrome
Absence of Uridine glucoronyl transferase
Presents early in life, patients die within a few years
Increased unconjugated bilirubin
Kernicterus is fatal
Treatment: plasmapheresis and phototherapy
TypeII responds to phenoarbital which increases liver enzyme synthesis
Dubin Johnson syndrome
Deficiency of bilirubin canalicular transport protein defective liver excretion
Autosomal recessive
Increase conjugated bilirubin
Dark liver
Dense pigment composed of epinephrine
Icterus during stress or oral contraceptive use
Increased urinary coproporphyrin
(Rotor syndrome similar without liver discoloration)
Biliary tract obstruction
Assoicated with gallstones, pancreatic carcinoma, cholangocarcinoma, parasites, and liver fluke
Increased conjugated bilirubin
Decreased urine urobilinogen and increased alkaline phosphatase
Clinical: dark urine and pale stool
Pruititis due to increased plasma bile acids
Hypercholesteronlemia with xanthomas
Steatoorrhea with malabsorption of fat soluble vitamins
Extravascular hemolysis
High levels of unconjugated bilirubin overwhelms the conjugating ability of the liver
Increased unconjugated bilirubin
Clinical: dark urine due to increase urine urobillinogen
Increased risk for pigmented bilirubin gallstones
Cirrhosis
Chronic hepatitis leads to continued loss of hepatocytes and fibrosis
Primary Causes: alcohol abuse, viral hepatitis, and non-alcoholic steatohepatitis, biliary disease and iron overload
Histology: bridging fibrous septa form scars that link portal tracts with one another and with terminal hepatic veins
Parenchymal nodules containing heptocytes encircled by fibrosis -from cycles of hepatocyte regeneration and scarring
Collagen Types I and III deposited in space of Disse creating fibrotic septal tracts and loss of fenestrations of sinusoidal endothelial cells impairing their function
Vascular architecture is disrupted by the parenchymal damage
Fibrosis mediated by TGF B from stellate cells
Leads to portal hypertension, asterixis, mental status changes, gynecomastia, spider angiomata, jaundice, hypoalbunemia, coagluopathy
Portal Hypertension
Increased resistance to portal blood flow (cirrhosis) at level of the sinusoids
Leads to
Ascites, congestive splenomegaly, hepatic encephalopathy
Esophageal varices: Left gastric to esophageal shunt
Caput medusa: paraumbilical to small epigastric veins of he anterior abdominal wall shunt
Anorectal varices: superior rectal to middle and inferior rectal shunt
Hepatic Steatosis related to alcholic liver disease
Excessive alcohol consumption lading cause of liver disease in Western Countries
3 phases:
1. hepatic steatosis
even after moderate intake of alcohol, microvesicular lipid droplets accumulate in hepatocytes
Chronic intake lipid accumulates creating large clear macrovesicular globules that displace hepatocyte nucleus to periphery
Fatty liver is large soft organ that is yellow and greasy -hepatomegaly
substrates toward lipid synthesis leads to excess NADH, impaired lipoproteins leading to increased peripheral catabolism of fat
mild elevation of serum bilirubin and alkaline phosphatase
alcoholic hepatitis
alcoholic hepatitis-mediated by acetylaldehyde
or ROS by cytochrome P450 metabolism
impaired metabolism of methionine leads to decreased glutathione levels
induction of CYP2E1 and other cytochrome p450 enzymes
hepatocyte swelling and necrosis
Mallory bodies-scattered hepatocytes accumulate tangled cytokeratin intermediate filaments in complex with other proteins, eosinophilic (ubiquitin)
Neutrophilic reaction (recently drank)
Fibrosis by stellate cells
Nonspecific symptoms: malaise, anorexia, weight loss, upper abdominal discomfort, tender hepatomegaly
Hyperbilirubinemia, elevated alkaline phosphatase, and neutrophilic leukocytosis
may clear slowly after total cessation of alcohol consumption and proper nutrition
AST>ALT
Alcoholic cirrhosis
Final and irreversible
Evolves slowly but can develop in 1 or 2 years
First yellow-tan, fatty, enlarged liver becomes brown, shrunken, nonfatty organ
More prominent micronodularity
Bile stasis develops
Sclerosis around central vein
Elavated serum amnotransferase, hyperbilrubinemia, possible elevation of alkaline phosphatase, hypoproteinemia, and anemia
Increased Prothrombin time, hypoalbuminemia
Nonalocoholic Fatty liver disease
Hepatic steatosis with little alcohol use
Accompanied by non-specific inflammation and non alcoholic steatohepatitis (may progress to hepatitis)
liver biopsy for reliable diagnostic tool
Hepatocyte ballooning, lobular inflammation and steatosis with progressive fibrosis, mallory bodies
Strongly correlated with obesity, dyslipidemia, hyperinsulienemia and insulin resistance
ALT> AST (as opposed to alcholic liver disease where AST>ALT)
Autoimmune hepatitis
Chronic and progressive
May be triggerd by viral infections or certain drugs
Concurrent with other autoimmune disorders
Common in young and premenopausal women
Type I: ANA, anti-smooth muscle, anti-actin, anti-soluble liver Ag/liver-pancreas Ag Abs
type II: anti-liver kidney microsome-1 Abs
Anti-liver cytosol-1
Prominent inflammatory infiltrates of lymphocytes and plasma cells
High mortality and cirrhosis chances
Treat with prednisone or azathioprine or liver transplantation
Primary Bilary Cirrhosis
Middle aged women
Onset is insidious but presents with fatigue
Symptoms: pruritus, jaundice, dark urine, light stools, hepatosplenomegaly
Alkaline phosphatase and cholesterol are always elevated
Hyperbilrubinemia is late development (conjugated)
Antimitochondrial Abs
inflammmatory autoimmune disease causing granulomatous destruction of intrahepatic bile ducts
Dense accumulation of lymphocytes, macrophages plasma cells, and eosinophils
bile stasis turns liver green
Progresses to micronodular cirrhosis
Primary Sclerosing Cholangitis
Chronic cholestatic disorder characterized by inflammation, fibrosis and strictures of intra and extrahepatic bile ducts
periductal fibrosis with an onion-skin appearance
Injury to bile ducts
Anti-nuclear Abs, rhematoid factor, and p-ANCA
persistant elevation of alkaline phosphatase
increased conjugated bilirubin
Symptoms: progressive fatigue, pruritus and jaundice
Beading of bile ducts in contrast medium-ERCP is gold standard
Seen with ulcerative colitis and hypergammaglobulinemia (IgM)
Presents with obstructive jaundice
cirrhosis is late complication
Increased risk for cholangiocarcinoma
