Nelson: Liver 2 Flashcards
What is cirrhosis?
Hepatic disease characterized by widely distributed (diffuse) interconnecting fibrous scars with nodular parenchymal regeneration.
What is the MC cause of cirrhosis?
i. Alcoholic liver disease
ii. Viral hepatitis
iii. Biliary disease
iv. Hereditary hemochromatosis
v. Wilsons disease A1AT deficiency
vi. Cryptogenic cirrhosis (non-alcoholic fatty liver)
What are the 3 main causes of death associated w/ cirrhosis?
Progressive liver failure
complications of portal hypertension
hepatocellular carcinoma
What is hepatic failure?
Fibrosis destroying and impairing the normal vascular interconnection in the liver resulting in decreased hepatic profusion. May be the result of acute or (more commonly) chronic liver failure.
What causes Acute hepatic failure? What is the MCC?
secondary to massive hepatic necrosis (active Hep. A or B, drug/toxin). Most common cause is acetaminophen.
What causes chronic hepatic failure?
chronic liver disease associated with cirrhosis
How does hepatic failure manifest?
jaundice
Albumin/bleeding/ammonia/glucose/endocrine/drug metabolism changes
What are the MC causes of portal HTN?
Cirrhosis
What are the 4 main complications associated w/ portal htn?
ascites
portosystemic shunts (esophageal varices)
splenomegaly
hepatic encephalopathy
What is steatosis?
fatty liver
In early stages liver accumulates macro vesicular steatosis (large lipid vacuoles). Reversible with cessation of alcohol consumption.
What is steatohepatitis (alcoholic hepatitis)?
steatosis and evidence of hepatocyte injury and inflammation
Liver cell injury (swelling, necrosis), mallory bodies and neutrophillic inflammation are all signs of…
Steatohepatitis
What are mallory bodies?
cytokeratin aggregates that can also be seen in NADFLD and PBC
Describe the typical gross appearance of alcoholic cirrhosis in the early and late stages.
Early stages- liver is ENLARGED, FATTY and micronodular.
Late stages- SHRUNKEN, NONFATTY with variable size nodules and cholestasis is usually present.
What are the major causes of death in alcoholic cirrhosis?
Hepatic encephalopathy and coma
Massive GI tract hemorrhage (esophageal varices). Pic to right
Infection
Hepatorenal syndrome
Hepatocellular carcinoma (1-6% annual risk)
What is non-alcoholic fatty liver disease? What pt population can get this disease?
Hepatocyte injury similar to alcoholic steatosis and non-alcoholic steatohepatitis. (hepatocyte lipid accumulation and oxidative injury resulting in necrosis and inflammatory reaction)
Pts w/: metabolic syndrome obesity type 2 diabetes dyslipidemia insulin resistance.
What is non-alcoholic fatty liver disease? What pt population can get this disease?
Hepatocyte injury similar to alcoholic steatosis and non-alcoholic steatohepatitis. (hepatocyte lipid accumulation and oxidative injury resulting in necrosis and inflammatory reaction)
Pts w/: metabolic syndrome obesity type 2 diabetes dyslipidemia insulin resistance.
What is PBC?
Autoimmune cholangiopathy
Characterized
by:
progressive inflammatory destruction of small and medium intrahepatic bile ducts>
may lead to cirrhosis. Extrahepatic ducts spared.
Believed to be autoimmune, most patient have circulating antimitochondrial antibodies (AMA)
What pt typically gets PBC?
middle aged F of N european ancestry
*most have other autoimmune diseases
What lab findings are associated w/ PBC?
elevated alkaline phosphatase
GGT (cholestatic injury pattern)
positive AMA.
Biopsy determines loss of ducts and stage.
What are the 4 stages of PBC?
Stage 1 lymphocytic/granulomatous cholangitis in portal tracts. More commonly on change is loss of intrahepatic bile ducts with protal hepatitis
Stage 2 periportal hepatitis with periportal fibrosis
Stage 3 bridging necrosis with bridging fibrosis
Stage 4 cirrhosis (micronodular with bile stasis)
What are the 4 stages of PBC?
