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Internal Medicine

Hepatopulmonary syndrome

Syndrome of shortness of breath and hypoxemia caused by vasodilation in the lungs of patients with liver disease.

  • Triad:
    • Chronic liver disease or portal hypertension
    • Alteration of arterial oxygenation
      • Widened age-corrected alveolar arterial oxygen gradient ± arterial hypoxemia
    • Intrapulmonary vascular dilatations 

Pathophysiology

WJG-24-1285-g001
Schematic overview of the main pathways of the pathogenesis of hepatopulmonary syndrome. Liver cirrhosis and portal hypertension lead to endothelin-1 (ET-1) secretion. The binding of ET-1 to its receptor, activates pulmonary endothelial nitric oxide synthase (eNOS), leading to excessive production of nitric oxide (NO), a natural vasodilator. Bacterial translocation and the subsequent pulmonary macrophage accumulation result in the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), which contribute in NO-mediated vasodilatation through inducible nitric oxide synthase (iNOS)-enhanced expression. Carbon monoxide constitutes another pulmonary vasodilator produced by macrophage-induced heme oxygenase-1 (HO-1) increased expression. Pulmonary macrophage accumulation and TNF-α-increased circulation trigger vascular endothelial growth factor (VEGF) pathways, concluding in VEGF-mediated pulmonary angiogenesis. Mixed venous blood passes rapidly, due to hyperdynamic circulation observed in liver cirrhosis, through the dilated capillaries without completing gas exchange. An oxygen (O2) diffusion limitation occurs, as O2 molecules need to cross a longer distance to reach the center of dilated vasculature. As a result, there is an impairment of arterial oxygenation due to ventilation perfusion mismatch, also boosted by direct right-to-left shunt through arteriovenous communications. | Soulaidopoulos, S., Cholongitas, E., Giannakoulas, G., Vlachou, M., & Goulis, I. (2018). Review article: Update on current and emergent data on hepatopulmonary syndrome. World Journal of Gastroenterology, 24(12), 1285–1298. https://doi.org/10.3748/wjg.v24.i12.1285

Clinical features

Symptoms

  • Dyspnea
  • Platypnea
    • Dyspnea induced in upright position and relieved by recumbency
  • Orthodeoxia
    • Arterial deoxygenation accentuated in upright position and relieved by recumbency

Signs

  • Clubbing
  • Cyanosis

Diagnosis

  • Contrast echocardiography
    • M/sensitive test to demonstrate intrapulmonary shunting
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Four-chamber view of contrast echocardiography using agitated saline, showing microbubbles opacifying the left heart five beats after they were seen in the right heart. LA = left atrium, LV = left ventricle. | Lee, C.-H., & Cheng, S.-T. (2011). Shortness of breath while sitting up: hepatopulmonary syndrome. Canadian Medical Association Journal, 183(1), 80 LP-80. Retrieved from http://www.cmaj.ca/content/183/1/80.abstract

Management

  • Liver transplantation
    • Only established effective therapy

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