1. Cough
    • mechanism for clearing respiratory secretions
    • voluntary or reflex
    • afferent receptors provide stimulis, efferent receptors cause event
    • A cough is: inspiration, glottic closure, relaxation of diaphragm, muscle contraction of thorax, creating increased intrathoracic pressure, opening of glottis
  2. Causes of cough
    • Irritants: smoke, dust, fumes, foreign bodies
    • Endogenous stimulants: upper airway secretions, gastric reflux fluids
    • Disorders w/ inflammation, constriction, infiltration, or compression of airways
    • Stimulation may affect upper respiratory or lower respiratory receptors
    • Cough is either acute or chronic: 3weeks
  3. Etiologies of Cough
    • Infection: URI, pneumonia, lung abscess
    • Asthma
    • Neoplasms
    • Granulomatous dz
    • Compression from extrinsic masses
    • Interstitial lung dz
    • Congestive heart failure
    • Medications: Angiotensin-converting enzyme inhibitors
  4. Afferent receptors role in mechanisms of dyspnea
    • Sense that there is inadequate "air"
    • hypoxia, hypercapnia, acidemia
    • Bronchospasm or chest tightness
    • interstitial edema/vascular receptors
    • Hyperinflation
    • Exercise and chest wall/skeletal muscle
  5. Efferent receptors role in the mechanisms of dyspnea
    • Disorders of ventilation
    • Weak or fatigued respiratory muscles
    • A mismatch between sense of inadequate and amount of respiratory effort or function to compensate
    • Air hunger creates anxiety which also contributes to sensation and severity
  6. Causes of dyspnea: Respiratory
    • Inadequate gas exchange: Pneumonia, pulmonary embolis, pulmonary edema, aspiration, interstitial lung disease
    • Inadequate airways: COPD, asthma, chest wall alterations as in scoliosis, myasthenia
    • Stimulation to breath: pregnancy, metabolic acidosis, acute bronchospasm, pulmonary embolis, high altitude, respiratory stimulants.
  7. Causes of dyspnea: cardiac
    • High cardiac output: anemia, left to right shunts, obesity
    • Normal cardiac output: exercise, anaerobic metabolism, hypertension, aortic stenosis, hypertrophic cardiomyopathy, pericardial disease
    • Low cardiac output: coronary artery disease, nonischemic cardiomyopathies
  8. What are the multiple categories of pneumonia
    • Community acquired pneumonia (CAP)
    • Healthcare associated pneumonia
    • OR
    • Hospital acquired pneumonia
    • Ventilator associated pneumonia
    • Immunocompromised patient associated pneumonia
    • Subtypes: HIV, Transplant, Neutropenic
  9. Community acquired pneumonia
    • Pts have more severe problems
    • Long list of pathogens
    • Antibiotic resistance is important
    • Lab tests are inadequate
    • Risk factors are more severe (coexisting illness, physical exam findings, lab abnormalities)
  10. fever
    shortness of breath/dyspnea
    pleuritic chest pain
    symptoms of pneumonia
  11. headache
    abdominal pain
    Confounding symptoms of pneumonia (coexisting dz's alter presentations)
  12. Influenza viruses
    • Influenza A,B,C (orthomyxoviridae)
    • Influenza A subtypes
    • H1,H2,H3 have hemagglutinins
    • N1,N2 have neuraminidase as surface glycoproteins
  13. Spherical, enveloped viruses
    Segmented, negative sense, RNA genome
    Surface proteins: hemagglutinin, neuraminidase, M2
    Host range: _______ A => humans, swine, ducks; _______ B,C => humans
    Spread person-person by resp. droplets (virus remains virulent for up to 2 days outside of host)
    Biology of influenza viruses
  14. What is antigenic change?
    • allows continued circulation of new subtypes by human populations through processes of mutation and recombination.
    • Antigenic drift -- point mutations in the gene segment coding for HA or NA.
    • Antigenic shift -- marked changes in HA or NA or both due to acquisition of new gene segments.
  15. Strains: H7N2, H7N3 in N. America and Netherlands (other strains in SE Asia and Texas)
    H5 strains were confined to Hong Kong
    All are _____ strains and resulted from the slaughter of millions of ______.
