Hypoxemia: Oxygen Therapy and Ventilation/Perfusion (VQ) Mismatches

Hypoxemia is an abnormally low concentration of oxygen in the blood which can lead to dire consequences when left unmanaged. In most patients with hypoxemia, the application of supplemental oxygen is a quick bandaid therapy that is often applied to counteract the problem. However, have you ever applied supplemental oxygen to a patient experiencing hypoxemia and there has been a minimal effect? Have you ever wondered why the application of supplemental oxygen works in some patients but not others? It all comes down to what is causing the hypoxemia and understanding the pathophysiology behind a ventilation/perfusion (VQ) mismatch.

Ventilation/Perfusion (VQ) Relationship

In normal respiratory physiology, ventilation is the physical movement of air in and out of the lungs. The movement of air into the lungs is responsible for bringing with it a fresh supply of oxygen, and the movement of air out of the lungs is responsible for removing carbon dioxide from within the body.

As the oxygen within the lungs has to move into the bloodstream and the carbon dioxide within the bloodstream has to move into the lungs, it is important to have adequate perfusion through the pulmonary vasculature to ensure there is a fresh blood supply passing the alveoli within the lungs.

As such, there should be a normal relationship between the amount of air entering the alveoli within the lungs (VENTILATION) and the amount of blood passing the alveoli within the pulmonary vasculature (PERFUSION).

Ventilation/Perfusion (VQ) Mismatch

Based on the VQ relationship described above, there are two very important points associated with a VQ mismatch:

  1. Hypoxemia will occur if there is a problem getting air with a fresh oxygen supply into the alveoli, or getting that oxygen across the alveoli into the bloodstream.
    • This means that there is inadequate ventilation but adequate perfusion – otherwise known as a shunt
  2. Hypoxemia will occur if there is a problem with a fresh blood supply moving past the alveoli within the lungs.
    • This means that there is adequate ventilation but inadequate perfusion – otherwise known as dead space

Hypoxemia VQ mismatch shunt dead space
IMPORTANT: Don’t get confused because of the terms ventilation and perfusion; a ventilation/perfusion (VQ) mismatch is directly related to causing hypoxemia.

What Causes Shunt?

When you think shunt, you should be thinking anything that affects the ability for oxygen to get into or across the alveoli. Therefore, think about any condition that will reduce the amount of air coming into the alveoli or any condition that clogs up the alveoli to prevent the movement of oxygen into the bloodstream. I always remember “shunt” as good blood flow “shunting away” from poorly ventilated alveoli.

Hypoxemia VQ mismatch shunt

So what types of conditions will cause a shunt?

  1. Conditions that cause a collection of fluid or consolidation within the alveoli thereby reducing the ability of oxygen to move efficiently from the alveoli into the bloodstream
    • Acute pulmonary oedema
    • Pneumonia
    • Acute Respiratory Distress Syndrome (ARDs)
  2. Conditions that cause the collapse of the alveoli thereby reducing the ability to ventilate the alveoli, in turn reducing the ability of oxygen to move from the alveoli into the bloodstream
    • Atelectasis
    • Pleural effusion
    • Pneumothorax
  3. Conditions that reduce the amount of air reaching the alveoli, in turn reducing the amount of oxygen that can move from the alveoli into the bloodstream
    • Opioid overdose
    • Neuromuscular disease
    • Chest wall injury or rigidity
    • Upper airway obstruction
  4. Conditions that anatomically result in blood flow bypassing the alveoli, in turn bypassing the ability of oxygen to move from the alveoli into the bloodstream
    • Intracardiac right to left shunt
    • Arteriovenous malformation

IMPORTANT: Just remember that the majority of clinical conditions causing hypoxemia are associated with either fluid filled, consolidated or collapsed alveoli. If you remember that these are all forms of shunt, then it is easier to remember that shunt is related to issues with air entering the alveoli.

What Causes Physiological Dead Space?

When you think dead space, you should be thinking anything that affects the ability for blood to flow past the alveoli. Therefore, think about any condition that will reduce blood flow through the pulmonary vasculature. I always remember “dead space” as healthy ventilated alveoli that is essentially “wasted space” as there is no blood supply to participate in gas exchange.

dead space

So what types of conditions will cause a dead space?

