Hepatopulmonary syndrome.

The hepatopulmonary syndrome (HPS) is a rare complication of liver cirrhosis and is characterised by the typical triad of liver cirrhosis, arterial hypoxemia, and intrapulmonary vascular dilatation. Except for pleural effusions associated with liver cirrhosis no other disease of the lungs or the heart is detectable. The structural hallmark of HPS is dilatation of pulmonary precapillary vessels which impairs diffusion-perfusion and causes unequal ventilation-perfusion. The diagnosis of HPS is based on PaO2 measurements when breathing room air and 100% oxygen. The increased intrapulmonary vascular diameter allows microbubbles to traverse the lung capillaries when agitated saline is administered intravenously. Only on rare occasions is a patient limited by his pulmonary impairment, the leading morbidity is that of liver disease and its classical complications. Drug therapy is of no proven benefit, oxygen supplementation might improve dyspnea. Vascular embolisation of discrete arteriovenous shunts, if present, or liver transplantation may dramatically improve pulmonary function in selected patients.     

Effect of propranolol on hepatic blood flow in patients with cirrhosis

The effect of propranolol on systemic and hepatic hemodynamics was studied in patients with cirrhosis. One hour after 40 mg propranolol by mouth as well as during continuous oral dosing at doses that reduced heart rate 25%, cardiac output and the hepatic venous pressure gradient fell significantly, whereas arterial pressure and hepatic blood flow did not change significantly. In six patients with cirrhosis and surgical end-to-side portacaval shunts, cardiac output and the hepatic venous pressure gradient also decreased 15 minutes after intravenous propranolol (5 mg), whereas hepatic blood flow did not change significantly. In the patients with surgical shunts, systemic vascular resistance rose significantly but hepatic arterial vascular resistance fell. Our data show that in patients with cirrhosis, propranolol induces an increase in the fraction of cardiac output reaching the liver.     

Influence of sex, testicular development and liver function on the bioavailability of oral testosterone

The bioavailability of orally administered testosterone was investigated in normal and hypogonadal men, prepubertal boys, normal women, and in patients with fatty liver, liver cirrhosis and surgical portocaval shunts. Peripheral testosterone concentrations remained unchanged in normal men and men with fatty liver, whereas a steep increase was observed in all other groups. The greatest increase was seen in patients with compensated liver cirrhosis and with portocaval shunts. The steep increase of peripheral testosterone in boys, women and hypogonadal men is attributed to their having a lower activity of androgen-metabolizing liver enzymes than normal men. The increase in patients with cirrhosis is most likely caused by intra- and extra-hepatic portocaval shunts.     

Pulmonary hemodynamics in systemic hypertension

We reviewed cardiac catheterization data and the medical records of 30 patients with systemic hypertension to establish their pulmonary hemodynamic profiles and the relationship between certain clinical and demographic variables and increased pulmonary vascular resistance. Mean systemic arterial pressure ranged from 110 to 210 mm Hg, and systemic vascular resistance ranged from 17.6 to 47.0 units. Seven patients had normal pulmonary wedge pressure and normal pulmonary vascular resistance, one had elevated pulmonary wedge pressure and normal pulmonary vascular resistance, five had elevated pulmonary wedge pressure and increased pulmonary vascular resistance, and 17 had normal pulmonary wedge pressure and increased pulmonary vascular resistance. There were significant positive correlations between systemic vascular resistance and pulmonary vascular resistance and between mean systemic arterial pressure and mean pulmonary artery pressure, but there was no correlation between mean pulmonary wedge pressure and pulmonary vascular resistance. Of the 17 patients with normal pulmonary wedge pressure and increased pulmonary vascular resistance, seven had clinical or radiologic evidence of prior left ventricular failure. We conclude that increased pulmonary vascular resistance occurs commonly in patients with systemic hypertension. Although some cases of increased pulmonary vascular resistance relate to active or preexistent left ventricular failure, the majority remain unexplained, suggesting that neurohumoral or other factors may produce a hypertensive response in both the systemic and pulmonary arterial circuit.     

