Pulmonary Hypertension

Dr.CSBR.Prasad, M.D.

CSBRP-Dec-2012

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

Pulmonary Hypertension

Classification:

Primary: Idiopathic, no known cause,

6% - have family history (AD)

Secondary: Structural abnormalities in

cardiopulmonary area

CSBRP-Dec-2012

Pulmonary Hypertension

Classification:

Primary: Idiopathic, no known cause

6% - have family history (AD-vp)

Mutations in BMPR2 (bone morphogenic protein receptor type-2)

CSBRP-Dec-2012

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

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

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

Modifier genes are

those that control

vascular tone, e.g.,

endothelin,

prostacyclin

synthetase, and

angiotensin-

converting enzymes

The nature of the

environmental factors

remains unknown,

but presumably, they

cause dysfunction of

vasoregulatory

mechanisms

CSBRP-Dec-2012

Pulmonary Hypertension

Classification:

Secondary: Structural abnormalities in cardiopulmonary area

• COPD / interstitial lung disease

• Congenital / acquired heart disease

• Recurrent thromboembolism

• Autoimmune diseases

CSBRP-Dec-2012

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

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

CSBRP-Dec-2012

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

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

E N D

CSBRP-Dec-2012