4.3 Pancreas

most abudant pancreatic protein digesting ezyme

trypsin

what stimulates release of CCK

* intestinal hormone released into blood when acidic, fatty chyme enters duodenum WHERE????????

describe what happens to pancreatic ducts during pancreatitis

- foci acinar ectasia - formation of pan stones w/ high conc of stone prpotein -formation of protein plugs -acinar atrophy - chronic inflamation leading to fibrosis @these together with stricture formation due to periductal fibrosis eventually lead to ductal eclasia@

describe histology of panc w/ pancreatitis

- irregularly distributed fibrosis - reduction in size of langerhans islets - obstruction of pan ducts of various sizes

describe primary malfunction of chronic pancreatitis

- no secretion of bicarbonate and water from CENTROCINAR CELLS - results in high protein concentration of pancreatic juice in ducts - formation of protein plugs causing dilation of proximal ducts - secondary pressure generated in ducts cause pain and also damage to integrety of ductal epithelium and results in pancreatic necrosis

meconium ileus

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what stimulates release of secretin and where

...

name 3 chemical stimuli that cause pancreatic secretion, locate

1) ACh from parasympathetic vagus nerve endings and from other cholinergic nerves in the enteric nervous system 2) CCK Cholecystokinin - secreted by duodenal and upper jejunal mucasa when food enteres mucosa 3) Secretin - is also secreted by duodenal and jejunal mucosa when highly acidic food enters small intestine

Pan enzymes that digest fat

1) Pancreatic Lipase ~ hydrolyzing neutral fat into fatty acids and MonoGlycerides 2) Cholesterol Esterase ~hydrolysis of cholesterol esters 3) PhosphoLipase ~phospholipids to fatty acids

list reasons in why secretion of alkalin pan secretions are important

1) absorption of fat can only occur in formation of MICELLES in alkaline environement of intestinal lumen 2) pancreatic enzymes function in neutral or slightly alkaline pH 3) protection of duodenum from acidic chyme, stops formation of duodenal ulcers and damage to mucous epithelium

name phases for pan secretion

1) cephalic phase 2) gastric phase 3) intestinal phase //in the cephalic phase, AcH production by vagal nerve endings (same as in cephalic phase of gastric secetion //in gastric phase, nervous sstimulation of enzyme secretion continues (((((note that only small amounts of pan enzymes actually enter duodenum because AcH stimulates production of enzymes but very little water)))))) //in intestinal phase, SECRETIN stimulates secretion of water and sodium bicarbonate ions, here pancreatic secretion becomes copious as enzymes are washed into duodenum///

describe production of biacrbonate ions

1)Carbon dioxide from respiration enters pancreatic cell from blood 2) CARBONIC ANHYDRASE ENZYME causes CO2 + H2O ---> H2CO3 (carbonic acid) --> HCO3- and H+ (creating bicarbonate ion and hydrogen ion 3)bicarbonate ion HCO3- is actively tranported into lumen along with Na+ ions 4) the overall movmement of Na+ ions and Bicarbonate ions from blood to lumen also causes osmosis of water into pancreatic duct this froming an almost completely isosmotic bicarbonate solutio (having same osmotic pressure as blood)

name and describe inhibition methods of pancratic enzymes

1)Kazal inhibitors, that inhibit action of activated trypsin by complexing with it (this prevents autocatalitic activation of trypsinogen and also trypsin activation of MoTrypsinogen, ProCarboxyPeptidase, ProPhosphoLipase A, ProElastase, 2) Enzyme Y - enzyme Y is activated by trace presence of active trypsin, it decrades zymogen, 3) alkaline conditions and low Ca2+ concentration promote deregdation of innactive trypsinogen

ectasia

Dilation or distention of a tubular structure.[1] It occurs as part of a pathophysiological process.

name enzymes that trypsin activates

@ trypsinogen to trypsin @ChymoTrypsinogen to ChymoTrypsin @ProCarboxyPeptidase to CarboxyPeptidase

describe cell type of pancreatic lobule

@ACINAR CELLS - producer of enzymes @CENTROCINAR CELLS - producer of water and bicarbonate (neutralizing) substances @DUCT CELL - conduct pancreatic secretions into intercalating ducts

what is it called when an active form of an enzyme activates its innactive form? GIVE EXAMPLE, and also name another activation route

