8Small Intestine Site of greatest amount of digestion and absorption DivisionsDuodenumJejunumIleum: Peyer’s patches or lymph nodulesModificationsCircular folds or plicae circulares, villi, lacteal, microvilliCells of mucosaAbsorptive, goblet, granular, endocrine
9Movement in small intestine: Mixing: Segmental contraction that occurs in small intestineSecretion: Lubricate, liquefy, digestDigestion: Mechanical and chemicalAbsorption: Movement from tract into circulation or lymphElimination: Waste products removed from body
10Small Intestine Secretions MucusProtects against digestive enzymes and stomach acidsDigestive enzymesDisaccharidases: Break down disaccharides to monosaccharidesPeptidases: Hydrolyze peptide bondsNucleases: Break down nucleic acidsDuodenal glandsStimulated by vagus nerve, secretin, chemical or tactile irritation of duodenal mucosa
19Gallbladder Bile is stored and concentrated Stimulated by cholecystokinin and vagal stimulationDumps into small intestineProduction of gallstones possibleDrastic dieting with rapid weight loss
20Pancreas Anatomy Secretions Endocrine Pancreatic juice (exocrine) Pancreatic islets produce insulin and glucagonExocrineAcini produce digestive enzymesRegions: Head, body, tailSecretionsPancreatic juice (exocrine)TrypsinChymotrypsinCarboxypeptidasePancreatic amylasePancreatic lipasesEnzymes that reduce DNA and ribonucleic acid
243. Architecture of the Hepatic Parenchyma The hepatic lobule is the structural unit of the liver.Portal veinBile ductSinusoidsCentral veinLiver cells (Hepatocytes)Portal areaHepatic artery
25…each day around 600 ml of bile is produced… Bile acidPhospholipidsCholesterolBilirubinWaste productsElectrolytesMucin
26Functions of the Liver Bile production Storage Salts emulsify fats, contain pigments as bilirubinStorageGlycogen, fat, vitamins, copper and iron; huge blood reservoir of blood (storage); very high lymph flowNutrient interconversion – Metabolic functions (see next slide)DetoxificationHepatocytes remove ammonia and convert to urea; metabolizes drugs, hormones; has the Cytochrome P-450 enzyme system.Phagocytosis – Cleans the bloodKupffer cells phagocytize worn-out and dying red and white blood cells, some bacteriaSynthesisAlbumins, fibrinogen, globulins, heparin, clotting factorsThe liver is the largest gland in the body and performs an astonishingly large number of tasks that impact all body systems. One consequence of this complexity is that hepatic disease has widespread effects on virtually all other organ systems. At the risk of losing sight of the forest by focusing on the trees, I will only briefly mention the vasculare and metabolic functions of the liver. It is a storage of cabohydrate, lipid copper and iron as well as it is able to interconvert nutrients. It detoxificate the bloocd by removing ammonia and converting it to ureal. The vascular functions include formation of lymph and it is part of phagocytic system. The Kupfeer cells phagocytize old blood cells and the liver also syntezise important components of the wound healing.But we have focused on the very first one, the secretory and excretory functions of the liver, because it is the only one that directly affects digestion - the bile production which plays a critical role in the digestion and absorption of dietary lipids. However, the understanding the vascular and metabolic functions of the liver is critical to appreciating the gland as a whole.
