Pancreatic Functions & Chemical Pathology PDF

PANCREAS FUNCTION & CHEMICAL PATHOLOGY 26/11/2024 (Tuesday Groups) 27/11/2024 (Wednesday Groups) Prof. Dr. Halil RESMİ  The pancreas is an elongated, flattened pyramidal organ that is located mostly behind the stomach,  The tail points the spleen, and the head is nestled in...

PANCREAS FUNCTION & CHEMICAL PATHOLOGY 26/11/2024 (Tuesday Groups) 27/11/2024 (Wednesday Groups) Prof. Dr. Halil RESMİ  The pancreas is an elongated, flattened pyramidal organ that is located mostly behind the stomach,  The tail points the spleen, and the head is nestled in the duodenal loop,  It is a soft, easily traumatized gland lies behind the peritoneum, the membrane lining the abdominal cavity. 2 3  The exocrine secretions are drained by ductules that combined into a single pancreatic duct. In most individual, this duct join the common bile duct at the Ampulla of Vater. 4 5  Exocrine acinar cells  Exocrine acinar cells account for more than 98% of the pancreatic mass. About 1% of pancreas consist of cells clusters, the islet of Langerhans, that produce endocrine hormones. Pancreas contains about 1 million islets. 6  ENDOCRINE PHYSIOLOGY 8   Pancreatic endocrine secretion from the islets of Langerhans include the hormone ; 9  EXOCRINE PHYSIOLOGY 10  Normal Pancreatic Exocrine Secretion  The pancreas produces at least 22 digestive enzyme, 15 of which is proteases,  Pancreatic enzymes act on three major dietary sources of energy; proteins, lipids and complex carbohydrates.  The functional unit of the exocrine pancreas consist of acini that stores most of the digestive enzyme in inactive forms (zymogen) in zymogen granules. 11   The proenzyme forms of proteolytic enzymes prevents the autodigestion of the zymogen granules, the acinar cells, and the pancreas itself.  The pancreas also secretes protease inhibitors to neutralize any improperly activated enzymes.  Congenital deficiency of one of the major trypsinogen inhibitors, such as serine protease inhibitor Kazal type 1 causes inherited predisposition to acute pancreatitis. 13   In the duedonum, a brush border enzyme, enterokinase convert trypsinogen to trypsin and free trypsin activates other pancreatic proenzymes to their activated forms. 14  Normal Pancreatic Fluid Secretion  A normal adult secretes about 2 to 3 liters of pancreatic juice per day.  This fluid contains bicarbonate ions (120-300 mmol/day). 15   Pancreatic juice is also rich in enzyme,  It has an amylase and lipase activities about 500,000 to 1 million U/L.  Plasma has only approx. 1:10,000 of these enzyme activities.  A damage to pancreas thus can cause considerable increase in plasma amylase, lipase, trypsin and other digestive enzymes. 16  Control of Exocrine Pancreatic Secretions  Exocrine secretions are regulated both neural and hormonal ways.  The upper GI tract hormones; cholecystokinine (CCK), secretin and gastrin affect pancreatic juice secretion.  Ingestion of ethanol or distention of the duodenum by foods (as chyme) leads to release of all these hormones. 17 18  PATHOLOGICAL CONDITIONS Disease of pancreas can be grouped into;  Islet disorders,  Diabetes  Glucagon excess  Exocrine insufficiency,  Inflammatory disorders(such as acute and chronic pancreatitis),  Neoplastic disorders (such as adenocarcinomas and islet cell tumors). 20  Endocrine Pancreatic Disorders Diabetes Mellitus  The major endocrine disorder is diabetes mellitus (DM)  Diabetes is characterized by; 1. Inadequate insulin secretion that called type 1 diabetes 2. Insulin resistance, type 2 diabetes  Pancreatic islet cell tumors often are associated with overproduction of hormones,  Different tumors thus can create distinct clinical syndromes. 21  Exocrine Pancreatic Disorders 22  Inflammatory or Necrotic Pancreatic Injury Acute Pancreatitis  Acute pancreatitis is an inflammatory disorder that associated with activation of local pancreatic anzymes,  This activation causes destruction of pancreatic tissue,  Severe form of acute pancreatitis can be a life- threating emergency. 23  Acute Pancreatitis  The most common reasons of acute pancreatitis;  Alcohol abuse,  Biliary tract obstruction by gallstone.  These two conditions are responsible for about 75% of cases of acute pancreatitis.  The inappropriate activation of pancreatic enzymes causes acute pancreatitis,  Gallstones cause inflammation because of an obstruction of pancreatic duct and prevent the fluid flow to duodenum. 24 25  Acute Pancreatitis  A lab tests of ALT over 150 U/L is predictive for gallstone pancreatitis.  The severity of pancreatitis increases the mortality risk.  Serum amylase and lipase are useful for diagnosis, but these enzymes are not useful to predict the severity of pancreatitis. 26  CRP in pancreatitis  The most important inflammatory marker in recent years is CRP, although it does not have a diagnostic value, it is useful to assess the prognosis. 