Pulmonary embolism

Definitions & Key takeaways

Pulmonary embolism (PE) is a blockage of the lungs main artery or one of its branches by a substance that has traveled from elsewhere in the body through the bloodstream (embolism). PE most commonly results from a deep vein thrombosis (commonly a blood clot in a leg) that breaks off and migrates to the lung, a process termed venous thromboembolism (VTE). This can cause serious damage to the lung tissue and can be life-threatening.

Symptoms vary by the amount of downstream lung tissue denied blood, which creates a ventilation-perfusion mismatch. They include shortness of breath, chest pain, and coughing. PE can also cause low blood oxygen levels, which can lead to confusion, loss of consciousness, and even death. Treatment of PE typically involves supportive therapy and blood thinning medications to dissolve the clot and prevent further clots from forming. Sometimes a filter is placed in the vena cava to trap clots before they reach the lungs.

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Introduction0:00–0:21

A pulmonary embolism happens when an embolus, which is a type of blockage, suddenly gets lodged inside a pulmonary artery.
Depending on which pulmonary artery or arteries are affected by the blockage, that can seriously decrease the amount of oxygenated blood that gets out to the body.

Physiology0:21–1:25

Normally, blood makes it back to the heart from all of the tissues and organs through a network of veins that merge over and over.
Superficial veins drain blood into deep veins, which rely on the skeletal muscle pump to move blood forward. The way it works is that the surrounding skeletal muscles compress the vein and propel blood forward, and the veins prevent blood from moving backwards by using one-way valves.
Ultimately, all of the blood ends up in the superior or inferior vena cava and dumps into the right atrium. From there the blood goes into the right ventricle and gets pumped into pulmonary artery and eventually into the lungs.
The pulmonary artery splits at a spot called the pulmonary saddle, which looks like a bit like a horse saddle, and then the right and left pulmonary arteries enter their respective lungs.
Subsequent branches off the pulmonary artery lead to smaller and smaller arteries, then arterioles, and finally capillaries that form nets around the alveoli, which is where gas exchange occurs.

Causes1:25–2:04

When a pulmonary embolism happens, a blockage in any of the arteries leads to a decrease in blood flow to lung tissue downstream.
The majority of the time, this blockage is caused by a broken off piece of a blood clot commonly associated with deep vein thrombosis.
A deep vein thrombosis most commonly develops in the lower legs, below the knee, although a blood clot can form in both superficial and deep veins and also in other parts of the body as well.
In fact, in the case of pulmonary embolisms, it is thought that most pulmonary emboli originate from leg veins above the knee.

Pathology2:04–6:18

Normally, the process starts with damage to the endothelium, or inner lining of blood vessel walls, after which there’s an immediate vasoconstriction or narrowing of the blood vessel which limits the amount of blood flow.
After that, some platelets adhere to the damaged vessel wall, and become activated by collagen and tissue factor, which are proteins that are normally kept separated from the blood by an intact endothelium.
These platelets then recruit additional platelets to form a platelet plug. This formation of the platelet plug is called primary hemostasis.
After that, the coagulation cascade is activated. First off in the blood there’s a set of clotting factors, most of which are proteins synthesized by the liver, and usually these are inactive and just floating around in the blood.
The coagulation cascade starts when one of these proteins gets proteolytically cleaved. This active protein then proteolytically cleaves and activates the next clotting factor, and so on.
The final step is activation of the protein fibrinogen to fibrin, which deposits and polymerizes to form a mesh around the platelets.
So these steps leading up to fibrin reinforcement of the platelet plug make up the process called secondary hemostasis and results in a hard clot at the site of the injury.
This cascade has a huge degree of amplification and takes only a few minutes from injury to clot formation. So the activation of the cascade is carefully controlled by anticoagulation proteins that target and inactivate key clotting factors.
For example, antithrombin inactivates Factors IXa, Xa, XIa, XIIa, VIIa and thrombin while protein C inactivates Factors Va and VIIIa.
As the clot grows in size, it limits the amount of blood able to pass by, and pressure in the vein increases. Usually the clot might start naturally breaking down, for example, enzymes like plasmin break down fibrin into fragments called D-dimers.
But sometimes, the increased pressure in the vein can cause a part of the main clot to break free, becoming a thromboembolus which can travel downstream towards the heart.
When that happens, a thromboemobolus - which is a blood clot on the move - can move from the spot of clot formation and get into the right atrium, and then into the right ventricle and get pumped into the lungs where it can get lodged some place - causing a pulmonary thromboembolism.
This is a life-threatening situation because it literally blocks blood from getting into the lungs to pick up oxygen. If there’s no blood flowing past an alveoli, then that means there are alveoli that are getting ventilated with fresh air but not getting perfused with blood.
We call this a ventilation perfusion mismatch or a V/Q mismatch. The body needs oxygenated blood to function and can therefore only tolerate a bit of a V/Q mismatch, before the lungs are no longer able to meet the needs of the body.
The amount of V/Q mismatch ultimately depends on the number, size, and location of the pulmonary thromboembolisms, which tells us the amount of lung tissue that’s being denied blood flow.
A physiologic response to all of this is hyperventilation. When that happens the body starts to rapid release carbon dioxide and that causes a respiratory alkalosis, which is a shift in the blood acid/base equilibrium resulting in an elevated blood pH.
Now, sometimes, individuals might have an atrial septal defect, which is a small opening between the right and left atrium.
In these individuals, it’s possible for a blood clot to go from the right atrium to the left atrium - bypassing the lungs completely.
Unfortunately, the clot goes into the left ventricle and can get pumped out to the body - often heading towards the brain and cutting off a blood vessel serving the brain, which can cause an embolic stroke.
Because of this, if someone has a pulmonary embolism, it’s important check for an atrial septal defect. There are three main factors that lead to a deep vein thrombosis, which are referred to as Virchow’s triad.