    • Avian influenza
    • All are avian and slaughter of chickens

    Asian flu (H5N1) also exists, mainly in SE Asia.
  16. Name the strain.
    Frist seen 3/09 in Mexico (in US by april)
    By August > 1 million cases
    In Jan 99.7% of cases were flu A and 99.4% of those were ____.
    8% mortality rate
  17. Differentiate between complicated and uncomplicated influenza pathogenesis
    • Initially infects resp. tract mucosa
    • Uncomplicated = degeneration of epithelial cells (loss of cilia), edema, hyperemia, mononuclear cell infiltration
    • Complicated = hemorrhagic airless lungs, loss of ciliated cells, hyaline membrane formation, mononuclear cell infiltration
  18. What causes the constitution symptoms of influenza?
    Cytokines -- increased interferon, increased TNF alpha and interleukin 6 in nasal mucosa and blood.
  19. What factors contribute to a bacterial superinfection in a Pt w/ influenza?
    • Damaged bronchial epithelium => disrupted mucociliary clearance => increase bacterial colonization.
    • Viral nucleoprotein inhibits PMN leukocyte chemotaxis and superoxide production.
    abrupt onset
    systemic symptoms(3-5 days): fever, malaise, headache, myalgia
    respiratory symptoms (2-4 wks): sore throat, cough, nasal dishcarge
    Dz more severe in smokers or pts w/ underlying cardiorespiratory dz.
    Influenza syndrome
  21. What are these complications associated with?
    Viral Pneumonia: mild-- patchy infiltrates on CXR; severe-- influenza syndrome followed by increasing cough, tachyapnea, dyspnea; ARDS, hemoptysis; 50% mortality; pulmonary fibrosis and chronic lung dz survivors.
    Secondary bacterial pneumonia: re-appearance of fever, increased resp. symptoms during recovery; commonly caused by strep pneumoniae and staph aureus.
    Non-pulmonary complications: Rare CNS syndrome, cardiac (myocarditis, pericarditis), acute myositis.
    Influenza complications
  22. Explain the lab diagnosis of Influeza
    • CPE observed in 3-5 days (in monkey cell lines)
    • Virus replication may be detected earlier by hemadsorption w/ pig or chicken erythrocytes; immunoflourescence using type specifc antisera.
    • Antigen detection
  23. How do you prevent/treat influenza?

    • Treatment: SYMPTOMATIC: antipyretics (avoid aspirin), antitussives, ventilatory support; ANTIVIRALS: early treatment reduces viral replication and duration of symptoms by 1-2 days
  24. Pneumovirus A,B
    Lipid bilayer envelope
    Peplomers (spike-like glycoprotein projections)
    Single stranded RNA (neg. sense)
    Large G glycoprotein => attachment
    Protein F => fusion
    NO hemagglutinins or neuraminidase (H influenza does have them)
    RSV (Respiratory syncytial virus)
  25. 2/3 of infants get this infection in the 1st year of life (mostly symptomatic)
    Very severe in children <6mo.
    Repeat infections are common
    Transmission: fomites, large particle aerosols, self-inoculation
    Peak incidence in winter (annual epidemics)
    Contributes to SIDS
  26. Describe the pathogenesis and clinical manifestations of RSV
    • Virus replicates in ciliated epithelial cells
    • Bronchiolitis: necrosis of bronchiolar epithelial cells, migration of lymphocytes into affected tissues, mucous plugging occludes smaller airways, air-trapping with overdistention.
    • Children: expiratory wheezing, air trapping, nasal flaring, subcostal retractions, cyanosis (fever<50%, apnea in 25-30%).
    • Complications include bacterial otitis media, sinusitis, bacterial pneumonia, reactive airway disease.
  27. How do you diagnose and treat RSV
    • Clinical presentation
    • Lab: antigen detection, cell culture (takes 3-5 days, characterized by syncytial pattern, combo of shell and immunofourescence staining => early detection)
    • Treatment: Healthy children >1 yr -- supportive therapy; Children <1 yr -- hospitalization req., iv fluids, O2 therapy; Immunocompromised children -- ventilatory support often needed, antiviral therapy.
