Lecture 28

Question 1

What is pulmonary hypertension due to?

Answer 1

Alteration in the structure and function of the pulmonary arteries

Question 2

What defines pulmonary hypertension?

Answer 2

Pulmonary artery pressure of >25 mmHg (normally is around 15 mmHg)

Question 3

What are the symptoms of pulmonary hypertension?

Answer 3

Non-specific symptoms: breathless, faLgue and chest pain

Symptoms develop gradually, when the disease is very advanced

Question 4

What are the two types of pulmonary hypertension? What are the causes of each of these? What percentage do each of these make up?

Answer 4

• primary PH: exact cause unknown (40%)
• secondary hypertension (60%: underlying causes include COPD, lung conditions, mitral valve disease, sleep apnea, sickle cell anaemia, HIV

Question 5

What two things can change the structure of the pulmonary arteries that contributes to pulmonary hypertension?

Answer 5

Arteriosclerosis and atherosclerosis

Question 6

How does artheriosclerosis and atherosclerosis change the structure of the pulmonary arteries to cause pulmonary hypertension?

Answer 6

There will be endothelial proliferation and fibrosis (collagen deposition in the vessel wall) and smooth muscle cell hypertrophy. Overall, it means that the intima and the media will thicken. This will mean stiffer arteries and impeding lumen so the pressure in the pulmonary arteries increases. In the later stages, there could be a thrombosis occurring which indicates that inflammation is important in the development of hypertension

Question 6

What is a thrombosis?

Answer 6

This is when a blood clot blocks the blood vessel wall

Question 7

What is the causes of the pulmonary artery remodelling?

Answer 7

• due to increased pressures (altered shear stress)
• inflammation
• endothelial dysfunction and proliferation which causes a disturbed vasodilator-vasoconstrictor balance

Question 8

What are some vasodilators and what are some vasoconstrictors that are disturbed due to endothelial dysfunction?

Answer 8

dilators: NO, prostacyclin
constrictor: endothelin, thromboxane

Question 9

What are the vasodilators and vasoconstrictors important for?

Answer 9

vascular control

Question 10

What happens when the endothelium releases NO? What about prostacyclin?

Answer 10

Via cyclic GMP it will cause relaxation of the smooth muscle cells which will cause vasodilation of the smooth muscle cells.
Prostacyclin causes vasodilation via a different pathway.

Question 10

What is the effect of endothelin?

Answer 10

It causes vasoconstriction of the smooth muscle cell via the endothelin receptors and also causes hypertrophy of the smooth muscle cells to ensure that they can be a stronger contraction of the smooth muscle cell leading to a vasoconstrictive state

Question 11

What is the effect of pulmonary hypertension on the vasodilators and the vasoconstrictor balance?

Answer 11

The NO and prostacyclin regulation will be less but there is more endothelin and thromboxane regulation

Question 12

What are the consequences of pulmonary hypertension?

Answer 12

• it is more difficult to pump blood into the lungs
• the pulmonary resistance will be really high due to an increase in pulmonary artery pressure
• this will lead to severe bronchial obstruction
• and decreased diffusion capacity of O2
• hypoxemia (decreased partial O2 pressure)

Question 13

Describe the pulmonary system

Answer 13

Low pressure - low resistance Receives ~100% of circulating blood

Question 14

Describe the pulmonary artery tree in relation to compliance and resistance

Answer 14

Compliance distributed over entire arterial system

Resistance distributed over entire arterial system

Question 15

Describe the compliance and resistance of the systemic arterial tree

Answer 15

Compliance located in aorta (80% of total compliance)

Resistance distributed over all resistance arteries in the different vascular beds

Question 16

What is the consequence of the resistance of the pulmonary system being distributed across the whole system?

Answer 16

Although the blood pressure in the pulmonary system is lower, the changes that are occurring due to the changes in resistance are much more severe. Increases in pulmonary resistance result in relatively larger increases in blood pressure (both systemic and pulmonary blood pressure)

Question 17

What is the consequence for cardiac function due to pulmonary hypertension?

