Pathophysiology: Respiratory Disorders

Respiratory disorders are best understood by linking the underlying mechanism to what clinicians see at the bedside: dyspnea, cough, wheeze, hypoxemia, hypercapnia, and fatigue. While the diseases differ, most fit into a few physiological patterns, including airflow obstruction, impaired gas exchange, ventilation perfusion mismatch, diffusion limitation, and failure of the ventilatory pump. This article reviews the pathophysiology of five common and high-impact conditions: asthma, COPD, pneumonia, pulmonary embolism, and respiratory failure, with emphasis on clinical manifestations and treatment principles.

Core physiological concepts that drive symptoms

The lungs are designed to move air to alveoli (ventilation) and exchange gases with blood flowing through pulmonary capillaries (perfusion). A useful framework is the ventilation perfusion ratio, written as $V/Q$. In an ideal world, ventilation and perfusion match closely throughout the lung. In real disease states:

• Low __MATH_INLINE_2__ means alveoli are perfused but under-ventilated, leading to hypoxemia (common in pneumonia and COPD exacerbations).
• High __MATH_INLINE_3__ means alveoli are ventilated but under-perfused, creating dead space (classic in pulmonary embolism).
• Shunt is an extreme form of low $V/Q$ where blood bypasses ventilated alveoli entirely, often causing hypoxemia that responds poorly to supplemental oxygen (seen in severe pneumonia or atelectasis).
• Diffusion limitation occurs when the alveolar-capillary membrane is thickened or surface area reduced, limiting oxygen transfer, especially during exertion.
• Ventilatory failure arises when the body cannot maintain adequate alveolar ventilation, causing carbon dioxide retention.

These mechanisms explain why different disorders can produce similar complaints but require different treatments.

Asthma: reversible airflow obstruction and airway hyperresponsiveness

Pathophysiology

Asthma is characterized by intermittent, usually reversible airway obstruction driven by airway inflammation and hyperresponsiveness. Key mechanisms include:

• Bronchoconstriction of airway smooth muscle, narrowing the lumen.
• Mucosal edema and mucus hypersecretion, further limiting airflow.
• Airway hyperreactivity, where triggers such as allergens, viral infections, exercise, cold air, or irritants provoke exaggerated narrowing.

Airflow obstruction is most prominent during exhalation because intrathoracic pressure narrows already inflamed airways. This leads to air trapping and dynamic hyperinflation, increasing the work of breathing.

Clinical manifestations

Typical features include episodic wheeze, cough (often worse at night), chest tightness, and shortness of breath. On spirometry, a reduced expiratory flow with bronchodilator responsiveness supports the diagnosis. Severe attacks can progress to fatigue, silent chest (minimal airflow), and respiratory failure.

Treatment principles

Treatment targets both bronchoconstriction and inflammation:

• Short acting bronchodilators relieve acute bronchospasm.
• Inhaled corticosteroids reduce airway inflammation and prevent exacerbations.
• Long acting bronchodilators are used with anti-inflammatory therapy for persistent symptoms.
• During severe exacerbations, systemic steroids, oxygen, and escalation of bronchodilator therapy are often required. Avoiding triggers and managing comorbid rhinitis or reflux can reduce symptom burden.

COPD: fixed airflow limitation, hyperinflation, and gas exchange impairment

Pathophysiology

Chronic obstructive pulmonary disease is driven most commonly by long-term exposure to cigarette smoke or other noxious particles. Two overlapping processes dominate:

• Chronic bronchitis physiology: airway inflammation, mucus gland enlargement, and increased sputum production increase airway resistance.
• Emphysema physiology: destruction of alveolar walls reduces elastic recoil and alveolar surface area, promoting airway collapse during exhalation and impairing diffusion.

The result is persistent airflow limitation that is less reversible than asthma. Air trapping leads to hyperinflation, flattening the diaphragm and increasing the energy cost of breathing. Gas exchange abnormalities arise from $V/Q$ mismatch and, in emphysema, reduced diffusion capacity.

Clinical manifestations

Patients develop chronic dyspnea, cough, sputum, wheeze, and reduced exercise tolerance. Exacerbations, often triggered by infections or environmental exposures, cause worsening dyspnea and sputum changes. CO2 retention can occur as ventilatory capacity declines, particularly during exacerbations.

