Weatherly's Woes - Vascular

PULMONARY HYPERTENSION

High blood pressure in the pulmonary vein and arteries, > 25 mmHg

Pulmonary HTN (PHTN) is high BP in the pulmonary vessels. Normally the mean pressure is about 14 (eg, 20/12). But in PHTN the mean pressure is over 25. The diagnosis is made using either pressure catheters within the pulmonary vessels, or using fancy echocardiogram techniques. There are two kinds of PHTN.

Pulmonary ARTERIAL Hypertension refers to a pathologic remodeling of the pulmonary arteries (without involvement of the veins). It’s a poorly understood condition, but it tends to occur in young adult women. The familial form is due to an inactivating mutation of BMPR2 (Bone Morphogenetic Protein Receptor 2), which causes vascular SMC proliferation in the pulmonary vessels. The vessel walls become big and beefy, expanding into the lumen, and raising the pressure. Unfortunately that remodeling is permanent. The prognosis is not good. But they have high levels of vasoconstrictors (endothelin), and we can modulate that process with 3 different drugs. Epoprostenol - this is just an analog of prostacyclin. It’s an IV drug. It can cause flushing and jaw pain. Sildenafil (Viagra) - a PDE-5 inhibitor that causes vascular relaxation all over the body (including the lungs!). This one is shocking - young women with lung disease poppin’ viagra - but it kinda makes sense. Bosentan - it blocks Endothelin-1 receptors, but it’s a little hepatotoxic. One final note on this disease, apparently in severe cases the pathologist can see something called “plexiform lesions,” where the lumen develops a swiss-cheese appearance, but I think this is low yield.

Secondary PHTN is caused by some other medical problem. It’s much more common. All pulmonary vessels (not just arteries) will be thicc. Treatment is aimed at correcting the cause. Left heart disease is the most common cause of PHTN. Look for hemosiderin-laden macrophages (hemosiderin is just the rusty sediment left behind when old red blood cells die). Chronic lung disease is the second most common cause. When an alveolus stops doing its job, the nearby capillaries vasoconstrict (this is the only situation in the body where hypoxia leads to vasoconstriction!). The strategy is to divert blood to alveoli that still work. But if the entire lung is bombed out (eg, COPD, pulmonary fibrosis), then the entire pulmonary vasculature clamps down. One surprising cause is the accumulated damage from lots of tiny pulmonary emboli. Each individual clot is asymptomatic, but when they occur repeatedly over a long time, large portions of the lung’s blood supply can become clogged up, which raises the pressure in the remaining patent vessels.

Pulmonary HTN results in dyspnea due to pulmonary edema. When the pressure builds up in the pulmonary capillaries, some of that extra fluid is ejected into the alveoli. Eventually, the pressure will back up into the right side of the heart. Given enough time that pressure will damage the right heart, resulting in cor pulmonale, which simply means isolated right heart failure caused by pulmonary hypertension.

Recall from cardiology that the second heart sound, S2, is actually composed of two overlapping sounds, A2 from the aortic valve closure and P2 from the pulmonic valve closure. In pulmonary HTN there is a loud P2 sound. That’s because the pressure at the pulmonic valve is quite high. That pushes the valve cusps a little further apart. And when they crash together to make the P2 sound, the extra distance makes the sound louder (try clapping your hands, first with your hands close together, then with them spread far apart).

PULMONARY EMBOLI

Clot in the lungs

A Pulmonary Emboli is a venous blood clot that occludes the lung’s vasculature. It is the 3rd most common cause of cardiovascular death (after MI and stroke). PEs form on valves within the deep veins of the leg (eg, Femoral vein). They can break off the valve and travel up the veins. All veins eventually terminate in the lungs. When they occlude the vessel, all tissue fed by that vessel will die. This creates a wedge-shaped red infarct on the lung.

The size of the clot will determine the severity of symptoms. Small clots are often asymptomatic. Over time, getting a lot of small PEs can result in pulmonary hypertension (through hypoxia-induced-vasoconstriction). Big clots are devastating. They immediately cut off a sizable chunk of blood flow to the lung. The largest possible PE is called a saddle embolus, meaning it is “sitting” on the bifurcation of the pulmonary arteries. If the clot “falls off the saddle” then the patient will probably die immediately from a major cardiovascular collapse.

