Chapter 14: The Liver, Biliary System, Flashcards
End stage liver damage
Diffuse bands of fibrosis and nodular regeneration destroys normal architecture of liver
Fibrosis is mediated by what?
Increased risk of hepatocellular carcinoma (HCC)
60-70% due to EtOH, or viral hepatitis, biliary disease, hemochromatosis
Portosystemic shunts partially alleviate portal HTN: esophageal varices, caput medusae, hemorrhoids
Cirrhosis
TGF-beta from stellate cells underneath the endothelial cells lining sinusoids mediate fibrosis
Results of what cause the following? Esophageal varices (=> hematemesis) Peptic ulcer (BOTH cause Melena) Splenomegaly Caput medusae Ascites Anorectal varices (=> hemorrhoids)
Effects of portal HTN
Results of what cause the following? Hepatic encephalopathy Scleral icterus Jaundice Fetor Hepaticus (breath smells musty) Liver flap = asterixis (coarse hand tremor) bleeding tendency (indecreased clotting factors, increased prothrombin time) anemia ankle edema Spider nevi Gynecomastia Testicular atrophy
Effects of liver cell failure
The last 3 are due to hyperestrogenism since damaged liver no longer breaks down estrogen
What does liver cirrhosis look like on CT? Histology?
CT = nodularity of liver contour secondary to regenerating macronodules Histology = regenerative nodules and bridging fibrosis
Decreased ceruloplasmin is seen in?
Wilson disease
Increased alk phos is seen in?
Obstructive hepatobiliary disease, hepatocellular carcinoma, bone disease
If ALT > AST?
viral hepatitis
If AST >ALT?
Alcoholic hepatitis
IF increased amylase?
acute pancreatitis or mumps
If increased gamma-glutamyl transpeptidase (GGT)?
Increased in various liver and biliary disease (like ALT)
BUT NOT INCREASED in bone disease
Associated with EtOH use
Increase lipase?
Acute pancreatitis (Most Specific)
Fulminant liver failure and encephalopathy in children with viral illness (which ones?) who take aspirin
Likely related to mitochondrial damage of hepatocytes
Mech: aspirin metabolites decrease beta-oxidation by reversible inhibition of mitochondrial enzyme
WHEN IS THE ONLY TIME A CHILD SHOULD GET ASPIRIN?
S/S: hypoglycemia, elevated liver enzymes, fatty liver, hepatomegaly and nausea w/vomiting, may progress to coma/death
Reye Syndrome
Viruses: VZV, influenza B
Kawasaki disease
Reversible change with moderate alcohol intake
Macrovesicular fatty change that may be reversible with EtOH cessation
Accumulation of fat in hepatocytes
Alcoholic liver disease:
hepatic steatosis or fatty liver
Requires sustained, long term EtOH consumption
Chemical injury to hepatocytes due to acetaldehyde
Swollen and necrotic hepatocytes w/neutrophilic infiltration
Mallory bodies (damaged cytokeratin filaments, eosinophilic inclusions)
S/S: painful hepatomegaly and liver enzymes?
Seen with binge drinkers
EtOH hepatitis
Increased AST > ALT (ratio > 1.5)
Final and irreversible
long term complication of chronic EtOH induced liver damage
Micronodular
Irregularly shrunken liver with “hobnail” appearance
Sclerosis around central vein (zone 3)
jaundice, hypoalbuminemia
EtOH cirrhosis
Metabolic syndrome (insulin resistance, obesity) => fatty infiltration of hepatocytes => cellular ballooning and eventual necrosis
May cause cirrhosis and HCC
Independent of EtOH use, diagnosis of exclusion
Liver enzymes?
Non-alcoholic fatty liver disease
Increased ALT > AST (L=lipids)
Cirrhosis => portosystemic shunts => decreased NH3 metabolism => neuropsychiatric dysfxn
Spectrum:
Disorientation/mild asterixis to difficult arousal or coma (severe).
Triggers:
Increase NH3 production (due to dietary protein, GI bleed, constipation, infection)
Decreased NH3 removal (due to renal failure, diuretics, post-TIPS)
Treatment?
