Download Infectious Disorders

Infectious
Disorders
VIRAL HEPATITIS
.hepatic infection caused by hepatotropic
viruses (A, B, C, D, & E)
.clinicopathologic syndromes
-acute asymptomatic infection with
recovery (serologic evidence-HAV & HBV)
-acute symptomatic hepatitis with
recovery, anicteric or icteric (all types)
-chronic hepatitis, without or with
progression to cirrhosis (HCV)
symptomatic, biochemical, or serologic
evidence of continuing or relapsing hepatic
disease for more than 6 months
-fulminant hepatitis with massive to
submassive hepatic necrosis (HBV, HAV)
.diagnosis
-serological tests
-liver biopsy
-molecular studies
Hepatitis A Virus
.single stranded RNA picovirus with
incubation period of 3-6 weeks
.clinical features
-asymptomatic or mild, rare after
childhood
-rarely fulminant hepatitis (0.1%)
.occurs worldwide & is endemic in places
with substandard hygiene (people may
have detectable antibodies by age of 10y)
.spread is by contaminated water & food
(oral route)
.virus is shed in stool for 2-3 wks before &
1 wk after onset of jaundice
.can also be detected in serum & saliva
because HAV viremia is transient, bloodborne transmission occurs only rarely;
therefore, donated blood is not
specifically screened for this virus
.specific anti-HAV IgM antibodies at
onset of symptoms (diagnostic marker in
acute infection), titer declines in months
.IgG persists for years, providing
protective immunity against re-infection
by all strains of HAV
Acute viral hepatitis
Ballooning degeneration
Hepatitis B Virus
.DNA virus, incubation period 4-26 wks
.diseases
-acute hepatitis with recovery
-nonprogressive chronic hepatitis
-progressive chronic disease>cirrhosis
-fulminant hepatitis
-asymptomatic carrier state (presence of
HBsAg in serum for 6 months or longer)
-hepatocellular carcinoma
Chronic HBV hepatitis, ground-glass
hepatocytes
Chronic HBV hepatitis, immunoperoxidase stain for HBsAg
Fulminant viral hepatitis
Fulminant viral hepatitis
.modes of transmission
-vertical
.perinatal during childbirth (high
prevalence regions)
-horizontal
.through minor cuts in skin or mucous
membranes (intermediate prevalence
regions)
.sexual & intravenous (low prevalence
regions)
.prevention
-vaccination
-screening of donor blood & tissues
anti-HBs may persist for life, conferring
protection; a basis for vaccination using
noninfectious HBsAg
Hepatitis C Virus
.single stranded RNA, incubation period
2-26 weeks
.most common chronic blood-borne
infection
.routes of transmission
-inoculations
-blood transfusions
-sexual intercourse
-perinatal
.diseases
-acute hepatitis (rarely fulminant)
-chronic hepatitis
.characteristic clinical feature is episodic
elevations in serum aminotransferases
-cirrhosis
.in 20%-30% of patients with chronic
infection
.after 5-20y of acute infection
Chronic HCV hepatitis
Hepatitis D Virus
.RNA virus dependent for its life cycle on
HBV
.hepatitis arises in the following settings
-acute coinfection after exposure to serum
containing both HDV & HBV
.acute hepatitis (self-limited or fulminant)
.chronic hepatitis (persistent or
progressive)
-super-infection of a chronic carrier of HBV
.severe acute hepatitis
.exacerbation of preexisting chronic
hepatitis B, may progress to cirrhosis
& hepatocellular carcinoma
-latent infection in liver transplant
.hepatitis
Hepatitis E Virus
.single stranded RNA, incubation
period 6 weeks
.water-borne infection affecting young to
middle-aged adults (oral route)
.zoonotic with animal reservoirs (mokeys,
cats, pigs, and dogs)
.causes acute self-limiting hepatitis
.among pregnant women has a high
mortality rate (20%)
HIV and Chronic Viral Hepatitis
.because of similar transmission mode &
similar high-risk patient population, coinfection of HIV & HVs is now a common
clinical problem
.HIV infection exacerbates the severity of
liver disease caused by HBV or HCV
.less clear is the impact of HBV or HCV on
the course of HIV infection
.in addition, anti-HIV agents may cause
hepatotoxicity in some patients with
HBV or HCV co-infection
Autoimmune
Hepatitis
.chronic & progressive hepatitis of
unknown etiology
.pathogenesis
-T cell-mediated autoimmunity (defect in
regulatory T-cells), which may be
genetically determined
-injurious immune reaction may be
triggered by
.viral infections
.drugs (methyldopa, interferons,
nitrofurantoin)
.herbal products
.salient features
-clinical
.female predominance
.indolent or severe (fulminant hepatitis)
.cirrhosis in 40% of survivals
-serological
.absence of markers of viral infection
.elevated serum IgG & γ-globulin levels
.high serum titers of auto-antibodies
-histological
.lymphocytes & plasma cells in the
interface of portal tracts & hepatic lobules
Autoimmune hepatitis
Drug And
Toxin-Induced
Liver Disease
.general features
-genetic variability is a critical factor
-injury of hepatocytes or biliary
epithelium causing cell death or
disruption of cellular function may result
-from direct toxicity
-through hepatic conversion of a xenobiotic
to an active toxin
-through immune mechanisms, usually by a
drug or a metabolite acting as a hapten
.mechanisms
-predictable, occurs in anyone who
receives sufficient dose of an agent
-unpredictable (idiosyncratic), depends on
.rate of metabolism of the agent
.intensity of immune response
.morphology
-hepatocyte necrosis
-cholestasis
-chronic hepatitis
-micro & macrovesicular steatosis
.clinically & histologically is similar
to chronic viral hepatitis, distinction is
made by serology
.recovery upon removal of the drug
ALCOHOLIC LIVER DISEASE
.factors influencing development & severity
of liver disease
-quantity of alcohol
-duration of consumption
-gender, women are more susceptible to
hepatic injury than men
-genetic
-iron overload & infections (HCV, HBV)
.diseases, 3 overlapping forms
-steatosis (fatty liver disease)
.asymptomatic
.hepatomegaly & mild elevation of
serum bilirubin & alkaline phosphatase
-hepatitis (minimal to fulminant)
-cirrhosis
.pathogenesis
-hepatocellular steatosis
.increased lipid biosynthesis
.defect in assembly & secretion of lipoproteins
.increased peripheral catabolism of fat
-hepatitis
.acetaldehyde induces disruption of
cytoskeletal & membrane function
.reactive oxygen species react with cellular
proteins, & damage membranes
.low hepatic glutathione>oxidative injury
.morphology
-steatosis
-hepatitis
.hepatocyte swelling & necrosis
.Mallory bodies
.neutrophil infiltration
.fibrosis
-cirrhosis
Liver, steatosis
Alcoholic hepatitis
Alcoholic hepatitis, Mallory bodies, Masson
stain
Alcoholic cirrhosis
Alcoholic cirrhosis, Masson trichrome
Hepatic
Circulatory
Disorders
Liver infarcts, impaired blood inflow
Sickle cell anemia, impaired intrahepatic
blood flow
System circulatory compromise, impaired
intrahepatic blood flow
Budd-chiari syndrome, hepatic vein
outflow obstruction
Sinusoidal obstructive syndrome, hepatic
vein outflow obstruction