What is the most likely cause of a patient's symptoms with a history of respiratory infection, presenting with increasing shortness of breath (SOB), normal blood pressure (BP), tachypnea (respiratory rate of 22), severe hypoxemia (oxygen saturation of 78%), normal temperature, and an arterial blood gas (ABG) showing normal pH, bicarbonate (HCO3) and partial pressure of carbon dioxide (Pco2) but low partial pressure of oxygen (Po2)?

Most Likely Diagnosis: Acute Respiratory Distress Syndrome (ARDS) or Post-Infectious Pneumonia

The most likely cause is pulmonary edema (Option D), specifically ARDS developing as a complication of the recent respiratory infection, given the severe hypoxemia (PaO₂ 5 kPa/~38 mmHg, SpO₂ 78%) with normal ventilatory parameters (normal pH, PCO₂, HCO₃) indicating Type 1 respiratory failure. 1

Clinical Reasoning

Type 1 Respiratory Failure Pattern

• This patient demonstrates classic Type 1 (hypoxemic) respiratory failure: severe hypoxemia (PaO₂ 5 kPa) with normal or low PCO₂, indicating failure of oxygenation rather than ventilation 1
• The normal pH, HCO₃, and PCO₂ exclude Type 2 respiratory failure, which would show elevated PCO₂ (>6.0 kPa or 45 mmHg) 1
• The A-a gradient is markedly elevated, indicating intrapulmonary pathology rather than hypoventilation 2

Why Pulmonary Edema (ARDS) is Most Likely

• Post-infectious ARDS develops following respiratory infections when inflammatory mediators increase pulmonary vascular permeability, causing bilateral alveolar flooding 1
• The 5-day progressive course following respiratory infection fits the Berlin definition timeline: "respiratory symptoms developed/aggravated within 1 week after clinically known damage" 3
• Severe hypoxemia (PaO₂/FiO₂ ratio likely <100 mmHg on room air) with SpO₂ 78% indicates severe ARDS 1
• The tachypnea (RR 22) reflects compensatory hyperventilation maintaining normal PCO₂ despite severe V/Q mismatch and intrapulmonary shunting 4

Excluding Other Options

COPD (Option A) is unlikely because:

• COPD exacerbations cause Type 2 respiratory failure with elevated PCO₂ (normal or increased PaCO₂), not isolated hypoxemia with normal PCO₂ 3
• ABG in COPD shows "decreased PaO₂ with normal or increased PaCO₂" 3
• No history of chronic lung disease is mentioned 3

Drug overdose (Option B) is unlikely because:

• Opioid or sedative overdose causes hypoventilation with elevated PCO₂ and respiratory acidosis 3
• This patient has normal PCO₂ and pH, excluding central respiratory depression 1
• No drug exposure history provided

Myasthenia gravis (Option C) is unlikely because:

• Neuromuscular disorders cause Type 2 respiratory failure with hypercapnia due to ventilatory pump failure 1
• Would expect elevated PCO₂ from inadequate minute ventilation 1
• Typically presents with progressive weakness, not acute post-infectious deterioration

Pathophysiological Mechanism

• Intrapulmonary shunting is the primary mechanism: inflammatory exudate fills alveoli, creating non-ventilated but perfused lung units 1, 4
• Blood flows through consolidated/fluid-filled alveoli without oxygenation, causing severe hypoxemia refractory to supplemental oxygen 4
• Failure of hypoxic pulmonary vasoconstriction during acute inflammation allows persistent blood flow to consolidated lung, worsening shunt 4
• The normal PCO₂ despite severe hypoxemia indicates intact ventilatory drive and compensatory hyperventilation of remaining functional lung units 4

Critical Clinical Pitfall

Do not assume normal examination findings exclude serious pathology: early ARDS may have minimal auscultatory findings despite severe gas exchange abnormalities 3. The severe hypoxemia (SpO₂ 78%, PaO₂ 5 kPa) demands immediate intervention regardless of physical examination findings 3.

Immediate Management Required

• High-flow nasal oxygen (HFNO) should be initiated immediately, as it may reduce intubation rates in Type 1 respiratory failure with large mortality reduction (ARD -15.8%) 1
• Target SpO₂ >94% initially 1
• Prepare for potential intubation and mechanical ventilation if HFNO fails, using lung-protective strategies (tidal volume 6 mL/kg, plateau pressure <30 cmH₂O) 1
• Obtain chest imaging urgently to confirm bilateral infiltrates consistent with ARDS 3