Hepatic encephalopathy
Treat: lactulose (increases NH4+ generation), low protein diet, and rifaximin kills intestinal bacteria
Most common primary malignant tumor of the liver in adults
Associated with Hepatitis B and C, Wilson disease, hemochromatosis, alpha1-antitrypsin deficiency, alcoholic cirrhosis, and carcinogens (aflatoxin from Aspergillus induces p53 mutation)
May lead to Budd-Chiari syndrome
Findings: Jaundice, tender hepatomegaly, ascites, and anorexia, spreads hematogenously
Diagnosis: Increased alpha-fetoprotein, ultrasound or contrast CT
Hepatocellular carcinoma
Occlusion of IVC or hepatic veins w/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
Budd-Chiari Syndrome
Common, benign liver tumor; typically occurs at age 30-50 years. Biopsy contraindicated because risk of hemorrhage
Cavernous hemangioma
Rare, benign liver tumor
Subcapsular and grow with estrogen
Associated with oral contraceptive use or anabolic steroid use
Regress upon cessation of drug or could rupture spontaneously and have intraperitoneal bleeding
Hepatic adenoma
Malignant tumor of endothelial orgin
Associated with exposure to arsenic, vinyl chloride
Angoisarcoma
Result of backup of blood into liver
Commonly caused by R. sided heart failure and Budd-Chiari syndrome
Liver appears mottled
If condition persists: centrilobular congestion and necrosis can result in cardiac cirrhosis
Nutmeg liver
Misfolded gene product protein aggregates in hepatocellular ER => cirrhosis with PAS + globules in liver. Codominant trait.
In lung, decrease in this protein => uninhibited elastase in alveoli => decreased elastic tissue => panacinar emphysema
Alpha1-antitrypsin deficiency
Earliest sign involves sclera
High serum bilirubin at what level causes symptom?
Occurs 2ndary to increased production of bilirubin or defective metabolism
Jaundice
Bilirubin > 2.5 mg/dL
Where and what conjugates bilirubin?
What is urobilinogen all about? What happens to urobilinogen?
The liver
Uridine glucuronyl transferase
Intestinal flora turns Conjugated bilirubin to urobilinogen. Urobilinogen is oxidized to stercobilin (makes stool brown) and urobilin (makes urine yellow)
What diseases could cause unconjugated (indirect) hyperbilirubinemia? What would be in the urine?
Hemolytic, physiologic (newborns), Crigler-Najjar, Gilbert syndrome
Increased urine urobilinogen
What disease could cause conjugated (direct) hyperbilirubinemia? What would be in the urine?
Biliary tract obstruction: gallstones, pancreatic liver cancer, liver fluke
Biliary tract disease: Primary sclerosing cholangitis, Primary biliary cirrhosis
Excretion defect: Dubin-Johnson syndrome, Rotor syndrome
Decreased urine urobilinogen
What diseases could cause mixed (indirect + direct) hyperbilirubinemia? What would be in the urine?
Hepatitis, cirrhosis
Normal or increased urine urobilinogen
At birth, immature UDP-glucuronosyltransferase => unconjugated hyperbilirubinemia => jaundice/kernicterus (kernicterus involves severe mental defects etc)
Physiologic neonatal jaundice
AR disease
Mildly decreased UDP-glucuronosyltransferase conjugation activity => decreased bilirubin uptake by hepatocytes.
Asymptomatic (No jaundice) or mild jaundice
Elevated UCB (unconj bilirubin)
Jaundice during stress (severe infection) otherwise clinically insignificant, common
Gilbert Syndrome
Absent UDP-glucuronosyltransferase
Presents early in life; patients die within a few years
Jaundice, kernicterus (bilirubin deposition in the brain)
Very high UCB
Treatment?
Crigler-Najjar syndrome
(Type 2 less severe: responds to phenobarbital which increase liver enzyme synthesis)
Plasmapheresis and phototherapy
Deficiency of bilirubin canalicular transport protein to excrete
AR disease
Increased conjugated bilirubin
Liver is grossly black, otherwise benign
Dubin-Johnson syndrome
Conjugated hyperbilirubinemia due to defective liver excretion but VERY mild
NO grossly black liver
Rotor syndrome
AR disease
Defect of ATP7B gene chrom 13 in ATP-mediated copper transport
Inadequate hepatic copper excretion in bile and failure of copper to enter circulation as ceruloplasmin
Copper accumulation: liver, brain, joints, kidneys, cornea (Kayser-Fleischer ring)
Wilson Disease
Presents in childhood: cirrhosis, neurologic (behavioral changes, dementia, chorea, and Parkinsonian symptoms), Brown ring around cornea
Remember: Copper is Hella BAD
Wilson Disease
decreased Ceruloplasmin, Cirrhosis, Corneal deposits, Copper accumulation, Carcinoma (HCC)
Hemolytic anemia
Basal ganglia degeneration (Parkinsonism)
Asterixis
Dementia, Dyskinesia, Dysarthria
Excess body iron leading to deposition in tissues (hemosiderosis) and organ damage (______)
Tissue damage mediated by free radicals (Co can go in Fenton Rxn)
AR disease: defect in Fe absorption b/c HFE gene mutation (C282Y), associated with HLA-A3
OR chronic transfusions
Hemochromatosis
Classic triad presents in late adulthood
Cirrhosis
Diabetes Mellitus and Bronze skin (bronze diabetes)
Other: CHF (dilated cardiomyopathy), cardiac arrhythmias and gonadal dysfxn due to testicular atrophy
Increased risk of HCC
Treatment?
