liver Flashcards
portal triad and waht contaisn it
hepatic artery
portal vein
duct
hepatoduodenal ligaent
cells of liver
hepatocytes
cholangiocytes:intercellualr channels–>bile canaliculi
nonparenchy
–kupffer (macrophages)
–sinusoidal endothelial cells- no RBC; leaky barrier
–pit cells
–hepatic stellate cells -collagen synth
splenic vein branches
short gastric
pancreatic
L gastroepiploic
IMV
SMV
inferior pancreatoduodenal
R gastroepiploic
portal vein
superior pancreatic duo
L gastric
biliary system
canals of hering–>bile ductules–>terminal ducts–>segmental bile ducts–>R and L lobal ducts–>common hepatic ducts + cystic duct–>common bile duct–>sphincter of oddi
acinus
blood supply of a small portion of parenchyma that drains a particular bile duct
lobule
blood supply by several separated portal vein branches, each of which also supplies adjacent lobules
bile compromises
conjugated bilirubin
cholesterol, phospholipids
bile salts
water, electrolytes
what converts 1% conj bilirubin to urobilinogen
intestinal bacteria
places glucose 6 p can go
synthesis of glycogen
anaerobic glyclysis
pentose-phosphate shunt
what proteins are not made by liver
Igs
what else makes alk P
bone
gGT
biliary epithelium
liver disease changes bioavailablity of circulating vasoactive substances and endothelial dysfunction
eNOS increase in splanchnic and decrease in liver AND increase production of VC–>splanchnic dilation and liver resistance
PHTN syndrome
central VS of cns and kidney–>brain dysfunction and hepatorenal syndrome
vasodilation of splanchnic–>arterial hypotension–>decrease in PVR, hypervolemia–> well perfused skin, low BP
vasodilation of intrapulm circ–>dec O2–>hepatopulm
hyperdynamic circulation means that
system very suceptible to very minor changes
septicemia–>endotoxin medicated vasoC
Nsaids–>block kidney fx
diurectics–>increase VS
these drugs may improve cirrhosis
bblockers to decrease shear stress on hepatic/splanic vessels–>decrease endothelial damage–>decrease enos
a agonist–>VD
anti inflam agents
child pugh predicts
outcome of tx, variceal hemorrhage etc scored for freq of abnoramilties A: 5-6 B: 7-9 C: 10-15--decompensated cirrhosis
TIPS not recommendedchilds
grade b-c
ALT>AST
hepatitis
AST>ALT
alcohol or cirrhosis
dx test for ascites
SAAG
culture
cytology
CBC and HGB
SAAG >1.1
almost alaways decompensated cirrhosis
tx ascites
tx underlying liver dz
consider transplant if prognosis is poor
decrease dietary Na intake, fluid restriction, and diuretics
in diuretic ressistance patients
paracentesis
shunts:TIPS
extracorporeal ultrafilitartin of ascitic fluid
liver transplant
sequela of ascites
hepatic hydrothorax- fluid enters chest via diaphragmatic defects
umbilicl, inguinal hernias
spontaenous bacterial peritonitis: translocation of bacteria from mesenteric LN–>bacteremia–>bacterascites
hepatorenal fx (poor px)
main cause of jaundice
viral hepatitis
hep A
+ stranded RNA picornavirus w/o envelope
feval oral
dx hep a
HAV IgM
HBV
small DNA virus of hepadnavirus
–partially dsDNA + viral envelope + core, DNA polymerase and x particle
sexual transfer
mom–>child
clinical presentation of hepB
acute infection
CLD
extrahep-rash, gnitis, arthritis, vasculitis, angioneurogenic edema
testing hbv
+HbsAg= acute infection if anti-HBc (IgM is )+
+HBsAg w/ sx and - Igm- early acute
+HBsAg w/o sx- mild CLD
+anti-HVs(afe)–recovery/immunity
+HV DNA- best indicator for active viral replicatin
tx HBV
entecavir, tenofovir
HDV
defective RNa virus–requires HBV first
HEV
single stranded + RNA hepevirus
pigs are reservoir
HEV transmission
fecal oral
rare instates, but leading cause of jaundice in endemic areas–usually affects both sexes
clinical presenation of HEV
incubation 2-9 weeks
may cause acute liver failure
chronic form possible
mortality in HEV
increase sa ton in pregnancy esp third trimester
testing HEV
RNA for active rep + IGM= acute, +IGG= past hep
hep v
single + sRNa virus, eveloped, flavivirus
1-6 types
how do HCV invaide
