Pulmonary Mechanics, Gas Exchange, and Pathology

Pulmonary Reasoning Map

Pulmonary mechanics questions reward thinking in terms of resistance, compliance, and elastic recoil. Airflow is highest when driving pressure is high and airway resistance is low; resistance rises sharply as airway radius falls. In obstructive disease, narrowed or collapsible airways slow expiration, so FEV1 falls more than FVC and FEV1/FVC decreases. Air trapping raises residual volume and often total lung capacity. Asthma, chronic bronchitis, emphysema, bronchiectasis, and cystic fibrosis are the classic obstructive patterns.

In restrictive disease, the lung or chest wall cannot expand normally, so FVC and TLC fall; FEV1 falls too, but proportionally less, so FEV1/FVC is normal or increased. Interstitial fibrosis, pneumoconiosis, sarcoidosis, neuromuscular weakness, kyphoscoliosis, obesity hypoventilation, and neonatal respiratory distress can produce restrictive mechanics, although DLCO helps localize the problem. DLCO falls when alveolar-capillary surface area is lost or membrane thickness rises, as in emphysema, fibrosis, pulmonary vascular disease, and anemia.

DLCO can be normal in extrapulmonary restriction, such as myasthenia gravis or obesity, and increased in pulmonary hemorrhage because carbon monoxide binds intra-alveolar hemoglobin.

Compliance is change in volume over change in pressure. A highly compliant lung expands easily but recoils poorly, as in emphysema after elastic tissue destruction by proteases. A poorly compliant lung requires large pressure changes to inflate, as in fibrosis, edema, ARDS, and surfactant deficiency. The pressure-volume curve has hysteresis because surfactant function differs during inspiration and expiration. Type II pneumocytes synthesize surfactant, mainly dipalmitoyl phosphatidylcholine, which lowers surface tension most in small alveoli.

By Laplace law, pressure equals 2 times surface tension divided by radius; without surfactant, small alveoli would have higher inward pressure and collapse into larger alveoli. Surfactant therefore increases compliance, decreases work of breathing, and prevents atelectasis. Premature infants with deficient surfactant develop neonatal respiratory distress syndrome with diffuse atelectasis, hypoxemia, and hyaline membranes.

Adults with diffuse alveolar damage, as in sepsis, pancreatitis, aspiration, or severe infection, develop ARDS, where inflammatory injury to pneumocytes and capillary endothelium creates protein-rich edema, hyaline membranes, reduced compliance, and refractory hypoxemia.

Gas exchange depends on ventilation, perfusion, diffusion distance, surface area, and hemoglobin binding. The alveolar gas equation estimates PAO2 from inspired oxygen, water vapor pressure, PaCO2, and respiratory quotient. The A-a gradient compares alveolar oxygen to arterial oxygen. A normal A-a gradient with hypoxemia means alveolar oxygen is also low, usually from hypoventilation or low inspired oxygen at altitude. A widened A-a gradient means oxygen entered alveoli but did not reach arterial blood normally. The major categories are V/Q mismatch, diffusion limitation, and shunt.

V/Q mismatch is the most common mechanism of hypoxemia and occurs when some lung units receive ventilation and perfusion in unequal amounts. Low V/Q units, such as bronchoconstricted or fluid-filled alveoli, resemble partial shunt. High V/Q units, such as pulmonary embolus, resemble dead space. Supplemental oxygen usually improves V/Q mismatch because even poorly ventilated units receive more alveolar oxygen.

Diffusion limitation occurs when oxygen cannot equilibrate across the alveolar-capillary membrane during capillary transit. Fibrosis thickens the membrane; emphysema reduces surface area. It is worse during exercise because blood spends less time in pulmonary capillaries. Carbon dioxide diffuses more readily than oxygen, so isolated diffusion impairment produces hypoxemia before hypercapnia. True shunt means perfused blood bypasses ventilated alveoli or crosses through alveoli that receive no ventilation, as in intracardiac right-to-left shunt, severe pneumonia, atelectasis, or ARDS.

Shunt responds poorly to supplemental oxygen because shunted blood never contacts alveolar gas. Dead space is ventilated but not perfused, classically from pulmonary embolism; it increases wasted ventilation and can cause respiratory alkalosis early because hypoxemia stimulates hyperventilation.

