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hepatitis path
GI
41
Medical
Graduate
09/11/2010

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Term
what are the general patterns of hepatic injury?
Definition
degeneration and intracellular accumulations, inflammation, regeneration, and fibrosis. *fatty change may be interspersed throughout these different types of hepatic injury*
Term
what characterizes degeneration/intracellular accumulation as a general pattern of hepatic injury?
Definition
the hepatocytes begin to swell, (initially reversible, but can be come permanent), ballooning degeneration may occur, feathery degeneration (a kind of cholestasis where bile is not transmitted from one hepatocyte to another and accumulates: foamy hepatocytes), steatosis (micro/macrovesicular fatty change - usually reversible early on), and iron/copper may also accumulate (particularly in the case of metabolic disorders)
Term
what characterizes necrosis/apoptosis as a general pattern of hepatic injury?
Definition
*apoptosis can be either physiologic or pathologic, and cells affected by it are shrunken and pyknotic. *necrosis is always a pathologic process and can be centrilobular, periportal, or midzonal. necrosis can be lytic (cells swell/rupture, leave debris - associated with inflammation), focal (small group of cells becoming necrotic - can spread), interface necrosis (periportal areas become necrotic and join w/portal tracts), bridging necrosis (affects hepatocytes between 2 portal tracts, central vein to portal, or central vein to central vein), and submassive (severe, but involves small area)
Term
what characterizes inflammation as a general pattern of hepatic injury?
Definition
this is one of the main features of hepatitis. inflammation is incited by necrosis, where lymphocytes come in and destroy antigen-expressing hepatocytes and may collect in portal tracts, enter the periportal parenchyma or entire liver. there may be a preponderance of kupffer cells which engulf and destroy injured cells. a bx can help dx this (contraindicated in bleeding disorders).
Term
what characterizes regeneration as a general pattern of hepatic injury?
Definition
hepatocytes are usually stabile cells (exited cell cycle, in quiescent stage) - but under certain stimuli (injury, cell death, partial resection), they can be prompted to re-enter the cell cycle. if this happens, a proliferating liver will have hepatocytes in mitosis and *forming thickening string-like cords and the parenchyma often appears disorganized. in certain cases the bile ducts may undergo proliferation depending on the kind of injury - can help determine etiology.
Term
what characterizes fibrosis as a general pattern of hepatic injury? what is cirrhosis?
Definition
fibrosis usually occurs in the liver as a result of inflammation/toxic injury and is generally considered irreversible. if damage is significant, even a stabile hepatocyte may not be able to proliferate at an appropriate rate. cirrhosis is an advanced form of fibrosis and is characterized by *nodular formation in the parenchyma
Term
what characterizes hep A?
Definition
hep A = RNA virus which is shed into bile, then feces (*main route of transmission). it is not directly cytopathic, injury results from immunologic response. it *does not have a chronic disease state and is generally not severe. it is endemic in less-developed countries. incubation period is 3-4 wks and is detectable in liver 2 wks after infection. pts present w/jaundice, rise in LFTs, possibly flu-like symptoms.
Term
what characterizes hep B genetically?
Definition
hep B is a dsDNA virus, where one strand is longer. there are 4 genes associated with it, coding for: HBcAg, HBeAg, HBsAg. *HBsAg is immunogenic, but not infectious - basis for infection*. the dane particle is the portion containing DNA. it codes its own DNA polymerase and it has an X gene which activates viral transcription (possible link to hepatocellular CA).
Term
how is hep B transmitted?
Definition
hep B is found in most secretions and is fairly infectious - but not really transmitted via feces (unless blood). humans are the only significant reservoir.
Term
what kind of immunity is available to hep B?
Definition
synthetic vaccines confer lifelong immunity, though titer checks/boosters may be necessary.
Term
what characterizes hep B's pathogenesis?
Definition
the virus itself is not directly cytopathic (chronic carriers w/large viral burden are mostly asymptomatic), instead CD8 T cells respond to HLA molecules/viral antigen on infected cells and destroy them, causing inflammation. chronic hep B pts' blood infectivity declines over time w/virion replication decreases but chronic hep B can persist simply due to continual antigen production.
Term
what are the different clinical courses which hep B can follow?
Definition
acute, fulminant, and chronic
Term
what kind of cirrhosis is will hep B cause if it goes chronic (uncommon - different than subclinical)?
Definition
macronodular cirrhosis
Term
what characterizes acute hep B?
Definition
most pts will have self-limited disease w/lifelong immunity however there is a long incubation period (up to 6 mos) before pt knows they are sick. physical exam is usually normal, w/the exception of serology
Term
how would a liver bx of a pt w/acute hep B appear?
Definition
*ground glass cytoplasm*, and antigens will be prominent w/special stain (HBsAg in cytoplasm, and HBcAg in cytoplasm/nuclei)
Term
what characterizes fulminant hep B?
Definition
hepatic insufficiency occurs quickly (progresses to hepatic encephalopathy w/in 2-3 wks = confusion/stupor). hep B is a common cause, but it can be due to drugs/chemicals. the urea cycle becomes abnormal which leads to *high ammonia levels in random areas or the entire liver leading to massive necrosis. pts will present w/jaundice, mental status changes and/or ascites
Term
what characterizes chronic hep B?
