Pulmonary Pathology, Part I

1. Respiratory Pathology
By: Noel C. Santos, M.D.

2. General Categories
• Congenital Anomalies
• Atelectasis
• Pulmonary Vascular Disorders
• Pulmonary Infections
• Obstructive and Restrictive Diseases
• Pulmonary Tumors
• Diseases of the Pleura

3. Congenital Anomalies
• Agenesis or Hypoplasia
• Tracheal and Bronchial Anomalies: atresia, stenosis, TE
fistula
• Vascular Anomalies
• Congenital Lobar Overinflation (emphysema)
• Foregut cysts: bronchogenia, esophageal, enteric
• Congenital Pulmonary Airway Malformation
– Hamartomatous lesion, 5 types
• Pulmonary Sequestrations: extralobar, intralobar

4. Atelectasis
• Airless: incomplete expansion or
collapse
• Acquired
–Resorption or Obstruction
–Compression
–Contraction

8. Pulmonary Vascular Disease
• Edema
– Hydrodynamic or cardiogenic
– Microvascular Injury
• Adult Respiratory Distress Syndrome
– Diffuse Alveolar Damage
• Impair respiratory function
• Predisposes to infection

9. Pulmonary Edema
• Hemodynamic Edema
–Increased HP
• Microvascular Injury
–Injury to capillaries of alveolar septa
–Important contributor in the
development of ARDS

13. ARDS
• Diffuse alveolar capillary damage
• Respiratory failure
• Arterial hypoxemia refractory to O2 therapy
• Several causes: sepsis, trauma, cancer,
inhaled gases
• Differs from Hyaline Membrane of the
Newborn – deficient surfactant

14. ARDS
• Mechanisms:
–Oxygen-derived free radicals
–Aggregation of activated neutrophils
–Activation of lung macrophages
–Loss or damage to surfactant

18. Pulmonary Embolism, Hemorrhage &
Infarction
• Occlusion of pulmonary circulation
• Predisposing factors: bed-ridden, risk-associated
conditions, etc.
• Embolic from other sites: deep veins of legs
• Potential consequences: size, site, cardiovascular
status
– Respiratory compromise
– Cardiovascular compromise

20. Pulmonary Hypertension
• Normal: 1/8 of mean systemic pressure
• ¼ or above is Pulmonary HPN
• Primary or Idiopathic
• Secondary – lung disease, left-sided heart
disease, recurrent emboli
• Endothelial dysfunction and injury with trigger
mechanisms – persistent vasoconstriction

23. • Impaired defense mechanisms
• Lowered general resistance of the host
– Loss or suppression of the cough reflex
– Injury to the mucociliary apparatus
– Interference with the phagocytic or bactericidal
action of alveolar macrophages
– Pulmonary congestion and edema
– Accumulation of secretions
Pulmonary Infections

24. • Defects in innate immunity and humoral
immunodeficiency
→Pyogenic infections
• Cell-mediated immune defects
→intracellular microbes
→very low virulence

25. Pulmonary Infections
• Morphology
– Lobar Pneumonia
– Lobular Pneumonia or Bronchopneumonia
– Atypical Pneumonia
– Necrotizing Pneumonia and Lung Abscess
• Where?
– Community Acquired
– Hospital Acquired or Nosocomial Infection
• Time/Duration: Acute and Chronic
• Etiologic Agent
• Immunocompromised Host
• Aspiration Pneumonia

33. Necrotizing Pneumonia and
Lung Abscess
• Anaerobic bacteria with or without
mixed aerobic infection
• S. aureus, K. pneumoniae, S.
pyogenes. Type 3 pneumococcus

36. Pulmonary Tuberculosis

43. Aspiration Pneumonia
• Markedly debilitated patients
• Unconscious
• Repeated vomiting
• Abnormal gag and swallowing reflexes
• Partly chemical and partly bacterial (more than
one organisms; aerobes>anaerobes)
• Necrotizing, fulminant course
• Abscess formation as one of complications

45. Pneumonia in Immunocompromised Host
• CMV, P. carinii, M. avium-
intracellulare
• Invasive aspergillosis and
candidiasis
• “Usual” bacteria, viral and fungal
organisms

