Respiratory System
The respiratory system is a vital organ system responsible not only for gas exchange but also for maintaining homeostasis across various physiological domains. It plays a crucial role in balancing blood pH, thermoregulation, vocal communication, olfaction, immune surveillance, and metabolic function. This system interfaces directly with cardiovascular dynamics, acid-base buffering mechanisms, and neuromuscular control to ensure optimal cellular respiration and tissue oxygenation. Understanding the respiratory system's structure and function lays the foundation for diagnosing and managing numerous conditions such as asthma, COPD, ARDS, and metabolic acidosis. This course integrates key concepts across anatomy, physiology, pathology, and pharmacology to equip you with the high-yield knowledge essential for USMLE Step 1 and Step 2.
1. PHYSIOLOGY: Functional Anatomy & Gas Exchange
Primary Functions of the Respiratory System:
Gas exchange (O2 in, CO2 out): This essential process ensures the efficient delivery of oxygen to tissues throughout the body while simultaneously facilitating the removal of metabolic carbon dioxide waste.
Acid-base balance: The respiratory system plays a crucial role in maintaining a stable pH balance by effectively regulating the levels of carbon dioxide, which acts as a volatile acid in the blood.
Vocalization (phonation): Sound is generated as air flows over the vocal cords, allowing for the production of diverse tones and speech, enabling communication.
Immunologic defense: The body’s defense mechanisms include cilia, mucus, and alveolar macrophages, which work together to protect against harmful pathogens and inhaled particulates.
Other roles: Additional functions of the respiratory system encompass thermoregulation, olfaction (the sense of smell), and various metabolic activities, such as the activation of the angiotensin-converting enzyme (ACE).
Key Anatomical Zones:
Conducting Zone (Dead Space): Nose → Pharynx → Larynx → Trachea → Bronchi → Bronchioles
No gas exchange
Conditions inspired air (warms, humidifies, filters)
Lined with pseudostratified ciliated columnar epithelium (except terminal bronchioles)
Respiratory Zone: Respiratory bronchioles → Alveolar ducts → Alveoli
Site of gas exchange due to thin alveolar walls and an extensive capillary network
Alveoli:
Tiny sac-like structures (~300 million) increasing surface area to ~70 m²
Type I pneumocytes: Thin, flat cells covering ~95% of alveolar surface for diffusion
Type II pneumocytes: Cuboidal cells secreting surfactant and acting as progenitor cells
Surfactant (mainly dipalmitoylphosphatidylcholine): Reduces surface tension, prevents alveolar collapse (atelectasis), and increases lung compliance
Gas Exchange Mechanism:
Follows Fick’s Law: Rate of diffusion ∝ (surface area × pressure gradient) / thickness
Oxygen: Alveoli (high PO2) → blood (low PO2)
Carbon Dioxide: Blood (high PCO2) → alveoli (low PCO2)
Diffusion barrier includes: alveolar epithelium → basement membrane → capillary endothelium
Ventilation-Perfusion (V/Q) Matching:
Normal V/Q ratio ≈ 0.8 (ventilation ≈ 4 L/min, perfusion ≈ 5 L/min)
Apex of lung: Low perfusion due to gravity → high V/Q (more dead space-like)
Base of lung: High perfusion, relatively lower ventilation → low V/Q (shunt-like)
Clinical importance: V/Q mismatch is a major cause of hypoxemia in conditions such as pulmonary embolism, pneumonia, and emphysema
Oxygen Transport:
98% of oxygen is bound to hemoglobin (Hb), 2% dissolved in plasma
Oxyhemoglobin Dissociation Curve:
Sigmoid shape due to cooperative binding of O2
Right shift (↓ affinity): Promotes O2 release to tissues
Causes: ↑CO2, ↑H+ (acidosis), ↑Temperature, ↑2,3-BPG, Exercise
Left shift (↑ affinity): Retains O2, less available to tissues
Causes: ↓CO2, ↓H+, ↓Temperature, ↓2,3-BPG, fetal hemoglobin (HbF)
Mnemonic: CADET face Right → CO2, Acid, 2,3-BPG, Exercise, Temperature
2. CLINICAL CORRELATIONS
Neonatal Respiratory Distress Syndrome (NRDS): Caused by surfactant deficiency in premature infants
V/Q mismatch: Seen in pulmonary embolism, COPD, and pneumonia
Right-to-left shunt: Bypasses alveoli, causing hypoxemia that does not correct with 100% oxygen
High altitude exposure: Low atmospheric PO2 → hypoxemia → compensatory hyperventilation → respiratory alkalosis
3. CROSS-SYSTEM INTEGRATION
Renal System: Provides metabolic compensation for respiratory alkalosis/acidosis via HCO3− regulation
Cardiovascular System: Chronic hypoxia causes pulmonary vasoconstriction → right ventricular hypertrophy → cor pulmonale
Nervous System:
Central chemoreceptors (medulla): Respond to increased CO2 (pH change in CSF)
Peripheral chemoreceptors (carotid/aortic bodies): Respond to low PO2 and pH in arterial blood
4. MNEMONICS
“Lungs LIFT O2” → Left shift = Increased affinity = Fetal hemoglobin, low Temp, low CO2
“R to the Right” → Right shift = Release of O2
CADET: CO2, Acid, 2,3-BPG, Exercise, Temperature