第五节 实验室检查.doc

第五节 实验室检查Determining the optimal approach to nutritional assessment in the clinical setting is difficult because nonnutritional factors alter many of the parameters used to determine nutritional status. For example, the serum albumin level can be affected by body fluid redistribution, sepsis, hepatic or renal disease, or the postoperative state. Furthermore, the long half-life of serum albumin makes this measurement insensitive to rapid changes in nutritional status. Urine and fetal nitrogen excretion and immune skin tests require up to 48 hours for results. Difficulty in obtaining complete 24-hour collections of urine and feces poses another potential clinical limitation on assessment of nitrogen balance. While there is no single irrefutable measure of nutritional status, proficiency in detecting malnutrition in its early stages is essential for effective treatment and prevention of adverse clinical outcomes, and interval assessments of any nutritional intervention.实验室检查可提供客观的营养评价结果， 并且可确定存在哪一种营养素的缺乏或过量，以指导临床营养治疗。一、血浆蛋白The primary cause for concern with the use of plasma proteins as indicators of protein depletion and deficiency is the role of the acute-phase response in their regulation. Thus albumin, prealbumin (PA), transferring (TF), and retinol binding protein (RBP) are all negative acute-phase reactants. Although the relative importance of the acute-phase response, as opposed to nutritional factors, in the regulation of plasma proteins has yet to be systematically evaluated in many clinical situations, those studies that have been reported do demonstrate the importance of non-nutritional factors.Of the various classes of plasma proteins (transport, immunological, and acute-phase) albumin and the transport proteins (thyroid-binding prealbumin, retinol-binding protein and transferring have been most widely studied as indicators of the nutritional state. Fibronectin (FB), an opsonic glycoprotein, is a more recent addition to the catalogue. The shorter half-life and smaller pool size of PA, RBP, TF, and FB means that they can exhibit more rapid changes in concentrations and can thus be more sensitive indices of the immediate nutritional state than albumin. In children with kwashiorkor, one week of treatment induces a doubling of PA and RBP with no change in albumin or any measurable anthropometric indicator of nutritional status. Therefore distinction needs to be made between indicators of immediate as opposed to long-term nutritional state. Obviously TF is sensitive to iron status (increasing in response to a deficiency), and RBP will change in response to alterations in vitamin A status.A commercially available method is described for albumin that can be used manually or automated. For other proteins, reference is made only to the types of methods in general use.血浆蛋白水平可反映机体蛋白质营养状况。常用的指标包括白蛋白、前白蛋白、转铁蛋白、纤维素结合蛋白和视黄醇结合蛋白。1. 白蛋白（albumin）【临床意义】 在应激状态下，血清白蛋白的水平降低，如这种低水平维持一周以上，可表示有急性营养缺乏。血清白蛋白低于3.0g/100ml，临床上常出现蛋白质营养不良。在手术后或感染中，维持内脏蛋白的水平对病人的存活是非常重要的。白蛋白能有效预测手术风险程度，它只反映疾病的严重程度，而不是营养不良的程度。