Key Respiratory System Concepts for USMLE Step 1
COPD: Core Pathophysiology and Clinical Features
COPD is defined as a preventable and treatable disease characterized by airflow limitation that is not fully reversible, caused by chronic inflammatory response to noxious particles or gases. 1
Essential Pathophysiologic Mechanisms
- Tobacco smoke is the primary risk factor worldwide, though biomass fuels and α1-antitrypsin deficiency are increasingly recognized 1
- Chronic inflammation involves oxidative stress, proteinase-antiproteinase imbalance, abnormal immune responses, and accelerated lung aging 1
- Four anatomic compartments are affected: central airways, peripheral airways, lung parenchyma, and pulmonary vasculature 1
- Pathological hallmarks include emphysema (permanent destructive enlargement of airspaces distal to terminal bronchioles), mucus hypersecretion, ciliary dysfunction, and airflow limitation 1
Emphysema Subtypes (Critical for Step 1)
- Centriacinar emphysema: Destroys respiratory bronchioles, alveolar ducts, and central acinar alveoli; associated with more small airways disease and less elastic recoil loss 1
- Panacinar emphysema: Destroys the entire acinus 1
- Paraseptal emphysema: Occurs near connective tissue septae, predisposes to pneumothorax and bullae formation 1
Clinical Presentation and Severity Classification
- Mild COPD: FEV1 60-79% predicted with FEV1/FVC <70%; often presymptomatic 1
- Moderate COPD: FEV1 40-59% predicted; patients present with intermittent chest problems and work difficulty 1
- Severe COPD: FEV1 <40% predicted; significant symptoms with intermittent hospitalizations 1
Physical Examination Findings
- Early disease: Normal examination is common 1
- Progressive disease: Quiet breath sounds, prolonged expiratory duration, weight loss, and signs of hyperinflation 1
Asthma vs. COPD: Distinguishing Features
Airway Remodeling Differences (High-Yield)
Asthma features:
- Reticular basement membrane thickening 2
- Eosinophilic infiltration with CD4+ T-helper lymphocytes 2
- Bronchial hyperreactivity as a characteristic feature 1
COPD features:
- Epithelial squamous metaplasia and airway wall fibrosis 2
- BAL neutrophilia with CD8+ T-cytotoxic lymphocyte infiltration 2
- Emphysematous changes 2
Asthma-COPD Overlap (ACO)
- ACO represents overlapping clinical phenotypes with worse outcomes than either disease alone 3, 2
- Patients demonstrate features of both diseases with intermediate pathophysiology 2
- No universally accepted definition exists, making diagnosis challenging 2
Respiratory Mechanics: Fundamental Concepts
Key Mechanical Properties
Three fundamental properties determine ventilation mechanics:
- Airway resistance (Raw): Opposition to airflow through conducting airways 4
- Lung compliance (CL): Distensibility of lung tissue 4
- Chest wall compliance (CCW): Distensibility of thoracic cage 4
Pressure Relationships
- Ventilation depends on pressure gradients at the airway opening, alveolar space, pleural space, and across respiratory muscles 4
- These relationships govern both spontaneous breathing and mechanical ventilation 4
Exercise Limitation in Obstructive Disease
Peripheral Muscle Dysfunction
- Skeletal muscle alterations render muscles susceptible to contractile fatigue, particularly during cycling 1
- Increased lactic acid production occurs at lower work rates, increasing ventilatory requirements 1
- Lactic acidosis is exacerbated by CO2 retention, further increasing ventilatory burden 1
Respiratory Muscle Dysfunction
- Diaphragm adaptation: Greater fatigue resistance but mechanical disadvantage from hyperinflation 1
- Static and dynamic hyperinflation places respiratory muscles at suboptimal length-tension relationships 1
- Functional inspiratory muscle weakness contributes to hypercapnia, dyspnea, and reduced exercise performance 1
Comorbidities in COPD (Frequently Tested)
Cardiovascular Associations
- Exacerbations increase cardiovascular event risk 1
- Overlap syndrome (COPD + sleep apnea) requires CPAP treatment, which decreases mortality 1
- Pulmonary hypertension develops in advanced disease with persistent hypoxemia 1
Systemic Effects
- Limb muscle weakness occurs as a systemic manifestation 1
- Chronic multimorbidity is the rule rather than exception, particularly in elderly patients 1
Patient-Centered Outcomes (Emerging Concept)
Traditional physiological outcomes (FEV1, 6-minute walk distance) correlate poorly with patient-important outcomes. 1
Critical Distinction
- Surrogate outcomes: Physiological/anatomical measures (FEV1, imaging findings) 1
- Patient-centered outcomes: Dyspnea, quality of life, exacerbation frequency, hospitalizations, mortality 1
- Interventions improving surrogate outcomes frequently fail to improve patient-centered outcomes 1
Bronchodilator Therapy: FDA-Approved Use
Albuterol (Short-Acting Beta-Agonist)
- Duration of action: 4-6 hours 5
- Critical counseling point: Do not increase dose or frequency without physician consultation 5
- Warning sign: When treatment becomes less effective or symptoms worsen, seek immediate medical attention 5
- Paradoxical bronchospasm: Can occur; discontinue immediately if it develops 5
- Common adverse effects: Palpitations, chest pain, tachycardia, tremor, nervousness 5
Pulmonary Rehabilitation Principles
Exercise Training Framework
High-intensity endurance training (>60% maximal work rate) for 20-60 minutes, 3-5 times weekly maximizes physiologic benefits. 1
- Target intensity: Borg dyspnea/fatigue score 4-6 or RPE 12-14 1
- Walking vs. cycling: Walking is functional and improves walking capacity; cycling loads quadriceps more specifically and causes less desaturation 1
- Alternative for severe limitation: Low-intensity or interval training when high-intensity cannot be achieved 1