**Author details**

Dimitar Sajkov\* , Bliegh Mupunga, Jeffrey J. Bowden and Nikolai Petrovsky

\*Address all correspondence to: Dimitar.Sajkov@health.sa.gov.au

Australian Respiratory and Sleep Medicine Institute (ARASMI), Flinders Medical Centre and Flinders University, Flinders Drive, Bedford Park, Adelaide, Australia

### **References**


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**13. Conclusions**

34 Pulmonary Hypertension

**Acknowledgements**

**Author details**

Dimitar Sajkov\*

**References**

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Pulmonary hypertension in chronic lung disease and/or hypoxia is a relatively common complication caused by complex pathophysiologic processes. Alveolar hypoxia, either sus‐ tained or repetitively intermittent, triggers the development of PH, although other mecha‐ nisms are also important. Development of PH is associated with worsening dyspnoea with the long-term prognosis dependant on the underlying disease process. Treatment of PH is largely defined by the underlying lung pathology. Therefore, etiological diagnosis and assessment of PH byWHOfunctional class is criticalformanagement.Different classes ofdrug therapieshave beendevelopedasaresultofourcurrentunderstandingofthepathophysiologyofPH.Although the treatments have had some impact on the progression of PH, further research is required to

Supported by a research grant from Foundation Daw Park Inc., Australian Respiratory and Sleep Medicine Institute and Flinders Medical Centre Professional Development Fund.

, Bliegh Mupunga, Jeffrey J. Bowden and Nikolai Petrovsky

Australian Respiratory and Sleep Medicine Institute (ARASMI), Flinders Medical Centre

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\*Address all correspondence to: Dimitar.Sajkov@health.sa.gov.au

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**Chapter 3**

**Pathogenesis of Pulmonary Hypertension**

Pulmonary arterial hypertension (PAH), although rare, is a progressive disease with a high morbidity and mortality rate. In 1981, Ernst von Romberg, a German physician described pulmonary vascular lesions as "pulmonary vascular sclerosis", the first description of histological changes in PAH [Fishman 2004]. The average survival time for untreated patient is around 2.8 yrs [D'Alonzo 1991]. Despite remarkable progress made since then, the patho‐ genesis of PAH, however, is not yet well understood; because a large number of cardiopul‐ monary and systemic diseases can lead to PAH, and in addition, multiple signaling pathways have been implicated. Current advances in therapy, have improved the quality of life and delayed the progression of the disease, but have not provided a cure. Lack of cure in PAH is further underscored by a recent study showing persistent large plexiform lesions and inflam‐ matory infiltrates in patients despite having been on a long term prostacyclin therapy [Pogoriler 2012]. One of the main reasons for the failure of therapy is that the diagnosis is often made late because of vague symptoms; and by the time the diagnosis is made extensive pathologic changes have already taken place in pulmonary vasculature. From experimental studies, it is clear that pathological changes in the vasculature occur before the onset of PAH [Huang 2010]. Another problem is that a large number of signaling molecules implicated in PAH may not be relevant in all patients; and the activation of some of these molecules may

The current clinical classification updated in 2008 maintains five major groups [Simonneau 2009]. *Group 1*: Pulmonary arterial hypertension (PAH): Included in this group are idiopathic (IPAH) and heritable PAH (HPAH), PAH associated with congenital heart defects (CHD), connective tissue diseases, portal hypertension, infection, chronic hemolytic anemia, drug toxicity and persistent pulmonary hypertension of the newborn (PPHN). Pulmonary venoocclusive disease and pulmonary capillary hemangiomatosis are included in this group as a subcategory. Approximately 70% of HPAH and 26% IPAH exhibit heterozygous germline

> © 2013 Mathew; 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,

© 2013 Mathew; 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.

distribution, and reproduction in any medium, provided the original work is properly cited.

Additional information is available at the end of the chapter

Rajamma Mathew

**1. Introduction**

http://dx.doi.org/10.5772/56179

depend on the stage of the disease.
