Pathology - liver Flashcards
describe the histopathos in cirrhosis
diffuse bridging fibrosis and nodular regeneration via stella celsl that dursrupts the normal architecture of the liver.
what does cirrhosis increase the risk for
hepatocellular carcinoma
what cells cause the fibrosis
stellate cells
etiologies for cirrhoses
OH HepC HepB biliary disease metabolic disorders
describe the pathophys effects of cirrhosis
compresses sinusoids and central bile canals
- increased intrasinusoidal hypertension
- decreases number of functional sinuisoids
- increases hydrostatic pressure in the portal circulation
what is the result of a portosystemic shunt
partially alleviates portal hypertension
how do portosystemic shunts manifest in increased portal hypertension
A) esophageal varices (left gastri with esophageal)
b) caput medusa ( paraumbilica and small epigastrics)
c) anal varices (Superior rectal and middle/inferior rectals)
result of portal hypertension please
esophageal varices - hematemesis and melena peptic ulcer - melena congestive splenomegaly caput medusa ascites portal hypertensive gastrophaty anorectal varices
effects of liver cell failure
hepatic encephalopathy scleral icterus fetor hepaticus spider nevi gynecomastia jaundice testicular atropy liver flapasterixis bleeding tendency with increased PT anaemia dependeing pitting oedema/ankle oedema
how does cirrhosis show up on a CT
splenomegaly with also nodularity of the liver counter due to regeneration macronodules
cirrhosis: diffuse bridging fibrosis and nodular regeneration via stellate cells that disrupts liver architecture.
what does disruption of the urea cycle show up as in cirrhoses
decreased BUN and increased serum ammonium
what does disruption to gluconeogenesis and glycogenolysis present as in cirrhosis?
hypoglycemia
A-B balance in cirrhosis please
chornic respiratory alkalosis: tpxic prodcuts stimulate the respiratory centre to hyperventilated
metabolic acidosis - lactic acid build up bc cant be converted to pyruvate after the cori cycle brings lactate from other tissues
what happens to salt balance in cirrhosis
get hyponatremia due to secondary aldosteronism
hypoalbuminemia in cirrhosis results in
hypocalcemia - less carriage, no effect on free ca, just total
dependent pitting oedema
why do you see hypocalcemia in cirrhosis
decreased Vit D decreased albumin (carries in blood. decrease total but no effect on free Ca...confuses my brain?)
list dzs where you see increased alkaline phosphatase
cholestatic hepatobiliary disease obstructive hepatobiliary disease hepatocellular carcinoma infiltrative disorders bone disease
list diseases wher eyou see increased aminotransferase levels please
viral hepaitits ALT > HST
OH hepatitis AST > ALT
list dzs where you see increased amylase
actue pancreatitis
mumps
list dzs where you see changes in ceruloplasmin
decreased in Wilson disease
list dz where you see altered gamma-glutamyl transpeptidase
increased in liver and biliary disease - like AL[
NOT increased in bone disease
associated with alcohol use
list dzs where you see increased lipase
acute pancreatitis most specific marker
child
afebrile, quiet lethargic, sleepy
hepatomegaly
liver dysfucntion
reyes syndrome
what is reyes syndrome
rare
often fatal
childfood enchaphalopathy
discuss findins in reyes syndrome
mitochondrial abnormalities microvesicular fatty change in liver hypoglycemia vomiting hematpomegaly coma
what is reyes syndrome associated with
aspirin to treat viral infection especially VZV and influenza
what is the MOA of reyes syndrome
aspirin metabolies decreased beta oxidation by reversible inhibition fo mitochondrial enzymes
what is except to avoidance of aspirin in children
Kawasaki disease
fatty liver hypoglyecemia vomiting hepatomegaly coma child recent VZV or influenza
aspirin
reyes syndrome
what is hepatic steatosis
macrovesicular fatty change that may reversible with OH cessation
what causes OHic hepatitis
sustained, ong term consumption of OH
describe the histopathos of OHic hepatitis
swollen and necrotic hepaticyes with PMN infilriation
Mallory bodies - intracytoplasmic eosinophilc inlcuisons of damaged keratin filmaets
labs in OHic hepatitis
AST> ALT usually 1/5
what is OHic cirrhosis
final and irreversible form
histoatphos on OHic cirrhosis
micronodular, irregularly shrunken lvier with ‘‘hobnail’’ apperances
sclerosis around central vein aka zone III
microvesicular fatty change
reye syndrome
Mallory odies
OHic hepatitis
hobnail apperance
OHic cirrhosis
macrovesicular fatty chane
hepatit steatosis with OH
swollen and necrotic hepatocytes with lymphocytic infiltration
OHic hepatitis
drugs that can cause fatty change in the liver
amiodarone
methotrexate
drugs that can cause fibrosis in the liver
amiodarone
methotrexate
retinoic acid
what is non OHic fatty liver disease associated wtih
metabolic syndrome/insulin resistance
how does metabolic syndrome/insulin resistance cause non OHic fatty liver disease
increased fatty infiltration of hepatocytes – cellular ballooinign and evnetal necrosis
what can nonOHic fatty liver disease end up as?
