principle of infection-Med-2556 · 23/09/56 1 Principle of Infection La-or Chompuk, M.D. Department...
Transcript of principle of infection-Med-2556 · 23/09/56 1 Principle of Infection La-or Chompuk, M.D. Department...
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Principle of Infection
La-or Chompuk, M.D.Department of pathologyFaculty of Medicine
Infection
• Definition: Invasion and multiplication of microorganisms in body tissues
• No symptom, local cellular injury, localized symptom, dissemination
• Mechanism; competitive metabolism, toxins, intracellular replication, immune response
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Classification of infectious agents:- classification according to structure- classification according to pathogenesis- classification according to site of multiplication
Classification according to structure- Prion - Fungi- Viruses - Protozoa, metazoa- Bacteria - Ectoparasite- Rickettsia, chlamydia, mycoplasma
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Classification according to pathogenesis• Pathogenic agents;
- Virulence: the degree of pathogenicity of a microorganism- Indicated by the severity of disease, the ability to invade tissue
- high virulence- low virulence
• Opportunistic infection
Classification according to site of multiplication- obligate intracellular organisms; Prions, viruses, rickettsiae, chlamydia, some protozoa
- facultative intracellular organism; Mycobacteria, Actinomyces, Pseudomonas spp.
- extracellular organisms; mycoplasma, fungi, bacteria, metazoa
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Pathogenesis of Infectious Disease- Host- Pathogen; organism or parasite that cause disease
Host factors:1. General factors; socioeconomic status, behavior pattern, occupational, and internal factors
2. Natural defense mechanism; skin and normal flora, respiratory tract and mucociliary mechanism, Hcl production in stomach, or normal flushing action of urine
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3. Inflammation; acute inflammation, phagocytosis, complement, and production of interferon
4. The immune response; HMI and CMIHMI: Ag & Ab (B-cell)CMI: T- cell, macrophagesImmunocompetent Immunocompromised/ immunodeficiency
Organism factors:1. Transmission; congenital transfer (Rubella, CMV, HIV, HSV), directly contact, fomite, food and water, airborne, animal, sexual
2. Spread and dissemination; localized and disseminated infection
- viremia, bacteremia, fungemia, parasitemia- sepsis is a serious medical condition
characterised by a whole-body inflammatorystate caused by infection.
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Definition of sepsis• Sepsis is considered present if infection is highly
suspected or proven and two or more of the following systemic inflammatory response syndrome (SIRS) criteria are met:
- Heart rate > 90 beats per minute - Body temperature < 36 or > 38 °C- Hyperventilation (high respiratory rate) > 20
breaths per minute or, on blood gas: a PaCO2less than 32 mmHg.
- White blood cell count < 4,000 cells/mm3 or > 12,000 cells/mm³ or greater than 10% band forms (immature white blood cells).
- septicemia (blood poisoning; bacteremia with sepsis)
is the presence of bacteria in the blood (bacteremia) and is often associated with severe disease.
is a serious, life-threatening infection that gets worse very quickly.
is considered a subset of sepsis. It can arise from infections throughout
the body.
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Organism factors:
3. Number of organism-numerous low virulent organism cancause severe disease
4. Pathogenicity of organism; - ability to attach host cells; pili, adhesins, specific receptor
- ability to invade tissue; S.pyogenasehyaluronidase breakdown ground substance- toxin production; C. botulinum neurotoxin- multiplication- resistance to host defense mechanism - ability to cause necrosis- enzyme release; anthrax enzymevasculitis ischemia- immune evasion
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Immune evasion by microbes
• Replicate in sites that are inaccessible to the host response; S. typhi in gallbladder
• Varying antigens they express; influenza virus
• Escaping killing by phagocytes and complement; capsule
• Viruses can produce molecules that inhibit innate immunity; herpesvirus and poxvirus produce proteins that block complement activation
Example: specific attachment to host cells
Disease Organism Microbial ligand Target cells/ receptor
Influenza Influenzavirus
hemagglutinin Neuraminic acid on Respiratory Epi.
