Liver Path 2 - Nelson Flashcards by Alisha Lindberg

What is the early pathologic finding in liver of alcohol abuse?

Alcohol steatosis = fatty liver
Enlarged
Macrovesicular steatosis is seen microscopically (large lipid vacules)

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Is alcoholic steatosis reversible?

Yes, with cessation of alcohol consumption

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What are the 3 microscopic features of alcoholic hepatitis?

Liver cell injury = swelling/ballooning
Mallory Bodies
Neutrophilic inflammation

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What are mallory bodies?

cytokeratin aggregates

Can be seen in other liver diseases such as NAFLD and PBC

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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

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2 big causes of death in alcoholic cirrhosis?

Hepatic encephalopathy and coma

2. Massive GI tract hemorrhage (esophageal varices)

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What patient population gets non-alcoholic fatty liver disease?

Metabolic Syndrome
Obesity
Type 2 diabetes
Dyslipidemia
Insulin Resistance

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Fibrosis + nodules = ?

Cirrhosis

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What is primary biliary cirrhosis?

Autoimmune cholangiopathy characterized by progressive inflammatory destruction of small and medium sized intrahepatic bile ducts

May lead to cirrhosis

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Which bile ducts are destroyed in primary biliary cirrhosis?

INTRAHEPATIC bile ducts!

Extrahepatic bile ducts are spared

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Typical patient with PBC?

Middle aged females of northern european ancestry

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Key diagnostic lab test for PBC?

AMA = antimitochodnrial antibodies

Elevated alkaline phosphatase and GGT

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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

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What causes secondary biliary cirrhosis?

Secondary to any disorder causing prolonged EXTRAHEPATIC bile duct obstruction:
Stones
Tumor
Biliary Atresia
Cystic fibrosis
Choledochal cysts

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What is primary sclerosing cholangitis?

Autoimmune cholangiopahty

Progressive, random, unever fibroinflammatory destruction of EXTRA and INTRAHEPATIC bile ducts

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What distinguishing PBC and PSC?

PBC is only intrahepatic ducts

PSC is both intra and extra hepatic ducts

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What disease is primary sclerosing cholangitis (PSC) assoicated with?

Ulcerative cholitis

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What antibody is usually found in PSC?

p-ANCA

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How does PSC appear on cholangiogram?

Beaded appearance

Demonstrates strictures and dilations of extrahepatic and intrahepatic bile ducts

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Define hereditary hemochromotosis

Excessive iron absorption, resulting in the accumulation of iron in tissues, producing organ injury

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Pathogenesis of herediatry hemochromotosis

Decreased synthesis of hepcidin leading to excessive intestinal iron absorption

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Hereditary hemochormotosis has mutations in what gene? located on what chromosome?

HFE gene on chromosome 6

Most common mutation is C282Y

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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?

1. Direct hepatotoxicity = toxic to liver in a predictable, dose dependent fashion 2. 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?

1. 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