Pulmonary blood flow is low resistance and normally accommodates the entire cardiac output. Gravity creates regional differences. At the apex, alveolar pressure may exceed arterial and venous pressures, limiting perfusion. At the base, arterial and venous pressures exceed alveolar pressure, so perfusion is greatest. Ventilation also increases toward the base, but perfusion increases more, so V/Q is highest at the apex and lowest at the base. Hypoxic pulmonary vasoconstriction diverts blood away from poorly ventilated alveoli, improving matching locally.

In global alveolar hypoxia, as in high altitude or chronic lung disease, this response increases pulmonary vascular resistance and may cause pulmonary hypertension. Pulmonary hypertension also results from left heart disease, chronic thromboembolic obstruction, connective tissue disease, congenital shunts, or idiopathic vascular remodeling. Sustained pressure overload causes right ventricular hypertrophy; decompensation produces cor pulmonale with peripheral edema, hepatomegaly, and jugular venous distention.

Obstructive disease mechanisms are distinct. Asthma is reversible airway obstruction due to type I hypersensitivity in atopic disease or irritant-triggered bronchial hyperreactivity. Th2 cytokines promote IgE, eosinophils, mucus, smooth muscle constriction, and basement membrane thickening. Spirometry shows low FEV1/FVC that improves with bronchodilator. Chronic bronchitis is defined clinically by productive cough for at least 3 months in 2 consecutive years and is driven by smoke-induced goblet cell hyperplasia and mucus gland enlargement, measured by increased Reid index.

Mucus plugging and airway inflammation cause hypoxemia, cyanosis, and frequent infections. Emphysema is permanent enlargement of airspaces distal to terminal bronchioles with wall destruction and no significant fibrosis. Smoking recruits neutrophils and macrophages, increasing elastase and oxidants; alpha-1 antitrypsin deficiency reduces protease inhibition and classically causes panacinar emphysema, worse at lung bases and associated with liver disease. Loss of elastic recoil causes airway collapse during expiration, air trapping, barrel chest, and decreased DLCO.

Bronchiectasis is permanent dilation of bronchi from chronic necrotizing infection and impaired clearance, with copious purulent sputum. Cystic fibrosis, primary ciliary dyskinesia, and obstruction predispose by retaining secretions.

Restrictive and inflammatory pathology often centers on alveolar walls. Idiopathic pulmonary fibrosis has patchy interstitial fibrosis, fibroblast foci, honeycomb change, restrictive spirometry, decreased DLCO, and progressive exertional dyspnea. Pneumoconioses depend on particle and immune response: coal dust causes upper lobe macules and nodules, silica increases macrophage activation and tuberculosis risk, asbestos produces lower lobe interstitial fibrosis, pleural plaques, ferruginous bodies, and increased risk of bronchogenic carcinoma and mesothelioma.

Sarcoidosis forms noncaseating granulomas with bilateral hilar lymphadenopathy, elevated ACE, hypercalcemia from macrophage 1-alpha hydroxylase activity, and restrictive lung disease.

Pneumonia patterns connect gross distribution to host response. Lobar pneumonia fills one lobe with intra-alveolar exudate and classically progresses through congestion, red hepatization, gray hepatization, and resolution. Bronchopneumonia is patchy around bronchi and may involve multiple lobes. Interstitial pneumonia involves alveolar septa, often producing diffuse reticular infiltrates and dry cough. Aspiration produces dependent lung abscesses with foul sputum due to anaerobes; abscess can erode tissue and cause cavitation. Empyema is pus in the pleural space.

Atelectasis is alveolar collapse; resorption atelectasis follows obstruction, compression atelectasis follows pleural fluid or air, and contraction atelectasis follows fibrosis.

Lung cancer questions test cell type, location, and secreted products. Squamous cell carcinoma is central, strongly smoking-associated, forms keratin pearls or intercellular bridges, and can secrete PTHrP causing hypercalcemia. Small cell carcinoma is central, neuroendocrine, highly aggressive, and associated with ectopic ADH causing hyponatremia, ectopic ACTH causing Cushing syndrome, and Lambert-Eaton myasthenic syndrome from antibodies against presynaptic calcium channels.

Adenocarcinoma is usually peripheral, often gland-forming, and is the most common lung cancer in nonsmokers and women; it may involve EGFR, ALK, or KRAS pathways. Large cell carcinoma is undifferentiated and peripheral. Mesothelioma arises from pleura after asbestos exposure and can encase the lung.