AIDS HIV Gp 120 protein CD4 T-cells
Malaria P. VivaxP. falciparum
MerozoiteMerozoite
Duffy Ag on RBCGlycoprotein A, B on RBC
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Example: specific toxin on vulnerable cells
Disease Organism Toxin Effect and vulnerable cells
Cholera Vibrio cholerae Cholera toxin cAMP activation in intestinal epi.
Diphtheria Corynebacteriumdiphtheriae
Diphtheria exotoxin
Inhibition of protein synthesis in myocardium and nerves
Tetanus Clostridium tetani Tetanospasmin Spastic paralysis of skeletal muscle
Whooping cough
Bordetella pertussis Pertussis toxin Cell death in tracheal epi
Bacterial toxin
• Exotoxin:– Enzymes secreted by bacteria – Have local effect; C. difficile > >
pseudomembranous colitis• Endotoxin:
– Lipopolysaccharides from cell walls of GNB; E. coli
– Released on death of the bacterium– Activator of complement cascade > inflammation,Coagulation cascade> >DIC, IL-1 >> fever
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Summary: how microorganisms cause disease
1. They can contact or enter host cells and directly cause death
2. They may release toxins that kill cells at a distance, release enzymes that degrade tissue components, or damage blood vessels and cause ischemic necrosis
3. They can induce host cellular responses that usually by immune-mediated mechanisms. - Immune are necessary to overcome the infection but at the same time may directly contribute to tissue damage.
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Spectrum of inflammatory responses to infection
1. Suppurative Inflammation: Neutrophils
- complication of acute inflammation; liquefactive necrosis with abscess formation- extracellular organisms; bacteriaexcept Samonella typhi – neutropenia, macrophages
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1. Suppurative Inflammation
1.1 acute suppurative; neutrophil infiltrate, necrotic tissue, e.g.S. aureus, Klebsiella spp.
1.2 chronic suppurative; fibrosis, microabscess, and sinus draining e.g. filamentous bacteria or mycelial fungi in Medura foot
Pustule; acute suppurative inflammation
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Skin abscess from S. aureus
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Mycetoma; Medura foot
2. Chronic inflammation2.1 chronic inflammation with lymphocytesand plasma cells;
- obligate intracellular organisms esp. viruses- effect of CMI and HMI e.g. chronic hepatitis- cell necrosis, fibrosis
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Viral pneumonia
Syphilitic aortitis; plasma cell infiltrate to vasa vasorum
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2. Chronic inflammation2.2 chronic granulomatous inflammation;
Mycobacteria, fungus Graulomatous inflammation/ Granuloma: accumulation of activated macrophages called “epitheliod” cells, may fuse to form giant cells.
2.3 chronic inflammation with diffuse proliferation of macrophages; in abnormal CMI patient --- no distinct granuloma, foamy macrophages with numerous organisms
Spectrum of tuberculosis, granulomatous inflammation
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Foamy macrophages in mycobacterium avium complex in AIDS
2. Chronic inflammation
2.4 combined suppurative & granulomatous inflammation; epithelioid granulomas with central neutrophilic abscess, e.g. deep fungal infection, Lymphogranuloma Venereum, Mellioidosis, Cat-scratch disease
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Cat-scratch disease
2. Chronic inflammation2.5 chronic inflammation with Eosinophils
– response to multicellular parasites and certain fungi
– Splendore-Hoeppli phenomenon; radiating or anular eosinophilic deposits of host-derived materials, and possibly of parasite antigens, which form around fungi, helminths, or bacterial colonies in tissue
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Strongyloidiasis; eosinophilic infiltration
Strongyloid larva in duodenal tissue
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Splendore-Hoeppli phenomenon; fungal infection
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3.Cytopathic-Cytoproliferative Inflammation
- these reactions are usually produced by viruses- cell necrosis or cellular proliferation, usually with sparse inflammatory cells- some viruses replicate within cells and make viral aggregates that are visible as inclusion bodies (e.g. herpesviruses or adenovirus)
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Inclusion bodies of diagnostic use in viral infection
Virus Inclusion body
CMV Intranuclear inclusion surrounded by a halo
Rabies Eosinophilic rounded cytoplasmic inclusions (Negri bodies)
HBV Ground-glass cytoplasm in hepatocytes
Molluscumcontagiosum(Poxvirus)
Eosinophilic cytoplasmic inclusions
HSV Eosinophilic intranuclear inclusion
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Rabies: Negri bodies
3.Cytopathic-Cytoproliferative Inflammation
- some viruses induce cells to fuse and form multinucleated cells called polykaryons (e.g. measles virus or herpesviruses)
- focal cell damage in the skin may cause epithelial cells to become detached, forming blisters.