AUTOCATICAL ACTIVATION, the most common pan protein digesting enzyme is Trypsin, its innactive form is Trypsinogen, activated trypsin can activate trypsinogen, ENTEROKINASE is enzyme responsible for activating trypsinogen to trypsin, it is secreted by stomach mucosa when chyme comes to contact w/ mucosa

name enzymes that specifically stimulate enzymatic production in pancreas, describe and locate where these enzymes are produced

AcH and CCK (cholecystokinin) AcH is produced from parasympathetic vagus nerve endings and from other cholinergic nerves in the enteric nervous system * CholecystoKinin (CCK) is produced by duodenal and upper jejunal mucosa when food enters small intestine ///these two stimuli causes acinar cells of pancres (secretory cells of pancreas) to produce large quantities of pancreatic digestive enzymes but RELATIVELY SMALL AMOUNTS OF WATER AND ELECTROLYTES///w/o water most of these enzymes remain temporarily stored in acini and ducts until more fluid secretion comes along to wash them into duodenum//

name enzyme found in CentroCinar cell that is responsible for producing alkaline substance in pan secretion, describe

CARBONIC ANHYDRASE 2 : combines CO2 + H2O --> H2CO3 (carbonic acid) --> H+ and HCO3- (bicarbonate ion) ///the bicarbonate ion HCO3- is secreted out of centroacinar cell in exchange of Cl- exchange therefore eliminating the alkaline tide that is produced during gastric acid production in stomach, note that this process does not involve carbonic acid anhydrase 2///

which enzyme does CCK potentiate

CCK (which stimulates enzyme release by acinar cells) potentiate effect of secretin (which encourages HCO3- and water release by centroacinar cells near the acinar cells)

which enzyme activates same receptor as gastrin

CCK and Gastrin compete for same receptor perhaps explaining why CCK opposite effect as gastrin and prevents production of gastric acid

give name and formula of substance involved in production of H+ ions in gastric acid

CO2 + H2O --> H2CO3 (carbonic acid)

describe which cells of pan lobule are responsible for bicarbonate and water production

CentroCinar Cells

describe metabolites of pancreatic protein digesting enzymes

ChymoTrypsin and Trypsin digest proteins into peptides of various sizes but not individual amino acids CarboxyPolyPeptidase splits peptides into individual amino acids, thus completing digesting

describe when and why Cl- movement occurs in centrocinar cell

Cl- is exchanged into cell as HCO3- bicarbonate ion is pumped into lumen @ this occurs via CFTR conductance channel (Cystic Fibrosis Transmembrane Regualator) which is regulated by cyclic AMP @CFTR is coupled to Cl-/HCO3+ exchanger

innactive form of CarboPolyPeptidase enzyme

PRO - CarboPolyPeptidase carbopolypeptidase is the enzyme that is able to directly convert some peptides into individual amino acids thus completing digestion of some proteins all the way to amino acids

pancreatic enzyme that digests carbs, describe

Pancreatic Amylase ~~hydrolizes starches, glycogen, and most other carbs (excl cellulose) to form disaccharides and trisaccarides

state stimulus for bicarbonate release from centrocinar cells

SECRETIN or INCREASE IN cAMP

which enzymes stimulate acinar secretion, where are these cells located

Secretin - stimulates bicarbonate HCO3- and water production in centrocinar cells CCK CholecystoKinin - stimulates enzymatic production in acinar cells of pancreatic duct @thses hormones are produced by APUD cells in the duodenal mucosa in response to food constituents in duodenal chyme @

name activated ezyme that is autocatalitic and also activates other enzymes, name

Trypsin can activate its own innactivate form tyrpsinogen Trypsin can also activate @MoTrypsinogen @ProCarboxyPeptidase @ProElastase @ProPhosphLipase A

what enzyme prevents specific pan enzyme from digesting itself, where is it formed

