Pancreas complications

Diabetes mellitus is a complicated, chronic disorder characterized by either insufficient insulin production by the beta cells of die pancreas or by cellular resistance to insulin. Insulin insufficiency results in elevated blood glucose levels, or hyperglycemia As a result of the disease, individuals with diabetes are at greater risk for a number of disorders, including myocardial infarction, cerebrovascular accident (stroke), blindness, kidney disease, and lower limb amputations. 

Insulin is necessary for controlling type 1 diabetes mellitus that is caused by a marked decrease in the amount of insulin produced by die pancreas. Insulin is also used to control the more severe and complicated forms of type 2 diabetes mellitus. However, many patients can control type 2 diabetes with diet and exercise alone or with diet, exercise, and an oral antidiabetic drug (see section Oral Antidiabetic Dmgp ). Insulin may also be used in the treatment of severe diabetic ketoacidosis (DKA) or diabetic coma. Insulin is also used in combination with glucose to treat hypokalemia by producing a shift of potassium from die blood and into die cells. 

A patient with acute pancreatitis may develop many severe local and systemic complications. Local complications involve fluid collection, necrosis, or abscess in the pancreas. A pancreatic fluid collection (or pancreatic pseudocyst) is a collection of tissue, pancreatic enzymes, and blood that forms weeks after acute pancreatitis. Many pancreatic pseudocysts resolve spontaneously, but some require surgical drainage.5 Rupture of a pancreatic pseudocyst with associated erosion and hemorrhage of major abdominal blood vessels can have a mortality approaching 60% thus, continued monitoring of a pseudocyst is prudent.6... 

It is common practice to discontinue oral feedings during an attack of acute pancreatitis. In theory, discontinuation of oral intake will decrease the secretory functions of the pancreas and minimize further complications from the disease. Some patients can be fed with minimal oral intake. Tube feeding delivered via a nasojejunal tube will feed the patient beyond the ampulla of Vater, minimizing stimulation of the pancreas.15,16 If oral intake is discontinued for a protracted period, total parenteral nutrition must be used to maintain adequate nutrition.17,18... 

Large quantities of pure insulin are required for the treatment of diabetes mellitus (see p. 160). The annual requirement for insulin is over 500 kg in a country the size of Germany. Formerly, the hormone had to be obtained from the pancreas of slaughtered animals in a complicated and expensive procedure. Human insulin, which is produced by overexpression in genetically engineered bacteria, is now mainly used (see p.262). 

Tolbutamide is one of the most widely used antidiabetic agents. Its action is preferably connected with stimulatory action of j3-cells in the pancreas, which results in intensive insulin secretion. It is used for type II diabetes melhtus of medium severity with no expressed microvascular complications. Synonyms of this drug are mebenol, oramid, ora-bet, tolbuton, butamide, rastinon, and others. 

This drug is also a derivative of first generation of sulfonylurea, and it possesses stimulatory action on 8-cells in pancreas, as well as the same range of action as all other drugs of the group of examined compounds. Tolazamide is used for non-insulin-dependeut diabetes mellitus without expressed microvascular complications. Synonyms of this drug are uor-glycin, tolanase, and others. 

Cyclosporine has been approved for use in allogeneic kidney, liver, and heart transplant patients and is under study for use in pancreas, bone marrow, single lung, and heart-lung transplant procedures. It is recommended that corticosteroids, such as prednisone, be used concomitantly, although at half or less of their usual dose. Such combined therapy leads to fewer side effects, a decreased incidence of infectious complications, efficacy of lower doses of cyclosporine, and a better history of patient survival. 

Managing the Complications of Diabetes. Diabetes is more than just a disorder of elevated glucose it is a systemic disease that affects many organ systems. In addition to the metabolic problems there are numerous neurological, circulatory, and renal complications, even when the blood glucose level is properly controlled. The main reason is the unnatural administration of insulin by injection, instead of the constant secretion by the pancreas in response to changing blood glucose levels. Diabetics have a predisposition of atherosclerosis, with an increased risk for heart attacks and stroke. 

