Liver Path 2 - Nelson Flashcards
What is the early pathologic finding in liver of alcohol abuse?
Alcohol steatosis = fatty liver
Enlarged
Macrovesicular steatosis is seen microscopically (large lipid vacules)
Is alcoholic steatosis reversible?
Yes, with cessation of alcohol consumption
What are the 3 microscopic features of alcoholic hepatitis?
Liver cell injury = swelling/ballooning
Mallory Bodies
Neutrophilic inflammation
What are mallory bodies?
cytokeratin aggregates
Can be seen in other liver diseases such as NAFLD and PBC
What is the typical gross appearance of alcoholic cirrhosis? Early and late?
Early:
- enlarged
- Fatty
- Micronodular
Late:
- Shrunken
- Non-fatty
- Variable size nodules
- Choelstasis is usually present
2 big causes of death in alcoholic cirrhosis?
- Hepatic encephalopathy and coma
2. Massive GI tract hemorrhage (esophageal varices)
What patient population gets non-alcoholic fatty liver disease?
Metabolic Syndrome Obesity Type 2 diabetes Dyslipidemia Insulin Resistance
Fibrosis + nodules = ?
Cirrhosis
What is primary biliary cirrhosis?
Autoimmune cholangiopathy characterized by progressive inflammatory destruction of small and medium sized intrahepatic bile ducts
May lead to cirrhosis
Which bile ducts are destroyed in primary biliary cirrhosis?
INTRAHEPATIC bile ducts!
Extrahepatic bile ducts are spared
Typical patient with PBC?
Middle aged females of northern european ancestry
Key diagnostic lab test for PBC?
AMA = antimitochodnrial antibodies
Elevated alkaline phosphatase and GGT
Insidious onset of fatigue and anicteric pruritis…. what do you think it is?
Primary biliary cirrhosis
May also get xanthomas, steatorrhea, vit. D. malabsorption-related osteomalacia
What causes secondary biliary cirrhosis?
Secondary to any disorder causing prolonged EXTRAHEPATIC bile duct obstruction: Stones Tumor Biliary Atresia Cystic fibrosis Choledochal cysts
What is primary sclerosing cholangitis?
Autoimmune cholangiopahty
Progressive, random, unever fibroinflammatory destruction of EXTRA and INTRAHEPATIC bile ducts
What distinguishing PBC and PSC?
PBC is only intrahepatic ducts
PSC is both intra and extra hepatic ducts
What disease is primary sclerosing cholangitis (PSC) assoicated with?
Ulcerative cholitis
What antibody is usually found in PSC?
p-ANCA
How does PSC appear on cholangiogram?
Beaded appearance
Demonstrates strictures and dilations of extrahepatic and intrahepatic bile ducts
Define hereditary hemochromotosis
Excessive iron absorption, resulting in the accumulation of iron in tissues, producing organ injury
Pathogenesis of herediatry hemochromotosis
Decreased synthesis of hepcidin leading to excessive intestinal iron absorption
Hereditary hemochormotosis has mutations in what gene? located on what chromosome?
HFE gene on chromosome 6
Most common mutation is C282Y
Classic triad for hemochromotosis?
Cirrhosis
Diabetes
Skin pigmenetation
Best screening test for hemochromotosis?
Fasting transferrin saturation
Treatment for hemochromotosis?
Clear excessive iron from tissues using phlebotomy or iron chelating agents
Common cause of secondary hemochromotosis?
Parenteral iron overload (transfusions, iron-dextran injections)
How does liver biopsy of secondary hemochromotosis differ from hereditary?
2nd = iron initially accumulates in the KUPFFER CELLS, NOT HEPATOCYTES
What is Wilson’s disease?
Disorder of cooper metabolism resulting in impaired secretion of copper as ceruloplasmin as well as impaired excretion of copper into bile
Mutation in Wilson’s disease?
Mutation in ATP7B gene on chromosome 13
Defective copper-transporting ATPase protein
Diagnostic test for Wilson’s disease?
Low ceruloplasmin levels
Increased 24 hour urinary copper excretion
What can be seen on eye exam in Wilson’s disease?
Kayser-Fleischer rings
Copper ring deposits in eye
When should you consider Wilson’s Disease in your differential?
Liver disease in anyone
What do you see in Wilson’s disease on liver biopsy?
Increased hepatic copper
Define alpha-1-antirypsin deficiency
Abnormally low levels of A1AT which primarily inhibits neutrophil elastase (A1AT is a protease inhibitor)
How does pathogenesis of lung and liver injury differ in A1AT deficiency?
Liver disease is related to the ACCUMULATION of A1AT in hepatocytes
Lung = secondary to anti-protease/protease imbalance
What do you see on liver biopsy in A1AT deficiency?
Cirrhosis with PAS + globules
**misfolded gene product protein aggregates in heptocellular ER
Two main categories of drug induced liver injury?
- Direct hepatotoxicity = toxic to liver in a predictable, dose dependent fashion
- Unpredictable hepatotoxicity =
- not all exposed develop injury
- toxic reactions may relate to metabolism of drug or propensity of drug to develop immune response
What should you always include in a differential diagnosis for any form of liver disease?
Exposure to toxin or therapeutic agent!!
What would you expect if there is an outlfow problem (circulatory liver disorder in hepatic vein)
Centrilobular congestion
Budd-Chiari Syndrome
Hepatic Vein thrombosis with centrilobular congestion and necrosis
**Absence of JVD
What can cause nutmeg liver?
Budd-Chiari Syndrome
Right sided heart failure?
Sinusoidal obstruction syndrome
Presence of obstructive, non-thrombotic lesions of the small (central) hepatic veins in patients exposed to radiation and/or hepatoxins
Biliary atresia
Complete or partial obstruction of the lumen of the extrahepatic biliary tree within the first 3 months of life
Top 2 leading causes of granulomatous hepatitis?
- Idiopathic (50%)
2. Sarcoidosis (22%)
Define HELLP syndrome
Hemolysis
Elevated Liver enzymes
Low Platelets
During pregnancy
3 pregnancy associated liver diseases?
Preeclampsia
Acute fatty liver
Intrahepatic cholestasis
What is preeclampsia?
maternal hypertension
Proteinuria
Peripheral edema
Coagulation abnormalities
What do AST and ALT really tell you? Do they measure hepatic function?
NO!!! Elevations in these enzymes reflect hepatocellular damage
What lab tests mark cholestasis?
Alakline Phosphatase
GGT
What markers actually reflect global hepatic function?
Albumin
Prothrombin Time
Clotting factors (Factor V levels)
*true hepatic synthesis
Which is more specific to liver ALT or AST?
ALT!!! more specific to liver
AST is present in heart, muscle, brain, and kidneys too
AST > ALT suggests?
Alcoholic hepatitis
ALT > AST suggests?
Viral hepatitis
What is the primary stimulus for ALP production?
Bile duct obstruction
Can also see rise in bone disease
What test can assist if ALP rise is due to bone of liver?
GGT!
Associated with biliary epithelium
Do reasons for doing a liver biopsy?
Determine etiology of liver disease
Determine extent of damage to the liver
