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10.4 Liver II
8:30 by Dr. Ruiz
109
Pathology
Professional
10/04/2011

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Cards

Term
What bacterial infections commonly secondarily involve the liver?
Definition
sepsis, typhoid fever, miliary TB, secondary or tertiary syphilis
Term
What parasitic infections commonly damage the liver?
Definition
malaria, trematodes (opisthorchiasis, chlonorchiasis, fascioliasis), echinococcosis, amebiasis
Term
What are the causes of abscesses in developing coutneries versus developed countries?
Definition
developing= amebic
developed= pyogenic/bacterial
Term
By what routes can organisms get to the liver to cause liver abscesses?
Definition
biliary tract (ascending cholangitis) is the most common, arterial (sepsis), portal vein (pylephlebitis), direct extension, penetrating injuries
Term
What routes are used to cause multiple, small liver abscesses?
Definition
biliary, arterial, portal
Term
What routes are use to cause solitary abscesses?
Definition
direct extension, trauma
Term
The contents of an amebic abscess are often described as..
Definition
anchovy paste
Term
What is the route for amebic absceses? Are they multiple or solitary?
Definition
portal; solitary
Term
T/F Liver abscesses have a high mortality.
Definition
true: they can rupture into the abdominal cavity causes peritonitis and peritoneal abscesses, OR rupture into the thoracic cavity causes empyema or lung abscesses
Term
Which nonhepatotropic viruses cause viral hepatitis?
Definition
mononucleosis (epstein barr virus), yellow fever in children and immunosuppressed: CMV, herpesvirus, adenovirus, etc.
Term
Name the hepatotrophic viruses.
Definition
hepatitis A, B, C, D, and E
Term
Which hepatotropic viruses are unenveloped?
Definition
A and E
Term
What are the transmission characteristics of unenveloped viruses?
Definition
survive exposure to bile (emulsification) and shed in feces. Waterborne-fecal-oral transmission. Rare bloodborne transmission
Term
Are the unenveloped hepatitis viruses (A and E) linked to long term problems such as chronic hepatitis and hepatocellular carcinoma?
Definition
no linked to chronic hepatitis, no carrier state, not linke to hepatocellular carcinoma
Term
What is the genome of hep A?
Definition
single stranded RNA
Term
What is the incubation period of hep A?
Definition
2-6 weeks
Term
What are the symptoms of hepA?
Definition
prodromal state (malaise, anorexia, nausea, vomiting, fever) and icteric state (jaundice, improvement of symptoms).
May be anicteric, subclinical esp in children or could be fulminant
Term
When in the course of illness is HepA shed?
Definition
shed in feces 2-3 weeks before to 1 week after jaundice
Term
What can cause epidemics of hepatitis A?
Definition
contaminated agricultural products
Term
How do you diagnose HepA?
Definition
acute hepatitis with IgM anti-HAV in the blood and HAV RNA in the feces.
Term
How can you tell if a patient has had HepA in the past?
Definition
IgG anti-HAV and protective immunity
Term
Do we vaccinate against Hep A?
Definition
yes, since 1995
Term
What is the genome of Hep E?
Definition
ssRNA
Term
What is the incubation period of hep E?
Definition
2-9 weeks
Term
T/F HepE is enzootic/zoonotic.
Definition
true
Term
What population is mostly affected by hep E in developing countries?
Definition
young and middle age adults
Term
T/F Hep E can be subclinical in children.
Definition
true
Term
What population has a high mortality rate from hep E?
Definition
pregnant women. mortality is 20-30% in the third trimester
Term
What is the geographic distribution of hep E?
Definition
mexico, india, china, nepal, northern africa
Term
Hep E cases in developed countries are associated with..
Definition
older individuals (severity increases with age), pet ownership, and occupational exposure to pigs
Term
How do you diagnose acute Hep E?
Definition
igM anti-HEV in the blood and HEV RNA in the feces
Term
T/F Reinfections can occur with both hep A and hep E.
Definition
false, reinfections can only occur in hep E because of loss of IgG anti-HEV over time
Term
Is there a hep E vaccine?
Definition
vaccine is in phase III trials
Term
Which hep viruses are enveloped?
Definition
B, C, and D
Term
How are the enveloped hep viruses shed?
Definition
dirsupted by bile so not shed in feces. transmission by contact with body fluids (percutaneous, mucosal/sexual, vertical)
Term
Which hepatits viruses have long incubation periods, cause persistent viremia and chronic infection?
Definition
enveloped ones (B,C,D)
Term
What is defined as a chronic hepatis?
Definition
one that causes disease for more than 6th months
Term
Which hep viruses are linked to carrier states, hepatocellular carcinoma, and immune complex deposition?
Definition
enveloped (B, C, and D)
Term
What are the three classic problems with immune complex deposition?
Definition
arthralgia, vasculitis, glomerulonephritis
Term
What is the genome of hep B?
Definition
dsDNA
Term
What is the incubation of hep B?
