胰腺外分泌功能不全时非胰性脂肪消化酶的作用

消化食物脂肪的消化酶主要来自胰腺。在人类发现,非胰腺来源,即来自十二指肠以上部位的脂酶,可消化胃内脂肪,在小肠的作用次于胰腺。胰腺外分泌功能不全时,非胰性脂肪消化酶更显重要。作者曾报道胰腺囊性纤维变性(CF)患者Treitz韧带处非胰性脂肪消化酶占总消化酶的90%,主要有舌脂酶和胃脂酶,其特性与胰脂酶不同,最适pH较低,不依赖胆盐和辅脂酶。慢性酗酒引起的胰功能不全(API)患者餐后十二指肠     

急性胰腺炎的抗胰酶疗法

急性胰腺炎的发病是各种病因引起胰腺腺细胞的损害,胰腺和腺细胞内胰酶活化并逸脱到胰腺间质而导致胰腺自身消化。引起胰腺自身消化的始动因素是胰蛋白酶,少量胰蛋白酶原活化为胰蛋白酶,它可使胰蛋白酶原、糜蛋白酶原、弹力纤维酶原、羧肽酶原、血管舒缓素原、磷脂酶原A等胰酶相继活化,而损害胰腺组织。活化胰酶逸脱到血中可引起肾功不全、呼吸衰竭、肝功能障碍等多脏器损害,使病情恶化和发生休克,DIC等。因而抗胰酶疗法日益引起人们的重视,有人认为是治疗急性胰腺炎的内科疗法的中心。一、抗胰酶疗法的作用原理:胰酶活化后的破坏作用主要是通过胰蛋白酶和胰脂肪酶的消化作用产生的。弹力纤维酶原活化为弹力纤维酶破坏血管引起胰腺出血。磷脂酶原A活化为磷脂酶A使卵磷脂转变为溶血卵磷脂,溶血卵磷脂破坏细胞膜引起胰腺实质坏死及脂肪坏死。激肽原激活为各种激肽,特别是缓激肽,可引起内脏血管扩张、通透性增强、血容量减少     

轻度胰腺外分泌功能不足在消化疾患中的作用——文献复习

胰腺外分泌受下列因素的调节:交感、副交感神经、多种胃肠道激素、局部释放起作用的神经递质和胰-肠反射。胰腺外分泌有两种类型:1.导管型(对胰泌素起反应),分泌富含重碳酸盐的水样液体;2.腺泡型(对CCK-PZ起反应),分泌富含蛋白质的消化酶,包括淀粉酶、蛋白酶和脂肪酶。理论上,下列情况能引起胰原性消化不良状态:1,胰腺分泌完全缺乏或从肠道丧失;2,重碳酸盐分泌不足或不足以中和高胃酸;3,胰消化酶分泌不足。因此,胰原性消化紊乱可由高胃酸分泌状态、胰腺切除、肠旁路手术和胰腺的     

对脂肪胰的研究

脂肪胰以胰腺脂肪浸润或胰腺脂肪变性为主要表现,其病理生理学机制目前尚未完全明确,国内外也尚未形成统一的诊断标准或共识.组织学检查是脂肪胰诊断的“金标准”,临床上MRI、CT和腹部超声均能发现替代胰腺实质的脂肪组织,超声内镜（EUS）对脂肪胰的诊断具有一定优势.已有多项研究表明,脂肪胰与肥胖、T2DM、MS等疾病有关,胰腺脂肪变性的胰腺癌患者更易发生淋巴结转移及胰腺手术后的胰瘘,提示脂肪胰在以上疾病的诊断、治疗和预后判断上都有潜在价值,可能成为,如糖尿病、MS等代谢性疾病早期干预的指征之一.     

