Pulmonary hypertension

Question 1

Pulmonary hypertension definition

Answer 1

An increase in blood pressure in any part of the pulmonary circulation (arterial, venous, capillary or all)
Usually secondary to some other pathological or environmental condition
Rarely, pulmonary arterial hypertension of unknown cause and familial pulmonary hypertension

Question 2

Pulmonary hypertension classification (WHO)

Answer 2

1. Pulmonary arterial hypertension
2. Pulmonary venous hypertension resulting from left heart disease
3. Pulmonary hypertension resulting from lung diseases and/or hypoxia
4. Pulmonary hypertension due to chronic thrmobotic and/or embolic disease
5. Pulmonary hypertension of miscellaneous origin

Question 3

Pulmonary arterial hypertension

Answer 3

Primary- idiopathic (IPAH), familial (FPAH)
Secondary- PAH associated with many other conditions; form the majority of cases of PAH e.g. congenital systemic/ pulmonary shunts, HIV infection, portal hypertension and liver disease etc.

Question 4

IPAH

Answer 4

Very rare form, typical onset between 20 and 30 years old

Familial PAH even more rare, early presentation and equal gender distribution

Question 5

Pathology of IPAH

Proliferative coagulative pulmonary arteriopathy

Answer 5

Increased vascular resistance- pulmonary vasoconstriction
Proliferative/ coagulative pulmonary arteriopathy- medial/ intimal hyperplasia, vascular fibrosis, thrombosis/ platelet aggregation

Question 6

BMPR2

Answer 6

Possible genetic basis for FPAH and IPAH
Mutation of gene encoding bone morphogenetic protein receptor-2
Inherited as an autosomal dominant disease
Thought that signalling normally regulates cell growth and apoptosis in pulmonary vascular cells
Some evidence of decreased expression in secondary PAH

Question 7

Cor Pulmonale

Answer 7

Right sided heart failure as a consequence of PAH
Associated with enlargement of the right ventricle- hypertrophy and dilatation
Peripheral oedema, dyspnoea and fatigue
Most common cause of hospitalisation in all patients with PAH

Question 8

Treatment of IPAH

Answer 8

Life expectancy is 2-3 years in IPAH, death from heart failure or sudden arrhythmic death
Conventional IPAH therapy includes inhaled oxygen, oral anticoagulants, diuretics
High dose calcium channel blockers are effective for only a small minority
Newer vasodilator agents

Question 9

Pulmonary venous hypertension

Answer 9

Almost always secondary to left heart disease

Imposes a haemodynamic overload on the pulmonary venous circulation

Question 10

Pathology of PVH

Answer 10

Initially no increased resistance to blood flow in the pulmonary arterial circulation
Decrease pulmonary venous drainage leads to increased pulmonary blood volume and increased back pressure throughout the pulmonary circulation
Chronic PVH may lead in time to pulmonary vascular structural changes and increased vasoconstriction

Question 11

Treatment of PVH

Answer 11

Correct any structural defect e.g. mitral valve surgery or optimise left ventricular function e.g. ACE inhibitors, diuretics, spironolactone, B adrenoceptor antagonists

Question 12

Pulmonary hypertension resulting from lung disease and/or hypoxia

Answer 12

Many causes- COPD, interstitial lung disease, morbid obesity, chronic sleep-disordered breathing, chronic high altitude exposure, neonatal lung disease
COPD is the most significant cause of PH and cor pulmonale
Blue bloater- cyanosis and oedema

Question 13

Pathology of PH in COPD and hypoxia

Answer 13

Structural damage to the alveoli and associated structure

More important effects of reduced pO2 (hypoxic hypoxia), increased pCO2, decreased pH (hypercapnia)

Question 14

Hypoxic pulmonary vasoconstriction

Answer 14

In systemic tissues, low pO2 causes vasodilation to deliver more blood and oxygen
In lung, low pO2 causes vasoconstruction to divert blood flow away from poorly ventilated areas of lung to better ventilated areas

Question 15

Mechanism of HPV

Answer 15

Two phases: acute and sustained
Acute response is not endothelium dependent but sustained phase is linked to endothelium
Extremely complex and not yet understood in detail

Question 16

Pulmonary hypertension due to chronic thrombotic and/or embolic disease

Answer 16

E.g. pulmonary artery thrombosis- treat with fibrinolytics, endarterectomy, life-long anticoagulation
E.g. non-thrombotic pulmonary embolism- tumour emboli, parasites, fungi, foreign materials

Question 17

Pulmonary hypertension of miscellaneous origin

Answer 17

E.g. external compression of the pulmonary vessels by a tumour mass
Chronic inflammatory conditions in the lung or pulmonary vessels

Question 18

Treatment of PAH

Answer 18

Newer vasodilator approaches, especially for PAH
Endothelin receptor antagonists
Prostacyclin analogues
PDE-V inhibitors
Soluble guanylyl cyclase activator