Chapter 2-04: Diseases and Pathophysiology in Pulmonology

ALVEOLAR HEMORRHAGE

• Definition: Bleeding into the alveolar space due to disruption of the alveolar–capillary basement membrane

• Etiologies: See Table 2.5

• Clinical presentation:

  • - Cough, fever, hemoptysis, or diffuse GGOs + other concerning features (e.g., extrapulmonary signs of vasculitis, known condition associated with DAH, declining hemoglobin without clear reason)

  • - Pearl: Hemoptysis is only present in 50% of cases and absence does not predict hemorrhage severity

  • - Consider alveolar hemorrhage in a patient with GGOs who is failing to progress as expected (e.g., patient with suspected cardiogenic pulmonary edema who is not improving with diuresis)

• Diagnostics:

  • - Labs: CBC, BUN/Cr, UA, ESR, CRP. Consider rheumatologic w/u, which may include ANA, dsDNA, RNP, C3, C4, RF, CCP, ANCA, MPO, PR3, cryoglobulins, anti-GBM, RVVT, cardiolipin, B2-glycoprotein Ab

  • - Imaging: Noncontrast chest CT (consider contrast if suspect other causes of hemoptysis): Imaging shows patchy or diffuse GGOs

  • - Bronchoscopy: 1) Serial lavage – gets progressively more hemorrhagic; 2) Rule out infection; 3) Check cell count with differential to evaluate for eosinophilia

• Management:

  • - Capillaritis: Immunosuppression

    • For ANCA-associated vasculitis, typically give pulse-dose steroids first and then adjunctive therapies like cyclophosphamide, rituximab, etc. if lack of response

  • - Bland hemorrhage or diffuse alveolar damage:

    • Treat underlying cause, supportive care

OBSTRUCTIVE LUNG DISEASES

• Obstructive = ↑compliance, ↓elastance → problem emptying the lung.

  • - ↑TLC, ↑RV, problem pushing air out → air trapping

  • - ↓↓FEV₁ ↓FVC = FEV₁/FVC ratio <0.7

Chronic obstructive pulmonary disease (COPD)

• Epidemiology: Most common in former smokers (although can affect persons in cities with air pollution, women may develop with less significant smoking history). Typical onset age >40 yr

• Definitions:

  • - COPD: Persistent airflow limitation resulting from the consequences of chronic inflammation from smoking. Classic subtypes were chronic bronchitis and emphysema, although these are not included in the current definition

    • Chronic bronchitis: Clinical diagnosis of chronic productive cough for 3 mo/yr for >2 yr. Normal DLCO.

    • Emphysema: Pathologic diagnosis that describes permanent enlargement of the airspaces and destruction of the alveoli, which causes loss of diffusing capacity and reduced elastic recoil. ↓DLCO.

      • - Centrilobular: Tobacco activates PMNs, inhibits α1-antitrypsin, ↑oxidative stress. Upper lung predominant.

      • - Panlobular: Alpha-1 antitrypsin deficiency. Lung bases with bilateral basilar bullae and can also have liver disease (PAS+).

    • Small airway disease: Third characteristic feature of COPD. Small bronchioles are narrowed and reduced in number. Small airway destruction is a hallmark of advanced COPD.

  • - Asthma–COPD overlap syndrome (some reversibility with bronchodilators)

• Pathogenesis:

  • - Airways: Chronic inflammation, increased numbers of goblet cells and mucous glands; airway collapse due to the loss of tethering caused by alveolar wall destruction

  • - Lung parenchyma: Affects structures distal to the terminal bronchiole

  • - Pulmonary vasculature: Smooth muscle hypertrophy → chronic hypoxic vasoconstriction of the small pulmonary arteries

• Clinical presentation: Dyspnea, chronic cough, sputum production

• Physical exam:

  • - Early in disease: Normal or only ...