8. Pulmonary Vascular Disease Flashcards
PULMONARY CIRCULATION
• It is the only system through which the entire ____ passes
• It is a low-____, high-____ system
• Similar to airways, branching of vessels increases ____
• In response to increase in flow, increased ____ of vessels and vasodilation
• Kidney’s, stomach, other intestinal organs and muscles do not receive 100% of cardiac output
• When heart pumps, lungs receive 100% of output from right side of the heart
• Capillaries surrounding an alveolus are not fully distended - if there is increased demand (exercise, increased
blood flow, increased cardiac output), then capillaries ____
◦ This allows the change in pressure to be ____
• When you exercise, you are not supposed to develop high pulmonary pressures because you would ____
◦ This is what happens with pulmonary hypertension
cardiac output pressure flow total CSA recruitment engorge minimal syncopize
PULMONARY VASCULAR RESISTANCE
- PVR is calculated as ____ divided by ____
- Resistance in a vessel increases
- ____ of vessel
- Fluid ____
- 1/radius4 -> the ____ make up a substantial portion of PVR
• You need a starting point and an ending point, and you divide by the flow across those two points
• When talking about pulmonary vascular resistance, talking about the mean pulmonary arterial pressure in the ____
• The end point is when it gets to the ____ of the heart - the left atrial pressure
• The blood flow is the ____
• Even though the pulmonary vascular circulation has several branches that increase the total cross sectional area, because at these small vessels you have much higher resistance, most of the micro vessels are what make the highest proportion of the PVR
◦ NOT the____ or the lobar arteries
◦ It’s the tiny ____ that go to the pulmonary capillaries
transvascular driving pressure flow length viscosity microvessels
pulm arteries left side cardiac output large pulm arteries arterioles
PULMONARY VS. SYSTEMIC CIRCULATION
Pulmonary 3.1
mean arterial pressure: ____
resistance: ____
Systemic 3.1
mean arterial pressure: ____
resistance: ____
PC: high ____, low ____, low ____ circuit
• ____ are the same b/w pulmonary and systemic circulation
• The upper limit for the mean arterial pressure in the pulmonary circulation would be 20
• If you calculate the diff b/w the mean arterial pressure and the ____ for pulmonary circulation
divided by CO, you get the resistance
• If you calculate the mean arterial pressure and the ____ (because that is the end point) in the systemic, you get the systemic vascular resistance
◦ Comparing those 2 together, pulmonary circulation is a high capacity, low pressure, low resistance circuit compared to the ____ circulation
9-15
60-100
85-100
900-1200
capacity
pressure
resistance
cardiac indices
left atrial pressure
right atrial pressure
systemic
• The left side of the heart pumps out to the body and returns through the SVC and the IVC into the RA
◦ You use the mean minus the end (____), and you divide it by the CO
◦ Normally CO is 5 L/min
◦ You get a SVR of 17.6 Wood units
◦ If you multiple this by 8 (I think that’s what she said?), you get the other unit of measurement which is 9/ sec/cm^-5
• For the pulmonary circulation, the heart ejects from the right side of the heart into the pulmonary circulation into the lungs and back into the LA
◦ You use the mean arterial pressure in the pulmonary arteries minus the ____ and you divide by CO
◦ You get a PVR of 1.8 Wood units
right atrial pressure
left atrial pressure
Pulmonary artery catheter
• We use the pulmonary artery catheter to measure these pressures
• The catheter has several lumens - a ____ (opens into ____), a ____ (opens at the tip where the ____ is), a
____ that is inflated through the catheter, & a ____
proximal RA distal balloon balloon temp transducer
Right heart catheterization
- When you start in the right atrial pressure, you have an a wave with an ____ descent and a v wave with a ____ descent
- These a and v waves correspond to the ____ contraction - once the atrium contracts you get this bump (a wave)
- As the atrium relaxes, the ____ drops
- Then the ____ closes and you get another bump and an increase in ____ when the valve closes
• Once the catheter enters the ____, a sharp increase in systolic pressure - mid 20s
• in diastole, right ventricle and diastolic pressure is ____ mm Hg
• Catheter floats into ____, see a change in shape of wave
◦ similar systolic pressure unless ____
◦ diastolic pressure ____
◦ Also see ____ - when ____ closes
• once you wedge (let catheter go to smallest vessel it can fit) - see an a and v wave, but it’s ____ pressure
x y atrial pressure tricuspid pressure right ventricle 0-8 pulmonary artery pulmonary valve problem rises dicrotic notch pulmonary valve higher
