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Pathology Lecture 21 Pathology of Infectious Diseases 1) To outline a learning strategy for the study of infectious diseases in both the pathology and microbiology courses. Identify the infectious agent and describe the mode of action. Then describe the gross and histological changes that occur as a result of infection. Present this information in a table for memorization. 2) To define the general pathologic characteristics of injury caused by the major infectious agents. General pathologic characteristics of injury Release of chemoattractants for PMNs (e.g. peptides, cytokines, complement components). Inflammation can harm the host by interfering with the function of the involved organ or by the inability of an enclosed space to accommodate it. Infiltrates involve mainly macrophages, lymphocytes, and plasma cells. Granuloma may form from aggregates of altered macrophages, giant cells, and other mononuclear cells around a necrotic focus. Pathogens multiply inside macrophages. CMI involving cytotoxicity is required. Focal cellular destruction with little or no inflammatory response except that secondary to the death of the cells. Cells may fuse to form giant cells or alter their growth to form aggregates or neoplasms. Necrotizing lesions are produced by direct invasion of host cells followed by multiplication and destruction or through the production of toxins, which may directly injure the membrane or organelles. Chronic inflammation and scarring relative to the degree of necrotizing injury or inflammatory response. Some tissues repair and regenerate. Infectous agent Type Pyogenic Bacteria Suppurative (polymorphonuclear) Inflammation Viruses, intracellular bacteria, and intracellular parasites Mononuclar and Granulomatous Inflammation Viral Infection Cytopathic-Cytoproliferative Inflammation Many infectious agents Necrotizing Inflammation Specific pathologic characteristics of injury Gross: large area of lung consolidated Histo: alveoli filled with acute exudates evolving to chronic with notable lack of destruction. Alveolar septa remain intact. Gross: brain swollen with obvious exudates over the surfaces, meningeal vessels engoged, crebellar herniation possible. Histo: purulent exudates fills subarachnoid space, surrounds leptomeninges, and blood vessels. Gross: Multiple localized areas of caseous necrosis in the lung. Histo: granulomas alternate with necrosis, chronic inflammation and fibrosis acid. Gross: brain shows focal, hemorrhagic lesion in the temporal lobe. Histo: Neuronal and glial cell death with perivascular inflammation, some cells show viral intranuclear inclusions. Gross: Skin furuncle (boil). Microscopic lesions in the lung, kidney, or bone walled off as a firm tender nodule. Histo: microabcesses show focal destruction, purulent exudates, and when well developed, fibrous organization at the periphery. Gross: several small ulcers on cecum and colon. Liver abcess. Histo: flask-shaped ulcers scattered between near normal mucosa. Gross: lung is congested with many foci of hemorrhage, necrosis, and purulent exudates. Histo: acute formation of microabcesses with destruction of alveolar septa. Chronically organization and scarring of injured areas occurs. Infectious agent Streptococcus pneumoniae – Lobar pneumonia Many infectious agents Chronic inflammation+ scarring S. pneumoniae, Neisseria meningitides, or Haemophilus influenzae – Acute purpulent meningitis Tuberculosis Herpes encephalitis Staphylococcus aureus – Sthaphylococcal abcesses Entamoeba histolytica – amoebic colitis and liver abcess Necrotizing Bronchopneumonia 3) To relate the pathologic findings to the presence of specific infectious agents. Pathologic Findings Obligate intracellular parasites of prokaryotic or eukaryotic cells, composed of DNA or RNA and a protein coat, use cellular machinery to replicate, and are submicroscopic. Single-celled prokaryotic organisms containing DNA, RNA, ribosomes, and protein synthesis machinery, no organelles, most free living, and visible with a light microscope and stain. Single or multicellular eukaryotic organisms with a rigid cell wall with a unique molecular composition, mostly free living, and although some are microscopic (silver stain) some can be seen with the naked eye. Single or multicellular eukaryotic organisms ranging from simple amoebas to complex cysts, cuticles, and other structures, free living and obligate species exist, and have complex life cycles with different forms. Infectious agent Viruses Bacteria Fungi Parasites 4) To use pseudomembranous colitis as an example of the process involved in the discovery of a “new” infectious disease. a. Clinical – define a new set of clinical and pathological findings: acute diarrhea, abdominal pain, fever, leukocytosis, and occasionally megacolon (hospital). b. Epidemiologic – define a unique set of circumstances including transmission: syndrome recognized in the 50’s in relation to surgery and staph infection. Increase in the 60’s and 70’s associated with antibiotic therapy (clindamycin). c. Diagnostic – isolation of agent for subclinical detection in the population: studies show association with toxin produced by Clostridium difficile and culture with toxin detection allows differential diagnosis of pseudomembranous colitis. d. Pathogenesis – systemic evaluation (experimental) to understand the progress of the disease: Two toxins identified (A & B) one enterotoxic and the other cytotoxic. Spore formation allows pathogen to resist antibacterial treatment. e. Treatment – isolate etiologic agent and test for susceptibility to antimicrobics: susceptible to oral vancomycin.