Answer 17

The increase in the pressure of the pulmonary arteries affects mainly the right ventricle. Although the arterial systolic pressure in the pulmonary system is much lower than that in the systemic circuit, the relatively small increases in arterial systolic pressure leads to a much larger drop in stroke volume in the right ventricle compared to the left ventricle. Small changes in the resistance of the pulmonary arteries will cause a much larger afterload for the right ventricle than a similar change in systolic pressure does for the left ventricle

Question 18

What are the steps for cardiac remodelling?

Answer 18

• there is an increase in pulmonary vascular resistance
• this leads to RV hypertrophy
  These are the compensated states
• this increases the wall-stress
• this increases the RV work-load
• this leads to chamber dilation
• heart failure and LV diastolic dysfunction
  These are the decompensated states

Question 19

Explain the progression of compensated and then decompensated RV hypertrophy. What happens during the pre-clinical and symptomatic and decompensated states?

Answer 19

In the pulmonary artery, there is an increase in wall thickness which will lead to an increase in pulmonary artery wall thickness. In the preclinical state (compensated), the pulmonary artery pressure and pulmonary vascular resistance is increasing but the CO is not affected.
When it is symptomatic, the the pulmonary artery pressure and pulmonary vascular resistance is increasing and there is a small decrease in CO is not affected.
During the decompensated state, there is a severe pulmonary obstruction so the PAP flattens out, the PVR keeps increasing and CO drops a bit.

Question 20

What would we see if we took a cross-section of the heart in when there is RV hypertrophy?

Answer 20

There is the left ventricle, right ventricle and the septum in the middle. During hypertrophy, the right ventricle wall increases in size and a small increase in the size of the septum. There is also cellular hypertrophy because the cross-sectional area of the cardiomyocytes increases in size.

Question 21

What would we see if we took a cross section of the heart in the decompensated state?

Answer 21

First there was RV hypertrophy and this develops into RV dilation. The RV is now starting to fill

Question 22

What happens after the decompensated state?

Answer 22

There is LV dysfunction because the LV has deflated. The septum is impeding the filling of the LV. This means that the RV and LV contract at different times instead of at the same time

Question 23

Describe the feedback system of the cardiac remodelling

Answer 23

When there is chamber dilation, this feeds-back and further increases the wall-stress and increases the RV work-load which again, increases the chamber dilation

Question 24

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.

Answer 24

C. of the RV is increased, and of the LV is decreased.

Question 25

What is the survival rate of pulmonary hypertension?

Answer 25

Although the prevalence is not high, if you have it, you will die

Question 26

How did AMY WINEHOUSE die?

Answer 26

Emphysema - this induced vasoconstriction in poorly ventilated parts in the lung. This leads to a reduction in capillary capacity and this leads to an increased total peripheral pulmonary resistance. This leads to an increased PAP and this leads to pulmonary hypertension

Question 27

How can you treat pulmonary hypertension?

Answer 27

You need to fix the imbalance between the dilator and the constrictor. You could inhale NO but this doesn’t last long. You could take drug stimulate the guanalyl cyclase to convert GTP into cGMP or endothelin receptor antagonists to stop the binding of endothelin or PDE5-inhibitors so there is less breakdown of cGMP so there is more vasodilation or prostagladins

Question 28

Sildenafil is a PDE-5 inhibitor. What is it’s purpose?

Answer 28

In extreme heights, you could develop pulmonary hypertension. The PAP increases and so the acute PH increases. Sildenafil decreases this. The O2 saturation and VO2max both drops at high altitudes but they drop less if you take sildenafil.

Question 29

How does sildenafil work?

Answer 29

It blocks the breakdown of cGMP as it blocks the PDE-5 so it relaxes the smooth muscle cells and causes vasodilation

Question 30

What gives you the best survival chances?

Answer 30

PDE5i (PDE5-inhibitors) and ERA (Endothelin Receptor Antagonists)
Combination therapy most effective

Question 31

During pulmonary hypertension the diffusion capacity for O2 decreases BECAUSE total pulmonary vascular resistance is decreased during pulmonary hypertension
A. Both statements are correct and causally related.
B. Both statements are correct and NOT causally related.
C. Only the first statement is correct and the second statement is incorrect.
D. Only the second statement is correct and the first statement is incorrect.
E. Both statements or incorrect.

Answer 31

C. Only the first statement is correct and the second statement is incorrect.