Clinical Pearls: How To Work Up Hypoxia Part 1

I was recently drafting some material for a client who I am tutoring regarding hypoxia. She is in a pulmonary rotation and this is a very common reason for consult. I think when you are providing a consult service (which can receive a high volume of patients) keeping things focused on your organ system, standardizing your approach, and developing automation’s are the key to efficiency. The cool thing is that when you systematically work through the causes of hypoxia you can simplify the process of coming to the most accurate diagnosis. Then you can offer the primary team a suggested plan of action and be the hero (or maybe just uphold your reputation as a trusted colleague 😉). This article is designed to help ease the process of working through the etiology and focuses heavily on pathophysiology. If you can appreciate the pathway of oxygen delivery from the atmosphere all the way through to delivery at the tissue level you can better understand the disease states and more easily come to a diagnosis (or three, as is our common reality).

How To Work Up Hypoxia Inpatient

Think about the basics of pathophysiology first. At it’s core there is either a problem with getting oxygen into the lungs or getting oxygen to the tissues. Think through all the stages at which O2 delivery can fail. Bear in mind some disease states are affected by multiple stages of this process. There are many calculations (oxygen content, oxygen delivery, Aa gradient, etc) and while they can be useful to help understand the physiology of what’s happening, I don’t find them very practical for daily use. Much of the educational information out there gets too complicated and, IMO, loses the audience. The simplest way to learn about the etiology of hypoxia is to start with the main categories of how oxygen delivery can go wrong. In the follow up article we will get into algorithms to follow for work-up and management.

Let’s start with the five main ways O2 delivery fails.

  • Low FiO2 availability from the atmosphere/mode of delivery (delivery)

  • Difficulty getting it into the airways (delivery)

  • Difficulty getting it through the airways (delivery)

  • Difficulty getting it into the healthy alveoli and then into the bloodtream (V/Q mismatch)

    • difficulty getting blood flow to the alveoli to accept the O2 (dead space)

    • difficulty getting diffusion from the alveoli to the bloodstream (shunt)

  • Difficulty delivering oxygen from the heart to the tissues (tissue perfusion)

Hypoxemia: Low oxygen levels in the blood

Hypoxia: Low oxygen levels in the tissue

Low Inspired Oxygen (poor availability)

Fairly straightforward problem here:

  • Healthy pt: High Altitude

  • Pt with pathophysiology can desat when Fio2 is removed and this problem arises from the inherent issue itself not necessarily from the supply of oxygen and as such is classified below.


Difficulty Getting FiO2 Into The Airways (hypoventilation)

Starting with poor ventilation which will include an increased CO2 probably with a respiratory acidosis:

  • Central causes of hypoventilation

    • CNS depressants, sedation, drug overdose. Opioids and Benzos are biggies here. But even polypharmacy or higher doses of percieved “benign” drugs like seroquel, gabapentin, anti-cholinergics, etc. When we are sleepy we reduce our respiratory rate so anything that induces fatigue/sleep + known pulmonary or other cause of breathing issues = higher risk factor for hypoventilation.

    • Neurological injury affecting respiratory drive: stroke, tumor, TBI, seizure, global anoxia, cerebral edema, decreased GCS from any cause, OHS.

  • Neuro-muscular problem affecting ability to breathe

    • Respiratory muscle weakness (intercostal muscles, diaphragm)

      • Guillian Barre Syndrome, Myasthenic crisis, Critical Illness Polyneuropathy, ALS

    • Innervation of muscles

      • C-spine injury,

  • Chest wall/diaphragm expansion limitations

    • Kyphosis, scoliosis, trauma, distended abdomen


Difficulty Getting FiO2 Through The Airways (hypoventilation)

  • Upper airway issues (the below order tries to follow the path of anatomy from peripheral to central)

    • At any point in the airways: trauma, tumor, abscess, obstruction of any kind

    • Problems in this area often involve clinical signs like stridor, wheezing esp expiratory, reduced or hard to appreciate lung sounds (may be charted as poor airway entry auscultated), poor GCS, not a lot of visual chest expansion.

    • Orpopharyngeal: ludwigs angina, angioedema, aspiration of food or foreign body, anatomical changes from radiation injury, prior surgery, trauma, etc.

    • Laryngospasm

    • Cricoid issues

      • subglottic stenosis (narrowing of the airway just after the cord but prior to the trachea)

        • commonly caused by prior intubation esp if prolonged

    • Tracheal issues

      • dislodged or obstructed tracheostomy

      • tracheal muscle weakness like ALS or obstructive sleep apnea

      • tracheomalasia (weakened or damaged cartilage ring issues making it hard to stent open the trachea)

    • Neurological problem leading to inability to protect airway via gagging, coughing, swallowing saliva

      • dementia or any of the above issues that reduce GCS

  • Lower airway issues: bronchial problems

    • airway inflammation like asthma, anaphylaxis, bronchospasm, repeated persistent aspiration

    • obstruction like COPD, tumors

  • Neurological problem leading to inability to protect airway via gagging, coughing, swallowing saliva

    • dementia or any of the above issues that reduce GCS

  • Complex stuff

    • Morbid Obesity Hypoventilation Syndrome

      • Multi-factorial problems contribute to hypovolemia including central causes of reduced ventilation (possibly related to Leptin) with hypercarbia + reduced lung volumes.