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Tzanck test
HSV: intranuclear inclusion, multinucleation
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3.Cytopathic-Cytoproliferative Inflammation
- some viruses can cause epithelial cells to proliferate (e.g. veneral warts caused by human papillomavirus or the umbilicated papules of molluscum contagiosum caused by Poxviruses)
Human Papilloma virus: HPVWarts
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HPV: Koilocyte
Poxvirus: Molluscum contagiosum
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3.Cytopathic-Cytoproliferative Inflammation
- viruses can cause dysplastic changes and contribute to the development of malignant neoplasms;
- EBV: Burkitt lymphoma- HBV and HCV: Hepatocellular carcinoma- HPV: Squamous cell carcinoma of cervix,
penis
Burkitts lymphoma; EBV
EBER; ISH
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Hepatocellular carcinoma; HBV/HCV
Squamous cell carcinoma of penis/ cervixHPV
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4. Necrotizing inflammation
- Clostridium perfringens and other organisms that secrete powerful toxins can cause rapid and severe necrosis.
- Clostridia are often opportunistic pathogens that are introduced into muscle tissue by penetrating trauma or infection of the bowel in a neutropenic host.
Gas gangreneClostridium perfringens
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4. Necrotizing inflammation
- Entamoeba histolytica causes colonic ulcers and liver abscesses characterized by extensive tissue destruction with liquefactive necrosis and without a prominent inflammatory infiltrate.
Amebic colitis
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4. Necrotizing inflammation
- By entirely different mechanisms, viruses can cause widespread and severe necrosis of host cells, with inflammation, as exemplified by total destruction of the temporal lobes of the brain by herpesvirus or the liver by HBV.
Herpes encephalitis
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Normal liver
Chronic HBV infection; ground glass appearance
5. Chronic inflammation and scarring
- chronic HBV infection; cirrhosis of liver- sometimes the exuberant scarring response is the major cause of dysfunction (e.g., the “pipe-stem” fibrosis of the liver or fibrosis of the bladder wall caused by schistosomal eggs or the constrictive fibrous pericarditis in tuberculosis)
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HBV, liver cirrhosis
Schistosomal periportal fibrosis
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Summary: tissue responses to infection
Type of inflammation Example
Exudative inflammation Pyogenic bacteria
Necrotizing inflammation GNB, amebiasis
Granuloma Mycobacteria, fungi
Histiocytic inflammation Rhodococci, Legionella, Whipple’s disease, MAC
Eosinophilic inflammation Fungi, parasites
Cytopathic change Viruses
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Clinical evaluation:1. Clinical history
- Prevalence of infectious disease- Assessment of immune status- Exposure to animals- Travel history
Prevalence of infectious disease- Community-acquired infection- Hospital-acquired infection/Nosocomial infection
Increased susceptibilityUsed of invasive procedureNumerous source of infectionUse of antibiotic
- Opportunistic infections
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Candida Infection
2. Physical examination3. Investigation
- Microbiological tests- Immunological tests- Histological examination of tissue specimens- Immunohistochemistry, PCR, DNA probe, DNA microarray
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References:1. Vinay Kumar, Abul K. Abbas and Nelson Fausto.
Robbins and Cotran Pathologic Basis of Disease, 8th
ed. Elsever Saunders, Pennsylvania, 2010.2. Cedric Mims, Hazel M Dockrell, Richard V Goering
and et al. Medical Microbiology, updated third edition. Elsevier Mosby, 2004.
3. Rubin R, Strayer DS. Rubin’s pathology, 6th ed. Baltimore: Lippinkott Williams & Wilkins, 2012: 329-433.
4. Kradin RL. Diagnostic pathology of infectious disease. Philadelphia: Saunders Elsevier, 2010: 3-15.
5. JCE Underwood. General and systemic Pathology, 3rd
ed. Churchull Livingstone, 2000: 43-56.