第五讲 胰酶与消化

胰液中的消化酶主要由胰腺的腺泡细胞合成、贮存和释放的。胰液的酶组成非常复杂,胰酶由不同成分按不同比例混合。胰液中蛋白质浓度为0.7%~10%,大部分为酶和酶原,其余为血浆蛋白、胰蛋白酶抑制物和粘蛋白。淀粉酶、脂肪酶和蛋白酶为三类主要的胰消化酶。在胰腺内除淀粉酶、脂肪     

胰酶替代治疗的临床实践

胰腺外分泌功能是指胰腺分泌胰酶和胰液.胰酶主要包括脂肪酶、蛋白酶(糜蛋白酶、胰蛋白酶)及淀粉酶.一般而言,慢性胰腺炎迁延近10 a才会出现脂肪酶分泌减少,而蛋白酶的变化则在15 a左右.当胰酶分泌量低于正常的10%时,临床上出现脂肪痢、粪中氮质增加、腹痛,淀粉吸收不良,其中以脂肪痢较突出[1].长期的吸收障碍将导致体重减轻、营养不良及 VitA,D,E,K缺乏.胰酶替代治疗的意义就在于其补偿缺乏的胰酶以改善症状、提高生活质量.然而,口服胰酶制剂受到胃酸、十二指肠酸度、胃排空和胰酶之间相互作用的影响,不同的剂型有其各自的优缺点.     

胰酶替代疗法在慢性胰腺炎中的应用

随着慢性胰腺炎的发病率逐年上升,越来越多的慢性胰腺炎患者出现胰腺内、外分泌功能不全,而胰腺外分泌 功能不全常表现为腹泻、脂肪泻、腹部不适、体重减轻、甚至营养不良等,严重影响了患者的生活质量。胰腺外分泌 功能不全主要保守治疗方式是胰酶替代疗法。近期研究证实,胰酶替代疗法可改善慢性胰腺炎患者的脂肪吸收率、 氮吸收率、粪便脂肪排泄、粪便氮排泄,以及腹痛和腹胀等症状,无明显不良事件发生。     

胰腺疾病时弹力酶的分泌

弹力酶是胰腺蛋白酶中唯一能水解固体弹力纤维的酶.急性出血性胰腺炎中血管损伤的发生被认为主要是弹力酶的作用.曾有报告,急性胰腺炎和其他胰腺疾病时血清内测得弹力酶I的免疫活性增高.本文旨在估价十二指肠液中弹力酶及其他胰酶在促胰酶素-胰泌素试验(PS试验)中的诊断价值.     

第五讲急、慢性胰腺炎的酶学变化

胰腺是一个具有内分泌和外分泌双重功能的重要器官。其中胰岛是内分泌腺 ,能分泌胰岛素、胰高糖素、生长抑素等激素。胰腺腺泡是外分泌的功能单位 ,其所分泌的胰液含有丰富的碳酸氢盐和消化蛋白质、脂肪和糖类的酶。本文主要复习急、慢性胰腺炎时的酶学变化。　　一、胰腺细胞内酶的研究正常胰腺分泌多种消化酶 ,其中以淀粉酶、蛋白酶和脂肪酶为主 ,还有磷脂酶Ａ2 、弹性蛋白酶、核糖核酸酶等[1] 。在胰腺内除淀粉酶、脂肪酶和核糖核酸酶为活性酶外 ,其余均以无活性的酶原形式存在 ,因而可防止胰腺自身消化。目前的共识认为 ,急性胰腺炎最基…     

甲状旁腺功能亢进症合并重症急性胰腺炎1例报告

急性胰腺炎(acute pancreatitis)是常见的急腹症之一,是多种病因导致胰酶在胰腺内被激活后引起胰腺组织自身消化、水肿、出血甚至坏死的炎症反应。临床以急性上腹痛、恶心、呕吐、发热和血胰酶增高等为特点。其不仅是胰     

