Portopulmonary hypertension pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; {{AE}]
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Overview
Pathophysiology
PPH pathology arises both from the humoral consequences of cirrhosis and the mechanical obstruction of the portal vein.[1] A central paradigm holds responsible an excess local pulmonary production of vasoconstrictors that occurs while vasodilatation predominates systemically[2]. Key here are imbalances between vasodilatory and vasoconstricting molecules; endogenous prostacyclin and thromboxane (from Kuppfer Cells) [3][4] or nitrous oxide (NO) and endothelin-1 (ET-1).[5] ET-1 is the most potent vasoconstrictor under investigation[6] and it has been found to be increased in both cirrhosis[7] and pulmonary hypertension. [8] 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. [9]
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 a smooth muscle hyperplasia and hypertrophy. [10]. 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.[11] The muscular pulmonary arteries fibrose 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.[12] This thickening and remodeling forms a positive feedback loop that serves to increase PAP and induce right heart hypertrophy and dysfunction.
References
- ↑ Budhiraja et al. Portopulmonary Hypertension: A Tale of Two Circulations. Chest. 2003;123:562-576.
- ↑ Moller et al. Cardiopulmonary complications in chronic liver disease. World J Gastroenterol 2006;12;526-538
- ↑ Christman et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med 1992;327:1774-78
- ↑ Maruyama et al. Thromboxane-dependent portopulmonary hypertension. Am J Med. 2005;118:93-94
- ↑ Bejaminov et al. Portopulmonary hypertension in decompensated cirrhosis with refractory ascites. Gut 2003; 52:1355-1362
- ↑ Giaid A. Nitrous oxide and endothelin-1 in pulmonary hypertension. Chest. 1998;114;208-12S
- ↑ Gerbes. ET1 and 3 plasma conc in patients with cirrhosis: role of splanchnic and renal passage and liver function. Hepatology 1995;21:735-9
- ↑ Stewart. Increase plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann Intern Med 1991;114:464-9
- ↑ Luo et al. Increased pulmonary vascular ETb receptor expression and responsiveness to ET-1 in cirrhotive and portal hypertensive rats. J Hepatol 2003;38:556-63
- ↑ Egermayer et al. Role of serotonin in the pathogenesis of acute and chronic pulmonary hypertension. Thorax 1999;54:161-168
- ↑ Schraufnagel DE, Kay JM. Structural and pathologic changes in lung vasculature in chronic liver disease. Clin Chest Med 1996; 17: 1
- ↑ Matsubara O, Nakamura T, Uehara T, Kasuga T. Histometrical investigations of the pulmonary artery in severe hepatic disease. J Pathol 1984; 143: 31.