011215 hepatic inflam and fibrosis Flashcards
in fibrosis, where is periportal fibrosis?
around portal triad and extending a bit beyond
what stage is cirrhosis called?
stage 4
hepatic necrosis
ACUTE cell death
can lead to acute liver failure
fulminant liver failure
acute liver failure complicated by coagulopathy and encephalopathy
most common causes of acute and fulminant liver failure
meds (acetaminophen) viral hepatitis (causes fibrosis, which takes longer, and necrosis, which is acute)
pathophysiology of alcoholic liver disease
increased NADH increased acetaldehyde (activates stellate cells to form collagen, microfilaments that maintain intracellular skeleton are sheared causing ballooning, Kupffer cells produce TNFalpha)
what changes do you see at the microscopic level with alcoholic liver disease?
dense extracellular matrix laid down in the space of Disse
loss of fenestrations in the sinusoids
loss of microvilli on hepatocytes
activated Kupffer cell
what are the 3 complications of alcoholic liver disease
steatosis/fatty liver
alcoholic hepatitis
cirrhosis
alcoholic hepatitis
fat plus inflammatory cells
risk factors for alcoholic liver dis
more than 30g alcohol/day in men, 20g/day in women
alcohol outside of meals
binge drinking
lab abnormalities in ALD
AST/ALT ratio greater than 2 ALT usually under 300 IU/mL rarely raised alk phos low albumin increased INR (advanced disease) increased bilirubin
thrombocytopenia (advanced dis)
macrocytosis/anemia
tx for alcoholic HEPATITIS
abstinence, nutritional support
anti-inflammatory drugs (glucocorticoids, Pentoxifylline)
jaundice can be attributable to
many conditions
alcoholic liver disease is histoliogically like
non-alcoholic fatty liver dis
most common cause of elevated transaminases in the US
NAFLD
NAFLD is histologically categorized into 2 categories
non alcoholic fatty liver (NAFL)–abnormal liver tests, no ballooning of hepatocytes
non alcoholic steatohepatitis (NASH)–steatosis and inflam present. with hepatocellular injury (ballooning of hepatocytes) with or without fibrosis
prevalence of chronic liver disorders in US–what is most common?
nonalcoholic fatty liver, then
nonalcoholic steatohepatitis
then chronic hep C
then alcoholic liver dis
risk factors for non alcoholic liver disease
abdominal OBESITY
hypertriglyceridemia
high fasting glucose/diabetes
causes of steatosis and steatohepatitis
alcohol
meds
nutritional (TPN, etc)
insulin resistance
therapeutic strategies for NAFLD
WEIGHT LOSS
for NASH:
vitamin E (first line)
pioglitazine
HFE gene
mutated in hereditary hemochromatosis
what does HFE doe?
downregulates transferrin when iron supplies are adequate so that iron is not absorbed from small intestine
hemochromatosis occurs most commonly in what population?
Europeans
clinical presentation of hereditary hemochromatosis
liver fxn abnormalities
SKIN HYPERPIGMENTATION-BRONZE
DIABETES
what gene combination results in hereditary hemochromatosis
C282Y/C282Y (homozygous recessive)
C282Y is the mutant form of the wildtype gene
C282Y/H63D suggests
10% chance of developing hereditary hemochromatosis
tx for C282Y/C282Y hereditary hemochromatosis
if older than 40 or if elevated ALT/AST, consider biopsy to assess for cirrhosis
and phlebotomy
two defects in Wilson’s disease
gene mutation in ATB7B
also can’t make enough ceruloplasmin
pathophysiology of Wilson’s dis
due to mutation in ATB7B, liver can’t transport copper into biliary excretion to be fecally excreted
also, ceruloplasmin is reduced. so non-ceruloplasmin-bound copper deposits in liver
what is one of the few diseases that can cause necrosis and fibrosis
Wilson’s disease
damage in Wilson’s dis occurs mainly to
liver and brain
ceruplasmin test for Wilson’s dis
not the best test b/c high levels will occur in inflam and may lead to false negatives
Kayser Fleischer rings
Wilson’s disease
tx for Wilson’s dis
Trientine (binds unbound copper to excrete in urine)
zinc (prevents copper absorption from GI tract)
alpha1anti trypsin
inhibitor of the proteolytic enzyme elastase
M gene
normal gene for alpha1anti trypsin. this gene produces normal amts of the protein
the most common mutant form for alpha1 anti trypsin deficiency
Z
what organs are involved in alpha1anti trypsin deficiency
lungs
liver
the mechanisms for alpha1 anti trypsin deficiency disease
lung: loss of fxn mutation
liver: gain of fxn in that the small amts of A1AT are abnormal so they accumulate in liver and induce toxicity
what form of A1AT deficiency causes lung disease only?
PiSZ
and Pi null-null
what form of A1AT deficiency causes both lung and liver dis
PiZZ
what do you find in the serum of autoimmune hepatitis pts?
autoantibodies against hepatocytes (IgG)
the few things that have ALT, AST elevation over 1000
autoimmune hepatitis
viral hepatitis A, B
meds
ischemic
interface hepatitis
around the portal triad
seen in autoimmune hepatitis
plasma cell infiltrate
autoimmune hepatitis
ANA, ASMA are positive in
type 1 autoimmune hepatitis
anti liver kidney microsomal antibody is postive in
type 2 autoim hepatitis
associated conditions of autoim hepatitis
THYROID DISEASE
RA
other autoimmune diseases
tx for autoim hepatitis
prednisone and azathioprine combo
primary biliary cirrhosis is a misnomer b/c
the disease can actually have stage 1-4 of fibrosis (only 4 is cirrhosis)
PBC
chronic, progressive, cholestatic liver disease
destruc of intrahepatic ducts (the very small bile ducts)
AMA +
PBC
what markers do you see for PBC?
AMA positive
elevated IgM
AMA targets what?
PDC E2 on the membrane of biliary epithelial cells
symptoms of PBC
asymptomatic or
FATIGUE
PRURITUS
itching-think?
bile duct problem
xanthelasma (fat deposits)
PBC
consequences of PBC?
steatorrhea
deficiency of vit A,D,E,K
florid duct lesion
PBC
florid duct lesion-define
lymphocytes and mononuclear cells causing inflam changes around bile ducts
tx for PBC
ursodeoxycholic acid (a hydrophilic bile acid that balances the ratio of excessive hydrophobic bile acid accumulation in PBC)
for pruritis-use benadryl at night and cholestyramine during day
Wilson’s dis pt-what ages?
3-40
if synthetic fxn is intact, don’t think
cirrhosis
meds can cause hepatocellular injury or cholestatic injury?
both
can you burn out the bile ducts?
no (you can however burn out hepatocytes)