  28. Name the syndrome
    Almost always symptomatic
    Four phase dz
    Four corners outbreak
    Spread via a single rodent species (humans inhale airborn virus particles)
    No person-person spread
    Hantavirus Pulmonary syndrome
  29. Name the syndrome based on the following clinical manifestations
    Four-phase dz
    1) Prodrome(1-10 days): fever, myalgia, severe back and hip pain, nausea, vomiting, abdominal pain.
    2) Pulmonary edema/shock: abrupt onset of cough & dyspnea, O2 desaturation, progression to alveolar flooding is accompanied by centrally located infiltrates (need for intubation), thrombocytopenia, hemoconcentration, increased WBC.
    3) Spontaneous diuretic phase: recovery is rapid and Pt's are extubated within 12-24 hrs.
    4) Convalescent phase: several weeks to months of weakness and fatigue, recovery is usually complete.
    • Hantavirus pulmonary syndrome
    • confirmed w/ G1 type-specific antibodies, PCR on peripheral blood mononuclear cells.
  30. What is the treatment for Hantavirus?
    • Critical care management: intubation w/ mechanical ventilation, vasopressors rather than fluids to support blood pressure
    • Intravenous Ribavirin: placebo-controlled trials are ongoing (efficacy not established)
  31. Name the pathogen
    smallest free-living microbes
    NO cells wall (tri-layer membrane, stains poorly, insensitive to cell wall synthesis inhibitors)
    pleomorphic shapes from coccoid to rods
    Transmitted via droplet spread
    accounts for 20% of CAP (5-15 yrs old)
    Highly virulent
    Mycoplasma Pneumoniae
  32. Mycoplasma pathogenesis
    • Attaches to cilia and microvilli of cells lining bronchial epithelium
    • Intense bronchial and peribronchial inflammatory response w/ desquamation of involved mucosa
    • 3-13% if infected Pt's => pneumonia
  33. Name the pathogen based on these clinical manifestations
    symptoms similar to tracheobronchitis: cough becomes paroxysmal and productive of mucoid even blood streaked sputum (cough=> retrosternal chest pain)
    CXR: unilateral patchy segmental infiltrates, bilateral infiltrates, pleural effusions (25%)
    Extrapulmonary manifestations: related to autoantibodies, toxins & host response; deratologic, migratory polyarthritis, CNS conditions, hemolytic anemia, cardiac complications (5%), GI syndromes.
    >4x rise in serum antibody
    Mycoplasma Pneumoniae (confirmed by serology: complement fixation, ELISA, immunoflourescence techniques or Cold agglutinins)
  34. Name the pathogen
    obligate intracellular bacteria
    cell wall similar to gram neg. bacteria-LPS (no peptidoglycan)
    possess eubacterial ribosomes
    synthesize own proteins
    small DNA genome
    dependent upon host cell for energy (cannot synthesize ATP or reoxidize reduced NADP)
    Chlamydia sp.
  35. Chlamydia Pneumonia (transmission: resp. secretions)
    • Syndromes: severe pharyngitis w/ hoarseness, Sinusitis (5%), Otitis media.
    • 3rd or 4th most common cause of CAP (more common in elderly)
    • Pharyngitis proceeds pneumonia
    • Biphasic illness
    • Long interval from onset of symptoms to clinic visit
    • Diagnosis: Culture (50-75% sensitive), Serology: MIF (88% sensitive)-- 4x increase in IgM>16, IgG >512, pre-existing antibody --IgG, 8-256.
  36. Streptococcus pneumoniae
    • alpha hemolytic
    • usually grow in pairs
    • virulent strains are encapsulated
    • susceptible to lysis
    • Bile sensitive
    • Incidence highest in infants and alder adults (<2 and >60)
  37. Diseases caused by streptococcus pheumoniae
    • Pneumonia
    • Meningitis
    • Otitis media
    • Peritonitis
    • Bacteremia
    • Sinusitis
    • Septic arthritis
    • Mastoiditis
  38. Image Upload 2
    • Streptococcus pneumoniae (pneumococcus) causes lobar pneumonia
    • In this CXR you can see the clear line where the pneumonia is present in one lobe and not in another.