Pancreatic enzyme therapy for pancreatic exocrine insufficiency

Pancreatic exocrine insufficiency with steatorrhea is a major consequence of pancreatic diseases (eg, chronic pancreatitis, cystic fibrosis, severe acute necrotizing pancreatitis, pancreatic cancer), extrapancreatic diseases such as celiac disease and Crohn’s disease, and gastrointestinal and pancreatic surgical resection. Recognition of this entity is highly relevant to avoid malnutrition-related morbidity and mortality. Therapy for pancreatic exocrine insufficiency is based on the oral administration of pancreatic enzymes aiming at providing the duodenal lumen with sufficient active lipase at the time of gastric emptying of nutrients. Administration of enzymes in the form of enteric-coated minimicrospheres avoids acid-mediated lipase inactivation and ensures gastric emptying of enzymes in parallel with nutrients. Nevertheless, such factors as acidic intestinal pH and bacterial overgrowth may prevent normalization of fat digestion even in compliant patients. The present article critically reviews current therapeutic approaches to pancreatic exocrine insufficiency.     

Protein digestion and absorption in man. Normal mechanisms and protein-energy malnutrition.

Protein is an essential nutrient normally assimilated in an efficient manner following the action of gastric, pancreatic and small intestinal enzymes. After hydrolysis, protein digestion products in the form of amino acids and small peptides undergo mucosal uptake by distinct transport mechanisms. Although gastric and pancreatic enzymes are important, the small intestine appears to be the critical rate-limiting tissue in this process. Impaired intake, assimilation or excessive enteric protein loss may occur with several diseases leading to protein-energy malnutrition. Although the clinical and laboratory features of this condition are nonspecific and wide ranging in spectrum, their presence may provide a clue to underlying disease and serve as an index of patient nutritional status. Disease of the exocrine pancreas or small intestine may cause significant protein-energy malnutrition which, in turn, can cause major structural and functional abnormalities in these tissues.     

New diagnostic criteria of acute pancreatitis

Practical guidelines for the diagnosis of acute pancreatitis are presented so that a rapid and adequate diagnosis can be made. When acute pancreatitis is suspected in patients with acute onset of abdominal pain and tenderness mainly in the upper abdomen, the diagnosis of acute pancreatitis is made on the basis of elevated levels of pancreatic enzymes in the blood and/or urine. Furthermore, other acute abdominal diseases are ruled out if local findings associated with pancreatitis are confirmed by diagnostic imaging. According to the diagnostic criteria established in Japan, patients who present with two of the following three manifestations are diagnosed as having acute pancreatitis: characteristic upper abdominal pain, elevated levels of pancreatic enzymes, and findings of ultrasonography (US), CT or MRI suggesting acute pancreatitis. Detection of elevated levels of blood pancreatic enzymes is crucial in the diagnosis of acute pancreatitis. Measurement of blood lipase is recommended, because it is reported to be superior to all other pancreatic enzymes in terms of sensitivity and specificity. For measurements of the blood amylase level widely used in Japan, it should be cautioned that, because of its low specificity, abnormal high values are also often obtained in diseases other than pancreatitis. The cut-off level of blood pancreatic enzymes for the diagnosis of acute pancreatitis is not able to be set because of lack of sufficient evidence and consensus to date. CT study is the most appropriate procedure to confirm image findings of acute pancreatitis. Elucidation of the etiology of acute pancreatitis should be continued after a diagnosis of acute pancreatitis. In the process of the etiologic elucidation of acute pancreatitis, judgment whether it is gallstone-induced or not is most urgent and crucial for deciding treatment policy including the assessment of whether endoscopic papillary treatment should be conducted or not. The diagnosis of gallstone-induced acute pancreatitis can be made by combining detection of elevated levels of bilirubin, transamylase (ALT, AST) and ALP detected by hematological examination and the visualization of gallstones by US.     

