Hypoxia for the USMLE: 5 Causes

  • /Reviewed by: Amy Rontal, MD
  • It was time to sign out, but I was nowhere to be found. There I was, stuck in room 782, trying to figure out why Mr. Nelson was only satting 86%. Of course, these problems always present themselves when it’s time to sign out your crowded census!

    I sent a quick text to apologize, saying I’d be there as soon as I could. The senior I was signing out to left me a simple reply: “Dealing with hypoxia? It’s all good! Remember, there are only five causes!”

    Note: This is very useful information, not only for boards studying, but also for shining on rounds, and for real-time working up of patients. Similar to our hypotension discussion, working through differentials from a systematic perspective will assure you that every base has been covered and that you’re not missing anything.

    And so, let us open the can of worms:

    The Five Causes of Hypoxia

    Let’s start with the simple causes:

    1. Low inspired oxygen content

    This cause can quickly be ruled in or out based on circumstance and geographical (or maybe topographical!) location. Two areas where we worry about a low oxygen content are at high altitude, and the even-more-rare but close to this anesthesiologist, from a mechanistic failure in the OR.

    Remember that the percentage of air that is oxygen at high altitude is still 21%. However, to calculate the PO2 of air at high altitude, we multiply that 0.21 by the Patm, which decreases with higher altitude.

    In my old stomping ground of Breckenridge, Colorado, the Patm is only 580, compared to 760 in my current comfy confines of Philadelphia. Instead of a PO2 of 160, the high altitude locale only has a PO2 in the atmosphere of ~120. The diffusion of less oxygen molecules through the alveoli can lead to hypoxia.

    As a one-liner, in the operating room, mechanical failure can lead to the delivery of a hypoxic mixture (pure nitrous oxide without any oxygen). Many fail-safes prevent this, but something to consider.

    2. Hypoventilation

    Pretty straight-forward cause here. An apneic patient isn’t expanding the lungs to allow diffusion of fresh oxygen across the alveoli. CO2 can build up, occupy the alveoli, and leave less space for oxygen to make its way into the bloodstream. Etiologies include neuromuscular disorders (like extreme kyphosis, muscular dystrophy, spinal cord injury), oversedation (opioid-induced respiratory depression), and bronchospasm/laryngospasm.

    The claim to fame for these first two causes is a normal A-a gradient. Because there’s no difficulty in oxygen making its way across, but rather just not enough oxygen to make its way across, the delivered alveolar oxygen isn’t far from the arterial oxygen.

    3. Right-to-left shunt

    Remember all of those cyanotic congenital heart diseases? They begin with T. Tetralogy of Fallot, TAPVR, tricuspid atresia, transposition of the great vessels, and truncus arteriosus. These are cyanotic (ergo, HYPOXIC) lesions because of right to left flow of blood in the cardiac chambers. Deoxygenated blood from the venous system is making its way to the left heart and the systemic circulation without being oxygenated by the lungs.

    Shunt can also describe a V/Q mismatch, in which there is blood flow without ventilation.

    4. Diffusion impairment

    Enough oxygen is making its way to the alveoli, but something is preventing it from diffusing across pneumocytes into the arterial blood. Causes here include anything that disrupts the architecture of the diffusing cells of the lungs. Consider emphysema and pulmonary fibrosis.

    So your patient doesn’t have any of these problems. Then they probably fall somewhere on the catch-all spectrum of our final cause of hypoxia. It’s a concept dreaded by medical students until they grasp the idea and learn how to speak the language.

    Cause 5: V/Q Mismatch

    For simplicity’s sake, we’ve tackled V/Q mismatch in-depth in a separate post. Here’s the bare minimum to know:

    V = Ventilation

    Q = Blood flow

    Keep these in balance and the lungs and blood are happy. But disrupt blood flow (low cardiac output, pulmonary embolus, increased intrathoracic pressure), or disrupt ventilation (fill the lungs with pus, water, blood, atelectasis, or a peanut in the glottis), and the patient’s arterial oxygen content will suffer. We cover this in-depth in the above-linked post.

    At the bedside, or on your USMLE exam, so many of these causes are easy to rule out, whether by ABG, chest X-Ray, or most of all, patient history. More than likely, your patient is falling somewhere on the spectrum of a V/Q mismatch. Temporize with increasing FiO2 and considering some CPAP/PEEP while you work through your differential and come up with a more targeted treatment.