2. Pulmonary Hypertension
Pulmonary BP is only ⅛ of systemic BP
Def: Mean pulmonary arterial pressure
exceeding ¼ of systemic levels is PHT
CSBRP-Dec-2012
5. Pulmonary Hypertension
Primary: Idiopathic, Mutations in BMPR2
BMPR2 belongs to TGF-ß receptor superfamily
BMP-BMPR2 signalling play a role in:
- Apoptosis
- Cell proliferation & differentiation
- Embryogenesis
CSBRP-Dec-2012
6. Pulmonary Hypertension
BMP-BMPR2 signalling in vascular smooth
muscle:
- Inhibits proliferation
- Induces apoptosis
Hence mutations in this gene causes proliferation of
smooth muscle in the vessels
CSBRP-Dec-2012
7. Pulmonary Hypertension
How this gene gets deleted / rendered
useless?
TWO hit hypothesis:
First hit: genetic loss of one locus
Second hit: Environmental factor
Mutations in the other gene
Environmental factors: disruption of
vasoregualtory mechnisms involving Endothelin,
Prostacyclin synthase or ACE.
CSBRP-Dec-2012
8. Modifier genes are The nature of the
those that control environmental factors
vascular tone, e.g., remains unknown,
endothelin, but presumably, they
prostacyclin cause dysfunction of
synthetase, and vasoregulatory
angiotensin- mechanisms
converting enzymes
CSBRP-Dec-2012
10. Pulmonary Hypertension
Secondary: Structural abnormalities in cardiopulmonary
area
Endothelial cell dysfunction is produced by the process that
initiates the disorder, such as:
The increased shear and mechanical injury associated with
left-to-right shunts
The biochemical injury produced by fibrin in
thromboembolism
Decreased elaboration of prostacyclin, decreased
production of nitric oxide, and increased release of
endothelin all promote pulmonary vasoconstriction
CSBRP-Dec-2012
11. Pulmonary Hypertension
Morphology:
The arterioles and small arteries (40 to 300
µm in diameter) are most prominently
affected
1. Medial hypertrophy and
2. Intimal fibrosis
3. Plexogenic pulmonary arteriopathy
CSBRP-Dec-2012
13. Figure 15-30 Vascular changes in
pulmonary hypertension. A, Gross
photograph of atheroma formation, a
finding usually limited to large
vessels. B, Marked medial
hypertrophy. C, Plexogenic lesion
characteristic of advanced pulmonary
hypertension seen in small arteries.
CSBRP-Dec-2012
14. Pulmonary Hypertension
Clinical course:
Primary PHT is more common in females
Between 20-40yrs
Dyspnea and fatigue
Chest pain
Cyanosis
RVH
Death: in 2-5yrs in 80% of the patients
due to Cor pulmonale, pneumonia
CSBRP-Dec-2012
