Pulmonary and Extrapulmonary Contributors to Hypoxemia in Liver Cirrhosis

Mélot, Christian; Naeije, Robert; Dechamps, Philippe; Hallemans, Roger; Lejeune, Philippe

doi:10.1164/ajrccm/139.3.632

Cited by 65 publications

(26 citation statements)

References 17 publications

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“…A decrease in hypoxic pulmonary vasoconstriction was found by NAEIJE et al [9,10] and MELOT et al [11] in approximately 30% of patients with advanced cirrhosis. In a study by RODRIGUEZ-ROISIN et al [7], the group of cirrhotic patients with more severe liver failure had lower systemic and pulmonary vascular resistances, as well as less pulmonary vasoconstriction in response to hypoxia.…”

Section: Haemodynamics In Cirrhosis With Portal Hypertensionmentioning

confidence: 74%

Pulmonary vascular disorders in portal hypertension

Hervé

Lebrec²,

Brénot³

et al. 1998

Eur Respir J

327

239

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aaThis review focuses on the pulmonary vascular complications of chronic liver failure and portal hypertension. The wide spectrum of pulmonary vascular disorders in liver disease and portal hypertension ranges from the hepatopulmonary syndrome (HPS), which is characterized by intrapulmonary vascular dilatations, to pulmonary hypertension (portopulmonary hypertension), in which pulmonary vascular resistance (PVR) is elevated. The exact pathophysiological mechanisms of these pulmonary vascular disorders are unknown. However, since HPS and portopulmonary hypertension have been reported in patients with nonhepatic portal hypertension, the factor that determines their development must be portal hypertension.A brief review of the haemodynamic changes observed in cirrhosis with portal hypertension is summarized, and the clinical and experimental evidence suggesting that the liver exerts a critical influence on the regulation of pulmonary vascular tone and angiogenesis is described. Portopulmonary hypertension is then discussed, focusing in turn on its clinical presentations, management and potential mechanisms, and referring to our findings in 39 patients with portopulmonary hypertension and 140 patients with primary pulmonary hypertension (PPH) admitted between 1986 and 1996 at Antoine Béclère Hospital. Finally, HPS will be examined, with a discussion of the mechanisms of hypoxaemia and intrapulmonary vascular dilatation, as well as its clinical presentation, diagnosis and treatment, with special attention to liver transplantation. Haemodynamics in cirrhosis with portal hypertensionAn understanding of pulmonary haemodynamics in liver disease with portal hypertension is important to a study of the pulmonary vascular disorders seen in this setting. A hyperdynamic circulatory state with high cardiac output, low systemic vascular resistance and low PVR is present in 30-50% of patients with cirrhosis and also in animal models of portal hypertension [1][2][3][4]. Compared with healthy subjects ( fig. 1) The wide spectrum of pulmonary vascular disorders in liver disease and portal hypertension ranges from the hepatopulmonary syndrome characterized by intrapulmonary vascular dilatations, to pulmonary hypertension (portopulmonary hypertension), in which pulmonary vascular resistance is elevated. Since hepatopulmonary syndrome and portopulmonary hypertension have been reported in patients with nonhepatic portal hypertension, the common factor that determines their development must be portal hypertension. The clinical presentations are very different, with gas exchange impairment in the hepatopulmonary syndrome and haemodynamic failure in portopulmonary hypertension. The severity of hepatopulmonary syndrome seems to parallel the severity of liver failure, whereas no simple relationship has been identified between hepatic impairment and the severity of portopulmonary hypertension. Resolution of hepatopulmonary syndrome is common after liver transplantation, which has an uncertain effect in portopulmonary hypertension. The pathoph...

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Section: Haemodynamics In Cirrhosis With Portal Hypertensionmentioning

confidence: 74%

Pulmonary vascular disorders in portal hypertension

Hervé

Lebrec²,

Brénot³

et al. 1998

Eur Respir J

327

239

View full text Add to dashboard Cite

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“…Absent or reduced pulmonary vascular tone with impaired hypoxic vasoconstriction may also occur [33,34]. There are three well-known intrapulmonary determinants of arterial deoxygenation, namely alveolar ventilation-perfusion (V9A/ Q9) imbalance, increased intrapulmonary shunt (i.e.…”

Section: Pathophysiologymentioning

confidence: 99%

“…Systemic and pulmonary vasodilatation in cirrhosis and portal hypertension appears to be the consequence of a widespread decrease in vascular tone [92,93] that results in impaired responsiveness to vasoconstrictors [94,95]. Hypoxic pulmonary vasoconstriction is absent or mitigated iny30% of patients with advanced cirrhosis, with or without associated HPS, and appears to become less evident as liver disease worsens [33,34,[96][97][98]. Whether or not a progressive loss of pulmonary vascular tone as liver disease deteriorates contributes to IPVD and the development of HPS remains controversial [22,98,99].…”