  1. Conditions that reduce perfusion through the pulmonary vasculature, in turn reducing the blood supply required for oxygen to move into from the alveoli
    • Pulmonary embolism
    • Microvascular clotting
    • Severe hypotension associated with low cardiac output states
  2. Conditions that cause hyperinflation of the alveoli to compress the pulmonary vasculature, in turn resulting in an ability to allow blood flow to get past the alveoli
    • Asthma – airway limitation could also predispose the patient to a shunt
    • Chronic obstructive airways disease (COPD) – airway limitation could also predispose the patient to a shunt
    • Emphysema – loss of elastic tissue could also predispose the patient to a shunt

IMPORTANT: Do not confuse physiological dead space with anatomical dead space. Physiological dead space refers to a condition that results in reduced perfusion to well-ventilated alveoli, something that should not occur in healthy people. Anatomical dead space refers to the space in the respiratory system that doesn’t participate in gas exchange but that air has to travel through to get to the alveoli, something that is present in everyone.

Will Supplemental Oxygen Work?

This is the million-dollar question, and the answer lies in what pathophysiology caused the hypoxemia in the first place.

  • Absolute shunt: hypoxemia resulting from all anatomic shunts and alveoli that have collapsed or consolidated to a level where there is zero ventilation occurring
    • Supplemental oxygen is ineffective in rectifying hypoxemia as any oxygen being delivered never has the capability of reaching the blood that is perfusing the affected alveoli
  • Relative shunt: hypoxemia resulting from compromised alveoli that still has an element of ventilation occurring
    • Supplemental oxygen is effective in rectifying hypoxemia as it increases the quantity of oxygen available in the alveoli, which can still reach the blood via the affected alveoli

Does that mean that supplemental oxygen should never be applied to patients with absolute shunts? Not exactly! While supplemental oxygen will be ineffective in a true absolute shunt, there is likely to be an element of relative shunting occurring with all hypoxemic patients; supplemental oxygen may aid this component of hypoxemia. If hypoxemia does not improve with supplemental oxygen, this may confirm an absolute shunt being present and the patient can often have their supplemental oxygen reduced to minimise the deleterious effects of high oxygen concentrations with no impact on oxygen saturations.

  • Physiological dead space: if there is a significant amount of physiological dead space, supplemental oxygen is once again, relatively ineffective. Despite increasing the quantity of oxygen available in the alveoli, this will have minimal effect on hypoxemia if there is minimal blood supply passing the alveoli to facilitate the gas exchange.

The same rule applies to dead space as with absolute shunt; if the hypoxemia does not improve with supplemental oxygen, there is no point providing this additional oxygen as it will have no impact on oxygen saturations.

It is important to note that if the hypoxemia does not improve with the application of supplemental oxygen, this is known as refractory hypoxemia. This patient population can be very difficult to manage, and usually require more intensive management strategies including the application of positive end-expiratory pressure (PEEP), proning, pulmonary vasodilators and/or extracorporeal membrane oxygenation (ECMO). With any type of hypoxemia, cause rectification will always be the ultimate management strategy – everything else implemented is to buy us time to do this.
References

  • Darovic, G. O., & Zbilut, J. P. (2002). Pulmonary anatomy and physiology. In G. B. Darovic (Ed.), Hemodynamic monitoring: Invasive and noninvasive clinical application (3rd ed., pp 9-42). Philadelphia: Saunders Elsevier.
  • Pooler, C. (2009). Disorders of ventilation and gas exchange. In C. M. Porth & G. Matfin (Eds.), Pathophysiology: Concepts of altered health states (8th ed., pp. 701-738). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins.
  • Porth, C. M., & Litwack, K. (2009). Structure and function of the respiratory system. In C. M. Porth & G. Matfin (Eds.), Pathophysiology: Concepts of altered health states (8th ed., pp. 640-669). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins.
  • Theodore, A. C. (2020). Measures of oxygenation and mechanisms of hypoxemia. Retrieved from: https://www.uptodate.com/contents/measures-of-oxygenation-and-mechanisms-of-hypoxemia
  • Thoracic Key. (2016). Treatment of hypoxemia and shunting. Retrieved from: https://thoracickey.com/treatment-of-hypoxemia-and-shunting/

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