Pancreatic enzyme replacement therapy

Malabsorption due to severe pancreatic exocrine insufficiency is one of the most important late features of chronic pancreatitis. Generally, steatorrhea is more severe and occurs several years prior to malabsorption of other nutrients because synthesis and secretion of lipase are impaired more rapidly, its intraluminal survival is shorter, and the lack of pancreatic lipase activity is not compensated for by nonpancreatic mechanisms. Patients suffer not only from nutritional deficiencies but also from increased nutrient delivery to distal intestinal sites, causing symptoms by profound alteration of upper gastrointestinal secretory and motor functions. Adequate nutrient absorption requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. The following recommendations are based on modern therapeutic concepts: 25,000 to 40,000 units of lipase per meal using pH-sensitive pancreatin microspheres, with dosage increases, compliance checks, and differential diagnosis in case of treatment failure. Still, in most patients, lipid digestion cannot be completely normalized by current standard therapy, and future developments are needed to optimize treatment.     

The effect of enzyme substitution in patients with pancreatic insufficiency

Concentrations of pancreatic enzymes in the upper intestine during digestion of a meal were studied with and without different preparations of pancreatic extracts in 34 patients with severely decreased exocrine pancreatic function and in 17 patients with a partial gastrectomy (Billroth-II) and very low enzyme concentrations in the efferent loop. Granulated Pankreatin induced a dose-related increase in concentrations of amylase, lipase, and trypsin in the patients studied. The standard dose of 10 ml induced normalization of amylase and trypsin concentrations in a considerable number of patients, whereas the lipase concentration still was far below normal value. The increased concentrations of lipase resulted in a marked reduction of the fecal fat excretion. The induced increase in enzyme concentrations was for all enzymes significantly higher in the partially gastrectomized patients. Eight other pancreatic supplementary preparations were tested; only one of these was able to induce significant increases in enzyme concentrations.     

Elastase Secretion in Pancreatic Disease

To estimate the diagnostic value of elastase output in the duodenal aspirates during a pancreozymin secretin test, elastase as well as amylase, chymotrypsin, trypsin, and lipase was determined in 46 controls and 61 patients with various disease. The elastase output decreased significantly in chronic pancreatitis (mild exocrine insufficiency 13 and advanced eight), pancreatic cancer (n = 10), and liver cirrhosis (n = 14) when compared with the controls. The outputs of the four other enzymes also decreased in chronic pancreatitis and pancreatic cancer, not in liver cirrhosis. Low elastase output was found in four of 13 chronic pancreatitis patients with mild exocrine insufficiency, whereas low outputs of the other enzymes were observed in only one or less of the 13. The ratio of elastase to amylase alone was significantly lower in the pancreatic diseases. The results suggest that elastase is the most susceptible enzyme to pancreatic dysfunction and that its output and its ratio to amylase output provide a valuable index to assess the enzyme secretory capacity in the pancreatic diseases.     

Diagnosis and treatment of pancreatic exocrine insufficiency

Pancreatic exocrine insufficiency is an important cause of maldigestion and a major complication in chronic pancreatitis.Normal digestion requires adequate stimulation of pancreatic secretion,sufficient production of digestive enzymes by pancreatic acinar cells,a pancreatic duct system without significant outflow obstruction and adequate mixing of the pancreatic juice with ingested food.Failure in any of these steps may result in pancreatic exocrine insufficiency,which leads to steatorrhea,weight loss and malnutrition-related complications,such as osteoporosis.Methods evaluating digestion,such as fecal fat quantification and the13C-mixed triglycerides test,are the most accurate tests for pancreatic exocrine insufficiency,but the probability of the diagnosis can also be estimated based on symptoms,signs of malnutrition in blood tests,fecal elastase 1 levels and signs of morphologically severe chronic pancreatitis on imaging.Treatment for pancreatic exocrine insufficiency includes support to stop smoking and alcohol consumption,dietary consultation,enzyme replacement therapy and a structured follow-up of nutritional status and the effect of treatment.Pancreatic enzyme replacement therapy is administered in the form of enteric-coated minimicro-spheres during meals.The dose should be in proportion to the fat content of the meal,usually 40-50000 lipase units per main meal,and half the dose is required for a snack.In cases that do not respond to initial treatment,the doses can be doubled,and proton inhibitors can be added to the treatment.This review focuses on current concepts of the diagnosis and treatment of pancreatic exocrine insufficiency.     