肝移植围手术期血流动力学及血浆一氧化氮和内皮素含量的变化

目的探讨一氧化氮(NO)和内皮素(ET)对肝硬化患者肝移植围手术期体、肺循环的影响。方法24例终末期肝硬化患者接受改良背驮式肝移植术,术中持续监测心率(HR)、心排血量(CO)、平均动脉压(MABP)、平均肺动脉压(MPAP)、中心静脉压(CVP)、肺动脉楔压(PAWP)、心排血指数(CI)、体循环阻力指数(SVRI)和肺循环阻力指数(PVRI)。分别于麻醉后术前、无肝前10min、无肝30min、新肝30min和术毕5个时间点采集中心静脉血,用硝酸还原法和放射免疫法分别测定血浆NO和ET1水平。结果1MABP在下腔静脉和门静脉阻断及开放后短期内有一过性下降〔分别由(81±11)mmHg(1mmHg=0.133kPa)降至(79±9)mmHg,再降至(57±19)mmHg,P均<0.05〕,应用血管活性药物后,可基本维持稳定。2CVP、MPAP和PAWP在无肝期均显著降低(P均<0.05);而在新肝期显著增高并维持高于术前水平。3CI在无肝期显著降低(P<0.05),新肝10min后显著增高(P<0.05)。4SVRI和PVRI在无肝期均显著增高(P均<0.05);血管开放后新肝15min内SVRI和PVRI高于术前水平,新肝30min后SVRI显著低于术前水平。5与术前值比较:阻断后,血浆NO水平明显降低(P<0.05),新肝期和术毕均升高(P均<0.05);在无肝30min、新肝30min血浆ET1水平均升高(P均<0.05)。结论肝硬化患者肝移植围手术期血流动力学变化显著,新肝期易发生轻度肺高压。新肝期NO和ET增高,其临床意义有待进一步研究。     

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.     

Color Doppler sonographic evaluation of spontaneous portosystemic shunts and inversion of portal venous flow in patients with cirrhosis

PURPOSE: The aim of the study was to evaluate the usefulness of color Doppler sonography in the detection of spontaneous portosystemic shunts and abnormal blood flow direction in the portal vein in patients with cirrhosis. METHODS: Patients were 67 men and 42 women (mean age, 53 +/- 14 years) with cirrhosis confirmed by liver biopsy. All patients underwent abdominal gray-scale and color Doppler sonographic evaluations to detect the presence of spontaneous portosystemic shunts and to analyze portal vein blood flow direction. RESULTS: Spontaneous portosystemic shunts were found in 41 patients (38%), most often as splenorenal shunts (21%) and patent umbilical veins (14%). Less frequent were gastric collaterals, gallbladder varices, collaterals to thrombotic portal veins, mesoiliac shunts, and portorenal shunts to the right kidney. The presence of shunts was associated with that of esophageal varices (p < 0.01), ascites (p < 0.01), and inversion of portal flow (p < 0. 001) but not with splenomegaly. The direction of portal venous flow was normal (hepatopetal) in 80 patients (73%), hepatofugal in 10 (9%), and bidirectional in 7 (6%); 12 patients (11%) had partial portal vein thrombosis. CONCLUSIONS: Portosystemic shunts and the direction of portal venous flow are important features in the sonographic diagnosis of portal hypertension.     

Doppler in hepatic cirrhosis and chronic hepatitis.

Doppler ultrasound and color Doppler are being used routinely in the study of vascular structures of the abdomen, and more particularly the liver. Reports published in the literature to date have shown that all patients with hepatic cirrhosis and chronic hepatitis should be studied in the first stage of their illness and in follow-up by using Doppler techniques. With new ultrasound software and the latest generation of contrast agents, we can obtain a better and more complete vascular study of the liver, which previously could be achieved only with triple-phase CT. Therefore, hepatic cirrhosis and chronic hepatitis, as well as their vascular complications, can be followed up more closely. The vascular complications include flow alterations in the hepatic artery and veins, portal hypertension, portal vein thrombosis, portosystemic shunts, and vascularization associated with liver tumors.     