Section: Clinical Diagnosismentioning

confidence: 99%

Pulmonary-Hepatic vascular Disorders (PHD)

Rodríguez-Roisín

Krowka

Hervé

et al. 2004

European Respiratory Journal

699

600

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“…This allows mixed venous blood to speed through, or even bypass, gas exchange units. It is believed that hypoxaemia occurs as a result of one (or the combination of several) of these following mechanisms: 1) ventilation-perfusion mismatching (reflecting excess perfusion for a given ventilation); 2) true intrapulmonary anatomical shunts; and 3) diffusion-perfusion impairment (due to increased oxygen diffusion distance from alveoli to haemoglobin across the dilated vessels) [5][6][7][8][9]. Vascular dilatation can be observed using contrast-enhanced echocardiography or fractional brain uptake after lung perfusion of technetium-99m macroaggregated albumin lung scanning [10].…”

mentioning

confidence: 99%

The hepatopulmonary syndrome: NO way out?: Fig. 1.—

Dinh-Xuan¹,

Naeije²

2004

Eur Respir J

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"How diseases of the liver affect lung function?" is one of those puzzling questions that can turn obsessive for those who want to understand how two seemingly distinctive organs can interact and eventually lead to severe disorders [1,2]. The most common respiratory consequence of liver disease is hypoxaemia, which is often mild to moderate [3]. Seldom severe hypoxaemia occurs when the arterial pressure of oxygen (Pa,O 2 ) falls below 8 kPa (60 mmHg), heralding the occurrence of a condition known as the "hepatopulmonary syndrome" (HPS). HPS is characterised by a triad of conditions, namely: 1) advanced liver disease (with or without liver cirrhosis); 2) widespread intrapulmonary vasodilatation; and 3) alveolar-arterial oxygen gradient (PA-a,O 2 ) w2.6 kPa (20 mmHg) whilst breathing room air [2,3]. Clinical symptoms typically include shortness of breath, which may either worsen on standing (platypnoea) and/or be accompanied by a 10% fall in Pa,O 2 (orthodeoxia). As with other lung disorders, hypoxaemia results from impaired gas exchange, which, in HPS, is particularly perturbed by excessive and widespread dilatation of intrapulmonary vessels. After decades of careful investigations, the underlying mechanisms linking altered gas exchange and pulmonary vasodilatation are now well delineated [2][3][4]. Reduced tone causing vascular relaxation occurs at both ends of the capillary bed, i.e. affecting pre-capillary and post-capillary vessels. This allows mixed venous blood to speed through, or even bypass, gas exchange units. It is believed that hypoxaemia occurs as a result of one (or the combination of several) of these following mechanisms: 1) ventilation-perfusion mismatching (reflecting excess perfusion for a given ventilation); 2) true intrapulmonary anatomical shunts; and 3) diffusion-perfusion impairment (due to increased oxygen diffusion distance from alveoli to haemoglobin across the dilated vessels) [5][6][7][8][9]. Vascular dilatation can be observed using contrast-enhanced echocardiography or fractional brain uptake after lung perfusion of technetium-99m macroaggregated albumin lung scanning [10].As pulmonary vasodilatation is the main culprit, hunting endogenous vasodilators that reduce pulmonary vascular tone logically became a sound strategy for those whose quest was to unravel the missing "molecular" link between the diseased liver and the affected lung. Nitric oxide (NO), one of the most potent and prominent endogenous pulmonary vasodilators [11], soon appeared as a very likely candidate, not only for the hyperdynamic circulatory syndrome in cirrhosis [12], but also for HPS [13]. This hypothesis has been further consolidated in the light of clinical and experimental results from several recent studies [2]. First, pulmonary endogenous production of NO, which can be assessed by measuring exhaled NO [14], is increased in patients with HPS [15][16][17][18] and returns to normal values 3-12 months after orthotopic liver transplantation [17,18]. Interestingly, normalisation of exhaled NO concentrations was ...

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Pulmonary and Extrapulmonary Contributors to Hypoxemia in Liver Cirrhosis

Cited by 65 publications

References 17 publications

Pulmonary vascular disorders in portal hypertension

Pulmonary vascular disorders in portal hypertension

Pulmonary-Hepatic vascular Disorders (PHD)

The hepatopulmonary syndrome: NO way out?: Fig. 1.—

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