当然，能量与蛋白质摄入不足，不利于急性期病人血清白蛋白水平恢复。白蛋白的合成受很多因素的影响，在甲状腺功能减退、血浆皮质醇水平过高、出现肝实质性病变及生理上的应激状态下，白蛋白的合成速率下降。白蛋白的半衰期约为1820天。【评价标准】 3550g/L为正常，2834g/L为轻度不足，2127g/L为中度不足，21g/L为重度不足。2. 前白蛋白（prealbumin, PA） 前白蛋白可与甲状腺素结合球蛋白及视黄醇结合蛋白结合，而转运甲状腺素及维生素A，故又名甲状腺素结合前白蛋白。【临床意义】 主要由肝脏合成的一种糖蛋白，参与机体维生素 A 和甲状腺素的转运及调节，具有免疫增强活性和潜在的抗肿瘤效应。前白蛋白迅速的转化速率使得它能更加及时的反映营养状况和能量状况。在临床上常作为评价蛋白-能量营养不良和反映近期膳食摄入状况的敏感指标。【评价标准】 0.20.4g/L为正常，0.160.20g/L为轻度不足，0.100.15g/L为中度不足，0.10g/L为重度不足。3. 转铁蛋白（transferrin, TFN）【临床意义】 转铁蛋白为血清中结合并转运铁的球蛋白。在高蛋白摄入后，TFN的血浆浓度上升较快。能反映营养治疗后营养状态与免疫功能的恢复率，该蛋白的改变增加或减少较其他参数（血清白蛋白，体重，三头肌皮褶厚度）要快。血清转铁蛋白可反映缺铁性贫血等多种疾病。增多见于缺铁性贫血、急性肝炎、急性炎症、口服避孕药、妊娠后期。减少见于肾病综合征、肝硬化、恶性肿瘤、溶血性贫血、营养不良时。【评价标准】 2.04.0g/L为正常，1.52.0g/L为轻度不足，1.01.5g/L为中度不足，1.0g/L为重度不足。4. 视黄醇结合蛋白（retinol binding protein, RBP） RBP是一种低分子量的亲脂载体蛋白，属Lipocalin蛋白超家族成员。其功能是从肝脏转运维生素A至上皮组织，并能特异性地与视网膜上皮细胞结合，为视网膜提供维生素A。RBP可特异地反映机体的营养状态，是一项诊断早期营养不良的敏感指标。RBP与血清总胆红素、白蛋白、凝血酶原时间相关，故较前白蛋白有更高的敏感性。在肝脏、肾脏疾病的早期诊断和疗效观察中有重要临床意义。正常值为4070mg/L。5. 纤维结合蛋白（fibronectin, FN） FN 在饥饿时降低，恢复营养支持后可逐渐升高。血浆纤维结合蛋白含量持续降低多见于比较严重的疾病，如多器官功能衰竭，严重营养不良，广泛创伤、烧伤、手术及脓毒血症时、严重感染，重症肝炎，失代偿期肝硬化，肝癌转移等。作为肝功能评价指标，升高多见于急性肝炎、早期和代偿性肝硬化等，几种血浆蛋白的基本特征总结如下（表7-4-1）。 表7-4-1 血浆蛋白的基本特征 血浆蛋白 分子量（D） 合成部位 血清正常值范围 生物半衰期 白蛋白 转铁蛋白 前白蛋白 视黄醇结合蛋白 纤维结合蛋白 66460795505498020960440000肝细胞 肝细胞 肝细胞 肝细胞 肝细胞及其他组织 45（35-50） 3.3（2.6-4.3） 0.3（0.2-0.4） 0.3720.00731.820.1618-20天 8-9天 2-3天 12小时 4-24小时 二、血浆氨基酸谱在重度蛋白质能量营养不良时，血浆总氨基酸值明显下降。不同种类的氨基酸浓度下降并不一致。一般来说，必需氨基酸（essential amino acid, EAA）下降较非必需氨基酸（non-essential amino acid, NEAA）更为明显。在EAA中，缬氨酸、亮氨酸、异亮氨酸和甲硫氨酸的下降最多，而赖氨酸与苯丙氨酸下降相对较少。在NEAA中，大多数浓度不变，而酪氨酸和精氨酸出现明显下降。个别氨基酸（如胱氨酸等）浓度还可升高。不同疾病营养代谢的改变氨基酸谱随之改变。三、免疫功能细胞免疫功能在人体抗感染中起重要作用。蛋白质能量营养不良常伴有细胞免疫功能损害，这将增加病人术后感染率和死亡率。通常采用总淋巴细胞计数和皮肤迟发性超敏反应来评定细胞免疫功能。1.总淋巴细胞数目（total lymphocyte count, TLC）The number of lymphocytes in peripheral blood has been considered to be indicative of the degree of impairment of cell-mediated immune response in many nutritional disorders, in particular protein-energy malnutrition. In these cases lymphocyte count has been proposed as an important predictor of subsequent mortality.【临床意义】 TLC是评定细胞免疫功能的简易方法。但一些原发性疾病，如心功能衰竭，尿毒症，何杰金病，及使用免疫抑制剂肾上腺皮质激素等，均可使TCL降低，且TCL与预后相关性较差，因此TLC并非作为营养评定指数的可靠指标。临床上应结合其它指标作为参考评价。【计算公式】 【评价标准】 (2.53.0)l09/L为正常，(1.81.5)l09/L为轻度营养不良，(1.50.9)l09/L为中度营养不良，低于0.9l09/L为重度营养不良。2. 皮肤迟发性超敏反应（skin delayed hypersensitivity, SDH）Delayed cutaneous hypersensitivity (DCH) to a panel of ubiquitous antigens can be considered one of the oldest, most useful, and simplest tests for assessing cell-mediated immune function in vivo. In fact the development of an erythematous and indurative reaction at the site of the antigen injection implies an infect (afferent, central, efferent) response, confirming the ability to mount an efficient inflammatory response.【临床意义】 自从发现营养不良的病人有SDH反应异常，并可于接受营养治疗后恢复，SDH即作为营养状况，特别是细胞免疫功能判定的重要指标。常用抗原包括链激酶/链道酶(streptokinase-streptodomase, SK-SD)、流行性腮腺炎病毒素（mumps）、白色念珠菌提取液（candida）、植物血凝素（PHA）和结核菌素试验。将抗原于前臂表面皮内注射，待2448小时后测量接种处硬结直径。【评价标准】 直径大于5mm为正常。直径小于5mm时，表示细胞免疫功能不良，至少有重度蛋白质营养不良。四、维生素、微量元素维生素、微量元素是维持人体正常代谢和生理功能不可缺少的营养素。