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Because prostaglandins are cytoprotective (bydecreasing parietal cell acid production and increasing mucusproduction), the suppression of prostaglandins (especially PGE2)by NSAIDs can lead to ulcerations. The ulcerative effect isenhanced when the drugs are taken on an empty stomach or inthe presence of caffeine, which stimulates acid secretion. Stress,coffee, and NSAIDs (particularly when taken on an emptystomach) may have additive effects in aggravating existing ulcers.Treatment is with PPIs (and behavior modification).Gastric ulcer inwall of stomachDuodenal ulcerUlcerations of Stomach and DuodenumPANCREATIC BUFFER ANDENZYME SECRETIONSThe pancreas synthesizes and releases both endocrine secretions (into blood) and exocrine secretions (through ducts).The exocrine secretions serve to help buffer the acidic chymeand are crucial for the proper digestion of chyme, becauseapproximately 70% to 75% of digestion occurs in the proximal small intestine by the pancreatic enzymes.
The exocrinesecretions exit the pancreatic ducts into the common bileduct, mixing with liver and gallbladder secretions. The bileduct enters the duodenum through the sphincter of Oddi, atthe papilla of Vater (Fig. 23.9A).Gastrointestinal PhysiologyKerckring280Valve ofGoblet cells and striated borderof human jejunal villus (azanstain, ⫻650)Three-dimensional magnificationof jejunal wallEpitheliumAFloor of crypt of Lieberkühn withgranulated, oxyphilic cells ofPaneth (hematoxylin-eosin, ⫻325)VillusLamina propriaLymph noduleCrypt of LieberkühnMuscularis mucosaeSubmucosaCircular muscleLongitudinal muscleSerosaBJejunum (low power)Figure 23.8 Crypts of Lieberkühn and Cell Types A, Micrographs of goblet and Paneth cells insmall intestinal mucosa.
B, Brush border lining of the small intestine, illustrating crypts of Lieberkühn withinvillus projections.Table 23.3Major GI HormonesGI HormonesSite of SecretionPrimary StimuliGeneral ActionsGastrinG-cells in antrum ofstomach and duodenumStretch, peptides andamino acids, vagus(through GRP)≠gastric H+≠gastric mixing≠lower GI tract motilitySecretinS-cells of the duodenumAcidic chyme≠pancreatic buffer (HCO3-) secretion≠biliary and small intestine buffer secretion↓gastric H+ (by ↓gastrin)↓gastric emptyingCholecystokinin (CCK)I-cells of the duodenumand jejunumSmall peptides andamino acids, fats≠pancreatic enzyme secretion contractsgallbladder and relaxes sphincter of Oddi↑pancreatic and biliary buffer secretion↓gastric emptying↑lower GI tract motilityGastric inhibitory peptide,aka glucose insulinotropicpeptide (GIP)Duodenum and jejunumFatty acids, glucose,amino acidsØgastric H+ secretion≠pancreatic insulin secretion↓gastric emptyingMotilinMo cells of the duodenumFasting≠phase III contractions of the MMCGRP, gastrin-releasing peptide; MMC, migrating myoelectric complex.(Reprinted with permission from Hansen J: Netter’s Atlas of Human Physiology, Philadelphia, Elsevier, 2002.)ACystic duct(pars spiralis)Neck ofgallbladderLeft hepatic ductCommonhepatic ductGland orificesSupraduodenalRetroduodenalFundusof gallbladderBRight hepatic ductCommon bile ductCorpus(body)of gallbladderCystic duct(pars glabra)InfraduodenalIntraduodenalIonic concentration (mEq/L)Gastrointestinal Secretions281Na+HCO3⫺1601208040CI⫺K+0.8 1.21.6 2.00.40Rate of secretion (mL/10 min)Concentration of major ions shownas function of secretory ratesGeneral circulationMajor papilla(of Vater)PancreaticductSympathetic fibersVagus fibers (parasympathetic)CCholecystokininCeliac ganglionSecretinSecretinPancreasSecretin-inducedsecretion (fluidand electrolytes)TrypsinogenPancreatic acinusPancreatic ductNeurogenic orcholecystokinin-inducedsecretion (enzymes)Portal veinEnterokinaseAmylaseStarchFatLipasesMaltotroiseFattyMaacidseGlinooldesAmSmall bowelLactealerSecretincoseptiaaltSecretinCholecystokininGluPeseMycProteinTrypsinltosCholecystokininPeptidacidsasesFigure 23.9 Structure and Secretion of the Pancreas A, Pancreatic, liver, and gallbladder secretions flow through the common bile duct and into the duodenum through the sphincter of Oddi at the papillaof Vater.
B, As the rate of pancreatic secretions increases, the concentration of electrolytes changes, producing high sodium bicarbonate buffer. C, In response to food/chyme in the stomach and duodenum, vagalefferents and hormones stimulate pancreatic buffer and enzyme secretions.Secretin, released in to the blood from duodenal S-cells inresponse to acidic chyme, binds to its receptors on the pancreatic centroacinar cells and stimulates electrolyte and fluidsecretion (for buffering) (see Fig. 23.9C).