Definition
4-26 weeks
Term
What is the course of hep B?
Definition
acute illness similar to hep A (jaundice occurs less often). May be fulminant or resolve completely. May become chronic (asympomatic-carrier state or symptomatic)
Term
What percent of patients with hep B make a full recovery?
Definition
>90%
Term
What is the most commonly reported hep viruses?
Definition
B
Term
What risk factors are reported in pts with hep B infection?
Definition
one third have at least 1 sexual risk factor. 6% sex with person known to have hep B. 38% have multiple sex partners. 11% are MSM.
15% are IVDU.
53% report no risk factor
Term
What is the risk of vertical transmission of hep B?
Definition
90%
Term
What's the risk of chronicity with hep B for immunocompetent versus immunocompromised adults?
Definition
<5% of immunocompetent
>50% of immunocompromised
Term
Do we have a hep B vaccine?
Definition
yes
Term
What is the dane particle?
Definition
HBV virion. Has HBsAG, HBcAg, HBeAg, HBx protein (replication, trans-acivate host genes), DNA polymerase, and HVB DNA
Term
What are the antigens of the HBV virion?
Definition
surface antigen (HBsAg)
nucleocapsid "core" antigen (HBcAg)
non-structural "e" antigen (HBeAg)
Term
What are the phases of hep B?
Definition
proliferative (episomal) and integrated
Term
What happens in the proliferative phase of hep B?
Definition
formation of complete virions, hepatocyte destruction
Term
What happens in the integrated phase of hep B?
Definition
virus integrated into the host's genome, cessation of viral replication, hepatocyte destruction subsides, continuous production of HBsAg
Term
What is the pathogenesis of Hep B? How does this explain the different disease course found in immunosuppressed individuals?
Definition
expression of HBsAg and HBcAg on hepatocytes activates cytotoxic T lymphocytes, responsible for the cell damage. This is why immunosuppressed patients suffer less cell damage but are more likely to develop chronicity
Term
T/F HepB can cause cancer.
Definition
true
Term
How do you diagnose an acute hep B infection?
Definition
HBsAg and IgM anti-HBcAg
Term
How do you determine if a pt with Hep B is having active viral replication/infectivity?
Definition
HBeAg and HBV DNA
Term
How do you determine if patient is having a chronic hep B infection?
Definition
symptoms for more than 6 months. Has HBsAg, HBeAg, and HBV DNA
Term
How do you tell if a patient has had a resolution of prior infection with hep B?
Definition
HBsAg, HBV DNA, and HBeAg disappear
anti-HBsAg and anti-HBcAg appear and persist
Term
What is the effect of hep B vaccination on patient labs?
Definition
anti-HBsAg WITHOUT anti-HBcAg because vaccine is made of recombinant HBsAg
Term
What histological finding is classical for HBV?
Definition
ground class hepatocytes, sanded nuclei, HBV core antigen seen with immunoperoxidase
Term
What is the genome of hep D?
Definition
small ssRNA virus
Term
Hep D has defective replication and therefore requires ___.
Definition
HBsAg
Term
What are the two types of diseases caused by hep D?
Definition
coinfection with Hep B: fulminant disease more likely. Chronicity <5%
superinfection of HBV carrier: fulminant less likely. Chronicity 80%
Term
In the US, the population that gets Hep D is mostly restricted to...
Definition
drug addicts, hemophiliacs, their sexual contacts
Term
How do you prevent hep D?
Definition
vaccinate for HBV
Term
What is the genome of hep C?
Definition
ssRNA; classified into 6 major genotypes
Term
Which genotypes of hep C cause most infections?
Definition
1a and 1b cause 70% of all infections in the US
Term
What is the incubation period of hep C?
Definition
2-26 weeks
Term
What is the disase course of hep C?
Definition
acute infection commonly subclinical; no fulminant presentation. High rate of chronicity 55-85% and high rate of progression to cirrhosis or HCC
Term
What percent of people with HCV go on to experienc chronic problems?
Definition
85%
Term
What are the risk factors for hep C?
Definition
IVDU (60%, highly efficient), sexual (less than 20%, rare b/t long term sex partners), needle stick (1.8 to 10%), no recognized source of infection for 10%
Term
T/F Perinatal transmission of hep C is low.
Definition
true
Term
Why is it difficult to develope hep C vaccine?
Definition
HCV genome is unstable and variable. IgG anti-HCV does not confer protection. Emergence of mutated strains (quasispecies) causes recurrences
Term
How do you diagnose hep C?
Definition
anti-HCV (EIA- enzyme immunoassay, RIBA-Recombinant immunoblot assay)
HCV RNA: qualitative and quantitative
Term
What's another name for hep G?
Definition
GB virus type C (GBC)
Term
What is the viral family of hep G?
Definition
RNA virus, flavivirus (same family as hep C, yellow fever, and west nile)
Term
How is Hep G transmitted?
Definition
parenteral, sexual, verticle transmission. Transmission by transfusion has been documented.
