Lecture 5: Pancreas

endocrine and exocrine organ located retroperitoneally in the upper abdomen overlying the spine is supplied by the gastroduodenal arteries and by branches of the splenic artery

Accounts for only 2% of the pancreatic mass Nests of cells - islets of Langerhans Four major cell types Alpha (A) cells secrete glucagon Beta (B) cells secrete insulin Delta (D) cells secrete somatostatin F cells secrete pancreatic polypeptide

Synthesized in the B cells of the islets of Langerhans 80% of the islet cell mass must be surgically removed before diabetes becomes clinically apparent Proinsulin, is transported from the endoplasmic reticulum to the Golgi complex where it is packaged into granules and cleaved into insulin and a residual connecting peptide, or C peptide

Secreted by the A cells of the islet Glucagon elevates blood glucose levels through the stimulation of glycogenolysis and gluconeogenesis Major stimulants Aminoacids, Cholinergic fibers, β-Sympathetic fibers Major inhibitors Glucose, insulin, somatostatin, α-sympathetic fibers

Secreted by the D cells of the islet Inhibits the release of growth hormone Inhibits the release of almost all peptide hormones Inhibits gastric, pancreatic, and biliary secretion Used to treat both endocrine and exocrine disorders

Cholecystokinin is the most potent endogenous hormone known to stimulate enzyme secretion.

Secretin is the most potent endogenous stimulant of pancreatic electrolyte secretion.

Secretion of water and electrolytes originates in the centroacinar and intercalated duct cells Pancreatic enzymes originate in the acinar cells Final product is a colorless, odorless, and isosmotic alkaline fluid that contains digestive enzymes (amylase, lipase, and trypsinogen)

Alkaline pH results from secreted bicarbonate which serves to neutralize gastric acid and regulate the pH of the intestine

Centroacinar cells and ductular epithelium secrete 20 mmol of bicarbonate per liter in the basal state Fluid (pH from 7.6 to 9.0) acts as a vehicle to carry inactive proteolytic enzymes to the duodenal lumen Sodium and potassium concentrations are constant and equal those of plasma Chloride secretion varies inversely with bicarbonate secretion

Major stimulants Secretin, Cholecystokinin, Gastrin, Acetylcholine Major inhibitors Atropine, Somatostatin, Pancreatic polypeptide and Glucagon

Bicarbonate is formed from carbonic acid by the enzyme carbonic anhydrase

Acinar cells secrete isozymes, trypsin, chymotrypsin, amylases, lipases, and proteases Major stimulants Cholecystokinin, Acetylcholine, Secretin, VIP Synthesized in the endoplasmic reticulum of the acinar cells and are packaged in the zymogen granules Released from the acinar cells into the lumen of the acinus and then transported into the duodenal lumen, where the enzymes are activated.

secreted by the pancreas in an active form functions optimally at a pH of 7 hydrolyzes starch and glycogen to glucose, maltose, maltotriose, and dextrins

function optimally at a pH of 7 to 9 emulsify and hydrolyze fat in the presence of bile salts

essential for protein digestion secreted as proenzymes and require activation for proteolytic activity duodenal enzyme (enterokinase) converts trypsinogen to trypsin Trypsin, in turn, activates chymotrypsin, elastase, carboxypeptidase, and phospholipase Within the pancreas, enzyme activation is prevented by an antiproteolytic enzyme secreted by the acinar cells

• basal secretion - every 1 to 2 hours by bursts of increased bicarbonate and enzyme secretion that last 10 to 15 minutes. 2.postprandial stage which results from a complex interaction of neural and hormonal mechanisms

Trypsin and chymotrypsin are the initiating enzymes; their release can in turn result in the release and activation of other proenzymes (including zymogen granules, procollagenase and phospholipases). Trypsin damages endothelial cells and mast cells, resulting in the release of histamine. This major inflammatory mediator enhances vascular permeability, leading to edema, hemorrhage and the activation of the kallikrein system, which in turn results in the production of vasoactive peptides or kinins

Acute Pancreatitis - Severe abdominal pain in which the pancreas appears to digest itself. Vomiting, nausea, pain radiating to back, chest - It is usually caused by gallstones, alcohol or is idiopathic. Chronic Pancreatitis - an irreversible scarring of the pancreas with permanent loss of pancreatic function that typically causes unrelenting abdominal pain. Hereditary Pancreatitis - a unusual form of acute and chronic pancreatitis that runs in families.

Alcohol Trauma Gall stones ERCP Damage to the pancreas leads to the activation of pancreatic enzymes IN THE PANCREAS Leading to pancreatic necrosis and autodigestion of the tissues of the abdomen

Lipase (> Sensitivity and >Specificity) Amylase Ca2+ Profile Triglycerides (above must be done first with first episode for etiology) CBC BUN/Cr LFT’s – ALT >150 IU/L high Spec for Stones Urinalysis (lipase, amylase so high leaks into ciruclation and excreted)

Amylase is the indicator of acute pancreatitis presence (NOT how severe) Lipase indicates presence of acute pancreatitis but not severity, more specific than amylase. if one increased then early pancreatitis, both then confirms Urinary TAP (Trypsinogen activation peptide) specific for severe acute pancreatitis, low level excludes severe acute pancreatitis Only found in plasma / urine in the case of SEVERE acute pancreatitis

Chronic pancreatitis is defined as a continuing chronic inflammatory process of the pancreas, characterized by irreversible morphological changes. Cause issues to endocrine and exocrine pancreas

No, sustained irreversible scarring and inflammation of the pancreas leading to fibrosis and calcification.