一例短肠综合征患者长期家庭肠外营养的铜过量事件
2010-03-12 20:16:08   来源：丁香园   作者：  评论：0 点击：

目的：短肠综合征患者使用肠外营养（PN）后可存活数十年，但是临床医生尚缺乏简单的方法测量微量矿物质（TM）的生理储备量。血浆TM水平并不能精确反应身体的营养储备。使用PN后，根据血液样本，可人为地提高血浆矿物质水平，但是实际组织储备却很低。相反的，也可能出现血浆TM水平很低，但是体内已有过量的TM。临床医生在进行营养支持时通常测定长期使用PN短肠综合征患者血浆中的铜元素水平，即使这些水平并不等同于生理储备量。循环中90%的铜结合为血浆铜蓝蛋白，但体内绝大部分的铜在肝脏中结合为金属酶。经口摄入的铜元素在近端小肠吸收，主要由胆汁排泄，少数由尿液排泄。腹泻或高位造瘘引流患者肠内铜流失较正常对照者多。患者由PN摄入的铜元素到达肝脏之前已经以游离或氨基酸结合铜形式经肾脏过滤由尿排除大部分。

　　方法：LH是一位53岁男性患者，既往有克罗恩病及丙型肝炎病史，曾行多段小肠切除，保留3英寸空肠行空肠造口术。他从2001年开始接受家庭PN，尽管肠道已经适应，他还是尽量摄入最少量宏量营养素，共1.7L液体，90克葡萄糖，30克氨基酸类，20克脂肪乳剂，电解质类，维生素类以及TM。1998年及2007年的肝脏活检提示轻度慢性活动性肝炎。他的PN包含标准量铜元素，每天1毫克，直至2004年，LH发现血浆铜水平很低。从2005年至2008年，PN补充的铜量逐渐增加至维持正常血浆铜水平。2008年6月，尽管每天从PN中补充7毫克铜，LH的血浆铜水平仍很低。

　　结果：LH的血浆铜水平低下最初被认为是由于每天造口引流液>2L所致。但是，当增加肠外铜未能维持正常血浆铜水平时，我们通过实验室试验测定了其铜平衡。测得血浆铜50mg/dL（75～155mcg/dL），血浆铜蓝蛋白11mg/dL（18～36mcg/dL），以及24小时尿铜111mg/24小时（15～50mcg/24小时）。这些试验结果提示可能是肝豆状核变性。因此中断了PN补充铜元素，2007年持续补充铜元素时肝脏活检组织发现由于铜沉积而着色，并进行肝豆状核变性基因检测。肝脏活检显示铜明显沉积，692mcg/g干体重（参考值：0～35mcg/g）。肝豆状核变性基因检测和眼科检查（Kayser-Fliescher环）结果阴性。从此以后他继续使用无铜PN，并通过监测血浆和尿铜水平以及临床表现来观察有无铜缺乏。

　　结论：每天从PN中补充标准剂量铜元素1.0mg患者出现铜缺乏现象尚未见报道。生理或临床无铜缺乏表现患者通过PN补充铜时应警惕铜过量。

Clinical Nutrition Week 2010 Nutrition Practice Abstracts

Abstracts of Distinction

Nutr Clin Pract. 2010 Feb;25(1):96.

P7 - The Danger of Treating a Number: A Case of Copper Overload in a Long Term Home PN Patient with Short Bowel Syndrome

Elizabeth Wall, MS, RD, CNSC1; Kalyani Meduri, MD, MS2; Gilbert Cusson, RPh, BCNSP1; Carol Semrad, MD1

1The University of Chicago Medical Center, Chicago, IL; 2Private Practice, North Liberty, IA.

Introduction: Patients with short bowel syndrome can live for decades with parenteral nutrition (PN); however clinicians lack simple methods to measure physiologic stores of trace minerals (TM). Plasma levels of TM may not accurately reflect body stores of the nutrients. Infusion of PN, relative to blood sampling, can artificially increase plasma mineral levels while true tissue stores are low. The opposite can also occur in which low plasma levels are measured despite excess deposits of TM throughout the body. Nutrition support clinicians often assess Cu nourishment in long term PN patients with plasma levels although they are not equivalent to physiologic stores. Ninety percent of circulating Cu is bound to ceruloplasmin, but the majority of the body's Cu is found in the liver bound to metalloenzymes. Oral Cu is absorbed in the proximal small bowel and excreted mainly in bile and to a lesser extent in urine. Patients with diarrhea or high ostomy effluent are known to have greater intestinal Cu losses compared to normal controls. Patients receiving Cu in PN have higher urinary losses due to free or amino acid-bound Cu filtration through the kidneys before arriving at the liver. Methods: LH is a 53 yo man with a history of Crohn's disease and hepatitis C status post multiple small bowel resections with 3 feet of jejunum remaining to an end jejunostomy. He has been maintained on home PN since 2001, though with bowel adaptation he requires minimal macronutrients in 1.7 L fluid, 90 g dextrose, 30 g amino acids, 20 g fat emulsion, electrolytes, vitamins, and TM. Liver biopsies in 1998 and 2007 demonstrated mildly active chronic hepatitis. His PN contained standard copper (Cu) supplementation of 1 mg daily until 2004 when LH was found to have low plasma Cu. From 2005 until 2008 the PN Cu supplementation was gradually increased to maintain normal plasma Cu concentrations (see Table). In June 2008 LH had low plasma Cu levels despite 7 mg Cu daily in the PN. Results: LH's low plasma Cu was initially thought to be real given his intestinal losses of > 2L ostomy effluent daily. However, when incremental increases of parenteral Cu failed to sustain normal plasma Cu concentration, laboratory tests were performed to determine his Cu balance. Plasma Cu 50 mcg/dL (75 -155 mcg/dL), ceruloplasmin 11 mg/dL (18-36 mg/dL), and 24 hr urine Cu 111 mcg/24 hr (15 - 50 mcg/24hr) were obtained. These tests revealed a Cu profile suggestive of Wilson's disease. Therefore the PN Cu was discontinued; liver tissue from his 2007 biopsy while on supplemental Cu was stained for Cu deposition, and genetic testing for Wilson's disease was obtained. The liver biopsy demonstrated significantly elevated Cu deposition of 692 mcg/g dry wt (0-35 mcg/g). Genetic testing for Wilson's disease and ophthalmic exam (Kayser-Fliescher rings) were negative. He has since been maintained on Cu-free PN with plans to monitor his plasma and urine Cu levels as well as for clinical manifestations of Cu deficiency. Conclusions: Clinical Cu deficiency in patients receiving PN with the standard dose of 1.0 mg Cu/day is undocumented. Caution should be taken in altering PN Cu supplementation without physiologic or clinical findings of deficiency.