Term
Coinfection with HIV and GBV-C causes....
Definition
possible improvement of prognosis of HIV infection
Term
What are some causes of non-infectious hepatitis?
Definition
autoimmune hepatitis, drug toxicity, alcoholic and non-alcoholic steatohepatitis, inborn errors of metabolism (wilson's and alpha-1 antitrypsin deficiency) and primary biliary cirrhosis
Term
What disease is morphologically similar to viral hepatitis?
Definition
AI hepatitis
Term
What characterizes AI hepatitis?
Definition
prominent plasma cell infiltrate, more severe than viral, high frequency of cirrhosis, female predominence (>70%), concurrent AI diseases, responds to immunosuppressive therapy
Term
What antibodies are associated with AI hepatitis?
Definition
anti-nuclear antibodies, anti-smooth muscle, anti-liver/kidney microsome 1 (LKM1), anti-soluble liver antigen
Term
What are the two types of drug and toxic liver injury?
Definition
predictable or intrinsic= occurs in anyone at sufficient dose (acetaminophen)
unpredictable (idiosyncratic)= immune response (halothane) or slow metabolism (isoniazid)
Term
List toxins that cause macrovesicular steatosis.
Definition
methotrexate, ethanol, amiodarone
Term
What toxins cause microvesicular steatosis?
Definition
salicylates (reyes), tetracycline
Term
What toxins cause centrilobular necrosis?
Definition
carbon tetrachloride and acetominophen
Term
What toxins cause massive necrosis?
Definition
isoniazid, acetaminophen, halothane, and amanita phalloides
Term
What toxins causes chronic hepatitis?
Definition
nitrofurantoin, methyldopa, isoniazid, phenytoin, oxyphenisatin
Term
What toxins cause granulomatous hepatitis?
Definition
phenylbutazone, sulfonamides, hydralazine, allopurinol, quinidine
Term
What toxins cause cholestasis?
Definition
erythromycin estolate, chlorpromazine, anabolic steroids, and contraceptives
Term
How is acetominophen toxic?
Definition
small amount of acetominophen is metabolized by cytochrome P450 to form toxic oxidative metabolites that are then inactivated by glutathione. Alcohol potentiation b/c alcohol induces cytochrome p-450 and depletes glutathione
Term
What causes Reye's syndrome?
Definition
children given aspirin for virus induced fever (resp or varicella). Defect in mitochondrial fatty acid oxidation. Fatty acids accumulate in the SER causing extensive microvesicular steatosis.
Term
What causes death in Reye's syndrome?
Definition
liver failure and hepatic encephalopathy
Term
What percent of hospitalized patients are there fore alcoholic liver disease? how does alcoholic liver disease rate as death causing disease?
Definition
25-30%; 5th leading cause of death
Term
Who is more susceptible to alcoholic steatohepatitis?
Definition
women > men, asians (slow aldehyde dehydrogenase) and african americans
Term
What percent of alcoholics develop cirrhosis?
Definition
10%
Term
What causes alcoholic steatohepatitis?
Definition
induction of cytochrome P-450 (increase in toxic metabolites), generation of free radicals, depletion of glutathione, acetaldehyde, lipid peroxidation and protein adduct formation, malnutrition
Term
How is alcohol metabolized?
Definition
Alcohol dehydrogenase and NAD to NADH + H ----> acetaldehyde
aldehyde dehydrogenase and NAD to NADH + H-----> acetate
Term
What is the etiology of alcoholic fatty accumulation in liver?
Definition
shunt metabolism toward lipid biosynthesis (alcohol dehydrogenase, aldehyde dehydrogenase generate excess NADH), impaired assembly and secretion of lipoproteins, increased peripheral catabolism of fat
Term
What are the histological features of alcoholic steatohepatitis?
Definition
steatosis (centrilobular), cell injury (ballooning, mallory bodies, necrosis, apoptosis), fibrosis (centrilobular), and cirrhosis (Laennec)
Term
What's another name for mallory body formation?
Definition
satellitosis
Term
What is NAFLD?
Definition
non-alcoholic fatty liver disease. continuum of steatosis, inflammation, cell injury (ballooning), fibrosis, and cirrhosis. NAFLD is a generic designation that includes non-alcoholic steatohepatitis (NASH)
Term
What is the major risk factor for NAFLD? other risk factors?
Definition
visceral adiposity insulin resistance (glucose intolerance)/type 2 diabetes and hypertriglyceridemia
Term
T/F Prevalence and severity of NAFLD increase with age.
Definition
true
Term
What percent of americans are affected by NAFLD?
Definition
17-30%
Term
What is NASH?
Definition
when you have NAFLD and also have significant inflammation and hepatocellular injury. Likelihood of progression to cirrhosis
Term
How do alcoholic steatohepaitis and NASH compare morphologically?
Definition
similar but NASH is less severe
Term
What labs could you run to determine if a patient has NASH?
Definition
asymptomatic elevation of aminotransferases
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