Stage 1 lymphocytic/granulomatous cholangitis in portal tracts. More commonly on change is loss of intrahepatic bile ducts with protal hepatitis
Stage 2 periportal hepatitis with periportal fibrosis
Stage 3 bridging necrosis with bridging fibrosis
Stage 4 cirrhosis (micronodular with bile stasis)
What are possible causes of secondary biliary cirrhosis?
stones, tumor, biliary atresia, cystic fibrosis, choledochal cysts
What are possible causes of secondary biliary cirrhosis?
stones, tumor, biliary atresia, cystic fibrosis, choledochal cysts
What is PSC?
Autoimmune cholangiopathy, progressive random and uneven fibroimflammatory obliteration of extrahepatic and intrahepatic bile ducts
What key pt population does PSC often occur in?
Male age 40.
How does a 40 y/o M w/ PSC present?
fatigue
pruritis
jaundice
How do you dx PSC?
- cholangiography>
demonstrates strictures and dilation of extrahepatic and intrahepatic ducts (appears beaded) - Biopsy> demonstrates focal fibrosing cholangitis (used for staging)
What is hereditary hemochromatosis? Inheritance pattern?
Hereditary = due to deceased synthesis of hepcidin>
excessive absorption of Fe
What is the pathogenesis of hereditary hemochromatosis?
Excessive iron absorption>
accumulation of iron in tissues>
tissue injury
What are the clinical manifestations of hereditary hemochromatosis?
- Liver- iron accumulation in hepatocytes (periportal initially), directly toxic leads to fibrosis and micronodular cirrhosis.
- Pancreas- hemosiderin deposits in acinar and islets- diffuse fibrosis and atrophy
- Heart- hemosiderin deposits can have interstitial fibrosis
- Skin- hemosiderin in macrophages and fibroblasts and increased melanin may get slate gray skin.
- Endocrine- deposits in thyroid, adrenal, pituitary glands, may get atrophic testis.
- Joint synovium- deposits.
What findings are found on liver biopsy in a pt w/ hereditary hemochromatosis?
Iron deposits in hepatocytes
How is hereditary hemochromatosis dx?
Classic triad:
cirrhosis
diabetes
skin pigmentation
*Can also present with arthralgias, lethargy, hypogonadism, ab pain and cardiomyopathy.
What test would you use to screen for hereditary hemochromatosis?
fasting transferrin saturation
How is hemochromatosis treated?
phlebotomy or iron chelating agents
What is secondary hemochromatosis?
Excessive iron accumulation in tissues from a non-hereditary source.
How does the liver biopsy of secondary hemochromatosis differ from hereditary hemochromatosis?
HH= iron accumulates in hepatocytes
S= iron accumulates in Kupffer cells
How does the liver biopsy of secondary hemochromatosis differ from hereditary hemochromatosis?
HH= iron accumulates in hepatocytes
S= iron accumulates in Kupffer cells
What is Wilson’s disease? Inheritance?
AR
Disorder of copper metabolism resulting in accumulation of toxic levels in tissues (liver, brain eye).
What abnormalities are present in a pt w/ wilson’s disease on key diagnostic tests?
LOW circulating ceruloplasmin levels (copper complexed to apoceruloplasmin, how it circulates in blood)
Increased 24 hour urine copper excretion.
Low serum copper levels.
What can be seen on an eye exam of a pt w/ Wilsons disease?
deposits of iron at limbus of cornea (Kayser-Fleischer ring)
What is increased on the liver biopsy in a pt w/ Wilsons disease?
biopsy will show increased hepatic copper which may present as negative stain but will be raised on quantitative testing
What is increased on the liver biopsy in a pt w/ Wilsons disease?
biopsy will show increased hepatic copper which may present as negative stain but will be raised on quantitative testing
What is alpha 1 antitrypsin def?
Codominant autosomal disorder
LOW levels of alpha-1-antitrypsin (protease inhibitor). Inhibits neutrophil elastase.
Liver produces A1AT glycoprotein at low levels
How does lung injury differ from liver injury cuased by alpha-1-antitrypsin def?
