B5-025 Liver Disorders I Flashcards
the dual blood supply of the liver comes from
2
- portal vein
- hepatic vein
macrophages that live in the sinusoids of the liver
Kupffer cells
lined with simple cuboidal epithelium
“string of pearls”
bile duct
blood in zone one is […] in oxygen
rich
blood in zone 3 is […] in oxygen
low
there is a more dense distribution of cytochrome p450 enzymes in zone […]
3
large cells with centrally located nucleus and prominate nucleolus
hepatocytes
hepatocytes are connected to their neighbor hepatocytes through a
bile cannaliculus
space between hepatocytes and sinusoids
space of Disse
stellate cells live in the
space of Disse
what do stellate cells do in their quiescient state?
store fat-soluble vitamins
ADEK
in a normal adult state, the cell plates should be […] cells thick
how many cells
1
2 cells max (regenerative state)
3+ indicates neoplastic process
feathery degeneration indicates an accumulation of
bile
steatosis can be due to
3
obesity, alcohol, diabetes
accumulation of iron in a canalicular distribution
hemochromatosis
accumulation of copper
Cu not excreted in bile
Wilson’s disease
accumulation of misfolded protein in the RER
a1 antitrypsin deficiency
old age/”wear and tear” pigment seen in hepatocytes
lipofuscin
- clumped cytokeratin filaments
- ballooned degeration
Mallory hylanine
steatohepatitis, alcohol use
- hyperpigmentation of the skin
- jaundice
- diabetes
genetic hemochromatosis
“bronze diabetes”
what lab values would you expect to be elevated in hemochromatosis?
4
- AST/ALT
- serum iron
- transferrin
- serum ferritin
treatment for hereditary hemochromatosis
weekly phlebotomy and deferoxamine
inheritance pattern of hereditary hemochromatosis
bonus points if you name the gene
autosomal recessive inheritance of HFE gene
HFE regulates
hepcidin
controls how much iron is absorbed in intestine
- caused by inappropriately high intestinal iron absorption
- results in excess body iron stores
hereditary hemochromatosis
why do most cases of hereditary hemochromatosis present after age 40?
- takes a long time to accumulate
- cirrhosis occurs when the body iron exceeds 30-40 g around age 40
risk factors for hereditary hemochromatosis
- male gender
- hepatitis C
- alcohol
PAS-diatase resistant globules
a1 antitrypsin deficiency
Piz allele
alpha 1 antitrypsin deficiency
present with cirrhosis of the liver
and early onset empysema, chronic bronchitis, asthma, etc
alpha 1 antitrypsin deficiency
all patients with PiZZ genotype accumulate […] in hepatocytes
alpha 1 antitrypsin deficiency
- resting tremor
- brownish ring around cornea
wilson’s disease
what labs would you expect to be abnormal in Wilson’s disease?
- decreased ceruloplasmin
- elevated urine copper
mutation in ATPase leading to defective conjugation of copper in ceruloplasmin
Wilson’s disease
increased copper absorption in gut but decreased excretion in bile
wilson’s disease
treatment for Wilson’s
penicillamine
copper chelation
what kind of stain is used to visualize copper?
rhodadine
apoptosis is commonly seen in
“dead reds”
viral hepatitis
zonal toxic necrosis is due to
ischemia or toxins
causes centrolobular necrosis
acetaminophen overdose
midzonal necrosis is caused by
2
adenovirus
acute hepatitis
submassive or massive necrosis is due to
toxins
viral hepatitis
laboratory tests to evaluate biliary function
4
- total bilirubin
- direct bilirubin
- alk phos
- GGT
laboratory tests to determine hepatocyte function
3
- serum albumin
- PTT
- serum ammonia
what labs would you expect to be elevated in an obstructive liver disease pattern?
alk phos
bilirubin
GGTP
all elevated
what labs would you expect to be abnormal in an acute hepatitis pattern?
elevated AST/ALT
bilirubin +/-
what labs would you expect to be abnormal in a cirrhosis pattern?
decreased albumin
decreased platelets
prolonged PTT
multinucleation, margination, molding
herpesvirus hepatitis
- seen in immunocompromised after liver/renal transplant
- microabscesses, “owl’s eyes”
CMV hepatitis
sinusoidal lymphocytosis (“string of pearls”) with portal inflammation
EBV hepatitis
one pill once a day for 12 weeks treatment for HCV
harvoni
really expensive
this histology with plasma cells is characteristic of
autoimmune hepatitis
- ANA, ASMA +
- AST, ALT > alk phos
- hypergammaglobulinemia
- absence of viral hepatitis
autoimmune hepatitis
features of metabolic resistance
5
- DM/insulin resistance
- hypertension
- dyslipidemia
- central obesity
- microalbuminemia
just fat globules with very minimal risk to progression of cirrhosis
steatosis
- fat globules plus inflammation and ballooned hepatocytes
- risk of progression to cirrhosis
steatohepatitis
cytokines released from Kupffer cells to activate stellate cells
2
TNF-a
TGF-b
what kind of cells deposit collagen in the liver?
stellate cells
store fat soluble vitamins
stellate cells
mallory hyaline =
alcoholic steatohepatitis
for testing purposes
cirrhosis
elevated AFP indicates
HCC
HCC
left: HCC
right: normal
mutations associated with the development of HCC
3
- b-catenin (activating)
- TERT
- TP53 (inactivating)
round globular inclusions of misfolded proteins in hepatocytes that stain bright pink with PAS-diastase
a1-antitrypsin deficiency
PAS stain removes […] with diastase
glycogen
interface and lobular inflammatory activity
viral hepatitis
broad fibrous bands and complete parenchymal nodules
cirrhosis
cirrhosis causes
portal hypertension
portosystemic venous shunts cause
3
- esophageal varices
- periumbilical caput medusa
- hemorrhoids
the livers inability to degrade estrogen in liver failure causes
4
- skin spider angioma
- palmar erythema
- testicular atrophy
- gyencomastia
increased ammonia levels in liver failure cause
2
asterixis
encephalopathy
decreased synthetic function in liver failure results in
low albumin
what causes the prolongation of PT in liver failure?
factor IIV degradation
how does alcohol cause hepatic steatosis?
excess NADH changes normal hepatic metabolism from catabolism of fat to anabolism of fats
results in decreased mitochondrial oxidation of fatty acids and increased triglyceride production
lobular disarray with apoptotic hepatocytes and lobular inflammation
acute hepatitis
AMA is associated with
primary biliary cholangitis
extremely elevated transaminanses are associated with
acute hepatitis
ANA is associated with
autoimmune hepatitis
p-ANCA is associated with
primary sclerosing cholangitis
interface activity and prominent lymphoplasmacytic infiltrate
autoimmune hepatitis
more common in females
may be asymptomatic or present with fatigue, nausea, pruritis
autoimmune hepatitis
associated with circulating anti-nuclear antibodies and high levels of serum immunoglobulins
autoimmune hepatitis
autosomal recessive genetic disorder characterized by excessive iron absorption and toxic accumulation of iron
hereditary hemochromatosis
diabetes, skin pigmentation, and cardiac failure
hereditary hemochromatosis
prussian blue stain binds
iron
hereditary hemochromotosis
heriditary hemochromatosis leads to
cirrhosis/HCC