Total fasting serum bile acids and beta-hexosaminidase in alcoholic liver disease

Total serum bile acid levels and beta-hexosaminidase activity were studied in 22 normal subjects, 35 non-cirrhotic patients with acute alcohol intoxication, 45 patients with alcoholic liver cirrhosis and 11 patients with alcoholic liver cirrhosis and surgical portal-systemic shunts. Comparison was made with traditional liver function tests. beta-Hexosaminidase was most frequently elevated in acute alcohol intoxication (94%) while total serum bile acids were elevated in all patients with alcoholic liver cirrhosis. Total serum bile acid levels were found to discriminate most efficiently between acute alcohol intoxication and liver cirrhosis. The combined determination of serum beta-hexosaminidase and total serum bile acids is proposed for evaluating alcoholic liver disease.     

终末期肝衰竭患者肝脏移植术后血流动力学变化

目的 :观察终末期肝衰竭患者肝脏移植术后的血流动力学变化。方法 :5例终末期肝衰竭患者行肝脏移植手术 ,监测其手术后 3日内中心静脉压 (CVP)、肺动脉压 (PAP)、肺小动脉楔压 (PAWP)、心排血量 (CO)和平均动脉压 (MAP)等参数的变化。结果 :患者术后进入 ICU当时的 MAP、肺毛细血管楔压 (PCWP)和 CVP均明显低于正常参考值 ,心率 (HR)显著增快 ;术后 3日内经过积极扩容 ,MAP、PCWP和 CVP显著升高(P均 <0 .0 1)。入 ICU后 8小时内的心脏指数 (CI)轻度降低 ,但与术后 2 4、4 8小时的 CI值比较均无显著性差异 (P均 >0 .0 5 )。入室后 8小时内的外周血管阻力指数 (SVRI)、肺血管阻力指数 (PVRI)轻度降低 ;术后 3日内上述指标逐渐恢复正常。结论 :终末期肝衰竭患者肝移植术后血流动力学不稳定 ,出现明显的血容量不足表现 ,如不及时纠正可能导致脏器灌注不足 ,乃至器官功能衰竭 ,因此 ,密切监测其血流动力学的变化 ,估计其血容量不足状态并予充分纠正 ,是肝移植患者安度围手术期的关键     

Pulmonary hypertension complicating portal hypertension: portopulmonary hypertension]

Portopulmonary hypertension is a condition with a poor prognosis, which is defined as precapillary pulmonary hypertension complicating portal hypertension mainly due to cirrhosis of various etiologies. A mean pulmonary arterial pressure greater than 25 mmHg at rest with a pulmonary capillary wedge pressure less than 15 mmHg and a pulmonary vascular resistance greater than 120 dynes.sec.cm-5, in the setting of the presence of portosystemic shunting has been proposed as hemodynamic criteria for portopulmonary hypertension. Prevalence of pulmonary hypertension ascertained by right cardiac catheterization was 2% among patients with cirrhosis, and reached to 4% particularly among candidates for liver transplantation. Hyperdynamic systemic circulation seen commonly in patients with cirrhosis appeared to be normalized by complication of pulmonary hypertension with a contraction of circulating plasma volume. Long term treatment by epoprostenol administration or nitric oxide inhalation could induce a gradual decline in pulmonary arterial pressure in patients with poor response to acute vasodilator administration.     

Portosystemic shunt on CT during arterial portography: prevalence in patients with and without liver cirrhosis

Background To review various portosystemic shunts (PS) and to evaluate their prevalence by CT during arterial portography (CTAP) using a multidetector-row CT (MDCT). Methods CTAP of 116 patients (liver cirrhosis 70 patients, non-liver cirrhosis 46 patients) was retrospectively reviewed. CTAP was performed with the catheter placed in the superior mesenteric artery using MDCT. Axial CT images of 0.625- and 3.75- or 2.5-mm thickness were obtained. Multiplanar reformation images and maximum intensity projection images were subjected to review. Results A part of the veins in the ileocecal region drained into the right renal vein or the inferior vena cava (IVC) via the right gonadal vein in 57 patients (81%). A part of the veins of the ascending colon drained via the right renal capsular vein into the IVC in 37 patients (53%). In 46 patients without liver cirrhosis, the right gonadal and right renal capsular veins were opacified on CTAP in 22 patients (48%) and 20 patients (43%), respectively. Conclusions Portosystemic shunts in retroperitoneum were frequently recognized on CTAP images in patients with liver cirrhosis. The right gonadal vein and the right renal capsular vein were the most frequent routes of the portosystemic shunts. They may exist in physiological condition.     

