Pulm Micro

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countchocula58
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Pulm Micro
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2015-02-28 00:02:16
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  1. Influenza (type of virus, genome, 2 main outer proteins, 2 inner shell proteins, 3 types of polymerase in nucleocapsid, and role of NP)
    • Orthomyxovirus
    • -ss RNA
    • Host derived bilayer contains:
    • HA (hemagglutinin)-binding in (determines classification HN)
    • NA (neuraminidase)-cleaving out (determines classification HN)
    • Inner shell (Matrix):
    • M1-assembly (determines classification ABC)
    • M2-uncoating channels
    • Nucleocapsid:
    • PB1, PB2, PA-polymerases
    • NP-binds RNA genome (determines classification ABC)
  2. Influenza Infection Mechanism
    • HA binds to cell, endocytozed (sheds lipid proteins?)
    • Uncoats and dumps RNA into nucleus to copy
    • Translate some into viral proteins in cytoplasm
    • NA cleaves to leave (grabs shedded proteins)
  3. Genetic drift vs shift (viral)
    • Drift-Random mutation changes through time within the virus strain
    • Shift-Reassortment with other influenza strain
  4. How to make a Flu Vaccine
    • Eggs with reverse adapted and cold genetic strains
    • (some cell culture based, the future?)
    • 3 viruses: A, A seasonal, B
  5. Rimantadine, Amantadine, Zanamivir, Oseltamavir
    • Flu drugs
    • Rimantadine and Amantadine target M2
    • Virus gets in and can’t uncoat unless mutant strain
    • Thus certain flus are immune
    • Zanamivir (Relenza) (nebulized) and Oseltamavir (Tamiflu)
    • Sialic acid analogue with permanent binding, so cannot cleave and leave
  6. Coronaviruses (genome, structure, diseases caused by coronaviruses, proteins on outer coat)
    • +ss RNA
    • Looks like a crown
    • S and He proteins for attachment and entry
    • Nonsegmented genome
    • MERS and SARS
  7. 3 Paramyxovirus genera (genome, and diseases within the genera (pneumo - 1, para - 2, morbi - 2)
    • -ss RNA
    • Pneumovirus: RSV
    • Paramyxovirus: Parainfluenza 1-4, Mumps
    • Morbillivirus: Measles, Canine Distemper Virus
  8. Paramyxovirus (the family) (mutation style and proteins)
    • Rarely shuffles
    • HN for hemagglutinin and neuraminidase, except measles is only H and RSV is G protein
    • F protein (F1 and F2) for fusion
    • M (matrix) protein
    • NP binds to RNA genome
    • P and L are polymerase
  9. Mumps (symptoms, spread of infection, complications, treatment)
    • Painful swelling of parotids
    • Humans are only resevoir
    • Children is self limited
    • Adults can get systemic disease
    • No treatment
  10. Parainfluenza 1-4 (symptoms, spread of infection)
    • Mild to influenza like (bronchitis, croup)
    • Get all 4 as a child and not as an adult
  11. Measles (symptoms, spread of infection, complications)
    • 10 day incubation
    • Dry cough, sore throat, conjuctivitis
    • Rash, Koplik’s spots (look like wheel and flare in mouth)
    • Complications are bronchopneumonia, otitis media, and SSPE (chronic encephalitis)
  12. RSV (symptoms, treatment)
    • URT
    • LRT in 50% for under 8 months old producing bronchitis, pneumonia, croup
    • No vaccine (because it made disease worse)
    • Treatments are respigram and palivizumab
  13. Picornavirus classes
    • Lots
    • Rhinovirus
    • Enterovirus
  14. Picornavirus (genome)
    • +ss RNA
    • Untranslated regions at 5’ and 3’
    • Single polyprotein cleaved thus protease is a good target
  15. Rhinovirus (how it infects, treatment)
    • 105 serotypes
    • URT damage to ciliated causes symptoms
    • Predisposes to secondary bacterial
    • Little to no cross protection
    • Treat with AG7088 protease inhibitor nasal spray
  16. Enterovirus (example, spread of infection, symptoms)
    • Coxackievirus
    • Seasonal and subclinical
    • Systemic: myocarditis, meningitis, and paralysis
  17. Adenovirus (genome, symptoms, proteins, treatment)
    • ds DNA
    • 30-40 genes
    • Respiratory, GI or eye
    • Usually asymptomatic and you get one by age 15 (47 types)
    • a “cold”
    • non enveloped and similar
    • Penton interacts with integrin
    • Fiber interacts with MHC receptor (and other receptors)
    • No treatment
    • Vaccine is used by military
    • Susceptible are military and infants
  18. Streptococcus pneumoniae (gram, shape, tests, virulence factor(s), infection, symptoms, clinical, treatment)
    • Gram positive, lancet shaped diplococci
    • Catalase negative, optochin-susceptible
    • Capsule (80 serotypes)
    • Pneumolysin forms pores, degrades hemoglobin to green and activates compliment
    • Peptidoglycan and techoic acid activate compliment