27Liver’s Role in Metabolism Carbohydrate MetabolismStorage of large amounts of glycogenConversion of galactose and fructose to glucoseGluconeogenesisFormation of many chemical compounds from intermediate products of carbohydrate metabolismFat MetabolismBeta-oxidation of fatty acids to supply energy to for other functions in the bodySynthesis of cholesterol, phospholipids, and most lipoproteins (and their receptors)Synthesis of fats from proteins and carbohydrates
28Liver’s Role in Metabolism (cont’d) Protein MetabolismDeamination of amino acidsFormation of urea for removal of ammonia from the body fluidsFormation of plasma proteinsInterconversion of the various amino acids and synthesis of other compounds from amino acids
29Exocrine Pancreas – Enzymes TrypsinogenChymotrysinogenCarboxypeptidasesPro-elastasePhospholipasepancreatic lipasePancreatic amylasePancreatic juice is composed of two secretory products critical to proper digestion: digestive enzymes and bicarbonate. The enzymes are synthesized and secreted from the exocrine ascinar cells, whereas bicarbonate is secreted from the epithelial cells lining small pancreatic ducts.Digestive EnzymesThe pancreas secretes a magnificent battery of enzymes that collectively have the capacity to reduce virtually all digestible macromolecules into forms that are capable of, or nearly capable of being absorbed. Three major groups of enzymes are critical to efficient digestion:ProteasesDigestion of proteins is initiated by pepsin in the stomach, but the bulk of protein digestion is due to the pancreatic proteases. Several proteases are synthesized in the pancreas and secreted into the lumen of the small intestine. The two major pancreatic proteases are trypsin and chymotrypsin, which are synthesized and packaged into secretory vesicles as an the inactive proenzymes trypsinogen and chymotrypsinogen.As you might anticipate, proteases are rather dangerous enzymes to have in cells, and packaging of an inactive precursor is a way for the cells to safely handle these enzymes. The secretory vesicles also contain a trypsin inhibitor which serves as an additional safeguard should some of the trypsinogen be activated to trypsin; following exocytosis this inhibitor is diluted out and becomes ineffective - the pin is out of the grenade.Once trypsinogen and chymotrypsinogen are released into the lumen of the small intestine, they must be converted into their active forms in order to digest proteins. Trypsinogen is activated by the enzyme enterokinase, which is embedded in the intestinal mucosa.Once trypsin is formed it activates chymotrypsinogen, as well as additional molecules of trypsinogen. The net result is a rather explosive appearance of active protease once the pancreatic secretions reach the small intestine.Trypsin and chymotrypsin digest proteins into peptides and peptides into smaller peptides, but they cannot digest proteins and peptides to single amino acids. Some of the other proteases from the pancreas, for instance carboxypeptidase, have that ability, but the final digestion of peptides into amino acids is largely the effect of peptidases in small intestinal epithelial cells. More on this later.Pancreatic LipaseThe major form of dietary fat is triglyceride, or neutral lipid. A triglyceride molecule cannot be directly absorbed across the intestinal mucosa. Rather, it must first be digested into a 2-monoglyceride and two free fatty acids. The enzyme that performs this hydrolysis is pancreatic lipase, which is delivered into the lumen of the gut as a constituent of pancreatic juice.Sufficient quantities of bile salts must also be present in the lumen of the intestine in order for lipase to efficiently digest dietary triglyceride and for the resulting fatty acids and monoglyceride to be absorbed. This means that normal digestion and absorption of dietary fat is critically dependent on secretions from both the pancreas and liver.Pancreatic lipase has recently been in the limelight as a target for management of obesity. The drug orlistat (Xenical) is a pancreatic lipase inhibitor that interferes with digestion of triglyceride and thereby reduces absorption of dietary fat. Clinical trials support the contention that inhibiting lipase can lead to significant reductions in body weight in some patients.AmylaseThe major dietary carbohydrate for many species is starch, a storage form of glucose in plants. Amylase is the enzyme that hydrolyses starch to maltose (a glucose-glucose disaccharide), as well as the trisaccharide maltotriose and small branchpoints fragments called limit dextrins. The major source of amylase in all species is pancreatic secretions, although amylase is also present in saliva of some animals, including humans.Other Pancreatic EnzymesIn addition to the proteases, lipase and amylase, the pancreas produces a host of other digestive enzymes, including ribonuclease, deoxyribonuclease, gelatinase and elastase.Bicarbonate and WaterEpithelial cells in pancreatic ducts are the source of the bicarbonate and water secreted by the pancreas. The mechanism underlying bicarbonate secretion is essentially the same as for acid secretion parietal cells and is dependent on the enzyme carbonic anhydrase. In pancreatic duct cells, the bicarbonate is secreted into the lumen of the duct and hence into pancreatic juice.
42Secretions of Large Intestine Mucus provides protectionParasympathetic stimulation increases rate of goblet cell secretionPumpsExchange of bicarbonate ions for chloride ionsExchange of sodium ions for hydrogen ionsBacterial actions produce gases called flatus
44Movement in Large Intestine Mass movementsCommon after mealsLocal reflexes in enteric plexusGastrocolic: Initiated by stomachDuodenocolic: Initiated by duodenumDefecation reflexDistension of the rectal wall by fecesDefecationUsually accompanied by voluntary movements to expel feces through abdominal cavity pressure caused by inspiration
46Digestion, Absorption, Transport Breakdown of food molecules for absorption into circulationMechanical: Breaks large food particles to smallChemical: Breaking of covalent bonds by digestive enzymesAbsorption and transportMolecules are moved out of digestive tract and into circulation for distribution throughout body
47Effects of Aging Death of myenteric plexus neurons Atrophy of sphincter musclesIncontinenceDecrease in mucus layer, connective tissue, muscles and secretionsIncreased susceptibility to infections and toxic agentsUlcerations and cancers