肝肺综合征研究进展

肝肺综合征(hepato-pulmonary syndrome,HPS)是在慢性肝病和(或)门脉高压的基础上出现肺内血管异常扩张、气体交换障碍、动脉血氧合作用异常,导致低氧血症及一系列的病理生理变化和临床表现,是终末期肝脏病的严重肺部并发症。动物实验表明肺微血管扩张、血管新生和血管内单核巨噬细胞聚集是导致气体交换异常的主要原因,但具体机制仍不明确。目前HPS尚缺乏有效的治疗药物,肝移植仍是最有效的治疗方法。本研究将重点讨论HPS的发病机制和临床诊治相关的新进展。     

Hepatopulmonary syndrome-attributed extreme hypoxemia and polycythemia revealing liver cirrhosis

We report an unusual case of severe hepatopulmonary syndrome with previously unrecognized cirrhosis, presenting with acute on chronic dyspnoea, extreme hypoxemia, secondary polycythemia as well as direct identification of arteriovenous communications on computed tomography angiography. Hepatopulmonary syndrome, defined as the combination of hepatopathy, arterial deoxygenation and pulmonary vascular dilatation, is increasingly recognized as a life-threatening complication in advanced liver disease and transplant candidacy. It is usually diagnosed in chronic liver disease patients following pre-transplant evaluation or mild dyspnea investigation. Diagnosis relies on the indirect evidence of pulmonary arteriovenous communications suggested by echocardiography with a bubble study. Clinicians need to be aware of this rare but potential acute presentation at the emergency room.     

对比增强超声心动图对拟肝移植患者肺内分流的评估价值

背景：晚期肝病患者的肺内血管异常可以导致肺内右向左分流及严重低氧血症，目前国内对筛查肺内血管扩张尚缺乏一种简便、敏感、有效的方法。 目的：评估对比增强超声心动图对晚期肝病肺内分流的临床诊断价值。 设计、时间及地点：前瞻性病例对比观察，于2004-02／2006-02在解放军第四五八医院肝病中心完成。 对象：解放军第四五八医院肝病中心收治的男性拟行肝移植的晚期肝病患者24例。 方法：在无任何血管扩张药治疗情况下例行常规检查。采用对比增强超声心动图筛查晚期肝病患者肺内右向左分流的发生率，并根据左心室微泡的显示程度半定量分析记录为1^＋～3^＋。将患者分为经超声心动图证实有肺内分流组和无肺内分流组。 主要观察指标：拟行肝移植的晚期肝病患者肺内右向左分流的发生率及临床特点。结果：①24例患者中10例（41．7％）经对比增强超声心动图证实肺内右向左分流，左心室显影异常程度1^＋～2^＋，其中6例1^＋，4例2^＋，出现在右心室显影后6～10余个心动周期。②两组患者的年龄、性别、动脉血气分析指标、肝功能指标差异无显著性意义（P〉0．05）。③经超声心动图证实肺内分流组患者的上消化道出血发生率、门脉高压指征脾脏厚度及右心功能参数肺动脉收缩压、Tei指数均高于无肺内分流组（P〈0．05～0．01）。 结论：晚期肝病合并肺内分流而无低氧血症时肺血管扩张比较常见，对比增强超声心动图为诊断肺内血管扩张提供了一种敏感、非创伤的早期检查手段。门脉高压症是发生肺内血管扩张的主要因素，右心室Tei指数可作为评估肺内血管扩张患者右心功能的重要参数。     

Growth hormone cocktail improves hepatopulmonary syndrome secondary to hypopituitarism: A case report