    • Only humans, small droplet contagious, most common cause of community acquired pneumonia, healthy individuals
    • Colonizes oropharynx and nasopharynx
    • Can cause meningitis and bacteremia (20%), especially young and old
    • Otitis media, bronchitis, sinusitis
    • Rusty sputum (or green/yellow), fever, pleuritic chest pain
    • Lobar pneumonia on CXR
    • Penicillin not as good as it once was
    • Get both pneumovax 23 and prevnar 13 (polysaccharide conjugated)
  19. Haemophilus influenzae (gram, shape, virulence factor(s), infection, symptoms, diagnosis, treatment)
    • Small gram negative
    • Aerobic and anaerobic
    • Polysaccharide capsule (6 types a-f)
    • Antiphagocytic
    • Vaccine (capsular conjugate so unencapsulated can still be “contagious”)
    • Endotoxin
    • One airway and life threatening epiglotitis and maybe meningitis in children under 6
    • Grow on chocolate agar because needs X and V factor
    • Treat with certain -cillins unless beta lactamase producing
  20. Mycoplasma pneumoniae (gram, shape, virulence factor(s), infection, symptoms, clinical, diagnosis, treatment)
    • Extracellular, lacking walls, pleiomorphic
    • P1 protein adhesin for adhering to epithelial in respiratory tract
    • Person to person, small droplets
    • Atypical pneumonia, bronchitis, pharyngitis
    • Insidious, cough, non-productive, flu like symptoms
    • Occasional neurologic abnormalities, rash, hemolytic anemia
    • Common in young people
    • CXR is better than clinical signs, reticulonodular (any pattern can be seen)
    • Sputum culture and antibody titers, cold hemmataglutin rise in 50% of cases
    • Certain antibiotics (not penicillin)
    • No vaccine
  21. Chlamydia pneumoniae (gram, virulence factor(s), infection, symptoms, clinical, diagnosis, treatment)
    • Related to gram negative, obligate intracellular
    • Atypical pneumonia
    • 5-20% of pneumonia cases in young adults
    • Often with pharyngitis
    • CXR looks like mycoplasma pneumonia
    • Sputum culture and antibody titers
    • Antibiotics and no vaccine
  22. Aspiration Pneumonia (symptoms, how it happens, clinical, organisms)
    • Can smell really bad
    • Low gag reflex (alcohol,old, seizure)
    • CXR shows consolidation
    • Causative organisms are normal flora (prevotella, fusobacterium, anaerobic cocci)
    • Abscesses or empyema
  23. Mycobacterium tuberculosis (shape, generation time, size)
    • Aerobic, lipid heavy cell wall
    • 22 hour generation time
    • 5 microns
  24. Pathogenesis of TB
    • Airborn, initially subpleural midlung Gohn complex in minority (most just have positive PPD)
    • Macrophage cage carries it to regional lymph nodes where it spreads
    • The antibody for it does nothing
    • Some cell mediated immunity with tissue hypersensitivity leading to granuloma, caseating necrosis 3-9 weeks after infection
    • Primary infection usually heals in 6 months or with immunosupression 10% risk each year of going to progressive primary TB
    • Latent TB all harbored in a few infected macrophages
    • 5% reactivation TB in 2 years, 5% after 2 years
    • Reactivation TB in upper posterior (classic is right)
    • 50% die or self cure in 3 years
  25. TB granulomas
    • necrotic center surrounded by macrophages, then T cells
    • Cells within macrophage ring are lysed (necrosis) preventing spread but also preventing immune cell entry
    • Epithieloid cells are highly stimulated macropahges
    • Langhans giant cells are fused macrophages, multinucleated
  26. PPD
    • Read with a pen >10mm
    • Cross reacts with BCG and Mycobacterium avian (MAI)
    • SN .75
  27. TB Clinical Presentation and symptoms
    • Primary Progressive (young, old, AIDS) has hilar or mediastinal adenopathy
    • Reactivation Apical posterior often with cavitation and no hilar adenopathy
    • Extrapulmonary TB (it can go anywhere)
    • Miliary TB
    • Flu like with hemoptysis, cough more than 2 weeks
    • TB can go anywhere, in spine is Pott’s
    • TB meningitis (50% abnormal CXR) death in 5-8 weeks, diagnosed by CSF
  28. Culturing TB techniques
    • Acid fast: Ziehl-Neelsen stain or Kinyoun stain (no heating necessary)
    • Fluorochrome staining is better (Auramine-rhodamine)
    • Solid media 3-8 weeks
    • Liquid 1-3 weeks
    • Xpert MTB/RIF test (super fast and tells Rifampin resistance)
  29. TB therapy
    • Standard 2 months of isoniazid, rifampin, ethambutol, pyrazinamide; then 4 months of isoniazid and rifampin
    • Sputum culture at 2 months
    • Extended treatment if positive sputum culture or cavitation on initial CXR
    • Extended treatment
    • Latent TB is either isoniazid 9 months, rifampin 4 months, or isoniazid plus rifapentine once weekly 2 months
  30. TB drug resistance classifications