Lung- imbalance between A1AT and neutrophil elastase (anti-protease/protease imbalance)> emphysema
Null-Null most severe
Liver- accumulation of A1AT in hepatocytes and not protease/anti-protease imbalance. Null-Null have no liver manifestation
What key finding can be seen on liver biopsy of a pt w/ alpha 1 antitrypsin def?
cytoplasmic globular inclusions and PAS stain
What key finding can be seen on liver biopsy of a pt w/ alpha 1 antitrypsin def?
cytoplasmic globular inclusions and PAS stain
What are the two main categories of drug induced liver injury?
- Direct hepatotoxicity
2. Unpredictable hepatotoxicity
What is unpredictable hepatotoxicity?
produce liver injury in an unpredictable manner
Not all exposed develop injury.
May be due to rate of metabolism or propensity for immune response.
What is unpredictable hepatotoxicity?
produce liver injury in an unpredictable manner
Not all exposed develop injury.
May be due to rate of metabolism or propensity for immune response.
What is Reye’s syndrome?
Rare acute POSTVIRAL illness with liver injury (microvesicular steatosis) and encephalopathy.
Also present with widespread mitochondrial injury.
What pt population does Reye’s syndrome usually affect?
Usually in children and teens following viral infection.
95% having received salicylates (asprin).
What is found on a liver biopsy in pts w/ reye’s syndrome?
Microvesicular steatosis, with small lipid vacuoles within hepatocytes.
*Can also be seen in acute fatty liver of pregnancy and tetracycline toxicity
What is found on a liver biopsy in pts w/ reye’s syndrome?
Microvesicular steatosis, with small lipid vacuoles within hepatocytes.
*Can also be seen in acute fatty liver of pregnancy and tetracycline toxicity
What is neonatal choletasis?
group of disorders with prolonged conjugated hyperbilirubinemia in neonates
What is neonatal hepatitis?
cause of neonatal cholestasis
Hepatitis during early infancy (1-2mo).
What is neonatal hepatitis?
cause of neonatal cholestasis
Hepatitis during early infancy (1-2mo).
What are some causes of granulomatous hepatitis?
a. Idiopathic
b. Sacroidosis
c. Drug related
d. TB
e. Other
What are the 4 major types of liver function tests?
AST
ALT
ALP
GGT
ALT
alanine aminotransferase only small amount in other tissues.
More specific indicator of HEPATOCELLULAR injury
AST
aspartate aminotransferase
present in other TISSUES elevation NOT liver specific.
80% found in mitochondria,
ETOH is mitochondrial toxin so AST:ALT ratio over 2 suggests ALCOHOLIC LIVER DISEASE disease.
ALP
Alkaline phosphatase
increase usually indicates bone or liver disease
Increase in liver disease due to increased synthesis of ALP.
Found in canalicular membrane. Stimulus is BILE DUCT OBSTRUCTION.
GGT
associated with biliary epithelium, assists in determining if ALP rise is due to BONE OR LIVER
What tests are used to determine viral hepatitis?
serology, nuclear testing DNA/RNA
What tests are used to determine AIH?
ANA
anti-smooth muscle ABs
What tests are used to dtermine Wilsons?
ceruloplasmin
What tests are used to determine a-1-a def?
a1at level
phenotype
What tests are used to determine hemochromatosis?
Fe
TIBC
transferrin saturation
genetics
What tests are used to determine primary biliary cirrhosis?
AMA-M2
How do liver fxn tests distinguish a hepatocellular injury pattern from a cholestatic injury pattery?
AST and ALT- do not measure hepatic fxn. Elevations of these enzymes reflect HEPATOCELLULAR DAMAGE
Alkaline phosphatase and GGT (gamma glutamyl transpeptidase)- reflect INJURY TO BILE DUCTS epithelium/canailicular membrane markers of cholestasis.
What reflects global hepatic synthesis fxn?
albumin
PTT
CF (factor V)
What are the two reasons for doing a liver biopsy?
determine cause of liver disease
determine extent of liver damage
What does grade mean on a liver biopsy for chronic hepatitis?
Severity of necro-inflammatory activity
i. Based on amount of lymphocytic piecemeal and lobular necrosis and inflammation present, also assessed with ALT elevation
What does stage mean on a liver biopsy for chronic hepatitis?
degree of fibrosis