BACKGROUNDMetabolic associated fatty liver disease frequently occurs in patients with hypopituitarism and growth hormone (GH) deficiency. Some patients may develop to hepatopulmonary syndrome (HPS). HPS has a poor prognosis and liver transplantation is regarded as the only approach to cure it.CASE SUMMARYA 29-year-old man presented with progressive dyspnea for 1 mo. At the age of 10 years, he was diagnosed with panhypopituitarism associated with pituitary stalk interruption syndrome. Levothyroxine and hydrocortisone were given since then. To achieve ideal height, he received GH treatment for 5 years. The patient had an oxygen saturation of 78% and a partial pressure of arterial oxygen of 37 mmHg with an alveolar–arterial oxygen gradient of 70.2 mmHg. Abdominal ultrasonography showed liver cirrhosis and an enlarged spleen. Perfusion lung scan demonstrated intrapulmonary arteriovenous right-to-left shunt. HPS (very severe) was our primary consideration. His hormonal evaluation revealed GH deficiency and hypogonadotropic hypogonadism when thyroid hormone, cortisol, and desmopressin were administrated. After adding with long-acting recombinant human GH and testosterone for 14 mo, his liver function and hypoxemia were improved and his progressive liver fibrosis was stabilized. He was off the waiting list of liver transplantation.CONCLUSIONClinicians should screen HPS patients'' anterior pituitary function as early as possible and treat them primarily with GH cocktail accordingly.     

Frequency, clinical characteristics, and respiratory parameters of hepatopulmonary syndrome

OBJECTIVES: To determine the frequency and the clinical characteristics of hepatopulmonary syndrome (HPS) in cirrhotic candidates for orthotopic liver transplantation and to identify the major respiratory parameters predictive of the presence of changes in arterial oxygenation. PATIENTS AND METHODS: Patients underwent transthoracic contrast-enhanced echocardiography, pulmonary scintigraphy, pulmonary function test with diffusing capacity of lung for carbon monoxide (DLCO), and measurement of arterial blood gases. RESULTS: Fifty-six patients were studied. Twenty-five patients (45%) presented with intrapulmonary vascular dilatations, but only 9 (16%) fulfilled the criteria for HPS. The clinical or demographic characteristics considered did not differ in the patients with and without HPS. The DLCO value was significantly lower in patients with HPS (P=.01). However, 32 (80%) of 40 patients with low DLCO values did not fulfill the criteria for HPS. An alveolar arterial oxygen gradient (AaPO2) of more than 20 mm Hg showed a higher diagnostic accuracy (91%) in the assessment of HPS than did the DLCO of less than 80% predicted (41%) and the AaPO2 of more than 15 mm Hg (71%). CONCLUSIONS: The AaPO2 proved to be a more reliable index than PaO2 and DLCO for the determination of changes in arterial oxygenation in HPS. The DLCO does not seem to be a good marker for HPS screening. Intrapulmonary vascular dilatations were frequent, even in patients who did not fulfill the criteria for HPS.     

Failure of hypoxic pulmonary vasoconstriction in patients with liver cirrhosis

The combination of arterial hypoxemia and low pulmonary vascular resistance in patients with liver cirrhosis is unexplained. Pulmonary microcirculatory dilation, but not gross arterio-venous shunts, has been the usual postmortem finding in patients with liver cirrhosis. When 10 patients with alcoholic liver cirrhosis breathed 10% oxygen in nitrogen, they failed to increase their pulmonary vascular resistance. However, four patients with functional murmurs, three patients with hyperkinetic heart syndrome, six patients with normal pulmonary artery pressures and intracardiac left to right shunts, and five patients with renal failure and anemia all increased their pulmonary vascular resistances when they breathed 10% oxygen in nitrogen. These findings suggested that in liver cirrhosis the normal regulating mechanism (hypoxic vasoconstriction) of the pulmonary circulation may be impaired, resulting in failure of the lung to match perfusion with ventilation.     