The relationship between diet and cancer risk is extremely complex (7). Factors that appear to enhance carcinogenesis under one set of conditions may have no effect or even inhibit carcinogenesis under different conditions (2). The link between dietary fat and cancer is complicated by many factors, in particular total calorie intake and fatty acid composition (2). Among the fatty acids that comprise lipid, only linoleic acid is clearly linked to the enhancement of carcinogenesis in rat manunary gland (5), pancreas (4) and colon (5). 

Diazoxide inhibits insulin release from the pancreas (probably by opening potassium channels in the beta cell membrane) and is used to treat hypoglycemia secondary to insulinoma. Occasionally, hyperglycemia complicates diazoxide use, particularly in persons with renal insufficiency. 

The closed-loop type artificial pancreas (specifically 8-cell), which consists of an automatic continuous monitor of blood glucose level (BGL) and an automatic injector of insulin which are coupled with feed-back system, has great potential for prevention of diabetic complication such as micro-angiopathies(l). A large-scale closed-loop type artificial pancreas for bedside use has already been developed and is clinically used at some laboratories and hospitals (2-4). However, this device is limited to only bedside use. On the other hand, the open-loop type artificial pancreas which consists of only a insulin injecting pump without an automatic continuous monitor of BGL, has been developed and is going to be clinically used(5-7). This system, however, can not completely control BGL as well as the bare pancreas in a normal body and often causes lower BGL(8-9). 

The sensitivity and specificity of plain film and contrast study in acute pancreatitis are low. Therefore, they are mostly used to demonstrate complications of AP. Percutaneous sonography is usually the imaging method of choice in patients with acute abdominal distress due to its wide availability, but in the case of AP the distended intestine often impairs adequate visualization of the pancreas. Still, sonography may be used as an excellent imaging modality for short-term follow-up studies, particularly in extremely ill patients who are unable to undergo computed tomography (CT). 

Human pancreatic secretory trypsin inhibitor (hPSTI) can be potentially assayed as an indicator of necrotic complications in AP (Ol). This protein is an inhibitor of trypsinogen, which is produced in acinar cells in the quantity of approximately 2% of the potential content of trypsin in pancreas. Trypsin binds with its inhibitor hPSTI, then with AMG, and only this complex, trypsin-o 2-macroglobulin, is eliminated from plasma (B10). Pezzili (P3) suggests that early attempts to determine the severity of the AP process based on the measurement of hPSTI within 24 hr from the first sensations of pain show a sensitivity of 79%, whereas an increase in CRP concentration has a sensitivity of 29% only (Table 3). 

H7. Hietaranta, A., Kemppainen, E., Puolakkainen, P., Sainio, V., Haapiainen, R., Peuravuori, H., Kivilaakso, E., and Nevalainen, T., Extracellular phospholipases A2 in relation to systemic inflammatory response syndrome (SIRS) and systemic complications in severe acute pancreatitis. Pancreas 18, 385-391 (1999). 

Pathogenesis and complications (A). Type I diabetes mellitus typically manifests in childhood or adolescence (juvenile onset diabetes mellitus) it is caused by the destruction of insulin-producing B cells in the pancreas. A genetic predisposition together with a precipitating factor (viral infection) could start an autoimmune reaction against B-cells. Replacement of insulin (daily dose-40U, equivalent to -1.6 mg) becomes necessary. 

The acinar cells of pancreas synthesize, not only structural proteins and enzymes for their own metabolism, but also exocrine or exportable enzymes which are carried into the duodenum for digestive purposes. To this dual function corresponds a rather complicated system involving, besides biosynthesis itself, segregation, transport, storage, and final excretion. 

In Type-I diabetes, which is due to the loss of insulin-producing cells as a consequence of autoimmune disorders, substitution of insulin is the most important measure. However, merely to inject one daily dose is not an adequate therapy. Here, the objective is to mimic the daily variations in plasma insulin which are closely related to food intake. One such attempt which has improved microvascular complications is intensified insulino-therapy through multiple daily injections of insulin. Another approach is to develop techniques of islet transplantation and using a bioartificial pancreas. In the case of islet transplantation, tissues will not only respond to changes in blood glucose levels but also to hormones of the entero-insular axis. 

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