What are the causes of hypoxia with a normal diffusion capacity (DLCO)?

From the Guidelines

Hypoxia with a normal diffusion capacity can occur due to several mechanisms that impair oxygen delivery despite intact gas exchange at the alveolar-capillary membrane. The main causes include:

• Ventilation-perfusion (V/Q) mismatch, which occurs when areas of the lung receive adequate blood flow but insufficient ventilation, commonly seen in conditions like asthma, COPD, pneumonia, and pulmonary edema 1
• Hypoventilation, resulting from inadequate breathing effort or mechanics, as in neuromuscular disorders, obesity hypoventilation syndrome, opioid overdose, or severe chest wall deformities
• Right-to-left shunting, which involves blood bypassing gas exchange entirely, occurring in conditions like pulmonary arteriovenous malformations, hepatopulmonary syndrome, or intracardiac shunts
• Low inspired oxygen concentration, such as at high altitude or in enclosed spaces with poor ventilation, which can also cause hypoxia despite normal diffusion capacity 1
• Anaemic hypoxia, caused by a reduction in oxygen-carrying capacity, as seen in anaemia or carbon monoxide poisoning 1
• Stagnant hypoxia, resulting from a low cardiac output state, which reduces oxygen delivery even in the absence of hypoxaemia
• Histotoxic hypoxia, due to an inability to metabolise oxygen at the mitochondrial level, which may be caused by severe sepsis or certain types of poisoning 1

These mechanisms cause hypoxemia because they affect oxygen delivery before the diffusion process occurs or allow blood to bypass areas where diffusion takes place, while the actual transfer of oxygen across the alveolar-capillary membrane (measured by diffusion capacity) remains intact. It is essential to identify and address the underlying cause of hypoxia to improve oxygen delivery and tissue oxygenation. According to the BTS guideline for oxygen use in adults in healthcare and emergency settings, oxygen therapy may only correct hypoxia due to hypoxaemia, and other ways to improve oxygen delivery to the tissues need to be considered 1.

From the Research

Causes of Hypoxia with Normal Diffusion Capacity

• Hypoxia can occur due to various factors, including anemia, which is a condition characterized by a decrease in the number of red blood cells or the amount of hemoglobin in the blood 2, 3, 4, 5, 6
• Anemia can lead to a decrease in oxygen delivery to tissues, resulting in hypoxia, even if the diffusion capacity is normal 2, 3
• Other causes of hypoxia with normal diffusion capacity may include:
  • Cardiovascular disease, which can impair oxygen delivery to tissues 5
  • Chronic kidney disease, which can lead to anemia and hypoxia 3
  • Iron deficiency, which can impair oxygen transport and delivery 4, 5, 6
• Treatment of anemia and iron deficiency may help improve oxygen delivery and reduce hypoxia, even if the diffusion capacity is normal 3, 4, 6

Anemia and Hypoxia

• Anemia is a common cause of hypoxia, and treatment of anemia can help improve oxygen delivery and reduce hypoxia 2, 3, 4
• Iron supplementation and erythropoiesis-stimulating agents can help increase red blood cell production and improve oxygen delivery 3, 4, 6
• Preoperative iron therapy can help reduce the need for blood transfusions and improve outcomes in patients undergoing surgery 6

Cardiovascular Disease and Hypoxia

• Cardiovascular disease can impair oxygen delivery to tissues, leading to hypoxia, even if the diffusion capacity is normal 5
• Beta blockers, angiotensin-converting enzyme inhibitors, and calcium-channel blockers can affect iron metabolism and contribute to anemia and hypoxia 5