三大营养素成分的正常代谢及某些生化反应和生理功能的进行均需有维生素和微量元素的参与。处于应激状态（手术、烧伤、败血症等）的危重病人，对维生素和微量元素的需要量显著增加。多种地方病及疑难病的发生发展均与维生素和微量元素失衡有关。因此维生素和微量元素在临床医疗救治及营养评价中受到越来越多的关注。 五、氮平衡 Nitrogen balance (B) is measured as the difference between intake (I) and all losses, including urine (U), feces (F), skin (S), and miscellaneous minor losses (M):B = I - (U + F + S + M)B may be positive, negative, or zero. (For additional pertinent formulas, see Section VIA.)Nitrogen balance is affected by total energy intake. When ingested calories exceed need, protein needs fall, and nitrogen balance remains positive. When energy intake falls to near or below requirements, protein needs rise, and nitrogen balance tends to become negative unless protein intake increases substantially. Amino acid requirements in men have been estimated to range from 0.5g/kg/day when energy intake is high (57 kcal/kg/day), to over 1 g/kg/day when energy intake is low (40 kcal/kg/day). Even with high intake of energy, however, essential amino acid consumption below required levels will result in negative nitrogen balance. In a state of normal health and dietary adequacy in an adult, nitrogen balance is maintained, with intake matching losses.【临床意义】 氮平衡（nitrogen balance, NB）可反映摄入氮能否满足体内需要及体内蛋白质合成与分解代谢情况，有助于营养治疗效果判断，是评价蛋白质营养状况的常用指标。每日摄入氮量经体内利用后的剩余部分及体内代谢产生的氮，90%从尿中排出，其中主要排出形式是尿素，其余尿酸、肌酸酐、氨基酸及氨等称为非尿素氮，每天丢失量约2g，每天粪便氮丢失量为12mg/kg，汗及毛发等氮丢失为5mg/kg。【计算公式】B = I - (U + F + S )其中，B：氮平衡；I：摄入氮；U：尿氮；F：粪氮；S：皮肤等氮损失。一般认为成人每日经肾脏排出非尿素氮2g，粪氮丢失约1g，皮肤丢失氮约0.5g，故上式可写作： 氮平衡(g/d)=蛋白质摄入量(g/d)6.25-尿尿素氮(g/d)3.5(g/d)创伤和某些严重疾病发生时，尿中尿素氮和非尿素氮的排出量明显改变，此时应测尿总氮排出量，再计算氮平衡。 氮平衡(g/d)=蛋白质摄入量(g/d)6.25-尿总氮(g/d)1.5(g/d)当病人出现消化吸收功能紊乱时应分别检测尿总氮和粪氮，再计算氮平衡。 氮平衡(g/d)=蛋白质摄入量(g/d)6.25-尿总氮(g/d)-粪肥氮(g/d)【评价标准】 氮平衡为摄入氮和排出氮相等，提示人体代谢平衡；正氮平衡为摄入氮多于排出氮，适于生长期儿童；负氮平衡为摄入氮少于排出氮，通常提示饥饿或消耗性疾病。六、肌酐身高指数The excretion of creatinine in the urine is related to muscle mass. Normalized for height the 24-h creatinine excretion is an index of muscle mass. However, it is dependent upon complete 24-h urine collections and urinary losses or oliguria may result in an inappropriate diagnosis of malnutrition. Patients on diuretics such as those with cardiac and liver failure and those with renal disease are especially likely to have low excretions of creatinine.肌酐是肌肉组织中肌酸的代谢产物，因此肌酐的排出水平与肌肉组织（muscle mass）密切相关。常用指标是肌酐/身高指数（creatinine height index, CHI），即尿肌酐（Ucr）含量与其身高标准体重Ucr的比值。【临床意义】 CHI是表示瘦体组织空虚程度的灵敏指标，其优点在于：成人体内肌酸和磷酸肌酸的总含量较为恒定，每日经尿排出的肌酐量基本一致；运动和膳食的变化对尿中肌酐含量的影响甚微。故在评定24小时尿肌酐时不必限制膳食蛋白质；经K40计数测定，成人24小时尿肌酐排出量与瘦体组织量一致；在肝病等引起水肿情况而严重影响体重测定时，显得价值更大（因为CHI不受影响）。【计算公式】 【正常值】 男性约为l0001800mg/d，女性为700l000mg/d。【评价标准】 CHI90为正常，80%90%表示瘦体组织轻度缺乏，60%80%表示中度缺乏，60%表示重度缺乏。身高相对应的标准肌酐值见表7-4-2： 表7-4-2 不同性别身高相对应的标准肌酐值男 性 女 性 身高(cm)体重 (kg)Ucr(mmol/L)身高(cm)体重 (kg)Ucr(mmol/L)157.3160.0162.6165.1167.6170.2172.7175.3177.8180.3182.9185.4188.6190.5193.056.657.659.160.362.063.865.867.669.471.473.575.677.679.682.211.411.712.012.312.613.013.413.714.114.514.915.415.816.216.7147.0149.9152.4154.9159.5160.0162.6165.1167.6170.2172.7175.3177.8180.3182.946.147.348.950.051.452.754.