Risk factors of deep vein thrombosis6:18–7:59

The first factor is slowed blood flow, called stasis, in the veins. Typically, blood continuously flows smoothly through the blood vessel, but if the blood flow becomes turbulent, the linear flow is disrupted and slow or static pockets of blood are formed.
Stasis can also happen during long periods of inactivity of the skeletal muscle pump like bed rest or long flights and car rides, or even during pregnancy when a growing baby compresses nearby veins.
During stasis, platelets and other clotting factors contact the endothelium, and prolonged interaction leads to clotting factor adhesion, and, ultimately, activation of the clotting cascade.
The second factor is a state of hypercoagulation, where altered amounts of clotting factors increase primary or secondary hemostasis.
This can happen for genetic or acquired reasons like surgery or taking certain medications like birth control pills. During surgery, physical damage to vessels activates the clotting cascade.
And birth control pills tip the balance towards clotting because they increase the levels of clotting factors and decrease the levels of some anticoagulation factors like protein C and antithrombin.
A third factor is damage to the endothelial cell lining of a blood vessel that exposes tissue factor and collagen. Damage can be caused by infections, chronic inflammation or toxins like those found in tobacco cigarettes.

Symptoms7:59–8:36

Now, a small pulmonary embolism might not cause any symptoms, whereas a large one can cause sudden and severe chest pain, shortness of breath, as well as fatigue.
If a large pulmonary thromboembolism happens at the pulmonary saddle, then it blocks blood from going to both lungs and this can cause sudden death.
If multiple thromboembolisms happen over time, then that can lead to pulmonary hypertension, or right ventricular failure, because blocked arteries cause an increase in resistance which requires the heart to supply more pressure to move blood past the obstructed arteries.

Diagnosis8:36–9:05

The diagnosis of a pulmonary embolism can be done with a CT pulmonary angiogram where a dye is injected into the blood vessels to identify blockages.
Also, a ventilation-perfusion scan, sometimes called a V/Q scan, can reveal areas of the lung that are ventilated but not perfused.
Other helpful labs include a D-dimer blood test to detect fibrin breakdown products which are usually around when there’s a blood clot.

Treatment9:05–10:00

Generally speaking the body makes and breaks blood clots all the time, and some small clots resolve on their own, but large clots that cause symptoms typically need an intervention.
Thrombolytic enzymes can be given to help break down the clot or a pulmonary thrombectomy also known as pulmonary thromboendarterectomy can be done to surgically remove the clot.
Long-term treatment to prevent future thrombi from forming can include anticoagulant medications like warfarin or heparin, which inhibit the clotting cascade and prevent clot formation.
Also, a filter can be surgically placed in the inferior vena cava to prevent pulmonary embolisms. Prevention of a deep vein thrombosis is also important - compression stockings and frequent calf exercises during long periods of sitting still can help move blood through the veins to prevent stasis.

Review10:00–10:47

Alright, as a quick recap … A pulmonary embolism is a blockage in the pulmonary arteries which deliver blood to the lungs to pick up oxygen.
Typically, a pulmonary embolism is a thromboembolism, which happen when a blood clot formed from a deep vein thrombosis lodges itself in the pulmonary arteries.
Symptoms vary by the amount of downstream lung tissue denied blood, which creates a ventilation-perfusion mismatch, so immediate treatment is important.