Treatment principles

COPD treatment aims to reduce symptoms, prevent exacerbations, and improve function:

• Bronchodilators (short and long acting) reduce airflow resistance and dynamic hyperinflation.
• Smoking cessation is the most effective intervention to slow disease progression.
• Vaccination, pulmonary rehabilitation, and structured exercise improve outcomes.
• Oxygen therapy is indicated in chronic severe hypoxemia.
• Exacerbations are treated with bronchodilators, systemic steroids, and antibiotics when bacterial infection is suspected, along with careful oxygen titration to avoid worsening hypercapnia in susceptible patients.

Pneumonia: alveolar inflammation, consolidation, and shunt physiology

Pathophysiology

Pneumonia is an infection of the lung parenchyma that fills alveoli with inflammatory exudate, impairing ventilation to affected units while perfusion may remain. This creates low $V/Q$ regions and can progress to physiologic shunt.

As consolidation spreads, lung compliance may fall, increasing the work of breathing. In severe cases, inflammatory injury can extend beyond localized infection and contribute to diffuse alveolar damage.

Clinical manifestations

Common findings include fever, cough, purulent sputum, pleuritic chest pain, tachypnea, and hypoxemia. Crackles and bronchial breath sounds may be present over consolidated areas. Hypoxemia can be disproportionate to the amount of visible disease when shunt is significant.

Treatment principles

Management combines supportive care with pathogen-directed therapy:

• Antibiotics are selected based on likely organisms and clinical setting.
• Oxygen and fluids support gas exchange and perfusion.
• Monitoring for complications such as pleural effusion, sepsis, or respiratory failure is essential, especially in older adults and those with comorbid disease.

Pulmonary embolism: perfusion defect, dead space, and hemodynamic strain

Pathophysiology

Pulmonary embolism occurs when thrombus, usually from the deep veins, lodges in the pulmonary arterial circulation. Ventilation to the affected lung units may remain intact while perfusion falls, producing high $V/Q$ and increased physiologic dead space.

Beyond gas exchange, PE can acutely increase pulmonary vascular resistance, straining the right ventricle. Large or multiple emboli can cause right ventricular failure and systemic hypotension.

Clinical manifestations

Symptoms may include sudden dyspnea, pleuritic chest pain, tachycardia, and sometimes hemoptysis. Hypoxemia is common but variable; dyspnea can be severe even when imaging shows modest parenchymal change because the primary issue is perfusion and cardiovascular stress.

Treatment principles

Therapy focuses on preventing clot extension and recurrence and supporting hemodynamics:

• Anticoagulation is the mainstay for most patients.
• In high-risk cases with hemodynamic instability, more aggressive measures may be required to restore perfusion.
• Addressing provoking factors and considering long-term risk reduction are central to preventing recurrence.

Respiratory failure: when gas exchange and ventilation break down

Pathophysiology

Respiratory failure is broadly categorized by blood gas abnormalities:

• Hypoxemic respiratory failure: inadequate oxygenation, commonly from $V/Q$ mismatch or shunt (pneumonia is a frequent cause).
• Hypercapnic respiratory failure: inadequate ventilation leading to CO2 retention, seen in advanced COPD, severe asthma, or respiratory muscle fatigue.

A practical way to view ventilation is through alveolar ventilation, where CO2 is inversely related to ventilation: $$P_{aC{O}_2}\propto \frac{V_{C{O}_2}}{V_A}$$ When alveolar ventilation $V_A$ falls due to airway obstruction, reduced respiratory drive, or muscle failure, $P_{aC{O}_2}$ rises.

Clinical manifestations

Patients may present with tachypnea, accessory muscle use, altered mental status, cyanosis, or exhaustion. Hypercapnia can cause headache, confusion, and somnolence. The trajectory matters: an acutely rising CO2 is often more symptomatic than chronically elevated levels with partial compensation.

Treatment principles

Management is cause-driven but follows consistent priorities:

• Stabilize oxygenation and ventilation with supplemental oxygen and appropriate ventilatory support.
• Treat the underlying pathology, such as bronchodilation for asthma, diuresis for cardiogenic contributors, antibiotics for pneumonia, or anticoagulation for PE.
• Avoid delays in escalation when there are signs of fatigue, deteriorating mental status, or worsening gas exchange despite initial therapy.

Putting it together: mechanism guides management

Respiratory disorders become clearer when symptoms are mapped to physiology. Wheeze and prolonged exhalation point toward airflow obstruction, often requiring bronchodilators and anti-inflammatory treatment. Crackles and focal hypoxemia suggest alveolar filling and shunt physiology, where treating infection and supporting oxygenation are central. Sudden dyspnea with minimal chest findings raises concern for perfusion defects such as pulmonary embolism, where anticoagulation is pivotal. Across all of these, respiratory failure represents the endpoint when compensation fails,