肝硬化急性肾损伤诊治进展

急性肾损伤(acute kidney injury,AKI)是肝硬化最严重的并发症之一。肝硬化背景下的肾损伤在临床上可分为AKI、慢性肾病和慢加急性肾病。Ⅰ型肝肾综合征(hepatorenal syndrome,HRS)是一种特殊类型的AKI,Ⅱ型HRS属于慢性肾功能衰竭,有学者还提出所谓具有肾脏结构性病变的Ⅲ型HRS。本文介绍了近年关于肝硬化AKI的诊断、分类、进展规律、预后及防治等方面的新进展。     

去甲肾上腺素治疗肝硬化合并肝肾综合征21例

肝肾综合征(Hepatorenal syndome,HRS)是肝硬化失代偿期常见的严重并发症,肝硬化患者HRS 1年和5年的发生率分别为20%和40%[1].根据临床特点和预后的差异,HRS又可分为1型和2型两个类型.1型表现为肾功能突然急剧恶化,病情进展迅速,中位生存期为1个月;2型病情进展缓慢,呈进行性肾功能减退,多发生于难治性腹水患者,中位生存期为6.7个月[2].因其病因复杂、致病机制又未完全阐明,故目前尚无特异性治疗方法,是肝病临床主要的难治性并发症之一.自2006年2月-2008年6月,我们在内科常规综合治疗基础上采用去甲肾上腺素(NA)治疗HRS 21例,取得了一定的临床疗效,现报告如下.     

血管活性药物在肝肾综合征治疗中的应用

肝肾综合征(HRS)是发生在肝硬化腹水患者中的一种并发症,临床上分为Ⅰ型和Ⅱ型HRS两型.Ⅰ型为快速进行性肾功能下降,定义为2周内最初的血肌酐增至226 mmol/L以上或最初24 h肌酐清除率下降50％至＜20 ml/min,平均生存期仅14天;Ⅱ型进展相对缓和,未达到Ⅰ型HRS的诊断标准,平均生存期6个月,病死率较Ⅰ型低,多发生在肝硬化难治性腹水患者中[1].近年来,随着对肝肾综合征发病机制的深入研究,血管活性药物在肝肾综合征治疗方面取得了一定进展.     

肝肾综合征的发病机制

肝肾综合征(HRS)是指严重肝病时,出现以肾功能损害、动脉循环和内源性血管活性系统显著异常为特征的综合征.临床以少尿或无尿、肌酐清除率降低及稀释性低血钠等为主要表现.因肾脏无器质性病变,又称为功能性肾衰竭.根据临床特征不同,HRS可分为2型.HRS Ⅰ型为HRS的急性型,常有诱因,如上消化道大出血、大量放腹水、过度利尿、外科手术后或感染等,后者最主要的是自发性细菌性腹膜炎.Ⅰ型HRS的主要表现为肾功能急剧恶化,2周内血肌酐超过原有水平的2倍至＞ 226 mmol/L.该型预后凶险,2周内死亡率可高达80％.Ⅱ型HRS通常发生于利尿抵抗型腹水患者,常表现为轻微的肾功能异常,即血肌酐133～226 mmol/L.该型患者肾衰竭多进展缓慢,部分患者病程可超数月.尽管Ⅱ型HRS患者平均存活时间长于Ⅰ型,但预后仍十分凶险[1].     

肝肾综合征83例临床特征分析

目的探讨在肝硬化腹水基础上发生肝肾综合征(HRS)患者的临床特点,指导临床对HRS进行有效的预防和治疗。方法回顾性分析2005年1月至2009年1月温州医学院附属第一医院消化内科收治的83例HRS患者及92例肝硬化腹水而未发生HRS患者(non-HRS)的临床资料,对两组患者的常见诱因、肝功能分级、交感神经张力、一般情况、病死率及预后等进行比较分析。结果(1)大量腹水及继发感染多见于HRS患者,而消化道出血则多见于non-HRS患者,在HRS患者中大量腹水多见于Ⅱ型HRS,而诱因不明者多见于Ⅰ型HRS。(2)Ⅰ型HRS患者肝功能最差,Ⅱ型居中,non-HRS最好。(3)HRS患者交感神经张力明显高于non-HRS患者。(4)一般情况比较中HRS患者血肌酐(Scr)明显高于non-HRS患者,而血钠(Na+)、24h尿量及平均动脉压均较后者低。(5)Ⅰ型HRS的病死率最高,Ⅱ型次之,non-HRS患者最低。HRS患者的存活时间明显低于non-HRS患者。结论(1)HRS常见诱因有大量腹水、感染、消化道出血、大量放腹水、水与电解质紊乱等,应尽量避免,一旦发现,应积极采取措施,及时治疗。(2)HRS患者交感神经张力明显高于非HRS患者,此可为临床诊治提供参考依据。(3)较之non-HRS患者,HRS患者的病情非常严重,病死率极高,预后极差,尤以Ⅰ型为甚。     

肝肾综合征的诊治

肝肾综合征(hepatorenal syndrome,HRS)为出现于肝病末期的一种无肾实质病变的肾功能衰竭,主要见于肝硬化患者,通常与腹水和低钠血症同时存在.伴发HRS的肝硬化患者预后严重不良,死亡率高.近年来,大量研究对HRS的发病机制、诊断以及治疗上进行了相关分析,为临床提供了一定的帮助.     

