Lec 33 Pulmonary Hypertension Flashcards
What types of vessels in pulm vasculatrue have most resistance?
small vasculature = arterioles and venules
What is flow/resistance of pulm circulation?
high flow
low resistance
What is capacitance of pulm circulation?
high capacitance to accommodate increased CO
What are the major causes of pulmonary hypertension?
- left heart disease
- chronic thrombotic or embolic disease
- parenchymal lung disease or chronic hypoxemia
- miscellaneous –> sarcoidosis
- pulmonary arterial hypertension
What is the most common cause of pulmonary hypertension?
left heart disease
What are the major causes of pulmonary arterial hypertension?
- idiopathic = primary pulmonary hypertension
- heritable
- drug/toxin induced
- associated w/ other disease
- persistant plum HTN of newborn
What is general definition of pulmonary hypertension?
resting mean pulm arterial pressure > 25 mmHg
What is general definition of pulmonary arterial HTN?
resting mean PAP > 25 AND
- PCWP/LAP/LVEDP < 15 mmHg
- pulmonary arteriolar resistance > 3 woods units
What 3 vascular changes happen in PAH?
- vasoconstriction
- smooth muscle and endothelial cell proliferation
- thrombosis in situ
What is effect of vascular remodeling in PAH?
decrease flow
increase resistance
What are plexiform lesions?
hallmark of advanced pulmonary HTN
proliferation of cells that compromise lumen of small pulmonary artery
What are the mechanisms leading to PAH?
- homeostatic imbalance of vascular effectors [vasoconstors, prothrombotic, mitogenic factors]
- environmental
genetic
What is role of prostacyclin and thromboxane A2 in PAH?
prostacyclin = vasodilator, inhibits platelet activation
TXA2 = vasoconstrictor, platelet agonist
in PAH levels of TXA2 > > prostacyclin
What is role of serotonin in PAH?
- vasoconstrictor
- promotes smooth muscle cell hypertrophy
- elevated in PAH
- impaired serotonin reuptake in PAH patients
What is role of Endothelin 1 in PAH?
- potent vasoconstrictor, stimulates smooth muscle cell proliferation
increased in PAH
What is role of NO in PAH?
- vasodilator, inhibits smooth cell proliferation
- endothelial isoform of NO synthase decreased in pts with PAH
What is role of hypoxia in PAH?
- in systemic circulation –> hypoxia induces vasodilation
- in pulm beds –> induces vasoconstriction [to improve V/Q mismatch]
chronic hypoxia –> structural remodeling, SMC proliferation
What is role of anorexigens in PAH?
- linked to higher risk for PAH
- fen-phen
What is role of CNS stimulants in PAH?
cocaine/methamphetamines cause medial hypertrophy of pulm arteries
What is role of TFG-B in PAH?
- bone morphogenetic protein receptor type 2 [BMPR2]
modulates growth of vascular cells
mutant –> lose control, extra growth
incomplete penetrance –> may be necessary but insufficient to cause disease
What genetic pathways predispose to PAH?
- TFG-B mutation
- serotonergic path mutation
What is role of serotonergic path in PAH development?
variant gene expression of serotonin receptor –> increase serotonin dependent vascular remodeling
WHat is theory of cause of PAH?
causes multiple hits to get the disease
risk factors + genetic predispostion + cell dysfunction + inflammation
What happens in presymptomatic/compensated PAH?
higher PAP pressure but able to compensate
CO ok
What happens in symptomatic/decompensating PAH?
RV facing consequences of years of pressure –> weakens –> CO starts to drop and RAP rises
manifests as fatigue, lower extremity edema, elevated neck veins
What happens in declining/decompensated PAH?
CO way down
RAP way up
pulm artery pressure reaches inflection point and starts to go down = sign of how poor your RV is function you can’t even get fluid into pulm vasculature
eventually get RV failure
What is prognosis of PAH?
3 year survival 60%
What are symptoms of PAH?
- dyspnea
- fatigue
- SOB
- chest pain
- syncope
- palpitations
- edma
What are physical findings in PAH?
- elevated jugular venous distension
- tricuspid regurg due to increase pulm artery P
- accentuated S2
- S3 gallop
- peripheral edema
- hepatomegaly, pulsatile liver, ascites
What doe you see on EKG with PAH?
- not sensitive enough to be a screening tool
see
- RV hypertrophy = big V1 QRS; big S in V5/6
- R axis deviation = I down; aVF up
- R atrium enlarged = big P wave in II, III, aVF
What do you see on CT with PAH?
- enlarged central pulm arteries
- reduced caliber of peripheral vessels
What diagnostic workup for PAH?
- do clinical exam
- look for sings of RV or RA enlargement or increased pressure
primary screening = do echo
rule out other common causes of pulm HTN
if you see high pressure on pulm arteries –> confirm with invasive cath lab measurement of pressures
What should you screen for if you think PAH?
- screen for thromboembolic disease
- work up for infectious disease or connective tissue disorder
- screen for chronic lung disease
What is treatment for PAH?
- give ox –> maintain saO2 > 90%
- routine vaccinations
- give diuretics carefully for volume overload symptoms
- maybe digitalis
- warfarin b/c of prothrombotic state of PAH
can give vasoactive agents
What should you avoid in PAH
- avoid vasoconstrictors –> nicotine, sympathomimetics
- avoid deep valsalva
- avoid pregnancy
How does phosphodiesterase 5 inhibitor help in pAH?
prevents breakdown of cGMP –> get vasodilitory effects of NO
