Card Set Information
GI gastrointestinal system
GI final session 5 westernU 2011
(A)What is the most common cuase of gallstone in the US?
(B)What are risk factors of gallstone?
(A) excess cholesterol to bile salts & lecithin
(B) fat (obesity), fertile (high estrogen), female of forty (age)
what are important factors in the progression of cholecystitis to cholangitis?
: Billiary obstruction -->calculi, tumor or stricture
E coli, klebsiella, Pseudomonas, enterobacter and
anaerobic infection like bacteroides
ascend from duodenum to billiary tract and then enter portal circulation to cause septicemia.
Person presents with fever, RUQ pain, jaundice. What is that called?
What are the clinical manifestations of acute cholangitis? if they become septic?
*clay colored stool, dark colored urine, & pruritis occurs in
if pt becomes septic: +confusion, HoTN --> now called Reynod's Pentad
Explain the studies needed to determine acute cholangitis.
LFTs show cholestatic pattern
: high conj.Bili, AlkPhos may be elevated
US (may see dilated common bile duct before stone) or CT
ERCP (endoscopic retrograde cholangiopancreatography)
: will show stones
if ERCP unsuccessful or post-cholecystectomy pt b/c ERCP is high risk with them
Exp. Tx for Cholangitis
-amp-sublactam or piperacillin-tazobactem or carbapenem
-OR metronidazole + (ceftriaxone or FQs)
-endoscopic sphincterotomy w/stone extraction &/or stent insertion
Tx of choice for biliary drainage in acute cholangitis
Sugery indiated in
-persistent abd pain
-HoTN despite adequate resuscitation
-Fever >39C (102F)
-Mental confusion (predicts poor outcome)
What is the route of spread of HepA?
what are the risk factors for HepA?
international travel (mexico, Asia, South Am., etc)
employee of daycare center
household contact of hepA pt
What is the “disconnect” between the HAV viral genome and its antigenicity?
+ssRNA means it is similar to mRNA and THUS can be immediately translated into protein (in comparison, HIV, although +, will
HepA (HAV) is a +ssRNA, there is only one serotype & therefore
infection or vaccine can give long-term immunity
What is important about the structure of HAV as it relates to its ability to infect humans?
HAV is a Heparnavirus in the Picornaviridae family
it is naked (NON-enveloped) THU can survive in environment longer (water/sea water for >months)
What is the cause of the pathology associated with HAV?
The virus replicates in hepatocytes and are shed from those cells and are released in the stool. HAV can also be found in saliva and serum NOT urine.
The damage associated with HAV is not directly due to the virus since it happens to be “non-cytolytic” virus and instead, much is due to the immune response against the virus.
What are the histological features of a HAV infection?
may see large pink cells undergoing "ballooning degeneration", later they will shrink to form an eosinophilic "councilman body"
mononuclear inflammatory cell infiltrate extends from the portal areas
What are the clinical features of HAV?
*mostly dz is aSxic/benign & self limiting but,
AFTER incubation of at least 30d can see:
: fatigue, malaise, N/V, anorexia, fever, RUQ pain
--Icteric phase a few days later
: jaundice, dark urine, acholic stool (
light colored stool
how to dx HAV?
serology (ELISA) looking for presence of AB vs virus.
infection--usually present 5-10d before onset Sxs & undetectable after 6mo's ([virus] in stool decreases after jaundice appears...~2wks)
IgG upon recovery (IgG rises much later!)
explain the timeline of HAV infection
what are the complications of HAV infection?
fulminant hepatitis-->requires liver transplant
what are pre-exposure porphylaxis recommendations for HAV?
routine vaccine for kids 12-23mo's
MSM, frequent blood/plamsa recipients, chronic liver dz (including HepB & C)
what do you Rx for active immunization? for travel?
: 2doses of vaccine 6mo apart
: vaccine of >2wks before travel & healthy; Ig if person is immunocompromised
what are the post-exposure prophylaxis for HAV?
Hep A vaccine alone for healthy <41yo
all others receiving passive immunization
: pooled Ig
(for kids <12mo, immuno compromised, pts w/chronic liver dz or have vaccine contraindications.)
Explain reasons for AST:ALT >2:1
alcohol-related liver dz
: strenuous exercise, hemolysis, myopathy, thyroid dz, macro-AST
explain risk factors for alcoholic liver dz
: 1 beer, 4oz wine, 1oz80proof all have ~12gEtOH; M >60-80g/d or F>20-40g/d x10yrs
: homozygous for ALDH*2 unable to oxidize acetaldehyde & don't tolerate EtOH
describe the pathogenesis fo alcoholic liver dz (image)
describe the pathogenesis of alcoholic liver dz.
short-term ingestion of <80gEtOH (6beers) over 1-2d produces mild, reversible hepatic steatosis.
daily intake of >80 = risk of injury
daily intake >160g/d x10-20 yrs -->severe injury
**however only 10-15% of alcoholics develop cirrhosis
gender - F>M; estrogen increases gut permeability to endotoxins --> increase LPS receptor CD14 in Kupffer cells --> predisposes to increased production of pro-inflammatory cytokines & chemokines.
ethnicity - rate cirrohsis AfAm > white
genetics - homozygous ALDH*2
: Fe overload & infections w/ HCV/HBV increase severity of alcoholic liver dz
describe the detrimental effects of alcohol on hepatocellular fn.
exposure --> steatosis, dysfn of mito & cellular membranes, hypoxia, oxidative stress
what causes hepatocellular steatosis specifically?
shunting of nL substrates away from catabolism & toward lipid biosynthesis due to generation of excess NADH + H+ (reduced form)
impaired assembly & secretion of lipoproteins
increased peripheral catabolism of fat
describe the factors in the pathogenesis of alcoholic hepatitis.