Effect of aminophylline on regional perfusion distribution in the lungs.

Using ten normal dogs, the right upper lobe of the lung was isolated in vivo by a balloon catheter and was artificially ventilated with nitrogen, air, 60% oxygen in nitrogen, and 60% oxygen and 20% carbon dioxide in nitrogen, while the rest of the lungs maintained a spontaneous breathing of ambient air. Aminophylline did not show a vasodilating action under severe alveolar hypoxia (PAO2: ca. 40 mmHg); on the contrary, it seemed to potentiate hypoxic pulmonary vasoconstriction. When the regional alveolar oxygen tension became less hypoxic (PAO2: ca. 70 mmHg) or higher than that in the rest of the lungs which spontaneously breathed ambient air, aminophylline showed a definite vasodilating action. Aminophylline also showed a vasodilating action in alveolar hypercapnia in the presence of alveolar hyperoxia.     

Hepatocellular carcinoma in advanced liver cirrhosis: CT detection in transplant patients

Computed tomography (CT) is being used as the standard pretransplantation imaging for recipients and donors in the evaluation of liver volume, liver reserve function, vascular anatomy, diagnosis of hepatocellular carcinoma and metastasis, and global information of the abdominal cavity. Whereas CT detection of hepatocellular carcinoma in noncirrhotic patients is satisfactory, detection sensitivity in severely cirrhotic patients is limited, with a reported sensitivity of 53% to 68%. Tumors smaller than 2 cm are more difficult to detect. Innumerable regenerative nodules, localized or diffuse fibrosis, arterioportal shunts, nodular surface, and distorted anatomy in end-stage liver cirrhosis make it difficult to detect small hepatocellular carcinoma. Because of the shortage of cadavers and living donors, judicious use of CT is necessary in the selection of candidates and the decision of priority for liver transplantation in patients with advanced liver cirrhosis.     

Portopulmonary hypertension

Portopulmonary hypertension (PPHT) is a respiratory complication of portal hypertension, defined as an increase in mean pulmonary artery pressure (PAP) of > 25 mmHg with an increase in pulmonary vascular resistance of > 240 dyn.s/cm(-5) and a normal pulmonary capillary wedge pressure ( < 15 mmHg), which often occurs in subjects with liver cirrhosis. Histopathological features of PPHT are endothelial and smooth-muscle cell proliferation and fibrosis leading to luminal obstruction in the resistance arteries. The pathogenesis of PPHT may result from an imbalance between vasoconstrictor and vasodilating factors. The most common pulmonary symptom is exertional dyspnea; fatigue, chest pain and syncope occur more often at an advanced stage. Edema, ascites and prominent jugular veins are signs of both decompensated hepatic cirrhosis and right ventricular failure. Right heart catheterisation is the gold standard for the diagnosis and defines PPHT in mild disease with PAP less than 35 mmHg, moderate disease with PAP between 35 and 45 mmHg, and severe disease with PAP of 45 mmHg or higher. The medical treatment of portopulmonary hypertension is based on the treatment of other forms of pulmonary arterial hypertension, including vasomodulating pharmacologic agents. Liver transplantation is accompanied by high risk of mortality, generally due to acute right ventricular failure and cardiovascular collapse. The prognosis of PPHT is poor with mean survival of 15 months.     

Chronic liver diseases

Insulin resistance (reduced insulin action to stimulate glycogen synthesis in muscle and occasionally to inhibit glucose output in liver) is well known to be frequently present in patients with chronic liver diseases, especially cirrhosis. It has been documented that 60% to 80% of patients with cirrhosis are glucose-intolerant, and 10% to 30% eventually develop overt diabetes mellitus when their impaired insulin secretion cannot meet the increased demand for insulin due to insulin resistance. Therefore, it seems rational to treat cirrhotic patients with such an insulin sensitizer as thiazolidinediones. However, it must be forbidden to use thiazolidinediones in cirrhotic patients whose liver function capacity is limited until the possible liver toxicity is clarified.     

Septic shock in patients with cirrhosis: hemodynamic and metabolic characteristics and intensive care unit outcome.