interact with surface proteins hepatocyte
enter cell by endocytosis
uncoat in the low endosomal ph
viral envelope fuses with endosome mebrane releasing RNa into cyto
rna interacts with ribo
single polyprotein produced
cleaved by proteases to mature viral protein
replicate
assembly
budding
risk of HCV
40-80%
higher than HBV
HCV can prodyuce
cryoglobinemia–accum of Igg related products in dependent ares- becoem insoluble in cold temp
screening tests
ELISA + RNA detection
anti HCV + HCV RNA +
active infection
anti HCV + , HCV RNA=
past infection
ANTI HCV -, HCV RNA+
acute HCV immunp sup
false positive RNA
HHC affects many organs
pituitary thyroid parathyroid heart liver panc gonads joints blood skin
pathiphys A1AT def
lung: A1AT blocks lung elastase in alveoli
- -if they lack this–>lung disease and COPD
liver: cuumulation of wrongly folded A1AT in cell ER–>cell damage–>apoptosis–>fibrosis and cirrhosis
what type of disease is A1AT
AR with codomiannt expression
M, S, and Z alleles on SERPINA1 gene on Ch16 (or >100 identified alleles)
most normal MM, Z abnormal
screening for A1At
recommended in patients with asthma and COPD
adults vs children presentaing
adults: lung > liver
kids: neonatal jaundice, hepatomegaly, failure to thrive, or acute LF
dx A1AT def
decrease serum A1AT (but can increase with iflam because it is an APP)
protein phenotyping
liver bx (nor req)
PAS + diastase resistant gloubles
most Fe in body found within
hemoglobin
most storage of Fe
macrophages and hepatocytes- small amounts in myoglbin
hepcidin
hormone produced in liver–>responds to Fe levels in blood
stimulates Fe transport into cells (macrophages, enterocytes, hepatocytes)
ferroportin
main Fe export protein on enterocytes, Mo, and hepatocytes
HFE protein
found on hepatocytes; sensory for circulating Fe
decrease in hepcidin
increase in circulating Fe
increase in hepicdin
increase in Fe transport into cells but decrease in export out because destruction of ferroportin
HFE-HC type 1
hereditary impairment of synthesis of fx of hepcidin
AR mutation on chr 6
1:7 hetero for C282Y and 1:3 hetero for H63D
what happens in HFEHC
impaired hepcidin synthesis–>increase circulating Ge–>incrase transferrin sat–>progressive Fe deposition in parencyma of liver, etc
tx HFE HC
phelbotomy
NonHFE HC
not assocaited with hepcidin function
transferrin saturdation is slightly increased or low
iron accumulates in RES and othe rcells
not responsive to phebotomy
dx hemochrom
increase LFT, inc ferritin, dec transferring, but inc trans sat (>45), decrease TIBC
wilson’s disease
AR disease involving accumulation of Cu in body secondary to defective secretion by a mutated Cu transporting Ptype ATPase on golgi in hepato
job of defective Cup transporting p typeprotein
chaperon Cu into bile by binding apoceruloplasmin to form ceruloplasmin which transports cu
wilsons dz presentation
liver portal htn nonhemolytic anemia** cns: mental dysability renal dysfx cardiac bone heme
kayser fleischer ring
cu depposit in descement membrane of cornea–>sunflower cataract seen in 95% of patients with neuropsych sx
usually normal vision
labs wilson
decrease in ceruoplasmin
decrease total Cu (because mostly bound to ceruplasmin)
but increase free total Cu fraction
tx willsons
d-pencillamine and trientine (chelators), zinc-absorption of excess Cu in the body, liver transplant
criggler najjer syndrome
ar disorder with decrease to absent UGT (more severe filbert)–type 1 incompatible with life, type 2 less severe
UCBemia in children
dubin johnson
D
ar disorder of apical canalicular membrane proteins resp for excretion of bili into intrahepatic ducts
obstructive with increase CB
black liver
rotor
similar to dubin with no black liver
oxidative metabolism alch
acetate is end product–>uses up O2 and NADH and produces centrilovular hypoxia in a region already low in O2
microsomal oxidation
not used much in normals but more in alcoholics, which is bad because acetyladehyde makes percentral zone produce collagen and also is the pathway used to oxidate tyelnol