47. Chronic Obstructive Pulmonary Disease
(COPD)
–Increased resistance to air flow
Restrictive Pulmonary Disease
–Reduced expansion of the lung parenchyma

48. COPD’s
• Emphysema
• Chronic Bronchitis
• Bronchial Asthma
• Bronchiectasis

49. Emphysema
• Abnormal enlargement of air spaces
distal to the terminal bronchioles
• Destruction of septal walls
• Decreased surface area of functional
pulmonary segments
• Classification:
1. Centriacinar
2. Panacinar
3. Paraseptal
4. Irregular

51. Centriacinar Emphysema
• Destruction and enlargement of
the central or proximal parts of
the acinus
• Upper lobes and apices
• Smokers

56. Panacinar Emphysema
• Uniform destruction and enlargement
of the acinus
• Basal zones of the lung
• Alpha1-antitrypsin deficiency

59. Paraseptal Emphysema
• Mostly the distal acinus
• Near the pleura and
adjacent to fibrosis
• Leads to pneumothorax

60. Irregular Emphysema
• Irregular involvement of
the acinus
• Associated with scarring
Others:
 Bullous Emphysema
 Interstitial Emphysema

62. Emphysema
• Imbalance between proteases and their
inhibitors
• Tobacco – recruit neutrophils, stimulate
release and enhance activities of
enzymes, inactivation of antitrypsin

64. Chronic Bronchitis
• Persistent productive cough
• At least 3 months
• At least 2 consecutive years
• Morphology: hyperemia and edema of mucous
membranes, mucinous secretions and casts,
hypertrophy of mucous glands with airway
plugging, inflammation and fibrosis, squamous
metaplasia/dysplasia

66. Bronchial Asthma
• Increased responsiveness to various
stimuli
• Paroxysmal contraction of airway
passages
–Extrinsic (Reagin-mediated,
Allergen)
–Intrinsic (Idiopathic or precipitated
by other factors, non-atopic or
non-reaginic)

68. Bronchial Asthma (cont.)
• Overinflated lungs with patchy atelectasis
• Occlusion respiratory passages
• Edema, bronchial inflammation,
hypertrophy of bronchial muscles & mucous
glands
• Curschmann’s spirals and Charcoat-Leyden
crystals

75. Bronchiectasis
• Chronic necrotizing infections
• Abnormal & permanent dilatation of
airways
• Cough, fever, purulent sputum
• Obstructive respiratory
insufficiency

76. Bronchiectasis (cont.)
• Atelectasis, diminished elastic forces
• Distal airways, lower lobes: dilatations – cylindrical,
fusiform or saccular
• Spectrum of inflammation (mild to necrotizing), fibrosis
• May lead to abscess formation
• Complications: cor pulmonale, metastatic abscesses,
systemic amyloidosis
• associated with bronchial obstruction,
congenital/hereditary conditions, immotile cilia syndrome,
necrotizing pneumonia

79. Restrictive (Interstitial) Lung Disease
• Clinical: dyspnea, decreased lung volumes
and compliance
• Radiologic: diffuse infiltrates, ground-glass
shadows
• Pathologic: diffuse, chronic inflammation
and/or fibrosis of alveolar interstitium

80. Interstitial Lung Disease
• Pathogenesis:
– Initial Event: injury to
epithelium/endothelium via inhaled or
blood-borne toxins/agents
– Early Acute Changes: alveolitis –
proinflammatory and fibrogenic
substances
– Late Effects: interstitial fibrosis

81. Interstitial Lung Disease
• Idiopathic
• Pneumoconioses
• Granulomas
• Hypersensitivity Pneumonitis
• Pulmonary Eosinophilia
• Bronchiolitis Obliterans – Organizing
Pneumonia
• Diffuse Pulmonary Hemorrhage
• Pulmonary Alveolar Proteinosis

