Lec 19 Pulmonary Vascular Disease Flashcards
What is ohms version of equation of Pulm artery pressure?
KNOW THIS!!
Ppa = (CO * PVR) + Pla
Pla = left atrial pressure
b/c change in P = CO * R
What is ohm’s version of equation of pulm artery pressure?
Psa = (CO*PVR) + Pra
Pra = right atrial pressure b/c changes in P = CO*R
How do pulm vessels differ from systemic vessels?
less muscle and elastin
What is definition of pulmonary hypertension?
mean Pa > 25
What are 3 mechs of what will cause increased pulm artery pressure?
- increased CO
- increase left atrial P
- increased PVR
What are some things that cause increased CO and thus lead to high pulm artery pressure?
- congenital heart defects w/ L to R shunt
- cirrhosis
- anemia
- A-V malformations
What are some things that cause increased left atrial P and thus lead to high pulm artery pressure?
- systolic/diastolic LV failure
- mitral valve disease
- restrictive cardiomyopathy
What are some things that cause incraesed PVR and thus lead to high pulm artery pressure?
- destruction pulm vascular bed in ILD, emphysema, PE
- hypoxic vasoconstriction in COPD, high altitude
- small pulm artery vasculopathy [PAH]
What is group 1 pulmonary hypertension?
pulmonary arterial hypertension
What is group 2 pulm HTN?
due to left heart disease
What is group 3 pulm HTN?
due to lung disease, hypoxia
What is group 4 pulm HTN?
due to thromboembolic disease
What is group 5 pulm HTN?
miscellaneous “other”
What are some pathological signs seen in pulmonary arterial hypertension?
- medial hypertrophy
- intimal thickening
- in situ thrombosis
- plexiform lesions
What is pathogenesis of pulmonary hypertension?
- increased endothelin pathway –> vasoconstriction and proliferation of smooth muscle
- decrease NO path –> less vasodilation/antiproliferation
- decrease prostacycline path –> less vasodilation and antiproliferation
What are 4 possible etiological categories of PAH?
- idiopathic
- genetic
- drug/toxin induced
- associated w/ other disease
What is genetic cause of pulmonary arterial hypertension?
- mutation in BMPR2
What drugs/toxins can cause pulmonary arterial htn?
- anorexigens [fen phen]
- grapeseed oil
- illicits
What are some diseases associated with PAH?
- connective tissue [SLE, scleroderma]
- congenital heart disease –> increased pulm pressure/flow
- portal htn
- HIV
- schistosomiasis
WHat is prevalence of PAH?
5-15 / 1 million adults
How prevalent is PAH in pts with CHD?
30% of pts who do not have CHD repaired will develop PAH
What is survival of untreated idiopathic PAH?
- median survial 2.8 years
34% survival at 5 years
What is difference RV and LV?
- LV concentric shape; thick free wall
- RV crescent shape; thin free wall; lacks circumferential constrictor fibers; more compliant
What is definition preload?
wall stress at end of diastole
What is definition afterload?
wall stress during ventricular ejection
What is contractility?
intrinsic ability of myocardium to contract independent of load
What happens to LV if dildate RV?
compress LV
Why do you get such rapid decompensation in PAH?
high pulm pressure means increased RV afterload
RV afterload –> increased RV wall stress –> ischemia and decreased output leading to decreased CO
RV afterload –> decreased RV output –> also decreases CO
RV afterload –> increase RV dilatation –> leftward septal shift and tricuspid regurg –> also decrease RV output and LV preload leading to more decreased CO
significant decrease LV —> leading to cardiogenic shock
What are symptoms of PAH?
from low perfusion
- dyspnea
- fatigue
- chest pain
- palpitation
from congestion –> ab pain and fulness, peripheral edema
What do you seen on physical exam in PAH?
- hypoxemia, tachycardia, hypotension
- JVP distension
- RV head, split S2, loud P2, systolic tricuspid murmur
- RV S3/S4
- hepatomegaly, pulsatile liver, ascites
- lower extremity edema
Do you see rales in pure PAH?
nope! no pulmonary edema in pure PAH
WHat do you see on chest xray in PAH?
dilated pulmonary arteries
restro-sternal space disappears in lateral view
What do you see on EKG in PAH?
