Download Patology pathology of infections hepatitis Atypical pneumonia

30.01.2015
Patology
lecture 8
prof. dr hab. n. med. Andrzej Marszałek
Categories of
INFECTIOUS AGENTS
pathology of infections
hepatitis
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Prions
*Viruses
Bacteriophages, Plasmids, Transposons
*Bacteria
Chlamidiae, Rickettsiae, Mycoplasmas
*Fungi: Yeasts, Hyphae
Parasites: Protozoa, Worms, Arthropods
Atypical pneumonia
Atypical pneumonia
•  Mycoplasma pneumonia
•  Wirusy
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RSV
Parainfluenza
Adenovirus
Influenza
inne
Chlamydia pneumonia
Chlamydia psittaci
Legionella pneumophila
Coxiella burnetti (Q fever pneumonia)
Francisella tularensis (Tularemia)
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Liver and bile duct diseases
liver
hepatitis (1)
hepatitis
•  liver infections almost
always are blood-born
•  majority of them are viral:
–  HAV, HBV, HCV, HDV,
HEV, HGV
–  EBV (→ infectious
mononucleosis)
–  CMV
–  yellow fever
–  rubella
–  adenovirus
–  herpes virus
–  enterovirus infection
•  other include:
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miliary tuberculosis
malaria
staphylococci
salmonellosis
candida
amebiasis
HAV
HBV (1)
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•  hepadnavirus
•  as: acute or chronic (even with cirrhosis) or fulminant or with
coinfection with HDV
•  chronic inflammation → carriers → active virus replication
•  HBV is cancerogenous → hepatocellular carcinoma
•  350 mln carriers worldwide (75% in Asia and Western Pacific)
•  available vaccine
•  during the infection virus present in all body fluids (exc. stool)
•  Possible vertical transmission (mainly: Africa and Southeast
Asia)
picornavirus
benign, self-limiting
mortality ±0.1% (alcohol, other hepatitis)
endemic → poor hygiene and sanitation (some cases related
to raw/steamed shellfish)
•  25% of clinically evident acute hepatitis
•  fecal-oral spread (no virus in saliva, nor semen, nor urine)
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HBV (2)
HDV
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HBcAg – ”core” antigen – a nucleocapside core Ag
HBeAg – ”e” antigen – precore and core → toward the blood
HBsAg – ”surface” antigen – envelope glycoprotein
DNA polymerase – reverse transcriptase (acts via
intermediate RNA)
•  HBx – protein from region X – necessary for viral replication,
transcription activator – role in cancerogenesis
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a replication defective virus
coinfection or superinfection
conifection:
–  acute mild or fulminant disease
–  almost no chronicity
•  superinfection:
–  acute/severe infection (in ”healthy” HBV carrier) may
–  mild HBV hepatitis → into fulminant
–  chronic and progressive disease (80% cases)
•  proliferative phase → episomal HBV-DNA, HBsAg and HBcAg
(+MHC class I) u activation of CD8+ cytotoxic T cells
•  integrative phase → viral DNA incorporated into host genome
u cancerogenesis ?
HCV
HEV
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Hepacivirus (flaviviride)
a major cause of liver diseases
infection: blood transfusion, i.v. drugs, sexual contacts (??)
