PATHOPHYS: PAH Flashcards
What are the 2 types of pulmonary HTN?
Idiopathic Pulmonary HTN
Secondary Pulmonary HTN
What is the definition of PAH?
Mean pulmonary arterial pressure >25 mmHg at rest or >30 mmHg with exercise
Mean pulmonary capillary wedge pressure/ Left ventricular end diastolic pressure < 15 mmHg
What does having a
mean pulmonary capillary wedge pressure/ left ventricular end diastolic pressure < 15 mmHg say about the cause of PAH?
it indicates that it is due to left heart failure
What is the most common cause of PAH?
PVH (pulmonary venous HTN due to LV dysfunction/heart failure)
How can parenchymal lung disease lead to PAH?
Hypoxemia leads to pulmonary vasoconstriction which backs up blood into the right heart
What is chronic thromboembolic disease?
small emboli occur all the time and there is gradual occlusion of arteries
List the 5 groups of PAH.
1) PAH (iPAH, Heritable, HIV-associated, etc)
2) PAH due to heart disease
3) PAH due to lung disease
4) CTEPH
5) PAH due to multifactoral etiology
What is the gene responsible for heritable PAH?
BMPR2
bone morphogenetic protein receptor type II
What is the characteristic pathologic sign of PAH?
plexiform lesions
What toxins are known to cause PAH?
Fen-phen
Aminorex
What 3 factors are associated with pathogenesis of PAH?
- Imbalance of vascular effectors
- Associated environmental factors
- Associated genetic abnormalities
What vascular disease is most commonly associated with pulmonary HTN?
systemic sclerosis
Why does thrombocytosis lead to PAH?
serotonin is released during platelet lysis and it serves as a vasoconstrictor
Why does sickle cell disease lead to PAH?
Free heme is a NO scavenger, so there is less vasodilation
In PAH, which vascular mediators are increased and which are decreased?
- Increased TXA2
- Decreased prostacyclin
What is NO and what does it do?
Chemical made by nitric oxide synthase in vascular endothelium that promotes vasodilation and inhibits smooth muscle growth
True or false: people with PPH have less nitric oxide synthesis–which is why they have vasoconstriction.
True! PPH patients show negligible immunohistochemical staining for nitric oxide synthase
What is endothelin 1? What does it do?
Potent vasoconstrictor and mitogen for smooth muscle cells that is produced by the vascular endothelium
What is going on with endothelin 1 in patients with PAH?
it localizes to the muscular pulmonary arteries
What role does VEGF play in the pathogenesis of PAH?
its role is speculative but it is expressed by endothelial cells in plexiform lesions
What are serotonin levels like in patients with PAH?
plasma serotonin levels are in higher concentrations in PPH patients than average
How does Phen-Fen cause PAH?
it blocks voltage-gated K+ channels, which makes intracellular K+ go down (so Ca2+ goes in) causing vasoconstriction
What is the mean age for PPH diagnosis?
36
What is the clinical presentation for PPH? What is it commonly mistaken for?
Fatigue Exertional dyspnea Exertional chest pain Exertional syncope Edema (commonly misdiagnosed as asthma)
What are some physical signs of PPH?
- Dyspnea
- Parasternal heave
- Palpable P2
- Widely split S2
What would a PFT of a patient with PAH show?
Normal FEV1, FVC, and TLC
Reduced DLCO
List the tests that should be performed for PAH diagnosis in order?
CXR
Echocardiography
V/Q Scanning/CT angiography
Complete right heart catheterizaiton (gold standard)
Why do you leave the best test for PAH (complete cardiac catheterizaiton) for last?
because it is very invasive
What parameter differentiates PAH from PVH?
LAP (LVEDP)
Why can you not just look at PAP for diagnosis of PAH?
Over time, the artery begins to fail (decompensate) due to the constant high pressure, so PAP actually begins to decline. However, PVR and the dyspnea keep getting worse (higher)
True or false: vasoreactive patients have a better prognosis than patients without vasoreactivity.
TRUE! people who respond to vasodilators have much better prognosis
What is “vasoreactivity”?
> 20% reduction in PAP and PVR with increased or unchanged CO and minimally reduced systemic blood pressure
What is the choice agent for vasoreactivity testing?
Nitric oxide (it is better tolerated than the other IV vasodilators)
If someone has a positive vasoreactivity test, what does that tell you?
they will also respond to CCBs
What is riociguat?
A new drug that increases cGMP by stimulating guanylate cyclase
What are some side effects of epoprostenol?
jaw pain
diarrhea
arthralgias
How is epoprostenol given?
portable IV infusion pump
What type of drug is epoprostneol?
prostacyclin analog
What type of drug is bosentan?
endothelin-1 antagonist
What are some adverse effects of bosentan?
Elevation of serum aminotransferase enzyme levels
Terratogenic
Interaction with other drugs
Why are patients with PPH at increased risk for intrapulmonary thrombosis and VTE?
- Sluggish pulmonary blood flow
- Dilated right heart chambers
- Venous stasis
- Sedentary lifestyle
What anticoagulant is used for PPH patients?
warfarin
What is the goal of warfarin anticoagulation?
INR of ~2
How long do people with PAH typically live?
mean is 3 years from diagnosis
What echocardiogram findings are associated with poor outcome in PAH?
- Large right atrial size
- Degree of septal shift during diastole
- Presence of pericardial effusion
What is required to make a definite diagnosis for PAH?
High index of suspicion
