11.3 Respiratory Pathology: Atelectasis, Edema, ARDS, Obstructive & Restrictive Disease, Vascular Disease, Infections, Tumors & Pleura

Why this area matters

The TOS lists:

• atelectasis;
• pulmonary edema and ARDS;
• obstructive and restrictive pulmonary disease (emphysema, chronic bronchitis, asthma, bronchiectasis, sarcoidosis, pneumoconiosis);
• diseases of vascular origin (embolism, infarction, hemorrhage);
• pulmonary infections (community-acquired, hospital-acquired and aspiration pneumonia, lung abscess, chronic pneumonia);
• pulmonary tumors;
• diseases of the pleura (effusion, pneumothorax, tumors).

Pneumonia and tuberculosis are among the leading causes of death in the Philippines, and COPD is common in smokers and households that burn biomass.

Atelectasis

Atelectasis is reversible except when caused by contraction. It predisposes the lung to infection.

Pulmonary edema

• Hemodynamic edema: high capillary hydrostatic pressure from left heart failure or mitral stenosis, or low oncotic pressure. The fluid is a transudate that collects first in the lower lobes, with heart failure cells.
• Microvascular injury (non-cardiogenic): sepsis, pneumonia, aspiration, trauma, toxic inhalation and drugs. This is the basis of ARDS. High-altitude and neurogenic edema have mixed mechanisms.

Pulmonary Pathology

Obstructive vs. Restrictive Pulmonary Disease

Pulmonary diseases divide functionally into obstructive (airflow limitation) and restrictive (reduced lung expansion) patterns:

$\text{Obstructive}: \frac{\text{FEV}_1}{\text{FVC}} < 0.70 \quad | \quad \text{Restrictive}: \frac{\text{FEV}_1}{\text{FVC}} \ge 0.70 \text{ with } \text{TLC} < 80\%$

Major Obstructive Lung Diseases

1. Emphysema: Permanent, abnormal enlargement of airspaces distal to terminal bronchioles accompanied by destruction of alveolar walls without gross fibrosis, leading to loss of elastic recoil and expiratory airway collapse.
   • Centrilobular (Centriacinar) Emphysema: Strongly associated with cigarette smoking; predominantly affects respiratory bronchioles while sparing distal alveolar sacs; concentrated in the upper lobes and apical segments.
   • Panacinar (Panlobular) Emphysema: Associated with homozygous alpha-1 antitrypsin (A1AT) deficiency (PiZZ genotype); uniformly destroys the entire acinus from respiratory bronchiole to terminal alveolus; concentrated in the lower lung bases. In the liver, misfolded A1AT protein accumulates as PAS-positive, diastase-resistant cytoplasmic granules in periportal hepatocytes, predisposing to cirrhosis.
2. Chronic Bronchitis: Clinically defined as persistent productive cough for at least 3 consecutive months in at least 2 consecutive years. Driven by smoke irritants causing submucosal gland hyperplasia and goblet cell metaplasia in the bronchi. Quantified by the Reid Index:

$\text{Reid Index} = \frac{\text{Thickness of Submucosal Gland Layer}}{\text{Thickness of Bronchial Wall (Epithelium to Perichondrium)}} > 0.50 \quad (\text{Normal } < 0.40)$

1. Bronchial Asthma: Reversible chronic inflammatory airway disorder characterized by hyperresponsive smooth muscle bronchospasm, mucus hypersecretion, and airway remodeling (subepithelial basement membrane thickening). Cytologic and microscopic hallmarks:
   • Curschmann Spirals: Whorled, twisted mucus plugs containing shed bronchial epithelial casts.
   • Charcot-Leyden Crystals: Slender, bipyramidal crystals composed of galectin-10 released by degenerating eosinophils.

Major Restrictive Lung Diseases & ARDS

• Idiopathic Pulmonary Fibrosis (IPF): Bilateral patchy interstitial fibrosis with spatial and temporal heterogeneity; microscopic hallmark is Usual Interstitial Pneumonia (UIP) featuring fibroblastic foci and end-stage cystic honeycomb lung.
• Pneumoconioses:
  • Silicosis: Inhalation of crystalline silicon dioxide ($SiO_2$) in sandblasters, quarry workers, and miners. Silicotic nodules show concentric whorls of hyalinized collagen fibers in upper lobes; hilar lymph nodes exhibit "eggshell" calcification. Marked susceptibility to pulmonary tuberculosis due to silica-mediated impairment of macrophage phagolysosomal function.
  • Asbestosis: Inhalation of asbestos fibers in shipbuilders, roofers, and plumbers. Diffuse interstitial fibrosis concentrated in the lower lobes. Pathognomonic asbestos (ferruginous) bodies (golden-brown, beaded, dumbbell-shaped rods coated with iron and protein, Prussian blue positive). Predisposes to pleural plaques and carries a markedly elevated risk for bronchogenic carcinoma (greater absolute risk than mesothelioma) and malignant mesothelioma.
• Acute Respiratory Distress Syndrome (ARDS): Clinical syndrome of severe acute hypoxemic respiratory failure with non-cardiogenic pulmonary edema. Histopathologic hallmark is Diffuse Alveolar Damage (DAD). Capillary endothelial and type I alveolar epithelial necrosis results in alveolar exudation of protein-rich edema fluid and cellular debris, which condenses into waxy pink hyaline membranes lining alveolar walls.

