Digestion• From food, humans must get basicorganic molecules to make ATP, buildtissues, and serve as cofactors andcoenzymes.– Digestion breaks polymers (carbohydrates,fats, and proteins) into monomer buildingblocks.• Via hydrolysis reactions– Absorption takes these monomers into thebloodstream to be allocated.
Hydrolysis of Polymers
Digestive Tract• Open at both endsand continuous withthe environment– Considered “outside”the body– Materials that cannotbe digested (cellulose)never actually “enter”the body.
Digestive Tract Functions1. Motility– Ingestion: taking food into the mouth– Mastication: chewing– Deglutination: swallowing– Peristalsis: one-way movement through tract– Segmentation: churning/mixing
Digestive Tract Functions2. Secretion– Exocrine: digestive enzymes, acid, mucus– Endocrine: hormones to regulate digestion3. Digestion– Breaking food down into smaller units4. Absorption– Passing broken-down food into blood or lymph
Digestive Tract Functions5. Storage and elimination– Temporary storage and elimination ofundigested food6. Immune barrier– Simple columnar epithelium with tightjunctions prevents swallowed pathogensfrom entering body.
GI Tract Layers• Layers are also called tunics• There are four tunics:Mucosa, Submucosa, Muscularis, and Serosa
GI Tract Layers1. Mucosa:inner secretory and absorptive layerin places it is folded to increase surface area (villi)contains lymph nodules, mucus secreting goblet cells, and athin layer of muscle
GI Tract Layers2. Submucosa:very vascular, to pick up nutrients; also has some glandscontains glands & nerve plexuses (submucosal plexus) thatcarry ANS activity to muscularis mucosae
GI Tract Layers3. Muscularis:smooth muscle; responsible for peristalsis and segmentationhas an inner circular & outer longitudinal layer of smooth musclemuscle activity moves food forward while pulverizing & mixing itregulated by Myenteric plexus containing symp. & parasymp.
GI Tract Layers4. Serosa:outer binding and protective layerconsists of areolar connective tissue covered with layer of simplesquamous epithelium
Regulation of the GI Tract• Parasympathetic division:• Via vagus nerve stimulates peristalsis and secretionin various organs of the digestive system• Sympathetic division– Inhibits peristalsis and secretion– Stimulates contraction of sphincters• Hormones:– From brain or other digestive organs
Regulation of the GI Tract• Intrinsic regulation:– Intrinsic sensory neurons in gut wall help inintrinsic regulation via separate entericnervous system– Paracrine signals
II. From Mouth to Stomach
Mouth• Mastication: Chewing breaks food downinto smaller pieces for deglutition andmixes it with saliva.• Saliva: contains mucus, an antimicrobialagent, and salivary amylase to startdigestion of starch.– Enhances taste and makes food slippary
Deglutition• initiated by receptors in the posterior oral cavityand oropharynx– Bolus is moved down esophagus to stomach viaperistalsisEsophagus10 inches longPasses through the diaphragm viathe esophageal hiatusUpper portion has skeletal muscle;lower portion smooth muscleLower esophageal sphincter opensto allow food to pass into stomach.It stays closed to preventregurgitation
Stomach: Functions• Stores food• Churns food to mix with gastric secretions• Begins protein digestion• Kills bacteria in the food (acid)• Moves food into small intestine in the formof chyme
Stomach Structure• Food is delivered tocardiac region.• Upper region =fundus• Lower region = body• Distal region =pyloris– Ends at pyloricsphincter• Lining has foldscalled rugae.
Stomach Structure• Gastric pits at base of folds lead to gastric glandswith secretory cells:– Goblet cells secrete mucus to help protect stomach liningfrom acid.
Stomach Structure– Parietal cells secrete HCl acid and intrinsic factor (helpssmall intestine to absorb vitamin B12).– Chief cells secrete pepsinogen
Stomach Structure– Enterochromaffin-like (ECL) cells secrete histamine andserotonin (paracrine signals).– G cells secrete gastrin (hormone).– D cells secrete somatostatin (hormone).
Stimulation of HCl Secretion• Gastrin: made in G cells; carried to parietal cellsin blood– Also stimulates ECL cells to make histamine• Histamine: also stimulates parietal cells via H2histamine receptors– Examples: Tagametand Zantac block H2 receptors.• Parasympathetic neurons: stimulate parietal andECL cells
Three Functions of HCl• Reduces pH to 2– Proteins aredenatured (allowsenzymes access).– Pepsinogen isconverted to activepepsin (digestsproteins).– Serves as theoptimal pH for pepsinactivity
Stomach Defenses• Acid and pepsin could eat the stomachlining.• Defenses that help prevent this:– Adherent layer of mucus with bicarbonate– Tight junctions between epithelial cells– Rapid epithelial mitosis that replacesepithelium every three days
Digestion and Absorption in the Stomach• Proteins begin digestion in the stomach.– Starches begin digestion in the mouth, butsalivary amylase is not active at pH 2, so thisactivity stops in the stomach.• Alcohol and NSAIDs (aspirin) are the onlycommon substances absorbed in thestomach (due to high lipid solubility).