The PE symptoms can be frustratingly vague, and the presentation can be variable. The PE is the “great imitator” of the cardiopulmonary world. Symptoms to look out for are dyspnea and pleuritic chest pain with a rapid onset. The vital signs are of critical importance in looking out for a PE -- they will always be tachycardic, tachypneic, hypoxic and sometimes they even have a low grade fever. I want to make an extra comment about the tachypnea -- CO2 removal is much more responsive than O2 uptake when you breathe faster (the reason why has to do with a particular molecular trait of CO2, and is not worth worrying about). Patients often have a normal or low CO2 level despite having a low O2 level. In other words, they have great ventilation but crappy oxygenation. Plus by getting rid of all that acidic CO2, patients often develop a respiratory alkalosis.

Making the diagnosis is tricky. The usual cardiac tests (EKG, chest x-ray, troponin) are normal. There are ways to diagnose it, but you’ll learn that there’s no easy PE test.

- - The EKG isn't helpful (there’s some interesting stuff on EKGs and PEs, but as someone who’s dived pretty deep into the literature, let me save you a lot of time and hassle -- it’s not helpful).
  - The chest x-ray is useless.
  - The most accurate test is a chest CT angiogram, but it’s expensive and radioactive. So we need a screening test -- enter the D-dimer.
  - The D-dimer lab test is elevated whenever you have a blood clot, but unfortunately, a lot of other conditions (kidney disease, pregnancy) raise it too. Despite its limitations, the D-dimer test is always going to be your first step. If your D-dimer is normal, then congratulations, you’ve ruled out a PE! If it’s elevated, then you want to get a chest CTA.
  - A lot of people (kidney disease, iodine allergy) can’t tolerate IV contrast, which makes it impossible to get a chest CTA. Thankfully there’s an alternative test. It’s called a VQ scan (VQ stands for ventilation perfusion). It creates a fuzzy image of the lungs. If there are irregular bits missing from the lung, then there’s a blood clot.
  - PEs are incredibly challenging to diagnose in pregnancy because (a) the d-dimer is always elevated in pregnancy and (b) they can’t get a CT or VQ scan because it would radiate the fetus. You won’t have to know the details until Step 2, but I just wanted to bring this dilemma to your attention for now.

So if the symptoms are variable, and the tests are cumbersome, how on earth do we ever spot PEs in real life? The answer is risk factors. There’s a decision tool called the PERC rule to help you out. It looks a little intimidating at first, but it’s actually pretty easy to conceptualize if you keep Virchow’s Triad in mind: venous stasis, endothelial damage and hypercoagulability. Some classic risk factors are long distance travel (sitting down too long leads to venous stasis in the legs), after a surgery (endothelial damage + laying down in a hospital bed for days), smoking (endothelial damage), cancer (hypercoagulable) pregnancy (hypercoagulable) and birth control pills (estrogen is pro-thrombotic). When patients are hospitalized longer than one or two days, they are usually given an anticoagulant like Heparin to prevent PEs.

One last point -- what exactly is an embolus? What material is it made of? 99.9% of the time it’s a blood clot, but in rare circumstances, the embolus is made up of something else entirely.

- - Clot - by far the most common. Lines of Zahn (stripe pattern seen on histology) are seen in clots that formed prior to death.
  - Fat - caused by long bone fractures and liposuction. The fat emboli shower across the entire body, causing a triad of hypoxemia (lungs), confusion (brain) and petechiae (skin), often on the ches.
  - Air - (a) air gets injected into an IV line or (b) nitrogen bubbles precipitate in ascending divers (the bends). Roll them onto their right side (so the bubble rises away from the pulmonary capillaries) and treat with hyperbaric O2.
  - Amniotic Fluid - a rare peripartum complication often following uterine trauma. Can lead to DIC and, usually, death.

Chest CTA showing a saddle embolus. Look at the pulmonary artery (the white upside-down Y). There’s a dark line above the bifurcation. That’s the PE.

(A) Normal VQ scan.

(B) VQ scan showing multiple PEs. Notice how there are irregular white patches. Each one represents a PE, because that tissue isn’t receiving any perfusion.

HEMOPTYSIS

Coughing up blood

The lung has two blood supplies

The Pulmonary Arteries (95%) are a low pressure system. Bleeds are mild. There are many causes (Bronchitis, CHF, Pneumonia, PE).

The Bronchial Arteries (5%) are a high pressure system. They run along the bronchioles. Bleeds are massive. There are only a few causes.

Causes of Massive Hemoptysis