Wedged PA catheter
- when catheter is wedged, have a closed column of fluid between balloon tip, the ____, the ____, and the ____
- Gives a reflection of the ____ and ____ pressure
- can see if the increase in pressure is ____ (problem with pulmonary arteries and pulmonary vessels) or a problem with ____ of the heart
- when we measure pulmonary wedge pressure, trying to get a reflection of ____
- if left ventricular end diastolic pressure is high & if no ____ valve pathology, it will transmit into the ____ and back all the way up - what the catheter picks up
capillaries
pulmonary veins
LA
left ventricular
diastolic
precapillary left side left ventricular end mitral left atrial pressure
PA Cath Measurements
- ____ pressure
- ____ pressure (systolic and diastolic)
- ____ pressure (systolic, diastolic and mean)
- ____ (PAWP)
RA
RV
PA
PCWP
MEASUREMENT OF CARDIAC OUTPUT
• Fick Principle: The total uptake or release of any substance by an organ is the product of ____ to the organ and the ____ difference of the substance
Qp = (____) / ____
• In absence of a shunt, the systemic blood flow (Qs) is estimated by ____
• There are two ways to measure CO:
◦ Fick principle - Qp = ____ and pulmonary circulation
◦ If know your arterial saturation minus the mixed venus = arteriovenous O2 difference
◦ oxygen consumption measured or estimated
• When have catheter wedged, if pull blood back, we are pulling blood from least oxygenated blood going to lung capillaries to get reoxygenated
• if don’t have abnormal connection b/w right and left side of heart (shunt) can assume that systemic blood flow is same as ____
◦ Qs = ____
blood flow
arteriovenous concentration
oxygen consumption
arteriovenosu O2 difference
pulmonary blood flow (Qp)
cardiac output
pulmonary
Qp
MEASUREMENT OF CARDIAC OUTPUT
- ____ method
- Cardiac output is determined by injecting a cold bolus of a sterile solution in the PA catheter’s ____ port. The temperature probe at the distal tip will sense the change in ____ as the injectate passes the catheter tip located in the PA.
• The other way to measure CO while doing the pulmonary artery catheter is to use
thermodilution
• You see there is a change in temp - temp ____ then goes back to ____
• If you know the volume you injected and the difference in temp, then you can calculate the ____
thermodilution proximal temperature decreases normal body temp blood flow
Resistance calculations
Pulmonary vascular resistance
PVR = (____ / pulmonary blood flow (CO)
Systemic vascular resistance
SVR = (____ / systemic blood flow (CO)
• you start at a point (mean PA pressure) and end point is the mean LA pressure
◦ the mean LA pressure is estimated by the ____ (PCWP)
• CO determined by either ____ method
mean PA pressure - mean LA pressure (PCWP)
mean arterial pressure - mean RA pressure
pulmonary capillary wedge pressure
thermodilution
Pulmonary Hypertension
• Defined as mean PA pressure ≥ ____ mm Hg
• PH is not specific as
Mean PA Pressure = ____
• Important to determine ____ to determine PH treatment
• normal pulmonary artery pressure is between ____ (up to 20) mm Hg
• between 20 and 25 is not technically pulmonary hypertension, but the slight elevations aren’t good for
patient
• If you take PVR equation and shuffle it, you get the mean PA pressure equation
◦ If you look at this equation, many things can raise the pulmonary artery pressure
◦ patients who have ____ - will get pulmonary hypertension because the high wedge pressure will drive the mean PA pressure to be high
◦ someone who’s anemic will have increased ____ - will cause elevation in mean PA pressure
• When we talk about PH, specifically pulmonary arterial hypertension (PAH), we are talking about an
____ problem with the pulmonary vasculature
◦ the little vessels are ____ and the ____ is high
• Treatments differ drastically
25
CO x PVR x PCWP
PH group
9-15 CHF CO intrinsic remodeled PVR
PH classification
• PAH is disease related to the pulmonary vasculature (____)
• PH owing to left heart disease is when you have ____ (____)
◦ all the dysfunctions drive up the PCWP and give you PH
• If have any ____, can give you PH (Group III)
• Special group is group IV
• ____ is a mixed basket of diagnoses
◦ all of the disorders can present as different groups
◦ when they have many different possibilities of presenting, we lump them here and decide on case-by-case
basis
• We will focus on PAH
◦ ____: we don’t know why they develop this pathology
◦ heritable: ____ mutations, ____ mutations, ____ mutations that lead to higher incidence of PAH in
families
group I left heart failure group II lung disease group V idiopathic BMPR2 ALK endoglin
PH classification (cont.)