Trypsin is potent protein digestor (it splits whole and partially digested proteins into peptides of various sizes while CarobxyPolyPeptidase relases single amino acids) and is inhibited from digesting the pancreas itself by TRYPSIN INHIBITOR ****it is formed by cytoplasm of glandular cells, it prevents activation of trypsinogen, and therefore stops AUTOCATICAL ACTIVATION, Note that trypsin also activates other enzymes aswell not just trypsinoge via autocatical activation*****

name enzymes that digest proteins originating from pancreas

Trypsin, ChymoTrypsin CarboxyPolypeptidase

what are APUD CELLS

a type of classification for endocrine (ductless - secrete hormones directly into blood) cells acronym A - Amine Uptake P, U - Precursor uptake (usually amine precursor) D - high concentration of enzyme amino acid decarboxylase for conversion of precursors into amines

how can acute pancreatitis be tested

alpha amylase in blood or urine, positive results show high value of this enzyme in blood and urine, \'\Hypocalcemia may be present partly due to loss of albumen with bound Ca2+, //this may lead to rise in haematocrit due to loss of plasma

name pancreatic enzymes secreted in active fomr

amylase, Lipase, Nuclease (note that these require ions are bile present in intestinal lumen to reach optimal activity)

where is water and bicarbonate ions secreted, what stimulates it

bicarbonate ions and water are secreted mainly by PANCREATIC DUCTAL EPITHELIUM when stimulated by hormone SECRETIN

describe what stimulates release of bile

bile is constantly created by liver but it does not always enter small intestine unless gallbladder contracts, ///parasympathetic input from vagus has minor stimulus for gallbladder contraction, MAIN STIMULUS IS CCK////

name neutralizing substance produced by pancreas, where are they produced

biocarbonate ions and also water secreted by epithelial cels of ductules and ducts that lead from acini

dilation or distension of hollow organ (usually tubular) pathologic is called

ectasia

where is enterokinase present, what does it do

enterokinase is found in brush border of duodenum and jejenum, it is responsible for activation of trypsinogen to trypsin

what is other name for enterokinase

enteropeptidase

describe drainage of pancreatic juice from tubuloacinar cells of pancreas

enzymes initially produced by tubuloacinar cells drain into INTERCALATED DUCTS, ----> INTERLOBAR DUCTS --> EXTRALOBULAR DUCTS --> then these empty into even larger ducts and eventually reach the MAIN PANCREATIC DUCT

what is innactive form of water stimulating enzyme

hormone SECRETIN ( produced by duodenum and upper jejunal tract) stimulates release of water and sodium bicarbonate form ductal epithelial cells of pancreas the innactive form of secretin is called PROSECRETIN which is found in S CELLS

name hormone that stimultes release of substance to neutralize stomach acid, name and locate where this is produced

hormone is called SECRETIN it is produced by duodenal and upper jejunal mucosa, //it stimulates the secretion of large quantities of water and sodium bicarbonate by pancreatic ductal epithelium// in contrast to Ach and CCK (cholecystokinin) that stimulates production of large quantities of enzymes and relatively little water

Insulin

insulin, lowers levels of sugar in blood causing liver to store it as glycogen ((a way to help remember it is that insulin causes muscle to take up sugar, creating INSULATION))

describe what happens in acute pancreatitis

major pancreatic duct becomes blocked whereby trypsin inhibitor is overwhelmed by large amounts of trypsin, via autocatical activation lots of trypsinogen is activated to become trypsin and pancreas itself is digested by enzyme within few hours ((conditions is lethal as it is associated with circulatory shock, if not lethal may lead to subsequent lifetime of pancreatic insufficiency))

what is precursor of most common pan enzymes that digests proteins

most common pan enzyme that digests protein is Trypsin, its percursor is tripsinogen, its activating enzyme is Enterokinse secreted by intestinal mucosa when chyme comes in contact w/ the mucosa

what stimulates release of scretin, WHERE

presence of HCl in intestine stimulates release of secretin, which encourages centroacinar cells of pancreatic ducts to relase HCO3- and water, WHERE IS SECRETIN PRODUCED?????

define chronic pancreatitis

progressive FUNCTIONAL damage to pancreas with or without evidence of inflammation

glucagon

raises levels of sugar in blood (gluca gluca blood sugar rush rush!))))

name major prpteon present n panc stones

stone protein that has high affinity fo Ca2+

describe sphincter of odd/ HepatoPancreatic Sphinchter in different occasions

when no digestion is occuring HepatoPancreatic Sphincter is close and bile backs up into gall bladder via cystic duct, //note that CCK can stimulate relaxation of sphincter///

which organelle stores pan enzyme precursors or enzymes

zymogan granules found in acinar cells of pancreatic tubules