    • MDR is at least INH and Rifampin, can be primary (started with it) or acquired (bad adherence)
    • XDR INH and Rifampin plus any fluoroquinolones and a TB 2nd line injectable
    • TDR all 1st and 2nd
  31. BCG Vaccine protection
    Protects against meningitis and protects for 10-20 years, booster doses do nothing
  32. NTM Diagnosis
    • Variable signs and symptoms
    • Diagnosed with Symptoms of TB, but you exclude MTB
    • OR 2 or more positive cultures from sputum
    • OR positive culture from BAL or wash
    • OR biopsy showing granulomatous inflammation or AFB and positive culture for NTM
  33. MAC organisms, symptoms, infection, treatment
    • Two organisms, M avium and M intracellulare
    • Pulmonary disease or diffuse disease (HIV) or cervical lymphadenitis
    • Common in water, soil, animals by inhalation or ingestion
    • Treat with susceptibility testing antibiotics (TB drugs) 3 drugs for 12-18 months with or without a 4th drug for the first 2-3 months
    • Surgical resection for when it fails
  34. Mycobacterium kansasii (infection, symptoms, treatment)
    • Mimics TB
    • environmental (no person to person)
    • Treat with susceptibility TB drugs for more than 18 months (1 year after negative cultures)
  35. Endemic v Immunosuppressive Fungal Pneumonias (just names of myoses)
    • Endemic are histoplasmosis, blastomycosis, and coccidioidomycosis
    • Immunosuppressive are aspergillosis and pneumocytosis
  36. Endemic Mycoses (names, morphisms, spread, culture facts)
    • Histoplasmosis, blastomycosis, coccidioidomycosis
    • Thermally dimorphic, hyphae and yeast
    • No human to human, just inhalation, even healthy people
    • If positive culture, you can be sure they have it
    • Slow growing and tedious culture
  37. Histoplasmosis (environment, morphism, symptoms, complications, diagnosis, histology, treatment)
    • Soil based (can be construction), river valleys (Ohio and Mississippi), guano
    • Caseating or non-caseating granulomas
    • Dimorphic mycelial to yeast
    • Mild flu like, Gohn complex that heals just like TB
    • Copmlications are mediastinal fibrosis, mediastinal lymphadenitis, cavitation, disseminiated (see on blood smear)
    • Diagnosed by culture or histopathology with acid Schiff/silver stain (GMS)
    • Antigen detection in urine, serum, BAL
    • Histoplasmosis can hide in macrophages
    • Don’t treat if less than 4 weeks
  38. Blastomycosis (environment, morphism, symptoms, complications, diagnosis, histology)
    • Warm soil with decaying vegetation, Great Lakes region
    • Dimorphic mycelial to yeast
    • Starts as pulmonary and goes to other sites even brain but especially skin and bone
    • Neutrophilic granuloma, non-caseatings, giant cells and epitheloid cells
    • Can be sexually transmitted
    • Diagnosed by culture (required for definitive), antigen of urine or serum or BAL, histology with pyogranuloma or silver stain, serologic assay
    • Broad based budding yeast
    • Mimics lots of things
  39. Coccidioides (environment, morphism, symptoms, complications, diagnosis, histology, treatment)
    • Soil, in south west
    • Dimorphic mycelia to endospores bigger than blasto and histo
    • Cell multiplication of endospores into a giant spherule that ruptures
    • Pulmonary nodules, chronic fibrotic pneumonia, disseminate to skin, bone, joints or brain (meningitis fatal within 2 years)
    • Diagnosed by stain (H&E, silver, acid-Schiff), culture is highly infectious, urine antigen, serologic is most frequent means of diagnosis
    • Usually resolves, so no treatment even if cavitary or nodule and asymptomatic; treat if severe, life long if meningitis or immunosuppression
  40. Aspergillosis (environment, symptoms, complications, diagnosis, clinical, histology, treatment)
    • Soil, water, food, air, inhalation but mainly immunocompromised
    • Crosses tissue plains and into blood vessels
    • Lungs but can go to sinuses, CNS, heart and skin
    • Diagnosed by chest CT with halo sign (nodule with ground glass infiltrate)
    • Histology with acute angle branching, antigen assay, serum, BAL, culture is diffinitive
    • Treat with voriconazole, and get neutrophils up
  41. Pneumocystis (environment, morphism, symptoms, complications, diagnosis, clinical, histology, treatment)
    • Inspired, global, most exposed by age 3-4
    • Morphology of cysts containing sporozoites to trophozoites
    • Immunocompromised and you can even diagnose them with HIV because they get it
    • Clinical as hypoxemia and elevated LDH, CXR of bilateral diffuse interstitial
    • Patchy ground glass CT
    • Diagnosed by sputum, BAL or biopsy
    • Treat with trimethoprim-sulfamethoxazole and corticosteroids

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