cirrhosis and HCC
labs in nonOHic fatty liver dsiease
ALT > AST
cellular ballonign and necrosis
non OHic fatty liver disease
swollen and necrotic hepatocytes with PMN infiltration
OHic hepatitis
how does hepatic encephalopathy come about? pathophys time
cirrhosis – portosystemic shunts – decreased HN3 metabolsi – neuropsychiatric dysfuction
describe cxpx of hepatic encephalopathy
spectrum: disorientation/asterixis to difficulr arousal or coma
altered mental status somnolence disordered sleep rhythma asterixa coma or death
hepatic encephalopathy
treatment of hepatic encephalopathy
lactulose - increased NH4 generation
rifaxamin
what causes decreased NH3 removal
renal failure
diuretics – cause alkalosis (loops and thiazides) – keep NH3 as is not excreted in H buffferint to NH4, hepatic blood flow post TPIS is bypassed
what causes increased HN3 production and absorption
dietary protein
gi bleed
constipation
infection
what to avoid in pts with hepatic encephaolpaty
dietary protein gi bleeds constipation infection renal failure diuretics portosystemic shunts man made.
what is most common primary malignant tumor in adults
hepatocellular carcinoma
what is hepatocellular carcinoma associated with
cirrhosis: including HepB, HepC, Oh and non OH fatty liver disease, autoimmune diseases, hemochromatisos, alpha1 antitrypsin def and wilsons and aflatoxin
what syndrome can hepatocellular carcinoma lead to
budd chiari syndrome
describe budd chiari syndrome presentation
congestive liver disease: hepatomegaly, varices, abdominal pain, eventual liver failure without JVD
jaundice tender hepatomegaly ascites polycythemia anorexia
renal cell carcinoma
how does HCC spread
hematogensouly
fever
pain
increased liver size
blood in ascistes fluid
hepatocellular carcinoma
how to diagnosis hepatocellular carcinoma
increased alpha fetoprotein
u/s
contrast CT/MRI, biopsy
what are paraneoplastic syndromes with hepatocellular carcinoma
EPO
PTHrP - hypercalcemia
insulin like factor - hypoglycemia
serum markers in hepatocellular carcinoma
increased alpha fetoprotein
increased ALP
increased GGT
NO AMINOTRANSFERASE DIFFS
what is the most common benign liver tumor
cavrernous hemangioma
what is typical tumor in 30-50 years old lvier
cavernous hemangioma
benign
histopathos of cavernous hemangioma please
biopsy is contraindicated due to risk of hemorrhage bc made up of a collection fo dilated blood vessels
what liver tumors have a risk of hemorrhage
caveronous hemangioma and hepatic adenoma
what is a hepatic adenoma
rare
benign liver tumor that can spontaneously regress or rupture - hemorrhage
who is like to get a hepatic adenoma
OCP and steroid useers
von gierke glycogen disease
hepatic tumor associated with von gierkes?
hepatic adenoma
abdominal pain and shock
rupture of a hepatic adenoma
what is an angiosarcoma
maligi tumor of epithelial origin
rf for angiosarcoma
vinyl chlorid
arsenic
torium dioxide in radiocontrast
vinyl chloride
arsenic
thorium dioxide/radiocontrast
angiosarcoma of liver
what mets show up in the liver
git, breas, lung
what is most common place to find mets
lvier
git
breast
lugn
hepatomegaly varices abdominal pain eventual liver failure no JVD
budd chiari syndrome
what causes budd chiari cyndrome
thrombosis or compression of the hepatic veins with centrilobular congestion and necrosis ie congestive liver disease
what is associated with budd chiari syndrome
NO JVD REMEMBE OR ELSE RIGHT HEART FAILURE hypercoaguable states polycythemia vera postpartum state HCC
what are these risk factors for: hypercoagbaule state, polycythemia vera, postpartum state, HCC
budd chiari
gross appearance of lvier in congestive liver disease
nutmeg: centrilobular congestion and necrosis of liver
mottled apperance
what is most common cause of budd chiari?
polycythemia veraq
enlarged painful liver
portal hypertension
splenomegaly
ascites
congestive liver disease
RHF if JVD
budd chiari if not
pathophys of alpha1 AT def
misfolded gene product protein aggregates in hepatocellular ER - red cytogranules
what is inheritance pattern of alpha 1 anti trypsin def
codominant AD
what is the normal allele for A1AT?
MM
what is worst allele for A1AT?
