Pulmonary arterial hypertension

Question 1

What is pulmonary hypertension?

Answer 1

Increased pulmonary blood pressure- gas exchange becomes much less efficient
mPAP greater than 25 mmHg
(mPAP= mean pulmonary artery pressure)

Question 2

What are causes of increased mPAP in pulmonary hypertension?

Answer 2

Hole in the heart- shunting pressure from the left to the right side of the heart
Thrombus formation- can be lodged in the lungs
Sustained pulmonary vasoconstriction- vessels become constitutively constricted
*pulmonary vascular remodelling- consequence of maintained vasoconstriction

Question 3

What are the consequences of raised mPAP?

Answer 3

Right ventricular hypertrophy
right heart failure
high morbidity and death

Question 4

Symptoms of PAH?

Answer 4

V difficult to diagnose as very common symptoms
breathlessness and chest pains
syncopal episode after exertion

Question 5

What are some investigations we can carry out and typical PAH results of these?

Answer 5

ECG- conductance of heart- right heart strain
CXR- chest xray- increased size of pulmonary arteries and right side of the heart
lung function test- test volume and capacity
echocardiogram- ultrasound imaging of the heart- give an estimate of pulmonary pressure
*CTPA- image of pulmonary arteries
*HRCT- image lung parenchyma
*Right heart catheritisation- how much blood is being pumped and measure blood pressure in the pulmonary artery

Question 6

What is PVR? Whats the equation

Answer 6

Pulmonary vascular resistance
very low in healthy lungs
PVR= mPAP- PAAWP/ CO
PAWP= pulmonary wedge pressure- estimates left atrial pressure

Question 7

Differentiation between PH and PAH

Answer 7

PH= mPAP of greater than 25 mmHG
PAH= mPAP of greater than 25mmHG
and PAWP/LVEDP less than 15mmHG
and PVR greater than 3 woods units 
PH is the syndrome

Question 8

What are the 5 types of PH, are they treatable and what are their man causes?

Answer 8

1. PAH
   -idiopathic
   -heritable
   rare
   treatment available
2. PH- left heart
   -systolic dysfunction
   -diastolic dysfunction
   no treatment available
3. PH- lung disease/ hypoxia
   -COPD- common
   -interstitial lung disease
   no treatment available
4. Chronic thromboembolic PH
   operable and inoperable
   rare
   result of pulmonary embolism
5. Multifactorial/ unclear
   -systemic disorders
   -haematological
   no treatment available

Question 9

Prevalence of group of PH?

Answer 9

15-50 people per 1 million

Question 10

PAH pathogenesis

Answer 10

Hallmark of PH= sustained vasocontriction
driving the vasoconstriction:
EC dysfunction/ apoptosis- barrier gets leaky
SMC proliferation/ migration- unregulated proliferation
This results in:
RV hypertrophy and eventually dilation
reduced LV function- RV squashes LV
Right heart failure

Question 11

Characteristics of PAH lesions

Answer 11

Concentric= layers and layers of endothelial cells- creates a ‘new intima’ tiny lumen
Plexiform lesions= rarer- tend to happen in the end stages- characteristic of pulmonary vascular remodelling- ECSs proliferation- in the wrong place- resistant to apoptosis
also see other cell types- inflammatory

Question 12

How is elastin affected in PAH?

Answer 12

Degraded
leads to vascular stiffness
promotes SMC proliferation and EC apoptosis
loss of vascular integrity= vascular leak

Question 13

Whats our current understanding of the pathogenesis?

Answer 13

EC dysfunction/ apoptosis-> causes serum leak-> cytokines, inflammatory cells enter vessel wall-> breaks down elastin-> growth factors and inflammation also degrades the ECs-> stimulates the proliferation and migration of the SMCs

Question 14

Whats the genetic insight with PAH

Answer 14

Falling cost of whole genome sequencing has lead to new discoveries
mutations in BMPR2 in familial primary PH
through looking at the disease transcriptome- identified the gene signature for the disease- saw BMP signalling was implicated