Pathology
It is possible that the lung has only a small number of responses to injury that feed into common final pathway mechanisms. Many insults can lead to the development of the acute respiratory distress syndrome (ARDS) but the pathology is similar (and not PPA) regardless of initiating injury. Similarly obliterative bronchiolitis seen as a consequence of rheumatoid arthritis or infection with respiratory syncytial virus in children is similar to that believed to be a form of chronic allograft rejection in lung transplant recipients.
In PPA there is an initial period of vasoconstriction followed by migration of smooth muscle cells from the inner half of the media of muscular pulmonary arterioles into the lumen. Here they become myofibroblasts that are capable of laying down both smooth muscle and fibrous tissue. The myofibroblasts proliferate in a concentric fashion and, upon sectioning, the vessels look like a cut onion, hence the term ‘onion skin proliferation’. This leads to a progressive reduction in the radial size of the vessel, the resistance to flow increases in accordance with Poiseuilles law (where among other things flow is proportional to the fourth power of the radius, r4) vessel rupture at proximal points of weakness (e.g. at branches) occurs. Haemorrhage ensues and primitive networks of blood vessels (a ‘plexus’, hence plexiform lesion) grow into the area. The combination of onion skin (or concentric laminar intimal) proliferation and plexiform lesions is known as PPA.
It is possible that patients may have a genetic predisposition or risk factor, such as a connective tissue disease or HIV, and that this causes a vascular injury or modification in antigenic determinants. Endothelial cell dysfunction follows with derangement of the normal release of endothelial derived factors, which facilitates inflammation and promotes loss of local vaso reactivity and thrombus formation. Decreased progression and vascular remodelling can then occur. The pulmonary endocrine cells immuno reactive for calcitonin and gastrin releasing peptide may adversely influence smooth muscle cells.