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
alpha 1 antitrypsin deficiency
AR
Synthesized by hepatocytes
inhibits proteases
Misfolded gene product protein aggregate in hepatocellular ER leading to cirrhosis
PAS+ (acid Schiff) globules in liver
Pulmonary panacinar emphysema and liver disease
Hepatomegaly, cholecystitis, increased hepatocellular enzymes, neonatal hepatitis and jaundice is common
Dyspnea and flattened diaphragm
Can lead to cirrhosis and hepatocellular carcinoma
Hemachromatosis
Excessive accumulation of body iron
Homozygous recessive disorder leading to excessive iron absorption
mutations of HFE (cysteine to tyrosine)
More often disease of males
Not iron excretion from body
Classic triad: pigment cirrhosis with hepatomegaly, skin pigmentation, and diabetes mellitus)
Also can have dilated cardiomyopathy, cardiac arrhythmias, and gonadal dysfunction
labs: increased ferritin, decreased TIBC, increased serum iron, increased iron saturation
Prussian blue stain distinguishes iron from lipofuscin (blue)
Tissue damage by generation of free radicals
Increased risk of hepatocellular carcinoma
Treatment is phlebotomy
Wilson Disease
AR in ATP mediated hepatocyte copper transport
Results in lack of copper transport into bile and lack of copper incorporation into ceruloplasmin
Copper leaks into serum and deposits in tissues
Presents in childhood with: Cirrhosis Neurologic manifestation (behavioral changes, dementia, chorea and parkinsonian symptoms due to copper deposition in basal ganglia) Kayser-Fleisher rings in the cornea Hemolytic anemia
Labs show: increased urinary copper, decreased serum ceruloplasmin and increased copper on liver biopsy
Increased risk of hepatocellular carcinoma
Treatment: D-penicillammine or trientine (chelates copper)
Hepatic encephalopathy
Presents with abdominal distension, decreased liver span, testicular atrophy and flapping tremor
Cirrhosis leads to portosystemic shunts and decreased NH3 metabolism
Triggers:
increased NH3 production (dietarry protein, GI bleed, constipation, infection)
Decreased NH3 removal (renal failure, diuretics, post-TIPS)
NH3 affects atrocytes and neurons
Astrocytes regulate metabolism of glutamate, glutamine, and ammonia
Glutamate taken up by neurons and converted to glutamine for NTs or a-ketoglutarate
Increased glutamine leads to hyperosmolarityy and mitochondrial dysfunction
Increased GABA
Treatment: lactulosse (incrasease NH4 generation), low protein diet, and rifaximin (kills intestinal bacteria)
Acute Pancreatitis
Inflammation and hemorrhage of the pancreas
Due to autodigestion of pancreatic parenchyma by pancreatic enzymes
Results in liquefactive hemorrhagic necrosis of pancreas
Most commonly due to alcohol or gallstones
Ethanol causes secretions that are prone to form plugs that obstruct lumen, causes spasm of sphincter of Oddi and direct toxic effect on acinar cells
other causes: trauma, hypercalcemia, hyperlipidemia, drugs (azothioprine, sulfasalzine, furosemide, valproic acid), scorpion stings, mumps, and rupture of duodenal ulcer
Clinical: epigastric abdominal pain that radiates to back, nausea and vomiting, periumblical and flank hemorrhage, elevated serum lipase and amylase (lipase more specific), hypocalcemia (Ca collects in fat necrosis soap products
Complications: shock, pancreatic pseudocyst, pancreatic abscess, DIC, ARDS
pancreatic pseudocyst
Created in acute pancreatitis
Due to preoteolytic enzymes disrupting the wall of pancreatic ducts causing leakage of pancreatic secretions into the peri pancreatic space
Induces inflammation leading to granulation tissue `
Chronic Pancreatitis
Fibrosis of pancreatic parenchyma secondary to recurrent acute pancreatitis
Most commonly due to alcohol, and cystic fibrosis
Clinical:
Epigastric abdominal pain that radiates to back
pancreatic insufficiency-malabsorption with steatorrhea and fat soluble vitamin deficiencies
Dystrophic calcification of pancreatic parenchyma on imaging
dilations of pancreatic ducts seen on imaging
Late diabetes mellitus
Increased risk for pancreatic carcinoma
Reye Syndrome
Fatal childhood hepatoencephalopathy
Findings: mitochondrial abnormalities, fatty liver (microvesicular fatty change), hypoglycemia, vomiting, hepatomegaly, coma
Associated with viral infection (especially VZV and influenza B) that has been treated with aspirin
mechanism: aspirin metabolites lead to decreased B oxidation by reversible inhibition of mitochondrial enzyme
Liver: increased ALT, AST, ammonia, bilirubin, prolonged PT and PTT
swelling, decreased mitochondria and glycogen depletion on EM
Avoid aspirin in children, except with Kawasaki disease
Budd Chiari Syndrome