: the major intermediate metabolite of EtOH, induces peroxidation & acetaldehyde-protein adduct formation, further disrupting cytoskeletal & membrane fn.
reactive O2 species (ROS)
that react w/ cellular proteins, damage membranes & alter hepatocellular fn.
alcohol-induced impaired metabolism of methionine --> decreased intrahepatic glutathione levels, thus sensitizing liver to oxidative injury
induction of CYP2E1 & other cP450's increases alcohol catabolism in the ER and enhances the conversion of other drugs to toxic metabolites
how does alcohol specifically play a role in the inflammation in alcoholic hepatitis?
release of bacterial endotoxin from the gut
into portal circulation --> inflamatory responses in the liver
-->activation of NF-kB, release of TNF, IL-6, TGF-a
release of endothelins
from sinusoidal endothelial cells --> vasoconstriction & contraction of activated sellate cells (myofibroblasts) --> decreased hepatic sinusoidal perfusion
what are signs of "fatty liver"?
tender hepatomegaly w/ mild elevation of serum bili & AlkPhos.
describe this image:
globular red hyaline
material w/in hepatocytes =
aka "alcoholic" hyaline. they are aggregates of intermediate filaments in cytoplasm from hepatocyte injury.
**can also see the eosinophilic
in hepatocytes in Masson stain (stains fibrous tissue blue)
will also have swelling of hepatocytes, necrosis & PMN's
what are some clinical signs of alcoholic hepatitis?
abd pain stimulating an acute abd
**majority are aSxic
what are diagnostic features of alcoholic liver dz?
-AST:ALT rise 2-7x AND >2:1
-mild increase in bili & AlkPhos
-determine fatty infiltration of liver
-size of liver
what is the prognosis of alcoholic liver disease? signs/complications?
30d mortality rates >50%
Signs/complications of severe alcoholic hepatitis:
-coagulopathy (PTT >5s)
-serum albulin [ ]s <2.5mg/dL
-serum bili >8mg/dL
Tx for alcoholic hepatitis
1st alcohol abstinence & nutritional suport
then, discriminant fn >/=32 (w/o comorbidity)
: Prednisolone 32mg POd x4wks, then taper4wks
: Pentoxifylline 400mg POtid x 4wks
how is HBV transmitted?
sex contact & IV drug use
*more efficient transmission than HIV-1!
describe HBV and what makes it unique.
an enveloped virion that produces a reverse transcriptase
: replicates via an RNA-intermediate
dsDNA, circulizes in host cell
viral genome surrounded by the hepatitis B core antigens (HBcAg & HBeAg) which is surrounded by the envelope that has the hepatitis B surface antigen (HBsAg)
complete virus called the Daneparticle
explain HBV replication
HBsAg allows attachment to liver cells
virus is non-cytolytic
viral genome can
integrate into host chromosome
--> make mRNA --> reverse transcriptase makes into DNA
one mechanism HBV evades immune response? what can result from this?
mass produced non-infectious viral proteins (HBsAg) may be antigenic “decoys” inhibits neutralizing Abs
immune complexes can form causing type III hypersensitivity reactions ( activation of compliment cascade & PMN's i.e. inflammation -->vasculitis,rash, renal damage)
what is polyarteritis nodosa and what is its relation to HBV?
it is a redish inflammation of small-medium sized arteries seen as slight hypermelanosis
there is a deposition of fibrinoid material & destruction of external & internal elastic lamae
there are PMN's & eosinophils, leukocytes
what are the clinical manifestations of
-if have Sxs:
what are the clinical manifestations of
: usually no Sx until onset end-stage liver dz
how do you dx HBV dz?
LFTs show AST and ALT >100U/L
liver biopsy needed to determine the grade & stage of chronic HBV disease
describe the images:
: show hepatocytes w/diffuse granular cytoplasm "ground glass hepatocytes"
: immunoperoxidase stain for HBsAg
describe the timeline for
window period = after disappearance of HBsAg & before HBsAb appear, where only HBcAb-IgM is + can suggest infection
describe the meaning of associated ag/ab's for HBV serology.
HBsAg (surface ag) = acute infection or chronic "carrier state"
HBeAg = pt is infectious
) = past exposure or immune from vaccine
-IgG = exposure, not protective
-IgM = acute infection
HBeAb (E ab) = low risk of infection
what differs acute vs chronic HBV?
: inflammation >6mo, HBeAg or HBsAg
will stay +
describe timeline of progression to chronic HBV.
describe serology for the following states of HBV:
acute, inactive carrier, chronic, prior exposure, prior vaccine.
what is the tx for ACUTE HBV
can use hepB Ig to prevent/lessen Sx's w/in 1wk of exposure, esp infants to HBsAg + moms
tx for CHRONIC HBV?
recommend antiviral Tx for:
-active HBV replication (+HBeAg or HBV DNA >100,000copies/mL)
-liver dz (ALT > 2x upper limit nL or modl liver dz &/or fibrosis on biopsy)
reverse transcriptase inhibitors (e.g.lamivudine)
nucleoside analogues (e.g. famcicovir)
what are complications of HBV infection?
hepatocellular carcinoma (HCC)
1. screen via US, repeat every 6-12mo to detect development
2. consider serum AFP but poor sens/spec
: need to confirm results w/US.
how can you prevent HBV infections?
vaccinate vs HAV
HBsAg is used in vaccine
who to vaccinate?
-all HCV infected
development of ab response can prevent initial infection of liver cells
describe family genus, genome, transmission, & chronicity of HepA, B, C, D, E.