As with the salivaryglands, as the secretion goes through the ducts, there is modification of electrolytes. As the rate of secretion increases, thecomposition of the fluid changes, becoming rich in HCO3−(see Fig. 23.9B).Cholecystokinin (CCK) is released into the blood from theduodenal I-cells and acts on the pancreatic acinar cells. Alongwith the vagus, CCK stimulates pancreatic enzyme secretions,which include:■Pancreatic proteases: Trypsin, chymotrypsin, and elastase, the major proteases, are stored and released asinactive zymogens (trypsinogen, chymotrypsinogen,282■■Gastrointestinal Physiologyand proelastase). This protects the pancreas and ductsfrom digestion.
When the zymogens enter the duodenum, enterokinase (in the duodenal brush border)cleaves trypsinogen to trypsin, and then trypsin can activate additional trypsinogen (autoactivation), as well asthe other proteases.Pancreatic a-amylase: Starch digestion begins in themouth with salivary α-amylase. Digestion continuesin the small intestine by pancreatic α-amylase, whichhydrolyzes the starch molecules to maltose, maltotriose,and isomaltose. The amylase is activated by Cl−.Pancreatic lipase and colipase: Pancreatic lipase hydrolyzes triglycerides to monoglycerides and free fatty acids;colipase is a cofactor for this process. Other lipasesconvert cholesterol esters to cholesterol and fatty acid,and phospholipids to lysophospholipids and fatty acid.However, pancreatic lipase cannot readily access thelipids in the small intestine because of the presence ofbile.
Colipase is released as precolipase and is activatedin the duodenum by trypsin. The colipase binds to bileand allows the pancreatic lipase to access the lipids (seeChapter 25).GALLBLADDER FUNCTIONThe function of the gallbladder is to store bile. The sphincterof Oddi relaxes early in feeding, via vagal stimulation, releasing the contents of the bile duct (bile, electrolytes) into theduodenum. When chyme enters the duodenum, CCK isreleased. CCK opens the sphincter and causes gallbladdercontraction.
The stored bile enters the duodenum and beginslipid emulsification (see Chapter 25).COLONIC SECRETIONSIn the colon, there is secretion of mucus, HCO3−, H+, and K+.The mucus is required to lubricate chyme as it is dehydratedand formed into feces. With colonic reabsorption of sodium(through Na+/H+ exchangers), H+ is secreted into the lumen.Cl− is also absorbed, in part through lumenal Cl−/HCO3−exchangers. Thus, H+ and HCO3− are secreted into the lumenof the colon. In addition, a concentration gradient developsfor K+, which then diffuses into the lumen.
Potassium secretion can also occur when aldosterone is elevated (duringvolume contraction), because aldosterone increases Na+/K+antiporters on the lumenal membrane, reclaiming additionalsodium in exchange for K+. Because of the relatively highHCO3− content of feces, chronic diarrhea can cause metabolicacidosis (see Chapter 20).Gasses are formed throughout the GI tract, diffusing in andout of cells, and for the most part we are unaware of the fluxes.CO2 is constantly produced, but in addition, bacterial actioncan produce H2, N2, and methane, for example.
Typically, aperson produces and expels (as flatus) about 200 milliliters(mL) of colonic gas each day. This can change, with dietshigh in carbohydrates and meat protein increasing gasproduction.CLINICAL CORRELATEZollinger-Ellison SyndromeGastrinomas are tumors (usually pancreatic) that secretegastrin, but do not have any of the normal feedback systemsthat control gastrin release.
These tumors cause ZollingerEllison syndrome, in which the constant secretion of gastrincauses uncontrolled, high levels of gastric HCl release and ulcerations of the stomach mucosa. In addition, the high acid secretion acidifies the duodenum and early jejunum, impeding theactions of digestive enzymes and precipitating bile. This especially affects lipid digestion and absorption, because the lowduodenal pH denatures pancreatic lipase, significantly reducinglipid digestion. This results in steatorrhea and excess bile saltsin the feces. Treatment is by removal of the tumor and the useof PPIs to further reduce acid secretion, allowing ulcerations toheal.283CHAPTER24Hepatobiliary FunctionOVERVIEW OF LIVER FUNCTIONSThe liver has a myriad of functions that revolve around vascular, metabolic, and secretory aspects. The hepatocytes arethe cells making up the parenchyma of the liver.
The basicfunctions of the liver include:■■■■■■■Regulation of carbohydrate, lipid, and protein metabolism: The liver receives newly absorbed nutrients throughthe portal vein, as well as contents of systemic blood, andprocesses them according to need. It produces albumin,fibrinogen, immunoglobulins, binding proteins, cholesterol, lipoproteins, and other important molecules.Regulation of cholesterol production and excretion: Thebody requires cholesterol, which the liver is able tosynthesize.β-Oxidation of fatty acids: While many tissues use βoxidation as an alternate energy source when glucose isnot present, the liver has a high rate of β-oxidationduring the interdigestive period.Bile acid production and secretion: Bile is necessary forefficient lipid absorption.
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