Occlusion of IVC or hepatic veins with centrilobular congestion and necrosis leading to congestive liver disease (hepatomegaly, ascites, abdominal pain, and eventual liver failure)
May develop varices and have visible abdominal and back veins
Absence of JVD
Associated with hypercoagulable states, polycythemia vera, pregnancy, and HCC
Secondary biliary cirrhosis
Extrahepatic biliary obstruction (gallstone, biliary stricture, chronic pancreatitis, carcinoma of pancreatic head) leads to increased pressure in intrahepatic ducts leading to injury/fibrosis and bile stasis
Presentation: pruritus, jaundice, dark urine, light stools, hepatosplenomegaly
Labs: increased conjugated bilirubin, cholesterol and increased ALP
Gallstones (Cholelithiasis)-Cholesterol
Increased cholesterol or bilirubin/decreased bile salts/ gallbladder stasis
Biliary sludge is common precursor
Cholesterol to bile acids uses rate limiting step with 7a-hydroxylase
Radiolucent (do no appear on X-ray)
80% of stones
Associated with obesity, crohn disease, cystic fibrosis, advanced age, clofibrate, cystic fibrosis, advanced age, estrogen therapy (increases HMG-CoA reductase), multiparity, rapid weight loss, Native American, fibrates, ocreotride, ceftriaxone, total parental nutrition
Fibrates block 7a-hydroxylase leading to low bile acid synthesis
Biliary sludge is common precursor: slow or incomplete emptying of gall bladder follwoing CCK stimulation
Results from bile precipitation contain cholesterol crystals, calcium and mucus
Cause cholecysitis, ascending cholangitis, acute pancreatitis and bile statis
Can lead to bilary colic and fistual between gallbladder and small intestine
Diagnose with ultrasound
Gallstones (chollithiasis)-pigment
Increased cholesterol or bilirubin/decreased bile salts/ gallbladder stasis
Biliary sludge is common precursor
Cholesterol to bile acids uses rate limiting step with 7a-hydroxylase
Cause cholecysitis, ascending cholangitis, acute pancreatitis and bile statis
Radipaque (seen on Xray)-black color
Common in asia, elderly and women
Seen in chronic hemolysis (sickle cell, B-thalassemia, spherocytosis), alcoholic cirrhosis, advanced age, and biliary infection (E. coli, liver fluke, opisthoschis sinensis, ascaris lumbricoides)
increase in unconjugated bilirubin
Can lead to bilary colic and fistual between gallbladder and small intestine
Bilary Colic
Neurohormonal acttivaton (CCK)
Triggers contraction of gallbladder forcing a stone into the cystic duct
May present without pain in diabetes
Due to morphine:(not meperdine)
causes contraction of smooth muscle in sphincter of Oddi leading to increased pressure
Severe pain and cramping in R. upper abdomen
Jaundice
use NSAIDS for pain control instead
Gallstone ileus
Patient with long standing gallstones
A large gallstone causes formation of cholecsytenteric fistula between gallbladder and gut tissue
gas enters gallbladder and biliary tree
gallstone travels to ileocecal valve leading to abdominal pain, tenderness, and tinkling bowel sounds, vomiting, distention, waxing and waning
Ultrasound to confirm
Cholecystitis
Acute or chronic inflammation of gallbladder
Edematous and enlarged gallbladder on ultrasound
Usually from cholelithiasis blocking cystic duct leading to secondary infection, rarely ischemia or primary infection (CMV)
stones disrupt protective layer leaving epithelium exposed to detergent action of bile salts
Positive Murphy sign-inspiratory arrest on RUQ palpation due to pain
Increased ALP if bile duct becomes involved
Complications: gangrene, perforation, with formation of pencholecystic abscess or peritonitis
Treatment: broad spectrum antibiotics
Diagnose with ultrasound or HIDA (gallbladder not visualized)
Porcelain gallbladder
Calcified gallbladder due to chronic cholecystitis
Found incidentally on imaging
Treatment: prophylactic cholecystectomy due to high rates of gallbaldder carcinoma
Biliary atresia
obliteration of extrahepatic and/or intrahepatic ducts
ducts replaced by fibrotic tissue due to acute or chronic inflammation
Clinical: progressive neonatal jaundice, white stool, dark urine
100% mortality
Hepatitis D
RNA delta virus
Transmission: parenteral, sexual, maternal-fecal
Yes Carrier
Incubation: superinfection (HDV after HBV) short
Co-infection (HDV with HBV) long
High HCC risk
Dependent on Hep B to encapsulate it
Superinfection has decreased prognosis
Heptatis E
RNA hepevirus
uneveloped
Diagnosis: HEV RNA or Ag found in stool
Transmission: fecal oral especially with waterborne epdemics
No carrier
Short incubation
No HCC risk
High mortality in pregnant women
Pregnancy and Gallstones
estrogen upregulates HMG-CoA reductase leading to bile becoming supersaturated with cholisterol
Progesterone reduces bile acid secretion and slows gallbladder emptying (hypomotility)
