L28 Flashcards
what is pulmonary hypertension
Alteration in the structure and function of the pulmonary arteries
Primarily not in other arteries of the body
what does pressure have to rise to in the pulmonary system to be classified as hypertension
> 25mmHg
normal = 15mmHg
what is the prevalence of pulmonary hypertension
15/100 people in 1 million
about 3200 people in australia AND NZ
only 100 people in NZ
describe the symptoms of hypertension
Non-specific symptoms such as breathless, fatigue and chest pain
Symptoms develop gradually, when the disease is very advanced
there are 2 types of PH what are they and what % of the prevalence to they make up
primary pulmonary hypertension = 40%
secondary pulmonary hypertension = 60%
what are the causes of primary and secondary pulmonary hypertension
primary = unknown
secondary = Chronic obstructive pulmonary disease (COPD )/ other lung conditions
Mitral valve disease
Sleep apnea
Sickle cell anemia
HIV
what are the underlying causes of secondary pulmonary hypertension
Chronic obstructive pulmonary disease (COPD )/ other lung conditions
Mitral valve disease
Sleep apnea
Sickle cell anemia
HIV
what form of remodeling do the pulmonary arteries undergo in PH
a combination of arteriosclerosis and atherosclerosis
what does thrombosis indicate
role for inflammation
what are the causes of remodelling in PH
Increased pressures - altered shear stresses and inflammation
this causes Endothelial dysfunction and proliferation
it could also be because of disturbed vasodilator/vasoconstrictor balance:
less Nitric oxide and/or Prostacyclin vs. more Endothelin and/or Thromboxane
how does NO cause vasodilation
through cGMP
what does endothelin cause
vasoconstriction by hypertrophy of the smooth muscle cells so they can have a larger contraction vasoconstrict
what are the consequences of PH on the pulmonary system
More difficult to pump the blood into the lungs
Pulmonary Resistance increases theefore increase in Pulmonary Artery Pressure (PAP)
Severe bronchial obstruction
Decreased diffusion capacity for O2
Hypoxemia (decreased partial O2 pressure)
normally the Pulmonary system is a….
Low pressure - low resistance
Receives ~100% of circulating blood
Pulmonary arterial tree
Compliance distributed over entire arterial system
Resistance distributed over entire arterial system
compeer this to the normal systemic system
Systemic arterial tree Compliance located in aorta (80% of total compliance) Resistance distributed over all resistance arteries in the different vascular beds
overall resistance and blood pressures are lower in pulmonary system
however what happens when you increase the resistance
increases in pulmonary resistance result in relative larger increases in blood
pressures (with more disastrous consequences)
Although the pressures in the pulmonary system are lower it makes the increase in resistance much severe therefore has worse concequences
what ventricle does PH affect
right ventricle
what is the difference between systemic hypertension and pulmonary hypertension in terms of the ventricles
In the left ventricle if you increase systolic pressure you increase the afterload and you decrease SV
In the right ventricle the graph is steeper therefore small changes in the resistance in the p arteries it causes a much larger afterload in the right ventricle than a similar change in the systemic arteries (afterload in the left ventricle)
there are 2 phases of PH cardiac remodelling
what are they
- compensated (concentric)
2. decompensated (eccentric)
describe compensated PH cardiac remodeling
an increase in vascular resistance causing right ventricular hypertrophy
describe decompensated PH cardiac remodeling
RV hypertrophy (compensated)
will eventually wall stress (tension) will increase therefore causing an increase in RV workload causing chamber dilation.
