胆汁淤积性肝病的诊断和治疗进展

胆汁淤积是指胆汁流的形成和排泌障碍,可由肝细胞或胆管上皮的胆汁分泌障碍或胆汁流的阻断所致.区分这两种胆汁淤积对于治疗有一定指导意义,因为主要用于促进胆汁分泌的药物并不适用于胆管阻塞的病例.但无论何种原因引起的胆汁淤积均可导致胆汁酸等毒性物质的潴留,引起肝细胞损伤和胆汁淤积性肝病.肝内胆汁淤积包括原发性胆汁性肝硬化(PBC)、原发性硬化性胆管炎(PSC)、妊娠期胆汁淤积、全胃肠外营养导致的胆汁淤积和药物诱导性胆汁淤积等.遗传性疾病如囊性纤维化和进展性家族性肝内胆汁淤积临床相对较为少见.     

胆汁淤积的诊断

胆汁淤积这一名称首先由Popper和Schaffner在1970年提出,并定义为形态学上胆汁在肝小叶肝细胞、毛细胆管、库普弗细胞内贮积.当今对胆汁淤积的定义是肝细胞内胆汁生成障碍、胆管分泌或胆汁流动受损所引起的结果[1].     

重视胆汁淤积性肝病临床管理

<正>胆汁由肝细胞和胆管细胞产生,人每天总胆汁流约600 mL,肝细胞提供胆盐依赖性胆汁(约225 m L/d)和非胆盐依赖性胆汁(约225 m L/d),胆管细胞提供另外150 m L/d的胆汁。胆汁淤积是胆汁流量或形成及排泄障碍所致^[1]。各种原因使肝脏病变导致胆汁淤积为主要表现的肝胆疾病统称胆汁淤积性肝病,胆汁淤积本身也会进一步加重肝脏的损害。     

胆汁的分泌、排泄和调节及胆汁淤积发生机制

胆汁的形成、分泌和排泄机制十分复杂,肝细胞和胆管细胞都具有摄取和分泌胆汁成分的功能,这主要依靠肝细胞和胆管细胞膜上的转运蛋白,其在肝脏的病理和生理过程中占有重要的地位。胆汁淤积可以由肝细胞内胆汁形成的功能性缺陷所致,也可由于小胆管或胆管内胆汁分泌或流动的障碍所致。本文就胆汁分泌、排泄和调节及胆汁淤积发生机制等方面进行了论述     

胆汁形成与胆汁淤积性疾病发生的机制

胆汁淤积是指在肝细胞水平或胆管水平胆汁生成,分泌或流动障碍[1].肝细胞与胆管细胞膜上存在众多的蛋白质是胆汁形成与分泌的重要转运体,随着对这些转运体的鉴定,以及对影响胆汁酸盐合成、转运的复杂信号网络系统的深入了解,为充分认识胆汁淤积形成的分子机制提供了重要价值[2-3].     

胆汁淤积的治疗

正胆汁淤积是指肝内外各种原因造成胆汁形成、分泌或排泄障碍,胆汁流减少所导致的一种临床综合征,以瘙痒、乏力、黄疸、血清碱性磷酸酶(ALP)和谷氨酰转肽酶(GGT)升高为特征。胆汁淤积可分为肝内胆汁淤积和肝外胆汁淤积,其中肝内胆汁淤积又可分为肝细胞性胆汁淤积、胆管性胆汁淤积及混合性胆汁淤积。其原因少部分为先天性遗传异     

肝内胆汁淤积发病机制

肝细胞膜可分为窦膜 (基膜 )、侧膜和毛细胆管膜 ,二个邻近肝细胞的胆管膜组成毛细胆管 (ｃａｎａｌｃｕｌｕｓ) ,胆管系统以此为起点 ,集合成小胆管 (ｄｕｃｔｕｌｅ)、叶间胆管 (ｉｎｔｒａｌｏｂｕｌａｒｂｉｌｅｄｕｃｔ)和间隔胆管 (ｓｅｐｔａｌｂｉｌｅｄｕｃｔ)。肝内胆汁淤积是指胆汁在上述途径中发生排泄障碍。胆汁排泄依靠细胞支架的功能完整。细胞支架由微丝和微管组成 ,微丝由肌动蛋白组成 ,起自细胞侧膜的带状桥粒 ,围绕毛细胆管 ,以维持其张力 ,使胆汁排泄至小胆管。在正常情况下 ,每日生成 6 0 0～70 0ｍｌ胆汁 ,其中肝细胞…     

肝内淤积的诊断

胆汁淤积 (Ｃｈｏｌｅｓｔａｓｉｓ)意指胆汁的滞留 ,自肝细胞基底外侧膜 (ｂａｓｏｌａｔｅｒａｌｍｅｍｂｒａｎｅ)至胆管与十二指肠连接处的任何部位胆汁流通受阻 ,皆可导致胆汁淤积。梗阻发生在胆总管或肝外胆管 ,俗称肝外胆汁淤积或外科黄疸 ,如肝细胞或肝内微胆管缺陷引起胆汁流通障碍 ,俗称肝内胆汁淤积或内科黄疸 ,二者治疗绝然不同 ,涉及手术与非手术治疗问题 ,即便外科黄疸 ,大部分能行手术治疗 ,也有部分不宜手术治疗。一、诊断程序对黄疸患者首先根据病史、体检和生化实验 ,大致确定是否为胆汁淤积或梗阻性黄疸。进一步确诊主要…     

胆汁淤积性肝病的治疗

正胆汁淤积性肝病是以胆汁淤积为主要表现的肝胆疾病总称,各种肝内外因素所致的胆汁流形成、分泌和排泄障碍均可导致胆汁淤积。根据病因,可将胆汁淤积性肝病分为肝细胞性胆汁淤积、胆管性胆汁淤积和混合性胆汁淤积,包括原发性胆汁性胆管炎(primary biliary cholangitis,PBC)、原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)、妊娠期肝内胆汁淤积症(intrahepatic cholestasis of     

药物性肝内胆汁淤积的进展

胆汁淤积是胆汁流障碍使正常数量的胆汁不能抵达十二指肠,伴有胆汁内成分如结合胆红素、胆汁酸、胆固醇及碱性磷酸酶(AKP)等反流至血液。临床上有黄疸、瘙痒、脂肪泻和脂溶性维生素 A、D、K 缺乏的症状。病理组织学特点为毛细胆管内微胆栓形成,Kupffer 细胞和肝细胞内有胆色素     

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.