Peptic Ulcers• Peptic ulcers: erosions ofthe mucosa of thestomach or duodenum– Helicobacter pylori:bacterium that reducesmucosal barriers to acid– Treatment for ulcerscombines K+/H+pumpinhibitors (Prilosec) andantibiotics.
Gastritis• Inflammation of the submucosa caused byacid eating at it– Histamine released as part of theinflammatory response can stimulate moreacid release.– Prostaglandins are needed to stimulateprotective alkaline mucus production.– NSAIDs inhibit prostaglandin activity and canlead to gastritis.– Tagamet and Zantac inhibit H2receptors.
IV. Small Intestine
Small Intestine Functions• Complete digestion of carbohydrates,proteins, and fats• Absorption of nutrients– Sugars, lipids, amino acids, calcium, and ironabsorbed in duodenum and jejunum– Bile salts, vitamin B12, water, and electrolytesin ileum– Very rapid due to villi and microvilli
Small Intestine Structure• Three sections:– Duodenum– Jejunum– Ileum• Mucosa andsubmucosa folded intoplicaecirculares;mucosa further foldedinto villi; and epithelialplasma membranesfolded into microvilli
Intestinal Enzymes• SI has no glands• has brush borderenzymes– These enzymes arenot released intolumen, but stayattached to plasmamembrane withactive site exposedto chyme
Intestinal Contractions/Motility• Smooth muscle contractions occur automatically.Contractions can be influenced by the autonomic nervoussystems• Peristalsis is weak. Movement of food is much slower dueto pressure at pyloric end.• Segmentation is stronger and serves to mix the chyme.
V. Digestion and Absorption ofCarbohydrates, Lipids, andProteins
Digestion and Absorption of Carbohydrates• Starch digestion begins inmouth with salivaryamylase and continues inintestines with pancreaticamylase.• Brush border enzymesfinish breaking downresulting products andother disaccharides(maltose, sucrose, lactose).• Monosaccharides areabsorbed across theepithelium into capillaries
Digestion and absorption of Proteins• Begins in stomach withpepsin to produce short-chain polypeptides• Finishes in duodenum andjejunum with pancreatictrypsin,chymotrypsin,elastase, and carboxypeptidase, andthe brush border enzymeaminopeptidase.• Free amino acids are alsoabsorbed into capillaries
Digestion of Fats• Fat digestion begins in duodenum when bileemulsifies the fat and the pancreatic enzymelipase breaks it down into fatty acids.• Phospholipase A (from pancreas) digestsphospholipids into fatty acids.
Absorption of Fats• Fatty acids and monoglycerides move into bile micelles andare transported to brush border.• Inside the epithelial cells, they are regenerated intotriglycerides, cholesterol, and phospholipids and combinedwith proteins to form chylomicrons.• These enter the lacteals.
Transport of Lipids Across IntestinalEpithelium
Summary of Major Digestive Enzymes
VI. Large Intestine
Large Intestine Structure• Chyme from ileum passes through ileocecalvalve into:CecumAscending colon Transverse colon Descending colon Sigmoid colon Rectum Anal canal Anus
Large Intestine Function• Absorption of water, electrolytes, vitaminK, and some B vitamins• Production of vitamin K and B vitamins viamicrobial organisms• Storage of feces
Large Intestine Function
Microbial Biota• Several hundred different species ofbacteria live in the large intestine. Some ofthem are useful• Microbes make vitamin K and some B vitamins.• They also make fatty acids from cellulose to be used for energyby large intestine epithelial cells. We can’t absorb the fatty acids,but they help absorb electrolytes such as sodium, calcium,bicarbonate, magnesium, and iron.• Disruption of normal microflora can lead to irritable boweldisease
Absorption of Fluids• Most absorption occurs in small intestine,but some is left for large intestine.• Not all water is absorbed; about 200 ml isleft per day to be excreted with feces.• Water is absorbed passively following anosmotic gradient set up by activeNa+/K+pumps.– Aldosterone stimulates greater salt and waterabsorption here.
Defecation• As material passes to the rectum,pressure there increases, the internal analsphincter relaxes, and the need todefecate rises.• The external anal sphincter controlsdefecation voluntarily.• During defecation, longitudinal rectalmuscles contract to increase pressure asthe anal sphincters relax.