  39. Streptococcus pneumoniae lab diagnosis
    • Gram stain: Gram + diplococci (associated w/ PMNs)
    • Detection of pneumococcal antigen in urine
    • Direct detection of nucleic acid in samples using PCR (no standardized method)
  40. Image Upload 4Image Upload 6
    Sterptococci Pneumoniae identification
  41. Pneumococcal vaccines
    • 23 valent polysaccharide vaccine: Major serotypes causing dz; not effective for young children and immunocompromised; Recommended for: immunocompetent adults and children >2 and immunocompromised Pt's at risk for serious pneumococcal dz.
    • 7-valent pneumococccal conjugate vaccine: serotypes 4,6B,9V,14,18C,19F,23F, coupled w/ non-toxic variant of diphtheria toxin CRM 197; first dose 2-6 months old-- also for Pt's w/ underlying conditions.
  42. Name the pathogen
    severe, necrotizing pneumonia
    second most common cause of superinfection in influenza
    complement deficiency
    multifocal dz w/ possible abscesses
    may have other primary focus of infection
    Staphylococcus aureus pneumonia
  43. a) Staphylococcus epidermidis, diptheroids, candida have high or low virulence?

    b) Staph aureus, TB, mycoplasma, Strep pneumoniae have high or low virulence?
    a) low

    b) high
  44. What type of things can decrease host resistance?
    cystic fibrosis, ciliary immotility, tumor, neurologic problems, defects in T or B cells, neutropenia, splenectomy
  45. Streptococcus pneumoniae
    most common bacterial pneumonia, can be lobar
  46. Staphylococcus aureus
    aggressive baterial pneumonia, can form abscesses
  47. H influenza
    causes bacterial pneumonia in young children in poor countries.
  48. Pseudomonas
    water contaminant, antibiotic resistance, common in CF, also seen in burn Pt's and urinary infections.
  49. Legionella
    aggressive, necrotizing, systemic symptoms, in water systems, hard to culture, test by urine Ag test.
  50. Image Upload 8
    Left = bronchopneumonia

    Right = Lobar pneumonia
  51. Image Upload 10
    • L: Bronchopneumonia
    • R: Lobar Pneumonia

    • Radiographs are key for finding pneumonia (CT and MRI are even better)
    • Infiltrates can persist for up to 6 weeks, so recheck the Pt 6 weeks after to make sure there isn't an underlying tumor.
  52. Image Upload 12
    • Bacterial Pneumonia(other side)
    • Gram stain(this side)Image Upload 14
  53. Image Upload 16
    Intravascular growth causes necrosis and abscess
  54. Abscesses are often seen with
    aspiration, anaerobes, staph, klebsiella, septic emboli, obstructing tumor
  55. Image Upload 18
    Neutropenic pneumonia (no neutrophils because Pt lacked them)
  56. Image Upload 20
    Empyema -- infected inflammation
  57. Image Upload 22
    Bronchiectasis -- scarred, irregularly dilated airways, rare except with cystic fibrosis
  58. Image Upload 24
    • Diffuse alveolar damage or acute alveolar injury or
    • ARDS
  59. Name the type of pneumonia
    atypical pneumonia
    cough, fever, but little to no sputum
    difficult to culture (cold agglutinin titers)
    necrotizing bronchiolitis with fibrinous exudate
    like legionella, nonpulmonary symptoms (rash, arthralgia, diarrhea, neurologic)
    Mycoplasma Pneumonia
  60. Mycobacterium Tuberculosis
    • Primary TB: peripheral granuloma and hilar lymph node involvement (Gohn complex)
    • Secondary TB: Reactivation or reinfection, cavitations and granulomas
    • Granulomatous: macrophages, giant cells and lymphocytes; caseous necrosis in center, eventually becomes fibrous scar or cavity when healed.
  61. Image Upload 26
    Secondary TB: nodules and cavities
  62. Image Upload 28Image Upload 30
    Image Upload 32Image Upload 34
  63. For TB AFB stains, should you trust a negative culture?
    No, false negatives happen all the time.
  64. Miliary TB
    disseminated tiny (2mm) granulomas all over the place. Occur mainly in immunocompromised Pt's.
  65. MAI
    think HIV
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