Respiratory dysfunction and pulmonary disease in cirrhosis and other hepatic disorders

End-stage liver disease and its complications are a leading cause of death among adults in the United States, and thousands of patients await liver transplantation. The liver plays a central role in health and homeostasis and thus the diseased liver leads to many deleterious effects on multiple organ systems, including the pulmonary system. We review the general effects of cirrhosis on the respiratory system, including mild hypoxemia, atelectasis, and hepatic hydrothorax. Cirrhosis is associated with 2 unique entities that affect the pulmonary vasculature: hepatopulmonary syndrome and portopulmonary hypertension. Hepatopulmonary syndrome, which is found in approximately 20% of patients awaiting liver transplantation, refers to the triad of hepatic dysfunction, hypoxemia, and intrapulmonary vascular dilations, and responds well to liver transplantation. In portopulmonary hypertension, cirrhosis and portal hypertension lead to pulmonary arterial hypertension, and portopulmonary hypertension has been considered a contraindication for transplantation. Currently, patients must have mild to moderate pulmonary hypertension to be considered for transplantation, and may still require long-term therapy with vasodilators to prevent right-ventricular failure and, consequently, failure of the newly transplanted liver allograft.     

The role of cardiac catheterization for diagnosis and treatment of pulmonary hypertension]

The role of the cardiac catheterization for diagnosis and treatment of pulmonary hypertension (PH) is very important. When mean pulmonary artery pressure increased more than 25 mmHg, then PH is defined. But this is measured accurately only by the catheterization. And we can discriminate the etiology of PH clearly by pulmonary capillary wedge pressure (Ppcw) or intra-cardiac shunt (L to R) by blood oxygen saturation step-up, and both parameters are obtained by this method. The etiology of PH is diagnosed as left sided heart failure, if Ppcw is increased more than 13 mmHg. PH is produced by congenital heart disease (ASD, VSD, PDA etc.), when the oxygen saturation step-up is recognized. And PH is induced by any pulmonary disease or pulmonary thrombo-embolism or collagen disease or liver cirrhosis or PPH, if Ppcw is normal and no oxygen step-up is recognized.     

Severe hypoxemia associated with liver disease: Mayo Clinic experience and the experimental use of almitrine bismesylate

Severe hypoxemia associated with chronic liver disease is an uncommon disorder most likely due to an intrapulmonary vascular abnormality that has characteristics of both ventilation-perfusion mismatching and diffusion limitation. Anatomically, the intrapulmonary vascular abnormalities can occasionally be detected by angiography. Physiologically, the gas exchange abnormalities can be substantiated by contrast-enhanced two-dimensional echocardiography. Although orthodeoxia and platypnea have frequently been found in these patients, echocardiographic data suggest that vascular abnormalities can exist in the absence of orthodeoxia. We describe 11 patients who had severe hypoxemia and chronic liver disease and review their pulmonary angiographic, contrast echocardiographic, and arterial blood gas findings. Among five of these patients who were given almitrine bismesylate, an experimental medication thought to alter ventilation-perfusion relationships in patients with chronic obstructive pulmonary disease, one had improved oxygenation. We recommend that patients with hypoxemia associated with chronic liver disease have detailed studies to rule out reversible forms of hypoxemia and that those with severe hypoxemia undergo testing to determine the existence of intrapulmonary vascular abnormalities, especially if liver transplantation is considered.     

Effects of infusion of prostacyclin on anatomical intrapulmonary right to left shunt: a useful model of human hypoxic vasoconstriction?

1. Eleven infants and children (mean age 4.3 years, range 0.2-12 years) with pulmonary vascular disease secondary to congenital cardiac anomalies (n = 6) or bronchopulmonary dysplasia (n = 5), were studied during cardiac catheterization while ventilated on 100% oxygen. 2. All had a raised pulmonary vascular resistance (mean 11.8 units, range 4.1-26.0 units, normal value less than 3 units) and a raised anatomical intrapulmonary right to left shunt (mean 22%, range 8-50%, normal value less than 5%). The elevated shunt was attributed to the effects of 100% oxygen and general anaesthesia causing alveolar collapse, with only partial compensation for impairment of gas exchange by compensatory local hypoxic vasoconstriction. 3. When prostacyclin was infused, pulmonary vascular resistance fell by 3.2 +/- 1.8 units (mmHg litre-1 min m2), and pulmonary blood flow rose by 1.0 +/- 0.7 litre min-1 m-2 (mean +/- 95% confidence intervals). 4. Intrapulmonary right to left shunt fraction increased in eight of 11 patients, with a maximal rise for the group of 5.9 +/- 4.6% (mean +/- 95% confidence intervals). However, even at doses of prostacyclin sufficient to cause systemic vasodilatation and tachycardia, there was no evidence for a selective increase in shunt fraction. 5. We suggest that studying the effects of therapeutic interventions on intrapulmonary shunt fraction may be a useful model in vivo of human hypoxic pulmonary vasoconstriction.     

Pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare and debilitating disease characterized by abnormal proliferation and contraction of pulmonary vascular smooth muscle cells. The resulting increase in pressure and pulmonary vascular resistance results in progressive right heart failure, low cardiac output, and ultimately death if left untreated. PAH is defined by a persistent elevation in pulmonary artery pressure with normal left-sided pressures, differentiating it from left-sided heart disease. Symptoms progress from shortness of breath and decreasing exercise tolerance to right heart failure, with peripheral edema and marked functional limitation. Exercise-induced syncope, worsening symptoms at rest, and intractable right heart failure indicate critical disease. PAH may be idiopathic with no identifiable cause or associated with collagen vascular diseases, drugs, HIV, liver disease, and/or congenital heart disease. Familial or genetically mediated PAH accounts for a small percentage of cases. Advances in the understanding of pathobiological pathways that contribute to vascular proliferation and remodeling have resulted in new therapies that improve quality of life and survival. Emerging therapies focus on the nitric oxide, prostacyclin, and endothelin pathways. Nursing interventions are critical to ensure patients' success with these expensive and complex treatments and their optimal adjustment to living with PAH.     

Multidisciplinary Conferences in Gastroenterology. Cardiovascular effects of severe liver disease.

This is the definitive review of the cardiovascular effects of liver disease. Physiologic and pathologic studies accomplished primarily in the 1950s and 1960s have been applied to a case of a 16-year-old boy with cirrhosis of the liver who presented with weakness, dyspnea, cyanosis, and clubbing. The probable mechanisms for his signs and symptoms are discussed in detail. The cause for the hyperkinetic circulation is unknown. By exclusion, the cyanosis is attributed to intrapulmonary shunting. Portapulmonary shunts are not quantitatively important. The suitability of the terms micronodular and macronodular cirrhosis is highlighted. Indications for various types of surgical portal shunts are discussed. The value of preoperative hemodynamic measurements of the portal circulation to the individual patient is debated. A liver transplant is considered in this case with no promising medical therapy and a very poor prognosis. The renal disease manifested by red cell casts in the urine is thought to be caused by an immunologic reaction in the kidney somehow related to his liver disease. This discussion is led by Dr. Jack Myers, but his opinions are correlated with those of a pathologist, radiologist, surgeon, and gastroenterologist. It is a clinical tour de force, although not all the predictions are confirmed by laboratory studies such as this patient's hepatic wedge pressure, pulmonary artery pressure, and cardiac fluoroscopy.     

Effect of nifedipine on oxygen delivery in canine asymmetric oleic acid lung injury

Increasing the ratio of tissue oxygen delivery (DO2) to oxygen consumption can improve the survival of critically ill patients, including those with acute respiratory failure. However, under conditions of ventilation/perfusion mismatch, the use of inotropic or vasodilator drugs to augment cardiac output could, in turn, worsen venous admixture. In a canine model of asymmetric oleic acid-induced pulmonary edema, we examined this possibility by studying the effect of 20 and 40-micrograms/kg doses of parenteral nifedipine on oxygenation variables, venous admixture, and intrapulmonary blood flow distribution. After oleic acid injury, nifedipine caused significant increases in cardiac index by 70% as systemic vascular resistance decreased proportionately by 61%. Stroke volume index (SI) and mean pulmonary arterial pressure increased, while venous admixture and the distribution of intrapulmonary blood flow did not change with nifedipine. However, nifedipine significantly improved the tissue DO2 index so that the coefficient of DO2 increased. Thus, nifedipine significantly increased SI in a dose-dependent manner, thereby improving the tissue oxygen supply-demand balance.     