27 28  Chronic Pancreatitis  Chronice pancreatitis is often a consequence of repeated acute pancreatitis, is not common disease,  In some cases there is a extensive destruction of the glands that causes diabetes.  During episodes of acute exacerbation, serum activities of amylase and lipase are increased, but between episodes it may be below the lower limit of normal in up to 60% of cases. 29  Cystic Fibrosis  It is an autosomal recessive inherited disease,  Cystic fibrosis is caused by a number of different mutation in the chloride transport gene,  These mutation lead to a nonfunctional CFTR protein which play a role in the selective up take of ions.  In CF, pancreatic secretions are viscous and of low volume that results in pancreatic obstruction.  Newborn screening test for CF based on serum immunoreactive tyrpsin (IRT) test. 30  Pancreatic Insufficiency  Reduction or loss of pancreatic exocrine function leads, in its late stages, to severe gastrointestinal disturbances;  Diarrhea,  Conspitation,  Malabsorption,  Weight loss,  Cachexia.  The exocrine pancreas has extensive reserve capacity; symptomes generally appears only after about 85% to 90% of acinar tissue has been lost. 31   The most common causes of pancreatic insufficiency;  In children; Cystic Fibrosis  In adults; Chronic Pancreatitis 32  Pancreatic Neoplasms Adenocarcinoma  Most pancreatic cancers are adenocarcinomas that rise from the ductal epithelial cells and have a worse prognosis. Islet Cell Tumors  Islet tumors account for only about 1% of pancreatic neoplasms,  They are often identified by hormone production,  Clinical pictures depend on the excess of hormone production. 33  Insulimoma  It is a insulin producing tumor of the pancreatic islets,  Excessive insulin causes hypoglycemia,  Although insulinoma is the most common islet cell tumor, it is a rare disease. Glucagonoma  Tumors that produce glucagon have distictive combination of hyperglycemia, weight lost, and peculiar skin rush. 34  EXOCRINE PANCREATIC TESTS  The best biological samples to evaluate pancreas function is duodenal fluid.  Bicarbonate and/or pancreatic enzymes (especially amylase, lipase and chymotrypsin) can be measured in this fluid,  The obtaining of this fluid is difficult and is not used. 36  Test on Feces  The low and moderate grade disorders of pancreatic acinar tissue are not reflected in stool,  Fat excretion becomes abnormal only after 85% to 90% of pancreatic acinar tissue is lost,  Tests for trypsin and chymotrypsin in feces are not sensitive.  The measurement of elastase 1 in stool controversial. 37  Indirect Test of Pancreatic Function  The well known indirect test is N-benzoyl tyrosyl para-aminobenzoic acid (NBT-PABA).  The test is used in only few laboratories to estimate pancreatic function.  Pancreatic enzyme tests measure the levels of pancreatic enzyme in the blood as markers of cellulary injury in the pancrease,  The two most widely used tests are amylase and lipase. 38  CHANGE IN ANALYTES WITH DISEASE 39  Amylase and Lipase  Although imagining studies often are used to identify pancreatitis, diagnosis is typically based on increased serum amylase, lipase, and immunoreactive trypsin.  The gradient of amylase between the pancreas and the plasma is high, making amylase a sensitive test of pancreatic injury. 40   Lipase is much more specific for pancreatitis than amylase.  The Guideline of American Gastroenterological Association suggests that the use of only one of enzymes is enough to diagnose pancreatitis.  UK guidelines state that lipase is the preferred test for diagnosis of acute pancreatitis. 41  Cancer Markers  The most widely used tumor marker is CA19-9.  It is not specific to pancrease.  There is a marked elevation of CA 19-9 blood levels in benign obstruction of the biliary tract, as well as in cirrhosis.  It can be used to evaluate patient’s response to treatment for some types of pancreatic cancer, especially advanced pancreatic cancer. 42  Endocrine Tumor Markers  About 20% of islet cell tumors are biochemically silent and do not secrete active hormones.  Islet cell tumors can secrete one or more of the following hormones;  Insulin  Glucagon  Gastrin  Vasoactive intestinal peptide (VIP)  Adrenocorticotropic hormone (ACTH)  Secretin  Serotonin  Calcitonin. 43  Insulin  Insulin levels are best reported by a ratio of insulin to glucose,  A ratio above 0.3 indicates inappropriate insulin production,  In insulinoma, the ratio increases along with elevated C-peptide,  Exogenous insulin administretion causes a high ratio but undetectable C-peptide. 44  Glucagon  Diagnosis of glucagonomas depend on measurement of plasma glucagon,  The upper limit is 200 pg/mL,  70% to 90% of cases have a glucagon levels greater than 1000 pg/mL,  Increased glucagon also occurs in renal failure, starvation, pancreatitis, but in these cases glucagon levels rarely above 500 pg/mL. 45