during delivery (but 4-10x lower risk than in HBV)
acute phase underdetected
in majority of patients leads to chronic infection → in 20% leads to
cirrhosis
•  persisten infection and chronic hepatitis
•  Anti-HCV present in 50% of HCC
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Clinicopathologic syndromes
Clinicopathologic syndromes
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•  acute asymptomatic infection
•  acute symptomatic infection with recovery
acute asymptomatic infection
acute symptomatic infection with recovery
chronic hepatitis
fulminant hepatitis
caliciviridae
water-born infections in middle-aged adults
self-limiting; no chronic state
epidemics: Asia, Indian subcontinent (more common than
HAV), sub-Saharan Africa, Mexico
•  Fatal outcome in pregnant (20%)
–  icteric
–  anicteric
•  chronic hepatitis
•  fulminant hepatitis
•  carrier state
–  without clinically apparent disease
–  with chronic hepatitis
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acute asymptomatic infection
acute symptomatic infection with
recovery
•  Minimal ↑ serum transaminases
•  Prensece of antiviral antibodies
•  caused by all types of viruses
•  uncommon for HCV
•  stages:
–  phase I – an incubation period
–  phase II – symptomatic preicteric
•  malaise, fagitability, nausea, loss of apatite (constatnt symptoms)
•  weght loss, low-grade fever, headaches, muscle and join aches,
pains, diarrhea (some cases)
•  fever, rash, arthralgias (serum sickness-like → Ag-Ab; HBV)
–  phase III – symptomtic icteric
•  mainly conjugated hyperbilirubinemia
•  typically in adults with: HAV, in 50% of HBV , some cases of HCV
–  phase IV – convalescence
chronic hepatitis
fulminant hepatitis
•  symptomatic + laboratory (biochemical or/and serological)
evidence of continuing or relapsing hepatic disease for more
than 6 months + histologically documented inflammation and
necrosis
•  may progress to cirrhosis
•  clinically:
•  development of hepatic encephalopathy within 2-3 weeks
after symptoms of hepatic insuficiency → mortality 20-90%
•  caused by:
–  fatigue (most commonly),
–  malaise, loss of appetite, mild jaundice
•  carrier state (patients with replicating virus)
–  no or little clinical/histologic effects
–  laboratory or histological evidence of chronic disease but with no
symptoms or disability
–  clinically symptomatic disease
–  HAV (?), HBV (!),
–  drugs and chemical injury (acetaminophen, isoniazid, halotane,
metyldopa, antidepresents (MAO inhibitors)
–  mycotoxins (Amanita phalloides)
–  other:
•  ischemia, obstruction of hepatic vein
•  neoplastic infiltration, Wilson disease, hyperthermia, microvesicular
steatosis (pregnancy)
•  morphology:
–  necrosis (entire liver or random areas) → liver weight 500-700g
–  malaise, loss of appetite, mild jaundice
Fatty liver (1)
fatty liver
•  Accumulation of trigliceride (TG) fat
droplets within hepatocytes
–  delivery > utilization
–  re-synthesis > secretion
–  abnormal lipoprotein formation
–  failure to secrete VLDL
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Fatty liver (2)
Fatty liver (2a)
•  steatosis
•  fatty metarmophosis
•  fatty change
•  Fatty changes may occur in:
–  heart*
–  muscle*
–  kidney*
*(anemia, chronic caloric malnutrition)
•  multiorgan:
–  Reye’s syndrome (liver, heart, kidney)
Fatty liver (3)
Fatty liver (4)
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N: there is less than 5% by weight of lipids
within the liver, BUT there could be even more
than 50% (mostly as TG)
•  Microvesicular (muliple tiny droplets without nuclear
displacement) → acute toxic hepatic injury
(less common):
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the fat as a minute fat droplets is found in
many cells, but may be not recognizable at the
light microscopic level
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the overaccumulation can be visible at the
gross level
–  Reye’s syndrome
–  acute fatty liver of pregnancy
–  Jamaican vomiting sickness
–  drugs, e.g.: valproic acid, tetracycline
–  toxins: yellow phosphorus, DDT; aflatoxins,
CCl4, hypoxia/anoxia
Fatty liver (5)
•  Macrovesicular (single large droplet with nuclear
displacement) → chronic injury:
–  alcohol, alcoholic liver disease**
–  DM
–  obesity
–  protein-calorie malnutrition (kwashiorkor)
–  total parenteral nutrition
–  jejuno-ileal bypass
–  chronic diseases: UC, pancreatatis, protracted heart
failure,
–  drugs: methotrexate, aspirin, vit A, glucocorticoids,
amiodarone, and synthetic estrogen
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