What are the causes of intrapulmonary shunt?

Causes of Intrapulmonary Shunt

Intrapulmonary shunt occurs when blood perfuses collapsed, fluid-filled, or non-ventilated alveoli and cannot be oxygenated regardless of administered FiO2, with the most common pathological causes being ARDS, pneumonia, atelectasis, and hepatopulmonary syndrome. 1

Physiological Context

• Normal intrapulmonary shunt represents less than 5% of total cardiac output, occurring through bronchial and thebesian veins 1, 2
• Pathological shunt becomes clinically significant when it exceeds this threshold, causing refractory hypoxemia that does not respond to supplemental oxygen 1, 2

Major Pathological Causes

Acute Respiratory Distress Syndrome (ARDS)

• Shunt exceeding 25% of cardiac output is common in ARDS, resulting from persistent perfusion of atelectatic and fluid-filled alveoli 1, 2
• Sepsis accounts for approximately 40% of ARDS cases, making it the most common underlying cause 3
• Pneumonia and aspiration of gastric contents are other primary direct lung causes 3
• The pathophysiology involves broad activation of inflammatory response mediated by neutrophils, cytokines, and oxidative stress 3
• Iatrogenic "second hits" including excessive fluid administration, blood transfusions, and harmful mechanical ventilation can worsen shunt by increasing pulmonary edema 3

Pneumonia

• Intrapulmonary shunt in pneumococcal pneumonia is principally caused by persistence of pulmonary artery blood flow to consolidated lung 4
• The mechanism involves relative failure of hypoxic pulmonary vasoconstriction (HPV) during acute infection, at least partially due to endogenous vasodilator prostaglandins associated with inflammation 4
• Inflammatory exudate fills alveoli, creating non-ventilated but perfused lung units 4
• During convalescence, arterial oxygenation improves as blood flow to consolidated lung decreases 4

Atelectasis and Alveolar Collapse

• Collapsed alveoli that remain perfused create anatomical shunt pathways 1
• In surfactant-depleted lungs, dorsal lung regions demonstrate high shunt fraction, high perfusion, and poor aeration in supine position 5
• Regional shunt shows a biphasic relationship with gas fraction: low shunt when gas fraction exceeds a threshold, with steep linear increase in shunt at lower gas fractions 5

Hepatopulmonary Syndrome

• Intrapulmonary vascular dilatation creates right-to-left shunt pathways that characterize this condition 6, 2
• Patients demonstrate hypoxemia with limited response to 100% oxygen and increased calculated shunt fraction 2
• Contrast echocardiography shows microbubbles appearing in left atrium 3-6 cardiac cycles after injection, confirming intrapulmonary (versus intracardiac) shunt 1, 2
• Screening is indicated when pulse oximetry shows <97% on room air in upright position, or with platypnea-orthodeoxia 2

Congenital Vascular Malformations

• Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) demonstrates prominent right-to-left intrapulmonary vascular shunt pathways linking systemic and pulmonary circulations that bypass the alveolar capillary bed 7
• These anatomical shunt pathways contribute to severe intractable hypoxemia 7

Pulmonary Arteriovenous Malformations

• Pre-capillary connections between arterial and venous circulation create anatomical shunt 8
• Exercise can recruit intrapulmonary arteriovenous shunts in healthy individuals, with shunt magnitude approximately 2% at maximal exercise 8
• Hypoxic exercise induces shunt at lower workloads than normoxic exercise 8

Factors That Modify Shunt Magnitude

Factors Increasing Shunt

• Endogenous vasodilator mediators and systemically administered vasodilator drugs increase flow to consolidated lung 4
• Positioning patient with affected lung dependent increases shunt 4
• Increasing positive airway pressure can worsen shunt 4
• Low mixed venous oxygen saturation (SvO2) amplifies hypoxemic effect of any given shunt percentage 2

Factors Decreasing Shunt

• Effective hypoxic pulmonary vasoconstriction reduces blood flow to non-ventilated areas 4
• Inhaled locally acting vasodilators preferentially act on ventilated lung 4
• Positioning patient with affected lung up reduces shunt 4
• Prone positioning in ARDS restores aeration and decreases shunt in dorsal regions while preserving perfusion 5

Clinical Recognition

• Shunt-mediated hypoxemia is refractory to supplemental oxygen because blood perfusing non-ventilated alveoli cannot be oxygenated regardless of FiO2 1, 2
• Alveolar-arterial oxygen difference (P(A-a)O2) >50 mmHg indicates likely pulmonary abnormality 1
• The classic shunt equation quantifies shunt: Qs/Qt = (CcO2 - CaO2) / (CcO2 - CvO2) 1
• Serial arterial blood gases assess PaO2 response and calculate shunt fraction 1

Critical Pitfall

In patients on ECMO, arterial oxygen levels may not directly reflect native lung gas exchange, making shunt assessment particularly important in this population 9. The shunt calculation becomes essential for distinguishing between oxygenation provided by the native lung versus the ECMO circuit 9.