• drugs and toxins: back in 80s, diet pills with fenfluramine that led to the development of PAH, nowadays see same thing with drug users and ____ and amphetamines
• a number of associated conditions lead to PAH
◦ ____ is one of the most common
‣ ____ or systemic sclerosis
‣ ____
‣ any connective tissue diseases can led to PAH
◦ HIV
◦ ____ - liver disease with evidence of portal hypertension
‣ patients with liver disease with increased portal pressure
‣ ____ is elevated but also ____ elevated to diagnose
◦ congenital heart disease ‣ \_\_\_\_ shunt causes PAH • ASD, VSD, PDA ◦ the most common cause of PAH worldwide is \_\_\_\_, which is a parasitic infection ‣ we don't see it here in the US
methamphetamine
connective tissue disease
scleroderma
SLE
portal hypertension
CO
PVR
right to left
schistosomiasis
PAH
- Pulmonary arterial hypertension is defined as:
- Mean PA pressure ≥ ____ mm Hg
- PCWP (Left ventricular end-diastolic pressure) ≤ ____ mm Hg
- PVR > ____ WU or ____ dynes/sec/cm-5
- ____: 10-15 cases per million
- More common in ____ than men
- Average time to appropriate diagnosis ~____ months
• You have to have a normal PCWP, meaning there is no ____
• need to have an elevated ____
◦ 1 Wood unit is 80 dynes/sec/cm^-5
• True PAH is rare
• Patients present with non-specific symptoms (shortness of breath) that are often misdiagnosed
25 15 3 240 rare women 12-18 left heart disease PVR
PAH Survival
• Back in 90s, NIH did a survival of patients with PAH (used to be called Primary Pulmonary Hypertension), and it was dismal
• by 5 years, only 35% were still alive
• nowadays, patients are doing better, but it is still a highly ____ condition
◦ at 5 years, ____% are dead, which is significant considering it is a disease mostly affecting young women
morbid
30
Determinants of survival
• What impacts their survival? • Functional class I = someone who has no limitations of \_\_\_\_ • Functional class II = only have symptoms when \_\_\_\_ with strenuous activity, but okay with doing activities of daily living • Functional class III = problems with \_\_\_\_ ◦ I.e. when walk from my bed to bathroom, short of breath • You should think about what patients might tell you • Functional class IV = uncomfortable at \_\_\_\_, short of breath not doing anything • when a patient presents when functional class they are in impacts their longterm survival • at 3 years, \_\_\_\_% of functional class IV cases are dead ◦ functional class IIs are mostly \_\_\_\_ • important to identify these patients early on so can intervene early on
exercise activity strenuous activity daily activity rest 75 alive
Determinants of survival
____ not hemodynamics determines survival
• other things that are crucial for survival in these patients is their ____ function, not pulmonary hemodynamics
• it doesn’t matter what mean pulmonary artery pressure is, it matters how right heart is dealing with it
◦ if right heart is compensating and can function normally, patient will do okay
• however, if right ventricle (____) is low, that’s when patients do poorly
• If you classify PVR by a cutoff, there is a difference in survival
◦ those who have a ____ PVR will do better
• when you add the right ventricular ejection fraction to PVR, it splits by who has a preserved right ventricular
ejection fraction vs. low right ventricular ejection fraction
• the key is how the ____ is handling the increased pressure
RV function right ventricular right ventricular ejection fraction lower right heart
Hemodynamic progression of PH
• The pulmonary circulation is a high flow, low pressure system
• you start normally with a low ____ and a normal ____
• As PAH starts to progress, start to have medial ____ and intimal ____
◦ as that happens, your New York Heart Association (NYHA) goes from class I to II - start to become symptomatic with more strenuous activity
◦ As you go from this to this, your PVR is ____ and your pulmonary artery pressure is increasing because that vessel has ____
◦ the PVR is inversely proportion to the ____ of the vessel^4
‣ when you have a slight decrease in vessel radius, have a ____ increase in the PVR
◦ your cardiac output is still doing ok - ____ still able to deal with slight increase
PVR CO thickening hypertrophy increasing remodeled radius much higher RV
Hemodynamic progression of PH (cont.)