      • Significantly reduced lung volumes which leads to small airway collapse (can occur both while awake and at rest, unlike OSA, but most commonly occurs at rest. OHS can occur if supine or upright, also unlike OSA)


Difficulty Getting Oxygen Into The Healthy Alveoli (V/Q Mismatch)

Sections of the lung parenchyma that participate in gas exchange (alveoli) are damaged. The circulatory system does not know to re-direct blood flow away from these areas. The net effect, depending on how many alveoli are affected, is difficulty getting a match between (V) ventilation/aka oxygenation/aka air and (Q) perfusion/aka blood flow leading to hypoxemia.

  • Any filling process of the alveoli

    • Infected fluid: Pneumonia

    • Edema: ARDS, pulmonary edema

    • Blood: Diffuse alveolar hemorrhage

  • Any collapse problem of the alveoli

    • Pneumothorax, hemothorax, chylothorax

    • Loss of surfactant: ARDS

    • Obstruction or collapse of the airway just proximal to the alveoli: atelectasis (could be severe enough to see entire hemithorax collapse aka “white out”, mucous plugs are common, OHS, COPD

    • Pleural effusions, cancer, mesothelioma

  • If it is severe hypoxemia it will not respond to additional supplemental FiO2 and this is a type of physiologic shunt.


Shunt (severe V/Q mismatch)

This is a problem where de-oxygenated blood passes from the right side of the heart to the left and never receives oxygen. This is a severe form of hypoxemia that does not respond to supplemental FiO2 (so why bother putting that pt on 100%, just cap out at 60%). This can be an anatomical (intra-cardiac) shunt where it never even makes it to the lungs or it can be a physiologic shunt where it flows through the pulmonary capillary beds and but does not receive oxygen.

  • Anatomical Shunt

    • ASD, VSD, PFO

  • Physiologic Shunt

    • Basically any of the above V/Q mismatch etiologies can become severe and progress to shunt. This is when blood flow does not match the area that is well ventilated. Or there is limited healthy alveoli at all. Covid is a classic example of this: horrible pneumona that dessimates the functional units of the lung.

    • Interstitial problems (diffusion defect) when the oxygen can’t diffuse through the space between the alveoli and the blood stream. Interstitial lung disease, fibrosis, ARDS, pulmonary edema.

    • Poor pulmonary blood flow from an obstructive cause (PE), a stricture problem (pulmonary hypertension), or engorged/vasodilated capillary beds (the blood flows rapidly past the alveoli and don’t slow down enough to participate in gas exchange) like vascular congestion or hepatopulmonary syndrome.


Dead Space (V/Q mismatch)

When the alveoli are ventilated well (no inherent lung tissue problem) but blood flow to the alveoli is impaired.

  • Obstructive cause (PE.)

  • A stricture problem (pulmonary hypertension).

  • A low flow state like hypotension (all causes) or pulmonic valve problem.

  • Engorged/vasodilated capillary beds (the blood flows rapidly past the alveoli and don’t slow down enough to participate in gas exchange) like vascular congestion or hepatopulmonary syndrome.

  • High amounts of PEEP. The over-distended alveoli squishes the capillary bed.


Tissue Delivery or Extraction Problem

The primary problem occurs beyond the level of the lungs and pulmonary blood vessels. Now we have downstream issues like poor delivery from a failing heart, impaired mode of delivery (pipes, low hemoglobin), or extraction problems from the tissue beds.

  • Failing heart

    • This goes without explaining really. If the cardiac output is poor the engine supplying the tissues is struggling and the downstream effect is tissue hypoxia.

  • Failing mode of delivery

    • Pipes. If the vessels are dilated and leaky like in sepsis there will be tissue hypoxemia

      • Conversely, if the pipes are clamped down, like when they are on pressors, there will also be peripheral ischemia.

    • Carrier. Hemoglobin is the vehicle that transports oxygen, therefore anemia = hypoxia.

  • Extraction problems

    • Poor diffusion (this time because the oxygen can’t get from the blood stream to the tissue)

    • Sepsis is the main culprit. Check a mixed venous to estimate ScVO2. In later stage sepsis it will be high, because more O2 is returned to the heart since it was not extracted.


The Acute Care Lab Membership will host it’s second live lecture July 17th at 7:30pm and we will be discussing how to read chest x-rays. Would love to see you there. Check out more here:


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