Definition
chronic hep b is defined as necrosis/inflammation in the liver for more than 6 mos. *HBs antigenemia does not resolve and HBs antibodies are not present in the blood.* most pts w/this are male. some pts produce an inadequate level of Ab (to HBc/e). there may be HBsAg-antiHBs complexes associated with serum-sickness like syndrome or glomerulonephritis. *also 1/3 - 2/3 of pts with polyarteritis nodosa are carriers for HBV*. some pts develop anti-HBs Ab over the years and can clear the virus, but others eventually progress to cirrhosis. pts with chronic hep B are also at a much more *significant risk for hepatocellular CA
Term
what is the pathogenesis of hep B?
Definition
the entire genome is not integrated into the host genome - *but fragments of it may be integrated, leading to production of antigens which can still induce chronic hepatitis even if the infectivity of the blood decreases
Term
what characterizes hep D infection?
Definition
synthesis of HBsAg is required in either a co-infection or superinfection. the clinical course is then similar to hep B, but a small % can lead to fulminant/chronic hepatitis. superinfection prognosis is worse.
Term
what characterizes hep C?
Definition
hep C is a ssRNA virus, genetically unstable w/mult genotypes and mutant strains (which can escape neutralizing Ab - make vaccination harder).
Term
is there a vaccine for hep C? what is the risk of transmission?
Definition
no, but hep C has a lower risk of transmission
Term
why does hep C generally go chronic?
Definition
there is often an inability for antiHCV IgG to completely clear the infection and the disease remains persistent and relapsing (more liver damage w/each infection) b/c the antigenic strain changes slightly over time.
Term
what is the route of hep C transmission?
Definition
blood-borne, similar to hep B. it is currently still considered to be the most common hepatitis associated with tranfusion.
Term
how does hep C incur liver damage?
Definition
hep C is not directly cytopathic, but cytotoxic T cells respond to the persistent viremia and end up injuring the hepatocytes
Term
what is the incubation period for hep C?
Definition
can be up to 6 mos but HCV RNA is detectable w/in 2 weeks and anti HCV Ab are usually detectable 7-8 wks post infection
Term
what is the clinical course of hep C? how does it appear to hep B?
Definition
usually mild, feels like flu/achy/fever/abdominal pain that passes compared to hep B (fever, malaise, jaundice, ab pain, anorexia, change in taste). hep C can cause *chronic disease (majority of pts) and increases risk of hepatocellular CA. alcohol consumption worsens the course of disease.
Term
what are other conditions which hep C may be associated with?
Definition
membranoproliferative glomerulonephritis, sicca syndrome (eat weird stuff), porphyria cutanea tarda (skin manifestation), and lymphoma
Term
what is the prognosis for hep C?
Definition
most pts go to chronic state and stable disease. fulminant hepatitis is rare.
Term
what is characteristic of hep C histologically?
Definition
*predominant lymphocytic infiltration surrounding the portal tract*
Term
how would a liver affected by cirrhosis due to hepatitis C appear grossly?
Definition
macronodular changes (may be some micro-)
Term
what characterizes the hep E virus?
Definition
the hep E virus is an RNA virus, transmitted through the fecal-oral route, it is seen in poorer regions, has no chronic/carrier state, generally self-limiting and is especially *dangerous in pregnant women (20-40% mortality rate)
Term
what characterizes the hep G virus?
Definition
similar to hep C. hep G is transmitted by blood, sexual contact. it is not hepatotrophic, does not cause increase in aminotransferases, does replicate in bone marrow/spleen and is *not known to cause disease in humans.
Term
what is the morphology of acute hepatitis?
Definition
evidence of hepatocyte injury, necrosis, apoptosis, regenerative changes (thickening of hepatic cords/disorganization), and sinusoidal cell reactive changes. in *hep B: ground glass hepatocytes/sanded nuclei
Term
what characterizes the portal tract in a liver affected by acute hepatitis?
Definition
bile duct proliferation w/increased bile, various degrees of inflammatory infiltration, necrotic hepatocytes, ballooning degeneration, apoptosis, infiltration of macrophages to clean up debris, cholestasis (brown/green discoloration to hepatocytes), and in *hep C: fatty infiltrate.
Term
what is the morphology of chronic hepatitis?
Definition
similar changes as w/acute hep, inflammation, fibrosis and in hep C: bile duct epithelial cell proliferation
Term
how does chronic hepatitis present clinically?
Definition
may/may not be symptomatic, biochemical/serologic evidence may not appear for up to 6 mos, pts will have fatigue/mild jaundice/anorexia. often due to hep C.
Term
what characterizes the portal tract in a liver affected by chronic hepatitis?
Definition
bridging fibrosis (portal-portal, portal-central, etc), periportal necrosis, hep B: ground glass/sanded nuclei, hep C: fatty change, apoptosis, necrosis, and macrophage infiltration
Term
what characterizes autoimmune hepatitis?
Definition
chronic hepatitis may occur in pts w/immune problems, often female. low serologic markers of virus and high titers of autoantibodies are indicative of this condition. genetically, *increased frequency of HLA B8 or DRW3 is seen.
Term
what is autoimmune hepatitis type I?
Definition
this is more common in younger females, 1/4 of which develop cirrhosis. these pts are often positive for many autoimmune antibodies including: anti-nuclear (ANA), anti-smooth muscle (SMA), anti-actin (AAA), and anti-soluble liver antigen/liver-pancreas antigen (SLA/LP)
Term
what is autoimmune hepatitis type II?
Definition
this is more common in children, often associated with DM type I and thyroiditis. these pts have antibody to liver and kidney microsomes and autoantigen CYP2D6
Term
how does autoimmune hepatitis appear histologically? grossly?
Definition
this resembles chronic viral hepatitis w/necrosis but specific to autoimmune there is *inflammation rich in plasma cells*. grossly - pronounced lobular inflammation.
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