alcohol increases
pmn infiltration
cytokines in alcohol
tnf and il6
HCT
may be only abnormal liver test
two measures of how bad alcholic liver disease is
MDF (pt and bili) >32 predicts 30 mortiality
MELD, >18 predicts 30 day mortality and >5 can get transplant
tx alch hepato
supprotive
prenisolone for severe or hepatic enceph
tnf inhibitor that decreses risk of renal disease
abstinance is key1
NAFL
steatosis
benign, reversible
NASH
fatty liver _ hepatocyte death
cirrhosis
regenerative nodules + fibrosis
abnormal production of hormones produced by fat
decreased adiponectin–>block FA uptake–>increase FA oxidation and lipid export–>increase insulinsensitivty
increase TNFa–>proapoptotic, recruits wbc, increase insulin R
liver function tests
AST, ALT ALT can suggest statosis
negative tsts other dz
gold standard of estimating severity
bx
tx NASH
weight loss increase insulin sens with metformin or proglitazone vitamin E/proglitazone change diet coffee
NAFL to cirrhosis
> 10 years, 3%
NASH + fibrosis to cirrhosis
5,10 years, 30%
autoimmune HLADR3
fibrosis and cirrhosis
antibodies for AIH
ana often + but nto specific
usually either SMA or microsaomal but not both
polyclonal gammopathy
IgG>IgM>IGa
liver bz shows
plasma cells
LFT >1000
viral hep
AiH
shock liver
acute drug or toxin liver injury
LFT >10000
acetaminophen tox/shock liver
other autoimmune dz
primary biliary cirrhosis
franulomatous destruction of interlobular bile ducts–>progressive ductopenia–>progressive cholestasis–>cirrhosis and liver failure
PE of PBC
hyperpih excoriations from prutitis jaundice xanthomas hepatosplen
labs PBL
lFTs cholestatic (ALP/GCT»>AST/ALT)
AMA*****antimitochondrial antibody
ANA+
tx of PBC
ursodeoxycholic acid works–improves LFTs and survive
PSC vs PBC
PSC0 macroscopic bile duct abnoramlity
PBC- microscopic
major comp of PSC
cholangiocarcoma (mc!)
ABCDE chronic hep
AiD B virus Cvirus Drug induced Etoh
portal triad and central vein collagen types
I, III
percellular reticulin in lobules collagen types
IV
causes of hepatic injury
toxin accum
inflam
ischemia
injury leads to
activiaton of hepatic stell cells–>proliferate, multiply, interact with kuppfer cells–>hepatocyte apoptosis & pro fibrosis (TGF B), loss of fenestrating–>cirrhosis
pathway of fibrosis
portal fibrosis–>periportal fibrosis–>inflammation that allows fibrosis to swpill over–>bridign fibrosis–>cirrhosis
main benign liver tumor
hemangioma
hepatocyte beign vs malignant
benign-hepatic adenoma, focal nodular hyperplasia
malignant- hepatocellular carcinoma, hepatoblastoma
biliary epithelium benign and malignant
benign- bile duct adenoma, biliary hamartoma
malignant- choiangiocarcoma
mesenchymal benign vs malignant
benign-hemangioma, angiomylipoma
malignant- angiosarcoma
biliary hamartoma is
normal tissue an abnormal location
hepatocellular adenoma
MC primary malignant
HNF1a –associated with MODY3
associated with oral contraceptive, steroids, or pregnancy
RUQ mass, pain, hemorrhage
focular nodualr hyperplasia
multiple fibrus septae with central scar
hepatoblastoma- least common malignant
kids; moms notice diapers arent fitting
produces hcg so virilization and precocious puberty
surgery and chemo
hepatocellular carcinoma
90% malig cancer 80% with HBV or HCV (90% in west) travecular and acinar bile in neoplastic cells compesnated -->decompensated wth rising afetoprotein level
what doesnt work with HCC
chemo and radioRx–need liver transplant
special subset HCC
fibrolammelar hepato–age 20-40, no association with CLD or cirrhosis
cholangiocarcinoma
adenocarcinoma arising from intra and extra hepatic bile duct epithelium
main site ampulla; no relation to cirrhosis
a/w pSC, choledocal cysts, liver flukes, etc
CEA
increased in bile duct carcinoma
mucin production
in bile duct carcinoma
none in HCC
bile duct carcinoma vs hepatocellualr carcinoma spreads through
HCC-veins
BD-lymphatics
gross appearance HCC vs BD
HCC-soft and hem
BD-hard whitish