• then it comes to a tipping point, and that’s when the ____ starts to fail and patients become way more symptomatic
◦ their BNP (brain natriuretic peptide) ____ bc the right side of heart is stressed and dilating
‣ it’s ballooning and failing
‣ start to see that the vessels have completely ____
‣ the vessels develop hypertrophy and in situ ____, and the PVR continues to ____ as the disease progresses
‣ once the ____ starts to fall, the pulmonary artery pressure falls bc the heart can’t generate that much pressure
‣ remember, mean pulmonary artery pressure = CO x PVR
• now CO is failing, the ____ won’t be as high
• that’s why it’s not important what the mean ____ is because it could be on this side of the curve or this side of the curve
‣ so you need to know what the CO is doing
• at this point is death
◦ the right ventricle is extremely ballooned out and hypertrophied
right ventricle elevates thickened thromboses increase CO pulmonary artery
Imbalance of vasoactive factors in PAH
• what drives these pathological changes?
◦ ____, cell proliferation, and ____
• several mediators are driving this
• thromboxane is the most potent ____ the body produces ◦ we have an imbalance in these substances
• everyone of us produces thromboxane, prostaglandin (one of the most potent ____), nitric oxide, etc
◦ it’s a matter of a ____ of these substances against each other
‣ increase thromboxane = more ____
• also decreased prostacyclin (prostaglandin)
• also have decreased NO, another vasodilator
• increased endothelin (another ____)
• increased serotonin
◦ these same drivers lead to cell proliferation
‣ increased VEGF
◦ and increased thromboses
vasoconstriction
thromboses
vasoconstrictor vasodilators balance vasoconstriction vasoconstrictor
PAH PATHOLOGY
____ lesion; ____ hypertrophy; ____ proliferation
• the pathognomonic lesion for PAH is a ____
• this is what should have been a regular vessel
• if you look more closely, the intimal layer is already ____
• the plexiform lesions are conglomerates of ____ cells that are abnormally multiplying
• it’s kind of like a cancer of the pulmonary vasculature
• if you look closely here, you have the muscle layer that is now highly thickened and proliferating
• you have smooth muscle hypertrophy and endothelial proliferation
• at the level of these capillaries, you should have one thin layer of ____, one thin layer of ____ so you can
have gas exchange occur with the alveoli
◦ this is not possible with what we are seeing
plexiform smooth muscle endothelial plexiform lesion thickened endothelial endothelium SMC
PAH PATHOLOG Y
In situ thrombosis
• the other common thing that we see is that these vessels ____ spontaneously
thrombose
RELE VAN T HIS TORY FOR PH
- ____ pain
- Raynaud’s syndrome
- ____conditions/cyanosis
- ____ disease
- Etoh/ drugs/ anorexigens/ tobacco
- ____
- Previous DVT or PE or family history of clots
- ____
• when you suspect pulmonary hypertension, what should you ask about?
◦ joint/musculoskeletal pain - trying to figure out if they have any ____ disease
‣ any other signs of scleroderma, ____, lupus
◦ Raynaud’s syndrome - fingers get cold and blue when exposed to cold
◦ childhood heart conditions - ____, cyanosis
◦ liver disease - want to know if have ____
◦ ask about alcohol - can lead to liver disease
◦ dugs - ____ are very common and a common cause of PAH
◦ anorexigens - in recent years ____ diet pills are off the market once they figured out they were
causing PAH
‣ still see patients today who took those pills back in the 90s and are presenting with PAH
◦ smoking - do they have ____
◦ ____ - can lead to PAH
◦ previous history of having deep vein thrombus in their leg or a PE or anyone in their family who has had history of clots
‣ or history of current abortions
◦ other chronic lung diseases - interstitial lung disease, sleep apnea, etc
joint/musculoskeletal childhood heart liver HIV chronic lung disease
CT RA murmurs portopulmonary hypertension methemphatamines fenfluramine COPD HIV