eventually wall stress will increase again and this process will happen again and again until the chamber dilates too much and you get heart failure
which phases of PH cardiac remodelling are in the clinical phase and preclinical phase
compensated = preclinical
decompensated = clinical
describe what happens in compensated hypertrophy
We start with the compensated right ventricular hypertrophy. This will increase the pulmonary artery wall thickness therefore resistance
increase in resistance = increase in pulmonary arterial pressure and pulmonary vascular resistance. CO will decrease
In the compeastated state the wall of the right ventricle will increase in size (left will stay the same)
You will also get cellular hypertrophy (more sarcomear)
what causes the decompleansted state
Severe Pulmonary obstruction which leads to an increase in pressure and resistance
CO decreases
in the decompensated state why do you get dilation of the RV
In this stage we already have right ventricular hypertrophy and you start to get dilation of the right ventricle (because you cant maintain this)
why does cardiac remodelling of the heart eventually cause heart failure
If this continues then the right ventricle will continue to deteriorate and the pulmonary artery will become really obstructed this causes pulmonary artery pressure to drop which means that the right ventricle can’t make the pressures required
the right ventricular dilation will then cause a decrease in CO which leads to left ventricular dysfunction
Healthy = the right and left contraction is synchronous (they contract at the same time) whereas in the end stage of PH the right and left are contacting at different times
You can also see that the septum has become part of the right ventricle and then the right ventricle contracts it pushes into the left ventricle therefore impeding on the filling of the left ventricle decreasing the CO into the systemic arteries
when do you become systematic of PH
in the late stages of compensated remodeling
describe what the heart looks like in the late stages of cardiac remodelling because of PH
Healthy = the right and left contraction is synchronous (they contract at the same time) whereas in the end stage of PH the right and left are contacting at different times
You can also see that the septum has become part of the right ventricle and then the right ventricle contracts it pushes into the left ventricle therefore impeding on the filling of the left ventricle decreasing the CO into the systemic arteries
In the late/end stages of Pulmonary Hypertension the end-diastolic volume:
A. of the RV is increased, and of the LV remains the same.
B. of the RV is decreased, and of the LV remains the same.
C. of the RV is increased, and of the LV is decreased.
D. of the RV is decreased, and of the LV is decreased
C is correct
this is Because the right ventricle is dilated which impedes on the left ventricle
why is PH known as the insidious killer
because it has a 5-6 year survival rate
used to be 70% of people die in this time but now it is more like 40% (which is still bad) because we understand it more
describe emphysema
Lung Emphysema (COPD) =
Loss of alveoli –> induced vasoconstriction in poorly ventilated parts in lung –>
reduction in capillary capacity -> increased total peripheral pulmonary resistance –> increased PAP –> development of PH
this is a irreversible degenerative disease because When you are an adult you have a certain amount of alveoli and you don’t make anymore therefore the ones that you loose you won’t get back
how can we decide treatments for PH
Cause of pulmonary hypertension is because of the imbalance of the vasodilators and constrictors of the vessels
therefore if we can synthetically replace/stimulate these we have a treatment
what are some possible treatments for PH
could you use NO
You could inhale NO but that wouldn’t last long
what are some things that would increase the effect of vasodilators (eg NO) as a treatment for PH
You could also look at guanylyl cyclase stimulators (to make more cGMP which causes vasodilation) or phosphodiesterase 5 inhibitors
What happens when they inhibit phosphodiesterase 5 is is that it stops the breakdown of cGMP therefore the vasodilation pathways last longer
what could you do to stop the effects of vasoconstrictors as treatments for PH
You could also use prostaglandins and endothelin receptors antagonists to block the receptors of the vasoconstrictors
Sildenafil is a PDE-5 inhibitor
what
Sildenafil opposes high altitude-induced pulmonary hypertension
who does Sildenafil opposes high altitude-induced pulmonary hypertension
Relaxes smooth muscle cells causing vasodilatation selectively in lung and penis
it does this by blocking the breakdown of cGMP
what is the most effective theropy for PH
PDE5i (phosphodiesterase 5 inhibitors) and ERA (Endothelin Receptor Antagonists)
when you combine these you increase the survival rate to 90%
During pulmonary hypertension the diffusion capacity for O2 decreases
BECAUSE
total pulmonary vascular resistance is decreased during pulmonary
hypertension
the first statment is true and the second is false
should say increased