- RV hypertrophy/strain
- RBBB
- right atrial enlargement
What is use of right heart cath? What does it tell you?
- confirms diagnosis of pulmonary hypertension
- tells you hemodynamic profile –> RAP, PAP, PCWP, CI, PVR
What does PCWP tell you about etiology of pulmonary hypertension?
- if PCWP > 15 suggests PH type 2 [due to left heart disease]
- if PCWP < 15 consistent w/ pulm HTN that occurs before capillaries = type I [PAH]; III [lung disease; or IV [thromboembolic]
What is natural history of pulmonary hypertension?
in asymptomatic/compensated: CO still pretty high and RAP low; PAP/PVR rising
in symptomatic/decompensated: CO declining; PAP/PVR really high
in overt R HF: high PVR but PAP starts to decrease as CO drops and RAP increase = signs of low perfusion and congestion
What are the names of the 4 Ca channel blockers?
amlodipine/nifedipine
diltiazem/verapamil
What is use of Ca channel blockers in pulm htn?
- result in pulmonary arterial vasodilation
- beneficial if positive vasoreactivity test [vasoresponder]
What is test to see if patient is vasoresponder?
- give short-acting vasodilator like epoprostenol/adenosine/inhaled NO
- a vasoresponder will have decreased PAP by > 10 to absolute < 40 without concurrent drop in CO
only makes up 13% of population of pts with idiopathic PAH
What is mech of prostanoids?
- stimulate adenylate cyclase –> incrase cAMP
- cause vasodilation, antiproliferation, platelet aggregation inhibition
What is effect of prostanoids?
- improve hymodynamics; functional capacity
What is the one prostanoid that increases survival?
epoprostenol
What are the 3 types of prostanoids and their mech of administratiON?
epoprostenol = IV treprostinil = SC, IV, PO, inhale iloprost = inhaled
How is eoprostenol administered? half life?
1/2 life = 3-5 min
continuous IV admin
Which prostanoid is just synthetic prostacyclin?
epoprostenol
How is treprostinil administered?
IV and subcutanous = bioequivalent
1/2 life is 2-4 hrs
Where are the two types of endothelin receptor antagonists located? action?
- ETA/ETB on smooth muscle cells and cardiac myocytes
- ETB also on endothelial cells
both cause vasoconstriction/ proliferation smooth muscle
ETB also mediates pulmonary clearance and induces production of local mediators
What are the 3 endothelin receptor antagonists?
- bosentan
- ambrisentan
- macitentan
What is order of highest affinity for ETA/ETB among the 3 endothilin receptor antagonists?
ambrisentan > macitentan > bosentan
affinity ETA: ETB
WHat is effect of endothelin receptor antagonists?
improve hemodynamics and functional capacity
WHat is mech/effect of phosphodiesterase 5 inhibitors?
- inhibits cGMP specific phosphoidesterase
cause vasodilation/ antiproliferation/ platelet aggregation inhibition
improve hemodynamics and functional capacity
What are the 2 phosphodiesterase 5 inhibitors?
sildenafil [PO/IV]
tadalafil [PO
What is mech of action of riociguat?
stimulates solumble guanylate cyclase [sGC] –> converts GTP to cGMP
What is effect of riociguat?
vasodilation, antiproliferation, platelet aggregation inhibition
improves hemodynamics and functional capacity
What are some things you need to consider when you are giving vasodilators?
- vasodilation will decrease SVR not just PVR –> caution in hypotensive patients
- abrupt medication withdrawal causes rebound pulmonary HTN –> need to wean gradually
- can worsen V/Q match leading to hypoxemia –> caution in intrinsic lung disease
What are side effects common of pulmonary vasodilators?
vasodilation –> headache, dizziness, flushing, nasal congestion
What is a side effect of bosentan?
liver tox
What are side effects common to endothelin receptor antagonists?
- teratogenic, peripheral edema, anemia
What are side effects of prostanoids?
jaw pain
What are general treatment measures of pulm HTN?
- give supplemental O2 to maintain saturation > 90%
- anticoagulation
- digoxin to improve contractility
- cardiopulmonary rehab to improve functional capacity
What surgical treatments available for pulm HTN?
- atrial septostomy –> unloads RV at cost of hypoxemia
- pulm thromboendarectomy in case of chronic thromboembolic pulm htn
- lung transplant