Hemachromatosis
If hereditary: repeated phlebotomy, deferasiroz, deferoxamine
Liver biopsy shows accumulation of brown pigment in hepatocytes
Why must you use Prussian blue stain?
Labs: Increased ferritin, Decreased TIBC, increased serum iron, and increased % transferrin saturation
Hemachromatosis
Prussian blue stain distinguises iron (blue) from lipofuscin
Extrahepatic biliary obstruction
Due to gallstone, biliary stricture, chronic pancreatitis, carcinoma of the pancreatic head, cholangiocarcinoma, parasites, liver fluke (Clonorchis sinensis), complicated by ascending cholangitis
Increased pressure in intrahepatic ducts => injury/fibrosis and bile stasis
S/S: pruritius, jaundice, dark urine, pale stool, hepatosplenomegaly, xanthomas, steatorrhea
Increased conjugated bilirubin, increased cholesterol, increased Alk phos, decreased urine urobilinogen
Secondary Biliary Cirrhosis
aka Biliary tract obstruction, obstructive jaundice
Autoimmune rxn => lymphocytic infiltrate => + granulomas => destruction of intralobular bile ducts
Associated with CREST, SjoS, RA, Celiac
Antimitochondrial Antibody
Presents with obstructive jaundice features, Increased conj bilirubin, cirrhosis a late complication
Classic in women 40 y
Primary biliary cirrhosis
Unknown cause of concentric “onion skin” bile duct fibrosis => alternating strictures and dilation with “beading”of intra-and extra hepatic bile ducts on contrast imaging
Associated with ulcerative colitis
p-ANCA positive
Increased risk of 2ndary biliary cirrhosis and cholangiocarcinoma
Primary sclerosing cholangitis
Stones in the gallbladder
Radiolucent = don’t show up on x-ray
10% can be radiopaque (why?)
Risk factors: Female, fat, fertile (pregnant), forty
(estrogen increases cholesterol uptake, clofibrate (increase HMGCoA reductase which increases cholesterol syn and decrease bile acids), Native American, Crohn disease (terminal ileum damage decreased bile salt/acid uptake), cirrhosis (decreased bile salts)
Cholesterol stones (cholelithiasis) Yellow grossly
Pigment stones in gallbladder
1) Radiopaque type (color?) = can be seen on x-ray
2) Radiolucent type (color?)
Risk factors: extravascular hemolysis (1) and biliary tract infections (2), alcoholic cirrhosis, advanced age
Cholelithiasis
1) black
2) brown
Most common complications of cholelithiasis
Usually asymptomatic
Comp: biliary colic, acute and chronic cholecystitis, ascending cholangitis, gallstone ileus, gall bladder cancer, bile stasis, acute pancreatitis
What is the Charcot Triad of cholangitis?
Jaundice
Fever
RUQ pain
What do the following infect? What are they?
E. coli
Ascaris lumbricoides
Clonorchis sinensis
infects biliary tract, increasing risk for gall stones, cholangitis, and cholangiocarcinoma
A. lumbricoides = roundworm, due to poor sanitation
C. sinensis = liver fluke, endemic in China, Korea, Vietnam
Waxing and waning RUQ pain
Due to gallbladder contracting against a stone lodged in the cystic duct
Relief if stone passes
Common bile duct obstruction may => acute pancreatitis or obstructive jaundice
Biliary Colic
Impacted stone in the cystic duct results in dilatation with pressure ischemia, bacterial overgrowth, and inflammation
S/S: RUQ pain, often radiating to the right scapula, fever with increased WBC count, nausea, vomiting, and increased serum alk phos (from duct damage, ascending cholangitis)
Acute Cholecystitis
Chemical irritation from long standing cholelithiasis, with or without superimposed bouts of acute cholecystitis
Characterized by herniation of gall bladder mucosa into the muscular wall, name the special name of this sinus!
What is a late complication?
S/S: vague RUQ pain, especially after eating
Chronic Cholecystitis
Rokitansky-Aschoff sinus (I hope to one day have a butthole malformation named after me, the Patel Pothole or something)
Porcelain gallbladder is a late complication (dystrophic calcification, shrunken hard gallbladder)
What would be a POM physical finding for cholecystitis?
+ Murphy’s sign BITCH, inspiratory arrest on RUQ palpation, due to pain.
Bacterial infection of bile ducts
Ascending infection with enteric gram - bacteria
S/S: sepsis (high fever and chills), jaundice, and abdominal pain
Increased incidence with choledocholithiasis (??)
Ascending cholangitis
Choledocholithiasis = stone in biliary ducts
Extremely elderly woman presents with cholecystitis, poor prognosis, used to have a lot of gallstones complicated by having porcelein gallbladder
Gallbladder carcinoma
