Contusions

Memar

Contusion

Memar

Contuse

Memar

The pathophysiology of PH can be simplified to include vasoconstriction, thrombosis and remodelling of the pulmonary vasculature. These often happen concomitantly, following an initial trigger, and may be determined by genetic predisposition. l Vasoconstriction: decreased activity of potassium channels causes membrane depolarisation, leading to calcium influx. Elevated cytoplasmic calcium concentrations cause pulmonary vasoconstriction and stimulate vascular smooth muscle proliferation. Dysfunctional potassium channels have also been linked to inhibition of apoptosis and contribute further to the medial hypertrophy [6, 7]. The production of vasodilators nitric oxide and prostacyclin is impaired and over-expression of vasoconstrictors such as endothelin is observed. l Thrombosis: changes in local blood flow, activation of inflammatory cascades, endothelial dysfunction and co-existing coagulation disorders favour the development of local intravascular thrombosis. l Vascular remodelling: morphological changes in the pulmonary vasculature that accompany PH are referred to as pulmonary vascular remodelling. Chronic hypoxia is well known to cause pulmonary vascular remodelling and PH, and it is the major mechanism implicated for the development of PH in patients with lung disease. Hypoxia-driven gene regulation in pulmonary artery fibroblasts results in mitogenic stimulation of adjacent smooth muscle cells causing pulmonary artery smooth muscle cell hyperplasia [8]. Remodelling accounts for sustained PH even after elimination of the primary causative factor, for example in drug-induced or chronic thromboembolic PH. l Genetic factors: a region on chromosome 2 encoding bone morphogenetic receptor type 2 (BMPR2) underlies a small proportion of familial and idiopathic PH [9]. BMPR2 signalling appears essential in regulating growth functions in pulmonary vascular cells, inhibiting the proliferation and possibly enhancing apoptosis in smooth muscular cells as well as endothelial cells [10]. Pathophysiology of right ventricular failure associated with pulmonary hypertension Pulmonary arteries have very little vascular tone and the pulmonary circulation has a great capacity to recruit vessels when required. This capacity enables it to handle large changes in blood flow with only small changes in pressure: a low pressure, low resistance circuit. The main function of the RV is to propel deoxygenated blood through this low impedance circulation. The resistance of the circulation is one-tenth that of the systemic circulation and requires a perfusion gradient of only 5 mmHg. Hence, the RV is thinner-walled than the LV and the complex architecture makes assessment of function difficult. In the critically ill, assessment of ventricular function is usually performed using echocardiography. Under normal circumstances the interventricular septum is functionally part of the LV; consequently the RV free wall contributes most to ejection through its long axis shortening. The thin wall and crescent shape make the RV highly compliant and therefore able to accommodate a large increase in preload with minimal change in end diastolic pressure. The primary compensatory mechanism of the RV is dilatation. RV volume overload is therefore well tolerated, with the RV becoming ellipsoid with increasing volume. By contrast the RV is less tolerant to increases in afterload. An acute pressure increase above 50 mmHg is beyond the capacity of the RV and will Pulmonary Hypertension and Right Ventricular Failure 371 result in rapid RV dilatation and failure (Figure 21.1) [11]. In the face of increased pressure, the interventricular septum will be displaced to the left. In addition, the RV prolongs its isovolumic contraction period, which may exceed that of the LV. This results in late systolic displacement of the interventricular septum from right to left, which is readily identifiable on M-mode echocardiography. Prolongation of systole (if there is no interventricular communication) will also result in tricuspid regurgitation of long duration. Thus, these patients are poorly tolerant of tachycardia. RV dysfunction can also occur as a consequence of direct myocardial injury, most commonly during cardiac surgery, but is also seen as a result of ischaemia, stunning or contusion.