Pulmonary Hypertension Flashcards
Key features of pulmonary circulation
High flow, low resistance, high capacitance
Pulmonary VR is what fraction of SVR
1/15 due to large cross-sectional area
What are some causes of pulmonary hypertension
LV dysfuction, left atrial disease, valvular disease
COPD
Chronic thromboembolic disease
What is Pulmonary arterial hypertension
It’s exactly what it sounds like and is not accounted for by any of the previous causes
Primary pulmonary arterial hypertension
Is idiopathic in nature
Some broad categories of things that cause PAH
Heritable, drug and toxin induced, associated with HIV/schisto/connective tissue disease
General definition of pulmonary hypertension
Resting mean pulmonary artery pressure >25
Definition of pulmonary arterial hypertension
Resting mean pulmonary artery pressure > 25, Left sided pressures 3 wood units
Some vascular changes associated with PAH
Vasoconstriction. Smooth muscle and endothelial cell proliferation. Thrombosis
Vascular remodeling associated with PAH
High flow low resistance system becomes low flow high resistance due to smooth muscle hypertrophy, in situ thromboses, intimal proliferation. Plexiform lesions
Pathology of pulmonary hypertension reveals
Medial thickening and compressed lumen. Intimal fibrosis, , and plexiform lesion formation
Mechanisms of PAH
Homeostatic imbalance of vascular effectors that favor vasocontriction, thrombosis and mitogenesis (growth).
Environmental and genetic factors too.
Prostacyclin
A vasodilator, inhibitor of platelet activation and is antiproliferative. Reduced in PAH in comparison to TXA2
Thromboxane A2
Released by platelets, vasoconstrictor. Levels are increased in PAH.
Serotonin in PAH
Acts as a vasoconstrictor, promotes smooth muscle cell hypertrophy. Elevated plasma levels in PAH patients
Endothelin 1
Potent vasoconstrictor that promotes smooth muscle cell proliferation. Levels increased in PAH. Levels are inversely proportional to magnitude of pulmonary blood flow.
NO
Vasodilator and inhibitor of platelet activation and smooth muscle cell proliferation. Endothelial NOsynthase is decreased in PAH
Hypoxia effect on systemic circulation and on pulmonary circulation
In systemic, hypoxia induces vasodilation.
In pulmonary, hypoxia induces vasoconstriction.
How does hypoxia contribute to PAH
Can lead to PA vascular remodeling
What drugs are associated w/PAH?
Fen-phen. Cocaine/methamphetamines (associated with medial hypertrophy of pulmonary arteries)
What genetic defects are associated with PAH
Mutations in the TGFß receptor pathway. Bone Morphogenic protein receptor (BMPR2) type 2 has been shown to modulate the growth of vascular cells. Incomplete penetrance though.
Also in serotonergic pathway. Depending on receptorq
Hemodynamic progression of PAH during presymptomatic/compensated period
Cardiac output still normal. Pulmonary artery pressure increasing, PVR increasing, right atrial pressure still low.
Progression during symptomatic/decompensating period
CO dropping due to increased PAP and PVR. RAP increasing because it can’t handle increased volume backing up from PA
Progresion during the declining/decompensated period
CO drops dramatically and causes right heart failure.
PVR increases still. RAP increases dramatically. PAP actually drops because RV can’t pump into pulmonary artery.
What is an ominous sign that PAH has gotten really bad
If pulmonary artery pressure drops during severe disease. This signals that the right heart cannot pump into the severely stenotic pulmonary arteries.
prognosis of PAH
Not good, 3 year survival is 58%
Symptoms of PAH
Dyspnea, Fatigue, Chest pain, near syncope, edema,
Signs of PAH
Elevated JVD, Tricuspid regurg due to increased PA pressures, grahm-steel murmur, Accentuated p2, S3 gallop on the right side, peripheral edema, hepatomegaly
EKG findings
Not sensitive enough to be a screening tool. However, frequently RVH – > big R wave in anterior prevordials (V1 v2 v3)
Roentgenogram findings for PAH
Enlargement of central pulmonary arteries, reduced caliber of peripheral vessels. Cardiomegaly w/ RV enlargement, enlargement of R and L PAs.
Best diagnostic test for PAH?
TTE
How to do the workup for PAh
Make sure that PAH isn’t just pulmonary hypertension. Look for chronic lung disease, look for infection, look for thrombi.
What should patients avoid doing with PAH?
Keep SaO2 high. Avoid vasoconstrictors, avoid valsalva, avoid pregnancy.
Treatment for PAH
PDE5 inhibitors, Prostacyclin derivatives to increase cAMP. Endothelin receptor antagonists.