OBJECTIVES: To examine the hemodynamic and metabolic characteristics and ICU outcome of septic shock in patients with cirrhosis. DESIGN: Prospective, comparative study. Measurements performed in the first 24 hrs of septic shock. SETTING: A general hospital ICU. PATIENTS: Twelve patients with cirrhosis and 23 patients without cirrhosis admitted for septic shock. MEASUREMENTS AND MAIN RESULTS: Arterial pressure was measured using an arterial catheter. Pulmonary arterial and right atrial pressures were measured by using a pulmonary artery catheter. Cardiac output was determined by using the thermodilution method. Pulmonary arterial L-lactate plasma concentrations were measured using an automated spectrophotometer, and blood temperature was measured using a cardiac output computer. Arterial and mixed venous PO2, PCO2, and pH values were measured by using specific electrodes. Oxygen saturations and hemoglobin concentrations were measured using a hemoximeter. Patients with cirrhosis had decompensated liver disease (grade C of the Child-Pugh classification). The number of Gram-negative infections and therapeutic interventions were similar in both groups. Patients with cirrhosis had higher cardiac indices (5.14 +/- 0.52 [SE] vs. 3.91 +/- 0.30 L/min/m2, p less than .05), plasma lactate concentrations (9.0 +/- 2.0 vs. 5.2 +/- 0.7 mmol/L, p less than .05) and ICU mortality rates (100% vs. 43%, p less than .05), and lower blood temperatures (35.5 +/- 0.6 vs. 37.6 +/- 0.2 degrees C, p less than .05) than patients without cirrhosis. Systemic vascular resistance, arterial pressure, pulmonary arterial pressure, oxygen delivery and consumption, and arterial and mixed venous acid-base status were not significantly different between the two groups. CONCLUSIONS: In patients with cirrhosis, septic shock was characterized by severe liver dysfunction, low blood temperature, marked increases in cardiac index and lactic acidemia, and a 100% ICU mortality rate. These findings should be taken into account if patients with cirrhosis are to be included in controlled studies on septic shock.     

Hypoxemia in pulmonary embolism, a clinical study

The cause of hypoxemia was studied in 21 patients with no previous heart or lung disease shortly after an episode of acute pulmonary embolism. The diagnosis was based on pulmonary angiography demonstrating distinct vascular filling defects or “cutoffs.” It was found that virtually all of the hypoxemia in patients with previously normal heart and lungs could be accounted for on the basis of shunt-like effect. The magnitude of the shunting did not correlate with the percent of the pulmonary vascular bed occluded nor with the mean pulmonary artery pressure. The shunts tended to gradually recede over about a month after embolism. Patients without pulmonary infarction were able to inspire 80-111% of their predicted inspiratory capacities, and this maneuver temporarily diminished the observed shunt. Patients with pulmonary infarcts were able to inhale only to 60-69% of predicted inspiratory capacity, and this did not reverse shunting. These data suggest that the cause of right-to-left shunting in patients with pulmonary emboli is predominantly atelectasis.     

Maximal oxygen consumption and pulmonary circulation in patients with chronic bronchitis

In order to study the relations between maximal oxygen consumption during exercise (VO2max) and the pulmonary circulation when pulmonary artery pressure (PPA) and pulmonary vascular resistance (PVR) are normal or close to normal, we evaluated twenty-three patients with chronic bronchitis, in stable clinical condition. All these patients performed a progressive exercise test on a bicycle ergometer until exhaustion (VO2max); they were also subjected to right heart catheterization at rest and during light exercise at constant load. In these patients with moderate functional impairment, we observed on average a significant, although weak, correlation (r = -0.52, P less than 0.01) between pulmonary vascular resistance at rest and VO2max. When VO2max exceeded 2 1 min-1, PVR was below 210 dyn s cm-5. From the heart rate during maximal exercise we computed the oxygen pulse (O2Pmax). In eight patients O2Pmax was reduced (less than or equal to 11 ml) with maximal heart rate close to its predicted value; in seven of these subjects PVR was abnormal and Ppa at rest was at least 20 mmHg. Thus it seems that in chronic obstructive bronchitis mild disturbances in pulmonary circulation may be a contributory factor in the limitation of exercise performance, and a maximal exercise test may help to detect pulmonary hypertension in these patients.