**1. Introduction**

Pulmonary hypertension (PH) is a hemodynamic state defined by a resting mean pulmonary artery pressure (PAP) at or above 25 mm Hg.[1] with normal left ventricular filling pressure (mean pulmonary wedge pressure) 15 mmHg or less.

Pre-capillary PH is defined as mean PAP ≥25 mm Hg in association with PAOP ≤15 mm Hg and a pulmonary vascular resistance (PVR) >3 Wood units. This include group 1, 3, 4 and 5 (Table 1). [2] Post-capillary PH (group 2 as shown in Table 1) is characterized by a mean PAP ≥25 mm Hg in association with PAOP >15 mm Hg and PVR ≤3 Wood units.[3] This differen‐ tiation in pre- and post-capillary PH is important as it narrows the differential diagnosis and also has treatment implications.

1. Pulmonary arterial hypertension (PAH) 1.1. Idiopathic PAH 1.2. Heritable 1.2.1. BMPR2 1.2.2. ALK1, endoglin (with or without hereditary hemorrhagic telangiectasia) 1.2.3. Unknown 1.3. Drug- and toxin-induced 1.4. Associated with 1.4.1. Connective tissue diseases 1.4.2. HIV infection 1.4.3. Portal hypertension 1.4.4. Congenital heart diseases 1.4.5. Schistosomiasis 1.4.6. Chronic hemolytic anemia

© 2013 Sharieff MBBS, FCPS, FRCPC; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 Sharieff MBBS, FCPS, FRCPC; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### 2 Pulmonary Hypertension


were identified, including systemic hypertension, obstructive lung disease, sleep apnea, and prior venous thrombo-embolism, which were not believed to represent the principal cause for

Pulmonary Arterial Hypertension: An Overview

http://dx.doi.org/10.5772/56055

3

The median interval from symptom onset to diagnosis remains unacceptably high at 1.1 years in current registry data, [6] unchanged from the experience from the 1980's.[9] Overall survival has improved somewhat, with 3-year survival of 48% in the NIH registry [10], compared to

Pulmonary arterial hypertension (PAH) is comprised of idiopathic, heritable and associated forms. IPAH was previously referred to as primary pulmonary hypertension. During the 4th World Symposium on pulmonary hypertension in 2008 at Dana Point, California, USA, the group updated the Evian –Venice classification of 2003 of pulmonary hypertension based upon

PAH is a proliferative vasculopathy which is histologically characterized by endothelial and smooth muscle cell proliferation, medial hypertrophy, fibrosis and in-situ thrombi of the small

**Genetic mutations** — Predisposition to pulmonary vascular disease may be related to genetic mutations in the bone morphogenetic protein receptor type II (BMPR2), activin-like kinase type 1, and/or 5-hydroxytryptamine (serotonin) transporter (5HTT) genes. Abnormal BMPR2 may play an important role in the pathogenesis of IPAH, with up to 25 percent of patients with

The pathophysiology of IPAH is not fully elucidated An elevated pulmonary vascular resistance seems to result from an imbalance between locally produced vasodilators and

Three major pathobiologic pathways (nitric oxide, endothelin, and prostacyclin) play impor‐

The endothelium-derived relaxing factor nitric oxide (NO), a potent pulmonary vasodilator, is produced in high levels in the upper and lower airways by nitric oxide synthase II (NOSII)

IPAH having abnormal BMPR2 structure or function. [15], [16], [17]

vasoconstrictors, in addition to vascular wall remodeling.

tant roles in the development and progression of PAH.

the patients' pulmonary hypertension. [6]

**3. Etiology**

mechanism. 2

**4. Pathophysiology**

**5.1. Nitric Oxide (N.O)**

(Table 1)

pulmonary arteries and arterioles.[13], [14]

**5. Pathobiologic basis of therapy**

67% in both US [11] and French [12] contemporary registries.


ALK1 = activin receptor-like kinase type 1; BMPR2 = bone morphogenetic protein receptor type 2; HIV = human immunodeficiency virus.

**Adapted from** Simonneau et al. Updated clinical Classification of pulmonary hypertension. J Am Coll Cardiol 2009; Vol. 54 (1): S43–54

Adapted with permission from ELSEVIER.(ref 11)

**Table 1.** Updated Clinical Classification of Pulmonary Hypertension (Dana Point, 2008)