Rehabilitating patients with hepatopulmonary syndrome using living-related orthotopic liver transplant: a case report

The objective of this study was to rehabilitate a patient with hepatopulmonary syndrome (HPS) who underwent living-related orthotopic liver transplantation (LT). HPS is rare; it presents severe complication in patients with liver disease. A 17-year-old woman with HPS developed portal hypertension after undergoing Kasai's surgery for congenital biliary atresia and underwent a living-related orthotopic LT. After LT, her allograft functioned well, but she continued to have hypoxemia and orthodeoxia. She was referred for rehabilitation for disuse atrophy, contracture of hip and shoulder joints, left common peroneal nerve palsy, and rehabilitation for respiratory dysfunction. By day 106 after LT, her orthodeoxia and disuse atrophy had improved because of daily exercise training and active joint range of motion exercises. Patients with HPS have orthodeoxia and poor responsiveness to oxygen therapy, and correction of hypoxemia after LT may be delayed. Therefore, rehabilitation approaches for patients with HPS should be based on the pathophysiology and characteristics of HPS.     

Pulmonary Vasodilator Responses to Nitroprusside and Nitroglycerin in the Dog

The objective of this study was to determine the direct actions of nitroprusside and nitroglycerin on the pulmonary vascular bed in the intactchest dog. These widely used nitrogen oxide-containing vasodilator agents decreased pulmonary arterial pressure and increased cardiac output without altering left atrial pressure. Reductions in pulmonary arterial pressure and pulmonary vascular resistance were small under resting conditions, but were enhanced when pulmonary vascular tone was elevated by infusion of a stable prostaglandin analog that increases pulmonary vascular resistance by constricting intrapulmonary veins and upstream segments. In studies in which pulmonary blood flow to the left lower lobe was maintained constant, nitroprusside and nitroglycerin caused small but significant reductions in lobar arterial and small-vein pressures without significantly affecting left atrial pressure. With constant blood flow, lobar vascular pressures that were reduced in response to the vasodilators were more greatly reduced when lobar vascular resistance was increased by infusion of the prostaglandin analog or serotonin. However, when lobar vascular pressures were elevated by passive obstruction of lobar venous outflow, vasodilator responses to nitroprusside and nitroglycerin were not enhanced. These data suggest that nitroprusside and nitroglycerin decrease pulmonary vascular resistance by dilating intrapulmonary veins and upstream segments. These responses were minimal under control conditions but were enhanced when vascular tone was increased. This vasodilator action is independent of passive factors such as changes in pulmonary blood flow or left atrial pressure and is not secondary to an effect of these agents on the systemic circulation. Pulmonary vasodilator responses to nitroprusside and nitroglycerin were, however, found to be dependent on the existing level of vasomotor tone in the pulmonary vascular bed.     

Prenatal diagnosis of intrapulmonary arteriovenous malformation: sonographic and pathomorphological findings.

Vessel malformations, which are very rare, can be diagnosed prenatally using color Doppler sonography. We present a case of a fetus which, at first prenatal presentation at 27 weeks, was diagnosed as having an intrapulmonary arteriovenous malformation. On the basis of the gray-scale sonographic findings of cardiomegaly and dilatation of the right pulmonary vein and right pulmonary artery, color Doppler sonography was performed which identified an arteriovenous malformation of the right lung. By means of pulsed Doppler sonography it was possible to determine the hyperdynamic blood circulation in the incoming and outgoing vessels of the vascular malformation: right pulmonary artery peak systolic velocity = 90 cm/s and end-diastolic velocity = 30 cm/s; right pulmonary vein peak systolic velocity = 60 cm/s and end-diastolic velocity = 30 cm/s. The fetus went on to develop hydrops as the result of an arteriovenous valve insufficiency. At 30 weeks' gestation a Cesarean section was performed and the neonate died due to respiratory and hemodynamic problems during catheter insertion. The autopsy provided pathoanatomical confirmation of the prenatal diagnosis of an arteriovenous malformation of the right lung. There was no evidence of hereditary hemorrhagic telangiectasia.     