Primary Carcinomas of the Lung

• Adenocarcinoma (35-40%): Most common lung cancer overall, in non-smokers, and in women. Located peripherally. Glandular architecture with mucin production (TTF-1 and Napsin A positive). Frequently carries targetable EGFR mutations or ALK gene rearrangements.
• Squamous Cell Carcinoma (25-30%): Strongly associated with cigarette smoking. Located centrally in main bronchi. Histopathology shows keratin pearls and prominent intercellular bridges (desmosomes). Frequently secretes PTHrP, producing paraneoplastic hypercalcemia.
• Small Cell Lung Carcinoma (SCLC, 15%): Highly aggressive neuroendocrine tumor strongly associated with smoking. Located centrally. Sheets of small round blue cells with scant cytoplasm, finely granular "salt-and-pepper" chromatin, absent nucleoli, high mitoses, and the Azzopardi effect (basophilic encrustation of vascular walls by leaked necrotic DNA). Positive for neuroendocrine markers (chromogranin, synaptophysin, CD56). Produces paraneoplastic Cushing syndrome (ACTH), SIADH (ADH), and Lambert-Eaton syndrome.

Bronchiectasis and sarcoidosis

• Bronchiectasis: permanent dilation of bronchi from chronic necrotizing infection, with cough and copious purulent sputum. It follows severe pneumonia, tuberculosis, measles and pertussis in childhood, cystic fibrosis, Kartagener syndrome and bronchial obstruction. The lower lobes are affected most.
• Sarcoidosis: a multisystem disease with non-caseating granulomas. Features include bilateral hilar lymphadenopathy, interstitial lung disease, uveitis, erythema nodosum, hypercalcemia (granuloma 1-alpha-hydroxylase) and raised ACE. Granulomas may contain Schaumann and asteroid bodies. Tuberculosis and fungi must be excluded first.

Pulmonary vascular disease

• Pulmonary embolism: most emboli come from deep leg veins.
  • Large emboli cause sudden death or acute cor pulmonale.
  • Medium emboli usually cause hemorrhage without infarction, because the bronchial arteries supply the lung.
  • Infarction occurs mainly when the circulation is already compromised, as in heart failure. Such infarcts are red, wedge-shaped and pleural-based.
• Pulmonary hypertension: medial hypertrophy and intimal fibrosis. Severe or idiopathic forms show plexiform lesions. Causes include heart and lung disease, recurrent emboli, chronic hypoxia, schistosomiasis and BMPR2 mutations.
• Diffuse alveolar hemorrhage: Goodpasture syndrome (anti-GBM antibodies), granulomatosis with polyangiitis, SLE, and leptospirosis. Pulmonary hemorrhage is a feared complication of leptospirosis in the Philippines.

Pulmonary infections

• Community-acquired bacterial pneumonia: Streptococcus pneumoniae is the most common cause. Others are Haemophilus influenzae, Moraxella, Klebsiella (alcoholics; currant-jelly sputum), Staphylococcus aureus (after influenza) and atypical organisms (Mycoplasma, Chlamydophila, Legionella).
  • Lobar pneumonia stages:
    1. Congestion: vascular engorgement and bacteria.
    2. Red hepatization: neutrophils, red cells and fibrin.
    3. Gray hepatization: red cells break down and fibrin and exudate persist.
    4. Resolution: enzymatic digestion and clearance.
  • Bronchopneumonia is patchy, centered on bronchioles and often bilateral and basal.
  • Complications include abscess, empyema, organization and bacteremia.
• Viral and atypical pneumonia: interstitial inflammation with lymphocytes. Severe cases cause diffuse alveolar damage. Examples are influenza and COVID-19.
• Hospital-acquired pneumonia: gram-negative bacilli such as Pseudomonas, Klebsiella and Acinetobacter, and MRSA, often associated with ventilators.
• Aspiration pneumonia and lung abscess: aspiration occurs when consciousness is impaired (alcohol, seizures, stroke, anesthesia). Oral anaerobes plus aerobes form necrotizing pneumonia and abscesses, most often in the right lower lobe or the posterior upper-lobe segments when the patient is supine.
• Chronic pneumonia: tuberculosis, histoplasmosis and other fungi, and nocardiosis cause granulomatous inflammation and cavities.
  • Primary tuberculosis forms the Ghon complex; it may heal as a calcified Ranke complex.
  • Secondary tuberculosis forms apical cavitary lesions.
  • Miliary tuberculosis spreads millet-seed nodules through the lungs and organs.
  • Aspergilloma may colonize old cavities.
• In AIDS: Pneumocystis pneumonia (foamy alveolar exudate), tuberculosis, CMV, fungi.

Pleural diseases

• Effusions:
  • Transudates come from heart failure, cirrhosis and nephrotic syndrome.
  • Exudates meet Light criteria: a pleural-to-serum protein ratio above 0.5, a pleural-to-serum LDH ratio above 0.6, or pleural LDH above two-thirds of the upper normal serum limit. Causes are pneumonia (parapneumonic effusion, empyema), tuberculosis (lymphocytic exudate with high adenosine deaminase), cancer and pulmonary embolism.
  • Special effusions are hemothorax and chylothorax.
• Pneumothorax:
  • Spontaneous primary pneumothorax occurs from rupture of apical blebs in tall, thin young men.
  • Secondary pneumothorax occurs in COPD, TB and cystic fibrosis.
  • Traumatic pneumothorax follows injury or procedures.
  • Tension pneumothorax is a one-way valve leak that shifts the mediastinum away and causes shock.
• Pleural tumors:
  • Malignant mesothelioma follows asbestos exposure after a latency of 25 to 40 years. It encases the lung and is calretinin positive.
  • Pleural metastases from lung and breast cancer are more common.
  • The solitary fibrous tumor is benign.