Acute respiratory distress syndrome

Definitions & Key takeaways

Acute respiratory distress syndrome (ARDS) is a life-threatening lung condition that results in non-compliant lungs and poor blood oxygenation. It is associated with diffuse alveolar and endothelial injury. ARDS can be caused by a number of things, including pneumonia, sepsis, and trauma. Symptoms include shortness of breath, rapid breathing, and blue lips and fingernails.

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Acute Respiratory Distress Syndrome, or ARDS, is exactly what it sounds like. ‘Acute’ means that it happens rapidly.
‘Respiratory distress’ means that a person becomes unable to breathe and oxygenate their blood, and ‘syndrome’ means that it is a group of symptoms that may be caused by any number of underlying conditions.
In ARDS, the alveoli and the capillaries that surround them - the site of gas exchange in the lungs - are damaged by an inflammatory process like pneumonia or sepsis.
Air enters the lungs through a series of airways that branch and narrow until they end in clusters of alveoli, which look kinda like a bunch of grapes.
The alveoli are covered in nets of capillaries that allow gas exchange into and out of the blood. Gas exchange happens efficiently between alveoli and capillaries because each of their walls is only one cell thick!
Capillaries are lined with a single layer of endothelial cells and alveoli are lined with a single layer of epithelial cells.
These cell layers are fused to one another by the basement membrane and surrounding the alveoli and blood vessels is connective tissue made up of mostly proteins and water - in a space called the interstitial space.
The alveolar epithelial cells—called pneumocytes—come in two types. The vast majority are type I pneumocytes, which are thin and have a large surface area, a shape that allows oxygen and carbon dioxide to pass through them easily.
There are also type II pneumocytes scattered around which are smaller and thicker, and are important because they make surfactant, an oily secretion that coats the alveoli.
The alveoli are so tiny that their walls end up being really close together. Surface tension from water molecules lining the alveolar walls can easily attract one another, and pull the walls together, making the alveoli collapse.
Surfactant contains various phospholipids and is a bit like a droplet of oil that coats the inside of the alveoli, blocking the surface tension, so that the alveoli stay open.
In addition to the pneumocytes, there are alveolar macrophages, which are also called dust cells because they consume dust and dangerous particles before they enter the bloodstream.
The process of ARDS gets started when inflammatory molecules arrive in the lungs. More specifically, these are cytokines like TNF-alpha and interleukin 1, that come through the bloodstream due to a systemic illness like a massive infection, or get released locally by alveolar macrophages in response to a lung injury.
Whatever the source, these cytokines cause capillary endothelial cells to secrete inflammatory molecules, and express adhesion molecules on their surface that help circulating immune cells to adhere or stick to them.
Neutrophils—some of the first responders of the immune response—then stick to the endothelium and migrate out of the capillary and into the alveoli.
These neutrophils launch into inflammatory mode, releasing proteases, enzymes that digest protein, reactive oxygen molecules, that cause free radical damage, and cytokines, which perpetuate the cycle of inflammation.
As a result of this inflammation, a few important things happen. First, some inflammatory molecules are pro-coagulant, meaning they make the blood more likely to clot.
Second, the endothelium becomes leaky, allowing fluid to seep into the interstitium—causing pulmonary edema—and the fluid then seeps into the alveoli—causing an infiltrate to show up on a chest Xray.
Third, the pneumocytes themselves get injured and die, which means that type I pneumocytes don’t do a good job with facilitating gas exchange, and type II pneumocytes produce less surfactant.
Without surfactants there’s more surface tension within the alveoli and that makes them more likely to collapse. Finally, dead cells and protein-rich fluid start to pile up in the alveolar space and over time it forms a waxy hyaline—or glassy-appearing—material: a telltale finding of ARDS.
Hyaline membranes can be seen lining the inside of alveolar walls, and that makes gas exchange even more difficult. So in summary - some areas of the lung can’t ventilate properly, meaning they can’t fill with air because of edema, infiltrates, or alveolar collapse.
But the lungs still have good perfusion, or blood flow, and that leads to a ventilation-perfusion mismatch. This means that deoxygenated blood is flowing by the alveoli as it normally does, but there’s very little fresh oxygen for the blood to pick up.
Together, this results in hypoxemia, or poorly oxygenated blood, Over time, as the inflammation calms down, new pneumocytes replace the ones that have died off and the alveoli slowly recover.
Unfortunately, this is also when overeager macrophages are cleaning up old cell debris. The presence of these macrophages attract and activate fibroblasts, which are cells that secrete collagen and form scar tissue in the alveolar walls.
If there’s enough scar tissue, it can lead to restrictive lung disease. ARDS is generally a severe and often life-threatening situation that starts with shortness of breath hours after the initial alveolar injury occurs and then rapidly worsens to the point of respiratory failure.
Hypoxemia can lead to cyanosis, which is a bluish discoloration of the skin, and excess fluid in the lungs can cause a crackling sound called rales which is the sound of collapsed alveoli popping open with inspiration.
A diagnosis of ARDS is typically made when a person in respiratory distress meets four criteria. First, the symptoms have to be “acute” meaning an onset of one week or less.
Second, a chest X-Ray or CT scan shows opacities—or “white out”—in both lungs, which is due to massive pulmonary edema. The third relates to what’s called the PF ratio, but is actually a proportion.
It’s the partial pressure of oxygen in the arterial blood—Pa02—divided by the percent of oxygen in the inspired air, also called the fraction of inspired oxygen or Fi02.
In ARDS the PF ratio is below 300 mmHg, and the lower this ratio gets, the more severe the ARDS is. As a quick example here, let’s say your PaO2 is 85 mmHg and your vent is set at 35% FIO2 or 0.35.
Then, just simply divide your PaO2 by the FIO2, and you get a PF ratio of 85/0.35 = 243 mmHg, which is less than 300 mmHg.
Fourth, the respiratory distress must not be explained by heart failure. In heart failure pulmonary edema develops because the heart can’t pump blood effectively, and as a result the pulmonary blood pressure goes up, and fluid starts moving into the lung interstitium.
In ARDS, pulmonary blood pressure is normal, since the problem is with the alveoli getting damaged. Pulmonary blood pressure can be measured using a catheter that is wedged into the pulmonary artery, so a normal pulmonary capillary wedge pressure suggests ARDS rather than heart failure.
Often times, this fourth criteria is assessed clinically and by using a cardiac ultrasound to look for evidence of heart failure.
Treatment of ARDS depends on the underlying illness, but because the alveoli are damaged, supportive care for breathing, usually in the form of supplemental oxygen or mechanical ventilation, is really important.
Generally speaking, it’s important to maintain positive end-expiratory pressure, which is where the pressure in the lungs is kept slightly above atmospheric pressure, even after exhalation, because that helps prevent the alveoli from collapsing.
It’s also good to have low tidal volumes to prevent over-inflation of the damaged alveoli. Even with supportive care, the mortality rate of ARDS can be quite high, and those that survive can have some degree of chronic lung damage.
All right, as a quick recap...Acute Respiratory Distress Syndrome happens when inflammation causes diffuse alveolar injury, pulmonary edema, infiltrates, and hyaline membrane formation.
The four criteria of ARDS are: that it develops within a week, affects both lungs, causes the PF ratio to dip below 300 mmHg, and doesn’t cause pulmonary blood pressures to rise which indicates that it’s not due to heart failure.
Treatment includes supplemental oxygen and mechanical ventilation.