血液滤过对严重创伤后并发急性呼吸窘迫综合征患者氧合功能和血流动力学的影响

目的 研究血液滤过对严重创伤后并发ARDS患者氧合功能和血流动力学的影响。方法 选择严重创伤后ARDS患者12例，在呼吸机辅助或控制呼吸下行血液滤过治疗，于血液滤过后1－5d内用Swan-Ganz漂浮导管监测血流动力学和肺氧功能的变化。结果 与血液滤过前比较，滤过后第1天CVP、MPAP、SVRI、PVRI显著降低，整个血液滤过时间PaO2／FiO2升高非常显著，MAP、PCWP、HR、CI、DO2、VO2、ExtrO2、Qs/Qt无显著变化。结论 血液滤过对严重创伤后ARDS患者的血流动力学和氧合功能无明显影响，但可使氧合指数升高。     

肝肺综合征患者肝移植术中体、肺循环血流动力学变化

目的:分析终末期肝病肝肺综合征(HPS)患者肝移植术中体、肺循环血流动力学的变化。方法:26例HPS患者为HPS组;20例无低氧血症、无原发心肺疾病的原位肝移植术患者为对照组。两组病例均接受改良背驼式原位肝移植术,观察术中体、肺循环血流动力学的变化及术后转归。结果:(1)与对照组相比,HPS组术前心排量(CO)较高,平均肺动脉压(MPAP)、肺动脉楔压(PAWP)、体循环阻力(SVR)及肺循环阻力(PVR)均较低;术中SVR、PVR均较低,而PAWP在新肝期较低。(2)与术前相比,HPS组CO在新肝15min时较低,新肝30min后无差异;对照组在新肝15min时差异无显著性,新肝30min后上升。(3)与术前相比,HPS组PVR在新肝30min后差异无显著性,SVR下降;对照组在新肝30min后PVR、SVR均下降。(4)HPS组患者围术期死亡6例,死亡率为23.1%,对照组全部存活。结论:HPS患者肝移植围术期表现为高心排量、低体及肺循环阻力的状态,其围术期死亡率高。     

Hypercoagulation and thrombophilia in liver disease.

A complex balance exists between endogenous procoagulants and the anticoagulant system in liver disease patients. Hypercoagulable events occur in cirrhosis patients despite the well-known bleeding diathesis of liver disease. These events may be clinically evident, such as in portal vein thrombosis or pulmonary embolism, but these conditions may also be a silent contributor to certain disease states, such as portopulmonary hypertension or parenchymal extinction with liver atrophy as well as thrombosis of extracorporeal circuits in dialysis or liver assist devices. Moreover, liver disease-related hypercoagulability may contribute to vascular disease in the increasingly common condition of non-alcoholic fatty liver disease. Despite the incidence of these problems, there are few widely accessible and practical laboratory tests to evaluate the risk of a hypercoagulable event in cirrhosis patients. Furthermore, there is little research on the use of commonly accepted anticoagulants in patients with liver disease. This article is a result of an international symposium on coagulation disorders in liver disease and addresses several areas of specific interest in hypercoagulation in liver disease. Critical areas lacking clinical information are highlighted and future areas of research interest are defined with an aim to foster clinical research in this field.     

Role of Nurse Practitioners in the Management of Cirrhotic Patients

Patients with end-stage liver disease (ESLD) often suffer from complications that require ongoing management with outpatient providers. Complications include ascites, hepatic encephalopathy, hyponatremia, pulmonary vascular complications, and esophageal varices. Patients with cirrhosis need to be referred to a hepatologist to establish care and potential evaluation for liver transplantation. Nurse practitioners (NPs) involved in the care of cirrhotic patients are well positioned to provide supportive care, improve symptom management, and prevent complications associated with further decompensation. This article discusses the role of NPs in the management of patients with cirrhosis.