PPH pathology arises both from the humoral consequences of cirrhosis and the mechanical obstruction of the portal vein. A central paradigm holds responsible an excess local pulmonary production of vasoconstrictors that occurs while vasodilatation predominates systemically. Key here are imbalances between vasodilatory and vasoconstricting molecules; endogenous prostacyclin and thromboxane (from Kupffer Cells). or nitrous oxide (NO) and endothelin-1 (ET-1). ET-1 is the most potent vasoconstrictor under investigation and it has been found to be increased in both cirrhosis and pulmonary hypertension. Endothelin-1 has two receptors in the pulmonary arterial tree, ET-A which mediates vasoconstriction and ET-B which mediates vasodilation. Rat models have shown decreased ET-B receptor expression in pulmonary arteries of cirrhotic and portal hypertensive animals, leading to a predominant vasoconstricting response to endothelin-1. In portal hypertension, blood will shunt from portal to systemic circulation, bypassing the liver. This leaves unmetabolized potentially toxic or vasoconstricting substances to reach and attack the pulmonary circulation. Serotonin, normally metabolized by the liver, is returned to the lung instead where it mediates smooth muscle hyperplasia and hypertrophy. Moreover, a key pathogenic factor in the decline in status of PPH patients related to this shunting is the cirrhotic cardiomyopathy with myocardial thickening and diastolic dysfunction. Finally, the pulmonary pathology of PPH is very similar to that of primary pulmonary hypertension. The muscular pulmonary arteries become fibrotic and hypertrophy while the smaller arteries lose smooth muscle cells and their elastic intima. One study found at autopsy significant thickening of pulmonary arteries in cirrhotic patients. This thickening and remodeling forms a positive feedback loop that serves to increase PAP and induce right heart hypertrophy and dysfunction.
Portopulmonary hypertension
Chronic thromboembolic pulmonary hypertension
Pulmonary hypertension
Asthma
Emphysema
Cardiac asthma
Portal hypertension
Reactive airway disease