Pulmonary Arterial Hypertension and Interstitial Lung Diseases (eBook)

Pulmonary Arterial Hypertension and Interstitial Lung Diseases: Clinical Guide Editors: Roberto G. Carbone MD Robert P. Baughman MD Giovanni Bottino MD General Principals Chapter 1 Interstitial lung disease: Introduction Roberto G Carbone MD, FCCP, Fabio Montanaro MB, Giovanni Bottino MD Chapter 2 Pulmonary hypertension in Interstitial Lung Disease Roberto G Carbone MD, FCCP, Assaf Monselise MD, Giovanni Bottino MD Chapter 3 Idiopathic Interstitial Lung Disease and Associated Pulmonary Hypertension: Genetics, Pathobiology, Diagnosis, and Management Keith C. Meyer, MD, MS, FACP, FCCP, Ganesh Raghu, M.D.,FCCP, FACP Chapter 4 Lung Pathology Andre L. Moreira, M.D., PhD, William D. Travis , M.D. Chapter 5 Pulmonary Hypertension: Evaluation and Treatment Roberto G Carbone MD, FCCP, Giovanni Bottino MD Specific Lung Disorders Chapters 6 Bronchiolar disorders Joseph P. Lynch III, M.D., Rajeev Saggar, M.D., Robert D. Suh, M.D., Michael C. Fishbein, M.D. Chapter 7 Hypersensitivity Pneumonitis Moisés Selman MD, Guillermo Carrillo, MD, Carmen Navarro, MD, Miguel Gaxiola MD Chapter 8 Connective Tissue Disease and Vasculitis Associated Interstitial Lung Disease Alan N. Brown, MD, Charlie Strange, MD Chapters 9 Pulmonary hypertension in idiopathic pulmonary fibrosis Fernando J. Martinez, M.D., M.S. Chapter 10 Occupational Interstitial Lung Disease Update Lee S. Newman, MD, MA Chapter 11 Sarcoidosis Robert P. Baughman MD, Elyse E Lower MD, Peter J Engel MD

Severe or Very Severe PH (S. 20-21)

In patients with severe or very severe PH, a mean PAP of 30–45 mmHg at rest correlates with decompesation and lung diseases. A mean PAP of 40–70 mmHg at rest correlates with decompensation and chronic pulmonary embolism. Finally, a mean PAP of between 65 and 120 mmHg at rest correlates with Eisenmenger’s Syndrome. When patients are at rest, there is reduced cardiac output.

Right ventricular adaptation is one of the most important prognostic factors in pulmonary hypertension. Initially, right ventricular hypertrophy compensates for the increased after load. The chamber decompensates when the pressure increases more rapidly than the adaptation mechanism. A moderate increase of pulmonary resistances and a slow progression of disease are good conditions for the development of right ventricular adaptation. On the whole, the factors that influence right ventricular remodeling are largely unknown. There is evidence that the local ACE system of the heart might be activated during PH [38].

Pulmonary arteries develop structural changes in parallel with the chronic vasoconstriction. In situ thrombosis develops, accelerating the remodeling of small cells. As a consequence, there is a reduction of the vascular cross-sectional area and a loss of compliance. Structural changes in pulmonary arteries differ between small and large vessels: the latter assume aneurismal forms, whereas the lumen of the former is progressively diminished as the result of the remodeling process.

The term remodelling is used to describe changes in small diameter pulmonary vessels [39,40]. Normal-appearing pulmonary arterial vessels have a continuous media down to a diameter of approximately 80 µm. Distally to this point, vessels are partially muscular and contain so-called intermediate cells, which range in their properties somewhere between pericytes and smooth muscle cells. In the most peripheral vascular areas, there are only few pericytes, and the remaining cell population consists of endothelial cells. The process of vessel remodeling results in (1) intimal fibrosis, (2) hypertrophy of the media, and (3) the formation of myocytes ex novo.

The smooth muscles of the media grow distally, initially in a longitudinal direction, providing a complete muscular layer to smaller pulmonary arterial vessels having a diameter down to 15 µm. The smooth muscle cells produce extracellular matrix proteins such as glycoprotein and elastin. At same time, there are changes in other vascular layers, such as the adventitia and intima. The adventitia shows a proliferation of fibroblasts with migration of these cells in the vessel wall.

The intimal cells responsible for fibrosis are poorly characterised and are described as my fibroblasts secreting extracellular matrix proteins such as collagen type I and III. As for the intima, changes involve the glycocalyx layer of the endothelial cells, with a reduction of heparan sulphate, which can trigger smooth muscle proliferation. It seems that endothelial cell mediators shift from an anticoagulatory to protrombotic profile. The internal elastic lamina is fragmented and allows cells to migrate into the intimal layer.