ZZ
how does alpha1 antitrypsin manifest?
at lungs - panacinar emphysema
at liver - cirrhosis
what is the most common cause of cirrhosis in children
alpha1 anti trypsin deficieincy
what causes jaundice
tis abnormal yellowing of skin and or sclera due to bilirubin deposition
when does jaundice occur
in the face of increased production ofdefective metabolism of bilirubin – when reach levels of > 2.5 mg/dL
what causes unconjugated/indirect hyperbilirubinemia
physiologic neonatal jaundice
gilbert
crigler-najjar
hemolytic anaemia
what causes conjugated/direct hyperbilirubinemia
biliary tract obstruction: gall stones, cholangiocarcionma, pancreatic or liver cancer, liver fluke
bilary tract disease: primary sclerosing cholangitis, primary biliary cholangitis
excretion defects: dubin Johnson and rotor syndrome
what are biliary tract obstructive causes that lead to conjugated/direct hyperbilirubinema
gall stones cholangiocarcionma pancreatic cancer lvier cancer liver cluke (chlonoarchis sinusis)
what are bilary tract diseases that can cause conjugated/direct hyperbilirubinema
primary sclerosing cholangitis
primary biliary cholangitis
what causes mixed indirect/direct hyperbilirubinemia?
hepatitis
cirrhosis
pathophys of physiologic neonatal jaundice please
immaute UDP glucuronosyltransferase – unconjugated hyperbilirubinemia – jaundlse and kernicterus
what is kernicterus
deposition of water insoluble unconjugated bilirubin the the brain particularly at the basal ganglia
basal ganglia deposition of liver messing up
Wilson - copper
kernicterus - unconjugated bilirubin
how to treat physiologic neonatal jaundice
phototherapy
asymptomatic or mild jaundice with increased unconjugated bilirubin without overt hemolysis
gilbert syndrome
clincali consequences of gilbert syndrome
none hurrah
pathophys of gilbert syndrome
mildly decreased UDP-glucuronosyltransferase conjucation
AND
impaired bilirubin uptake
what makes bilirubin increased in gilberts
fasting and stress
what is the pathophys of crigler najjar type I?
absent UDY-glucuronosyltransferase
jaundice
kernicterus
increased unconjugaster bilirubin
early in life
crigler najjar syndrome type I
prognosis of crigler najjar type I
fatal in a few years of life
how to treat crigler najjar type Ii
less severe
tx with phenobarbital to increase liver enzyme synthesis
how dose phenobarbital work
increase enzyme synthesis for treatment of crigler najjar type II
grossly black liver
benign
dubin Johnson syndrome
pathophsy of dubin johnson
defective excretion
hyperconjugated bilirubinemia
what is roto syndrome
similar to dubin Johnson
hyper conjugated bilirubinemia
no black liver
what syndrome involved impaired uptake of bilirubin
gilberts
NOT crigler najjar
what is Wilson disease aka?
hepatolenticular degeneration
what causes Wilson disease
inadequate hepatic copper excretion and failure of coppuer to enter circulation and cerloplasmin
where do levels of coppu increased in Wilson diseas at first
liver
where do levels of copper increase in Wilson disease later on
after liver spews it out blood eyes kidney brain red blood cells joints
type of inheritance wilsons
chromosome 13
AR
ATP7B
how is copper normally dealt with in the liver?
excreted into bile via a hepatcoyte copper transporting ATPase that gets messed with an ATP7B mutation
blood levels in wilsons
low cu at fist
low cerylplasmin
describe effects of cu in organs
eyes - deposition in cornea - Kayser-Fleishcher rings
liver: cirrhosis - HCC
kidneys - fanconi syndrome
joints : dysarthria
brain: putamen - parkinsonism, subthalamic nuclei - hemiballismus and dementia
blood: hemolytic anaemia
asterixis dementia hemiballismus parkinsonism HCC fanconi syndrome hemolytic aneamia dysarthria KF rings
Wilson disease
how do you treat Wilson disease
penicillamine
trientine
oral zinc - inhibits absorption in intestine
what is hemochromatosis
the inherited cause of hemochromatosis - deposition of hemosiderine in tissues
what is the classic presenting triad of hemochromatosis
cirrhosis
DM
skin pigmentation
what are consequences of hemachromatosis
heart failure (restrictive)
testicular atrophy
increased risk of HCC
what are causes of hemochromatosis
primary - AR of HFE, C282Y, H63D in HFE gene with HLA-A3
secondary - chronic transfusion therapy ie beta thalassemia major
blood work for hemochromatosis please
increased ferritin
increased fe
decreased TIBC
increased transferrin saturation
how do you id iron on a biopsy
Prussian blue stain
how much body iron is enough to set off detectors at airport
50 g - can happen in hemochromatosis
HLA association with hemochromatosis
HLA-A3
HLA-A3
hemochromatosis
why is onset of hemochromatosis slower in women than men
meennsseesss
how do you treat hemochromatosis
phlebotomy
chelation with deferasirox, deferoxamine and deferiprone (oral)
typical nationality with hemochromatosis
northern European descent
list the organs affected in hemochromatosis
liver pancreas heart joints skin brain - pituitary
list the organs affected in wilsons
liver eyes joints blood brain - bg kidney
list the effects on organs by hemochromatosis
liver - cirrhosis - HCC
heart - restrictive cardiomyoatphy
brain - pit - infertility (decreased levels of Lh and FSH)
pancrease - DM I
skin - bronze - melanine production increased
joints - degenerative arthritis
list organs in Wilson vrs hemochromatosis and both
both: liver, joints, brain,
Wilson: eyes, kidney, rbc
hemochromatosis: heart, pancreas, skin