82. Idiopathic Pulmonary Fibrosis
• Progressive pulmonary fibrosis
• Hypoxemia, progressive resulting in pulmonary
insufficiency, cor pulmonale and cardiac failure
• 30 – 50 y/o; immune complex
• Early Stages: interstitial & intra-alveolar edema,
interstitial infiltration by leukocytes, type II
pneumocyte proliferation
• Intermediate Stages: interstitial & intra-alveolar
fibrosis
• End Stages: spaces lined by epithelium & separated
by inflammatory fibrous tissue (HONEYCOMB LUNG)

86. Pneumoconioses
• Inhalational disorders: mineral dusts, organic
dusts, fumes and vapors
• Factors:
– Amount: concentration, duration, clearance
mechanisms
– Size, shape, buoyancy (1 to 5 μm)
– Physicochemical reactivity and solubility:
quartz, highly soluble (toxic), resist dissolution

87. Pneumoconioses
• Carbon Dust – Coal Workers’
Pneumoconiosis
• Silicosis (mining, sandblasting, metal
grinding, manufacture of ceramics)
• Asbestosis
–Chrysotile: curled, flexible
serpentine
–Crocidolite: brittle, straight
amphiboles

88. Coal Workers’ Pneumoconiosis (CMP)
• Anthracosis: small harmless
• Simple CWP: macules
• Complicated CWP or Progressive
Massive Fibrosis (PMF): severe fibrosis
and scarring with disabling respiratory
insufficiency

90. Silicosis
• Promotion of persistent inflammation and fibrosis
• Release of oxidants, cytokines, growth factors
(fibroblast proliferation and collagen deposition)
• Collagenous nodules, coalesce, calcification
and/or blackening
• Hyalinized whorls of collagen, scant
inflammation, birefringent silica particles

93. Asbestosis
• Diffuse interstitial fibrosis with asbestos bodies
• Pleural Reactions: benign effusions, fibrous pleural
adhesions, dense fibrocalcific plaques
• Mechanisms:
– Release of enzymes, toxic free radicals
– Release of fibrogenic cytokines and growth factors
– Direct stimulation of fibroblast collagen
• Bronchogenic carcinoma and Malignant mesothelioma

95. Granulomas
• Infectious: Tuberculosis, fungal
• Non-infectious: Sarcoidosis, foreign bodies
• SARCOIDOSIS:
– Unknown etiology, F>M
– Non-caseating granulomas
– Asymptomatic to debilitating
– Elevated serum IgG and calcium

98. Hypersensitivity Pneumonitis
• Immunologically-mediated
• Inhaled dusts or antigens
– Farmer’s lung: actinomyces spores in hay
– Pigeon’s breeder’s lung: feathers, excreta
– Humidifier/Air-conditioner: HS, asthma, allergic
bronchopulmonary aspergillosis
– Idiopathic chronic eosinophilic pneumonia: focal
consolidation of lymphocytes and eosinophils; steroid
responsive

99. Bronchiolitis Obliterans – Organizing
Pneumonia
• Response to chronic infectious or inflammatory
injury of the lungs
• Cough, dyspnea, recent RTI
• Loose fibrous tissue plugs within bronchioles
and organizing pneumonia
• Improve gradually or with steroid therapy

101. Diffuse Pulmonary Hemorrhage
• Goodpasture’s syndrome
– Necrotizing, hemorrhagic interstitial pneumonitis with
progressive GN
– Ab’s against BM
• Idiopathic pulmonary hemosiderosis
– Chronic, episodic hemorrhage
– Unknown etiology
– Heavy hemosiderin deposition w/fibrosis
• Vasculitis-associated hemorrhage
– Wegener’s granulomatosis, SLE, HS angiitis

104. Pulmonary Alveolar Proteinosis
• Obscure etiology
• Radiologically: diffuse pulmonary opacification
• Pathologically: dense, amorphous, PAS-positive lipid-
laden material in intracellular spaces
• Clinically: respiratory difficulty (cough, sputum containing
gelatinous materials)
• Intraalveolar exudate: surfactant-like material, necrotic
alveolar macrophages and type II cells
• Exposure to irritating dusts and chemicals;
immunocompromised

107. Respiratory Pathology
By: Noel C. Santos, M.D.