In lobar pneumonia, the alveoli are filled with fluid and cellular debris, preventing ventilation (V ≈ 0). However, pulmonary blood flow (perfusion, Q) to this area continues. This creates an extreme V/Q mismatch known as an intrapulmonary shunt (V/Q ≈ 0). Deoxygenated blood passes through the pulmonary circulation without being oxygenated, leading to systemic hypoxemia.

A pulmonary embolism obstructs blood flow to a region of the lung. This creates an area that is ventilated but not perfused (or underperfused). This is known as alveolar dead space. The sum of anatomic dead space (conducting airways) and alveolar dead space is physiologic dead space. The large increase in physiologic dead space represents wasted ventilation, leading to a severe ventilation/perfusion (V/Q) mismatch and hypoxemia.

Fick's law states that the rate of gas diffusion across a barrier is inversely proportional to the thickness of that barrier. In pulmonary edema, fluid accumulates in the interstitial space and alveoli, increasing the distance that oxygen must travel from the alveolar air to the red blood cells in the pulmonary capillaries. This increased diffusion distance significantly impairs the rate of gas exchange, leading to hypoxemia.

This process is known as the chloride shift or Hamburger phenomenon. To maintain electrical neutrality as the negatively charged bicarbonate ion (HCO₃⁻) exits the red blood cell, a negatively charged chloride ion (Cl⁻) moves from the plasma into the red blood cell. This exchange is mediated by the anion exchanger 1 protein (band 3 protein). The reverse process occurs in the lungs.

Normally, the intrapleural pressure is negative (subatmospheric) due to the opposing elastic recoil of the chest wall (outward) and the lungs (inward). A pneumothorax occurs when the pleural space is breached, allowing it to communicate with the atmosphere. This causes air to rush in, and the intrapleural pressure equilibrates with the atmospheric pressure, becoming approximately zero, which leads to lung collapse.

Idiopathic pulmonary fibrosis is a restrictive lung disease characterized by the deposition of fibrous tissue in the lung interstitium. This makes the lungs stiff and difficult to inflate, which is defined as decreased lung compliance. A greater pressure change is required to generate a given change in volume, significantly increasing the work of breathing, particularly during inspiration.

Carbon dioxide is transported in the blood in three forms: dissolved in plasma (~7%), bound to hemoglobin as carbaminohemoglobin (~23%), and as bicarbonate (HCO₃⁻) ions (~70%). The majority of CO₂ diffuses into red blood cells, where carbonic anhydrase rapidly converts it to carbonic acid (H₂CO₃), which then dissociates into H⁺ and HCO₃⁻. The HCO₃⁻ is then transported out of the RBC into the plasma in exchange for Cl⁻ (the chloride shift).

Alveolar ventilation (Va) is the volume of fresh air that reaches the alveoli per minute and is available for gas exchange. It is calculated as: Va = (Tidal Volume - Anatomic Dead Space) × Respiratory Rate. In this case, Va = (400 mL - 150 mL) × 6 breaths/min = 250 mL/breath × 6 breaths/min = 1500 mL/min, which is equal to 1.5 L/min. This low alveolar ventilation is the cause of his respiratory acidosis.

Factors that shift the oxygen-hemoglobin dissociation curve to the right include increased temperature, increased PCO₂, increased 2,3-BPG, and decreased pH (acidemia). A rightward shift signifies a decreased affinity of hemoglobin for oxygen. This change facilitates the release (unloading) of oxygen from hemoglobin to the peripheral tissues, which is an adaptive response in states of high metabolic demand like sepsis.

The Haldane effect describes the phenomenon where oxygenation of hemoglobin in the lungs decreases its affinity for CO₂. This occurs because oxygenated hemoglobin is a stronger acid and releases H⁺ ions, which combine with bicarbonate to form CO₂. Additionally, oxygenated hemoglobin has a lower affinity for binding CO₂ directly (as carbaminohemoglobin). Both mechanisms facilitate the unloading of CO₂ from the blood into the alveoli.