VII. Liver, Gallbladder, andPancreas
Pancreas• Is located behindstomach• Has endocrine andexocrine functions– Endocrine: Islets ofLangerhans cells (alpha andbeta) make insulin andglucagon.– Exocrine: Acini cells makepancreatic juice, which isdelivered to the duodenumvia the pancreatic duct. Theducts secrete bicarbonate
• Contains water, bicarbonate, & digestive enzymes• Digestive enzymes include amylase for starch, trypsin forproteins, and lipase for fats– Brush border enzymes are also required for complete digestionPancreatic Juice18-72
Pancreatic Enzymes and How They AreActivated in Small Intestine• Most are inactive(Zymogens) untilthey reach the smallintestine.– Enterokinase activatestrypsinogentrypsin (todigest protein).– Trypsin activates otherenzymes.
Liver• Largest abdominal organ• Has amazing regenerativeabilities due to mitosis ofhepatocytes• Hepatocytes form hepaticplates separated by capillariescalled hepatic sinusoids– Very permeable – allowpassage of blood proteins, fat,and cholesterol
Blood Circulation Through DigestiveSystem and Liver• Products of digestionabsorbed in intestines aredelivered to the liver via thehepatic portal vein.• After circulating through livercapillaries, the blood leavesvia the hepatic vein.• Liver also receives blood fromhepatic artery and it mixes-upwith the blood coming throughhepatic portal vein
Liver Lobules• Are functional unitsformed by hepatic plates• In middle of each iscentral vein• At edge of each lobuleare branches of hepaticportal vein & arterywhich open intosinusoids
Liver Lobules• Blood from hepatic portalvein and hepatic arteries ismixed and processed byhepatocytes• The processed blood drainsinto central vein• Bile is secreted byhepatocytes in bile canaliculi– Empty into bile ductswhich flow into hepaticducts that carry bile awayfrom liver
Secretion of Drugs into Bile
Bile Production• The liver makes 250–1,500 ml of bile perday.• Bile is composed of:– Bile pigments (bilirubin)– Bile salts– Phospholipids (lecithin)– Cholesterol– Inorganic ions
Bile Salts• Bile acids: derived from cholesterol– Cholic acid and deoxy cholic acid– Most is recycled in enterohepatic circulation.– ½ gram of cholesterol is broken down and lost in thefeces through this pathway.• Form micelles with polar groups towardwater– Fats enter the micelle and are emulsified
Gallbladder• Stores and concentrates bile from the liver:Liver Bile ducts Hepatic duct Cystic duct Gallbladder Cystic duct Common bile duct (Sphincter of Oddi) duodenum
Enterohepatic Circulation• Some of the moleculesreleased into the bileare absorbed again inthe small intestine andreturned to the liver.• These molecules arepart of enterohepaticcirculation.
Enterohepatic Circulation of Bilirubin• Is produced in spleen, liver, andbone marrow from heme (RBSdestruction) and conjucated withglucuronic acid to make it soluble• Conjugated bilirubin is secretedinto the bile, where it is taken tothe small intestine.– Bacteria there turn it intourobilinogen, which makesfeces brown.– 30−50% is absorbed by theintestines and taken back tothe liver.– Some is used to make bile,and some remains in blood tobe filtered by the kidneys.
VIII. Neural and EndocrineRegulation of the DigestiveSystem
Regulation of Digestion• Regulation of digestion involves:– Intrinsic control via mechanical and chemicalstimuli– Endocrine control• Hormones from brain or other GI organs– Secretin, gastrin, CCK, GIP– Extrinsic control by CNS centers• Parasymp. (vagus nerve) stimulates peristalsis andsecretion• Symp. inhibits peristalsis and secretion; stimulatescontraction of sphincters
Receptors of the GI Tract• Mechano- and chemoreceptors respond to:– Stretch, osmolarity, and pH– Presence of substrate, and end products ofdigestion• They initiate reflexes that:– Activate or inhibit digestive glands– Mix lumen contents and move them along
Regulation of Gastric Function• Gastric motility & secretion occur automatically– ANS & hormonal effects superimposed on ANS activity• Three phases– Cephalic phase: sight, smell, & taste of food• Vagus n. increases gastric secretions/motility– Gastric phase: distension and chyme in stomach• Increase gastric secretions/motility– Intestinal phase: chyme enters duodenum• Inhibits gastric secretions/motility
• Secretion of pancreatic juice & bile is stimulatedby secretin & bile• Secretin secreted in response to duodenal pH <4.5– Stimulates release of HC03-into SI by pancreas &into bile by liver• CCK is secreted in response to fat & protein induodenum– Stimulates production of pancreatic enzymes– Enhances secretin– Stimulates contraction of sphincter of Oddi– Stimulates contraction of gallbladderRegulation of Pancreatic Function