Wk5 Liver Path pt2 Flashcards
early EtOH abuse
enlarged, lipid filled liver
How does it look microscopically?
Alcoholic steatosis–fatty liver
large lipid vacuoles
**reverses with abstinence
Alcoholic hepatitis = steatosis + ?
hepatocyte injury and/or inflammation
“steatohepatitis”
Cytokeratin aggregates in hepatocytes:
Associated with?
Mallory bodies
Alcoholic hepatitis
Usually seen surrounding Mallory bodies:
neutrophilic inflammation
Alcoholic hepatitis occurrence
pre-cursor to cirrhosis
steatofibrosis
**perivenular and pericellular
Grossly: fibrosis + nodules
cirrhosis
Liver in early stages of alcoholic cirrhosis
enlarged
fatty
micronudular (less 3 mm)
Liver in late stages of alcoholic cirrhosis:
shrunken
non-fatty
variable nodule size
cholestasis usually present
5 major causes of death from alcoholic liver disease:
- hepatic encephalopathy and coma
- Massive GI tract hemorrhage (esophageal varicies)
- infx
- hepatorenal syndrome
- hepatocellular carcinoma
NAFLD?
Patient profile?
Non-alcoholic fatty liver disease
- metabolic syndrome
- obesity
- DM2
- dyslipidemia
- insulin resistance
autoimmune cholangiopathy
progressive destruction of small and medium sized INTRAhepatic bile ducts
extrahepatic ducts are spared
middle age females
Primary biliary cirrhosis
AMA (antimitochondrial antibodies)
associated with other autoimmune disorders
Primary biliary cirrhosis
fatigue
anicteric pruritis
xanthomas
steatorrhea
vit D malabsorption
Primary biliary cirrhosis
Tx for PBC:
urodeoxycholic acid
liver transplant
Dx of PBC:
liver biopsy
Damage due to prolonged EXTRAhepatic bile duct obstruction
Secondary biliary cirrhosis
progressive
RANDOM
autoimmune
uneven fibroinflammatory
extra/intrahepatic bile ducts
Primary sclerosing cholangitis (PSC)
pANCA
IBD association
Primary sclerosing cholangitis
“beaded” appearance on cholangiogram
PSC
primary sclerosing cholangitis
disorders of excessive iron absorption resulting in accumulation of iron in tissues producing organ injury
hemochromotosis
Inheritance pattern of primary hemochromotosis
autosomal recessive
Liver protein decreased in hemochromotosis
hepcidin –> excessive intestinal iron absorption
Most common genetic mutation in hereditary hemochromotosis
HFE – chromosome 6
C282Y – 80% of cases in adults
**most common in male of northern european descent
low penetrance so not all homozygotes express disease
Causes of secondary hemochromotosis
parenteral Fe overloads (transfusions)
ineffective erythropoesis –> increased Fe absorption
-(B-thalassemis, sideroblastic anemia)
increased oral intake of Fe
Chronic EtOH liver disease
Reread slide 42
distribution of excess Fe
Early pathological finding of primary hemochromotosis:
periPORTAL iron deposits in hepatocytes
Early pathological finding of secondary hemochromotosis (different from primary):
Fe accumulates in Kupffer cells not hepatocytes
Classic triad for hemochromotosis presentation:
- cirrhosis
- diabete
- skin pigmentation
“Bronze diabetes”
**also may see sx in other organ systems (heart, joints, etc.)
Best screening test for hemochromotosis:
fasting transferrin saturation
if greater than 45% –> serum ferritin
if ferritin elevated –> HFE gene test
Reason for liver bx in hemochrmatosis:
concern for cirrhosis
Tx for hemochromatosis:
chelating agents / phlebotomy
Autosomal recessive
disorder of copper metabolism
Wilson’s disease
Genetic defect in Wilson’s disease
ATP7B gene
chromosome 13
ATP7B?
gene for liver copper transporting ATPase protein
impaired secretion as ceruloplasmin and impaired secretion into bile
–> toxic levels of Cu in tissues
Dx test for Wilson’s
plasma ceruloplasmin level
24 hr urine copper excretion
When to consider Wilson’s in your Ddx:
liver disease in anyone under 30 yo
Presenting sx of Wilson’s disease:
neurpsychiatric
KAYSER-FLEISCHER rings
-copper deposits at limbus of cornea
What is alpha-1-antitrypsin?
a protease inhibitor (primarily neutrophils elastase)
**without it, tissues get degraded unchecked
A1AT gene location
ch 14
Pathogenesis of liver disease in A1AT deficiency:
intracellular misfolding –> accumulation –> apoptosis of hepatocytes
Most commonly dx hepatic disorder in infants and childrren:
A1AT deficiency
PAS stain
A1AT deficiency
Always include what in Ddx of any form of liver disease?
Toxins
CPC – chronic passive congestion
slide 73
nutmeg liver
centrilobular hemorrhagic necrosis
thrombosis of two or more hepatic vein branches
classic triad:
hepatomegaly
ascites
abd pain
Budd-Chiari syndrome
most common causes of Budd-Chiari syn:
hyercoaguable states
Dx for Budd-Chiari
Doppler US
MRI/CT
looking for clots
obstructive, NONthrombotic lesions of small (central) hepatic veins
radiation/hepatotoxin exposure
BM tx
Sinusoidal obstruction syndrome
sudden weight gain
hepatomegaly
increased serum bilirubin
Sinusoidal obstruction syndrome (ACUTE)
prolonged conjugated hyperbilirubinemia in the neonate
neonatal cholestasis
Two causes of neonatal cholestasis
- biliary atresia (extrahepatic)
2. neonatal hepatitis
Causes of granulomatous hepatitis:
idiopathic 50%
sarcoid 22%
drugs 6%
TB 3%
other 19%
HELLP syndrome?
pregnancy
Hemolysis
Elevated Liver enzymes
Low Platelets
microvesicular steatosis in pregnancy
Acute fatty-liver of pregnancy
mild increase in conjugated bilirubin in pregnancy
Intrahepatic cholestasis of pregnancy
portal inflammation
lymphocytic cholangitis
“vanishing bile ducts”
chronic GVHD from BM tx
Tests that reflect hepatocellular damage
NOT hepatic function
AST/ALT
Reflect injury to bile ducts/canalicular membranes
markers of cholestasis
Alk Phos
GGT
Markers of hepatic function
Albumin
PT
clotting factors
Most specific test for liver damage
ALT
**AST is found in other tissues
Why is AST elevated preferentially in EtOH disease?
found in mitochondria
EtOH is mitochondrial toxin
Increased Alk Phos usually due to?
How to help differentiate?
bone or liver
GGT from biliary epithelium
Two purposes of Liver biopsy:
- determine possible cause of disease
2. determine extent of liver damage
Liver bx:
ground glass hepatocytes
chronic viral HBV
Liver bx:
plasma cells
autoimmune hepatitis
PBC (primary biliary cirrhosis)
Liver bx:
lymphocytic/granulomatous cholangitis
PBC (primary biliary cirrhosis)
Liver Bx:
Fibrous obliterative cholangitis
PSC (primary sclerosing cholangitis)
Liver Bx:
periportal hepatitis
mild steatosis
chronic viral HCV
Liver bx:
Globular hepatocyte inclusions
A1AT deficiency