The current managements of pancreatic diabetes in Japan

Pancreatic diabetes is secondary diabetes followed by progressions of pancreatic exocrine diseases, such as chronic pancreatitis, pancreatic neoplasm and post-pancreatectomy. Because of destruction and reduction of the pancreatic endocrine and exocrine functional compartments, patients with pancreatic diabetes frequently show malnutrition from maldigestion and malabsorption by insufficiencies in pancreatic digestive enzymes, and show unstable glycemic control and prolonged hypoglycemia by insufficiencies in synthesis and secretion of insulin and glucagon. Epidemiological studies have suggested that the incidence and development of pancreatic diabetes in patients with chronic pancreatitis (CP) depends on several risk factors, such as alcohol intake, the presence of pancreatic calcification and the long-term duration of CP. The clinical management of pancreatic diabetes is divided into two parts: one is the supplementation of pancreatic digestive enzymes and the other is the achievement of appropriate glycemic control. The appropriate and sufficient pancreatic exocrine replacement therapy is important for the maintenance of better nutrient conditions for patients with pancreatic diabetes. Furthermore, the intensive insulin therapy combined with short- or ultra-short-acting insulin and long-acting insulin glargine can be achieved for stable glycemic control and reduction of severe frequent hypoglycemia in patients with pancreatic diabetes. These current advanced management techniques against insufficiencies of pancreatic exocrine endocrine functions are beneficial for improving and maintaining the quality of life in patients with pancreatic diabetes.     

Behaviour of serum pancreatic enzymes in chronic pancreatitis

AIM: To establish whether serum pancreatic enzyme determination is useful in the identification of patients with chronic pancreatitis and in revealing the presence of exocrine pancreatic insufficiency PATIENTS AND METHODS: A total of 50 patients with chronic pancreatitis were included in the investigation: 19 were studied during a painful attack of the disease and 31 were observed during clinical remission of the disease and underwent a secretin-caerulein test; 21 of the 31 patients had severe pancreatic insufficiency. Thirty patients with non-pancreatic digestive diseases were also studied. Serum amylase, pancreatic isoamylase, lipase, trypsinogen and elastase- were determined in all patients. RESULTS: Serum levels of the 5 enzymes studied were significantly higher in patients with pancreatic pain than in those studied during a clinical remission of the disease, and in those with non-pancreatic digestive diseases. In patients with chronic pancreatitis studied during clinical remission of the disease serum levels of pancreatic isoamylase and trypsinogen were significantly lower than in those patients with non-pancreatic digestive diseases. Considering only low serum concentrations of the five enzymes studied in diagnosing chronic pancreatitis, trypsinogen showed a sensitivity of 28%, specificity of 100%, a predictive value of a positive test of 100% and a predictive value of a negative test of 96.4%. In the 21 patients with severe pancreatic insufficiency, abnormally low serum concentrations of trypsinogen were found in 12 patients (57%), of lipase and elastase-1 in 6 (29%), of pancreatic isoamylase in 5 (24%), and of amylase in 3 (14%). CONCLUSIONS: Serum pancreatic enzymes can not be considered a useful tool to identify patients with pancreatic insufficiency. However, of the five enzymes studied, serum trypsinogen appears to be a useful marker in the diagnostic work-up of chronic pancreatitis.     

Isolated co-lipase deficiency in two brothers.

Two normally developed Assyrian brothers with isolated pancreatic co-lipase deficiency are described. They presented at the age of 5-6 years with loose stools. They had steatorrhoea, and analysis of exocrine pancreatic enzymes in the small intestine showed co-lipase deficiency, while amylase, chymotrypsin, trypsin and lipase were normal. Intraduodenal infusion of purified co-lipase improved fat digestion measured by the triolein breath test. Their steatorrhoea diminished on treatment with enteric-coated pancreatic enzymes.