What use is the alveolar gas equation?

None! Just kidding; it’s useful for evaluating hypoxia because it can easily rule out hypoventilation as the cause.

For background, the alveolar gas equation is a way of calculating what the level of oxygen is in the alveoli, given the atmospheric pressure (pATM, usually 760mmHg), the fraction of inspired oxygen (FIO2, which is 21% for room air and increases if they’re on supplemental oxygen), the pressure of water vapour in the lungs (pH2O, usually 47mmHg), the arterial CO2 (paCO2, taken from your ABG), and the respiratory exchange ratio (RER, the amount of oxygen exchanged for carbon dioxide in one breath, usually 0.8). The equation is:

pAO2 = FIO2(PATM – pH2O) – paCO2(1 – FIO2[1 – RER]) / RER

The use of the alveolar gas equation is in the A-a gradient, the difference between what the alveolar gas equation says your alveolar oxygen is and what your ABG says your arterial oxygen is. If there’s lots of oxygen getting to the alveoli, then you should have lots of oxygen in the blood. A normal A-a gradient is approximately (age / 4) + 4, so it should be about 9 for a healthy young 20-year old and 24 for an 80-year old.

How is the A-a gradient useful? Well, there are only two things that cause hypoxia with a normal A-a gradient: hypoventilation (not moving enough air), and decreased PiO2 (that is, high altitude). Since I’m rarely doing my ABGs on a mountaintop, the A-a gradient is basically a quick and easy way to rule out hypoventilation as the cause of their hypoxia.

Read more: Adequacy of Ventilation in Chapter 306e: Disturbances in Respiratory Function, Harrison’s Principles of Internal Medicine 19e.

Three ways that supplemental oxygen causes hypercapneia

Supplemental oxygen can sometimes cause carbon dioxide to increase to dangerous levels, usually in patients with chronic lung diseases like COPD. I was originally taught that this was due to the extra oxygen blunting their respiratory drive, but it turns out that’s not the whole story. The mechanisms, in order of importance:

1. V/Q mismatch: Lungs autoregulate their circulation to match ventilation, so that low-oxygen blood only goes to the parts of the lung that have oxygen, which are usually the well-ventilated parts of the lung with lots of air moving in and out. If there’s extra oxygen diffusing to places that are poorly ventilated, it can cause vasodilation within that poorly-ventilated lung. As a result, blood is going to parts of the lung that aren’t well ventilated and can’t blow off CO2. Basically, it increases perfusion to physiologic dead space. Not good for getting rid of carbon dioxide.
2. Haldane effect: hemoglobin binds both oxygen and carbon dioxide in order to deliver oxygen from the lungs to the tissue and take CO2 from the tissue to the lungs. Unfortunately, when there’s high O2, the Haldane effect means that hemoglobin isn’t as good at carrying CO2. When there is also poor ventilation, this causes CO2 to build up in the blood.
3. Blunting of respiratory drive: respiratory drive is controlled by oxygen-sensing parts in the periphery and pH-sensing parts in the brain. It was once thought that chronic CO2 retainers lose their pH-based respiratory drive, and require their hypoxic drive to be working well in order for them to blow off any CO2. It turns out that this isn’t the case.

Read more: Abdo WF, Heunks LM. Oxygen-induced hypercapnia in COPD: myths and facts. Critical Care. 2012;16(5):323. doi:10.1186/cc11475.

The five causes of hypoxemia

There are five basic processes that result in hypoxemia:

1. Ventilation-perfusion (V/Q) mismatch: air isn’t getting to the parts of the lung that the blood is passing through. Causes includes pneumonia, asthma, COPD, ARDS, pulmonary embolism, heart failure, and interstitial lung diseases. V/Q mismatches usually respond well to supplemental oxygen.
2. Right-to-left shunt: blood bypasses the lung altogether. This can happen due to an anatomic shunt in the heart itself as in an ASD, VSD, or PFO or in the lung vasculature through an AVM, or as a physiologic shunt due to severe pneumonia, ARDS, heart failure, or atelectasis. Because blood isn’t getting to the alveoli, supplemental oxygen doesn’t help–all it does it bring O2 to places without blood flow.
3. Hypoventilation: the patient just isn’t moving enough air. It’s associated with an increase in CO2, and causes include CNS causes (sedation, stroke, tumours), neuromuscular disorders, airway obstruction (COPD, asthma, laryngospasm), and dead space ventilation.
4. Diffusion defect: oxygen isn’t getting from the air to the blood. Causes include emphysema, PJP, atypical pneumonias, and pulmonary fibrosis.
5. Low inspired oxygen content: high altitude! And not much else.

Read more in Chapter 49: Hypoxia and Cyanosis in Harrison’s 19e.

Speaking of hypoxemia, an anaesthesia fellow turned me on to an article from a few years back, Arterial Blood Gases and Oxygen Content in Climbers on Mount Everest by Grocott et al. (NEJM 2009), that includes the following table:

Those are some wild ABGs! If I saw those in a patient, I would be calling the ICU.

What’s the difference between IPF and UIP?

As a medical student, I found the various interstitial lung diseases (ILDs) to be horribly confusing. The most common idiopathic ILD is idiopathic pulmonary fibrosis, which is often used interchangeably with usual interstitial pneumonia (UIP). Is there a difference?

Well, yes. UIP is a histopathological description of a lung biopsy that has a specific pattern of fibrosis. (It’s a horrible name, but I was recently told that they tried to change it a decade or two ago and couldn’t come up with anything better.) UIP might also be used to refer to specific findings on high-resolution CT that has a very high correlation with UIP on histopathology. High-res CT is now so good that you usually don’t need the biopsy to know that a patient has UIP.

IPF, on the other hand, is what you call someone with UIP in the lungs if you don’t know why they have it. There are many things that cause UIP on CT and biopsy, including chronic hypersensitivity pneumonitis, connective tissue disorders, and drugs. If the patient doesn’t have any of those diseases or exposures, then it’s said to be idiopathic, and you call it idiopathic pulmonary fibrosis.

This distinction is actually very important, because IPF has a very poor prognosis and has no good disease-modifying treatments, whereas some of the other causes of UIP can be treated.

And now that you understand the difference between IPF and UIP, I’d like to add cryptogenic fibrosing alveolitis to your vocabulary—the fancy British way of saying IPF.

Read more: Idiopathic Pulmonary Fibrosis in Chapter 315: Interstitial Lung Diseases, Harrison’s Principles of Internal Medicine 19e.

Classifying pulmonary hypertension

Pulmonary hypertension (PH) is defined as resting mean pulmonary arterial pressure (mPAP) ≥25 mmHg, compared to a normal value less than 20 mmHg.

Classification of PH is broken into five categories by the WHO:

1. Pulmonary artery hypertension, the most common category that includes hereditary/idiopathic causes, drugs & toxins, connective tissue disorders like scleroderma/SSc, HIV, and schistosomiasis
2. Secondary to left heart disease, mostly heart failure with preserved ejection fraction (HFpEF)
3. Secondary to chronic lung disease and/or hypoxemia, including COPD and OSA as well as interstitial lung disease
4. Secondary to chronic thromboembolic pulmonary hypertension (CTEPH): fairly self-explanatory, I suppose
5. Secondary to everything else: weird things that you wouldn’t necessarily think of, including sickle cell disease, other chronic hemolytic anemias, chronic kidney disease, and a grab-bag of other things

A few interesting points:

• The most common cause worldwide is schistosomiasis (included in Group 1, above)
• Longstanding PH can lead to cor pulmonale, which is not good