血管活性药物在肝肾综合征中的应用进展

肝肾综合征(hepatorenal syndrome,HRS)是发生在肝硬化腹水患者中一种潜在的可逆性并发症,也可发生在急性肝功能衰竭或酒精性肝炎患者中。主要特征为肾功能受损,血流动力学明显改变,交感神经和肾素-血管紧张素系统过度活化。临床上分为两型：Ⅰ型HRS和Ⅱ型HRS。Ⅰ型为快速进行性肾功能下降,定义为最初2周内血清肌酐倍增到221 μ mol/L以上或最初24h肌酐清除率下降50％到＜0.33 ml/s,平均生存期仅14d,常见于急性肝功能衰竭或酒精性肝炎患者及肝硬化基础上发生急性失代偿患者;Ⅱ型进展相对缓慢,未达到Ⅰ型HRS的诊断标准,平均生存期6个月,病死率较Ⅰ型低,多发生在肝硬化难治性腹水患者[1]。虽然肝移植是治疗HRS的惟一确定有效的方法,但由于Ⅰ型HRS患者生存期短、费用高及肝源缺乏等原因,在临床实际应用中受限。近年来,随着国内外学者对HRS发病机制的深入研究,在内科治疗上取得了一定进展,尤其是血管收缩药治疗成为肝移植前的有效过度治疗。     

Ⅰ型肝肾综合征患者前列腺素I2和血栓素A2水平分析

目的 通过分析肝硬化腹水伴Ⅰ型肝肾综合征(HRS)患者的临床资料、实验室指标、前列腺素I2(PGI2)和血栓素A2(TXA2),探讨花生四烯酸代谢与Ⅰ型HRS发生的关系.方法 纳入肝硬化腹水伴Ⅰ型HRS患者38例(HRS组)及肝硬化腹水且肾功能正常患者50例(非HRS组),收集两组患者的一般资料和血液,分析肝肾功能、电解质、PGI2和TXA2水平.结果 HRS组和非HRS组的PGI2、TXA2、PGI2/TXA2水平分别为(32517±6023) pg/ml、(7432±2186) pg/ml、4.79 ±1.58和(29 597±3343) pg/ml、(5032 ±2104)pg/ml、7.50±2.38,HRS组TXA2水平高于非HRS组(t=2.385,P=0.027),而PGI2/ TXA2水平低于非HRS组(t=2.29,P=0.035),两组PGI2水平差异无统计学意义(t=1.233,P=0.23).结论 Ⅰ型肝肾综合征患者PGI2/TXA2比例失调,花生四烯酸代谢异常可能和Ⅰ型HRS发生有关.     

肝肾综合征的发病机制及诊治的研究进展

肝肾综合征(hepatorenal syndrome,HRS)是晚期肝硬化、急性肝衰竭的严重并发症之一.HRS发病率和死亡率高,其病理生理学机制复杂,具体机制尚未完全阐明,且治疗手段有限,其中,特利加压素联合白蛋白可作为一线用药,但肝移植仍是唯一有效的治疗方法.HRS预后差,生存期短,其早期诊断对诊疗方案的制订及预后改善有重要作用.目前,需进一步完善诊断方法的可靠性及治疗方案的可行性,提高患者生活质量,减轻家庭及社会经济负担.本文就近年来HRS的发病机制、诊断及治疗研究进展予以综述.     

肝肾综合征诊断及治疗研究进展

正肝肾综合征(Hepatorenal syndrome,HRS)是发生在重症肝病如肝硬化合并腹水、急性肝衰竭和酒精性肝炎患者中以肾功能损伤为主要表现的一种严重并发症~([1])。目前治疗HRS的主要药物是血管收缩剂如特利加压素和人血白蛋白,其治疗有效率仅为40%～50%,而且治疗有效的患者中有50%可能会复发。所有HRS患者在没有禁忌证时都应考虑首选行肝移植手术~([2])。HRS是临床诊断,其定义根据最近急性肾损伤(acute kidney injury,AKI)标准进行了更新并且使用生物标志物来帮助鉴别诊断。关于对HRS的研究旨在进一步提高HRS诊断的准确性及探求新的治疗方法。本文对肝肾综合征的诊断及治疗研究进展予以综述。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.