Human Physiology Chapter 18 Notes
Human Physiology Chapter 18 Notes BIOL 3160
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This 13 page Class Notes was uploaded by MBattito on Thursday April 21, 2016. The Class Notes belongs to BIOL 3160 at Clemson University taught by Dr. Tamara McNutt-Scott in Fall 2015. Since its upload, it has received 6 views. For similar materials see Human Physiology in Biological Sciences at Clemson University.
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Date Created: 04/21/16
Chapter 18: The Digestive System Digestive System • Organs of this system function to procure food, process it and eliminate generated wastes o Involves the processes of ingestion, digestion and absorption and waste removal • Without this system the body would be unable to obtain needed materials for fuel generation and cell maintenance • Overlooked point: absorbed nutrients from GI tract also use for structural elements Functions of the Digestive System: • Motility: movement of food through the digestive tract via o Ingestion – taking food into mouth o Mastication – chewing the food and mixing it with saliva o Deglutination – swallowing food o Peristalsis and Segmentation– rhythmic wave-‐like contractions (peristalsis) and mixing contractions in different segments (segmentation) move food through the GI tract • Secretion: exocrine and endocrine secretions o Exocrine: water, HCl, bicarbonate, and digestive enzymes are secreted into the lumen of the GI tract § Stomach alone secretes 2-‐3 intestine secrete hormones to regulate digestive system • Digestion: breakdown of food molecules into their smaller subunits, which can be absorbed • Absorption: passage of digested end products into the blood and lymph • Storage and elimination: temporary storage and subsequent elimination of indigestible food molecules • Immune barrier: o Tight junctions between epithelial cells provide a physical barrier o Cells of the immune system reside in the connective tissue located under the epithelium Digestive system can be divided functionally and anatomically • Gastrointestinal tract: o Oral cavity o Pharynx o Esophagus o Stomach o Small intestine o Large intestine • Accessory digestive organs: o Pancreas o Liver o Gallbladder o Teeth o Tongue o Salivary glands GI Tract Wall (from the inside out) • Mucosa: lines the lumen o Absorptive and major secretory layer o Consists of simple columnar epithelium supported by the lamina propria § Lamina propria – thin layer of areolar connective tissue with numerous lymph nodules à immune defense o Muscularis mucosa: thin layer of smooth muscle external to lamina propria § Responsible for numerous folds à increases surface area for maximum absorption o Goblet cells: specialized cells that secrete mucus • Submucosa: highly vascular layer of connective tissue o Absorbed molecules in mucosa enter into these blood and lymph vessels o Contains glands and nerve plexuses § Submucosal plexus: aka Meissner’s Plexus – provides a nerve supply to the Muscularis mucosae of the small and large intestine • Muscularis: responsible for the peristalsis and segmentation o Inner circular and outer longitudinal layer of smooth muscle o Myenteric plexus: located between the two muscle layers – provides the major nerve supply to the entire GI tract § Includes fibers and ganglia from both the sympathetic and parasympathetic divisions of the autonomic nervous system • Serosa: completes the GI tract wall o Areolar connective tissue covered with a layer of simple squamous epithelium o Continuous with the mesentery and visceral peritoneum Regulation of GI Tract • Parasympathetic nerves stimulate motility and secretions of the GI tract o Sympathetic nerves stimulate contraction of sphincter muscles and decrease peristalsis and secretions à antagonistic to parasympathetic • Submucosal and myenteric nerve plexuses are sites where parasympathetic preganglionic fibers synapse with postganglionic neurons that innervate the smooth muscle of the GI tract • Autonomic nervous and endocrine systems regulates GI tract extrinsically • Enteric system and paracrine regulators regulate it intrinsically o Intrinsic sensory neurons have their cell bodies within the gut wall – locally regulate digestive tract by enteric nervous system (complex neural network within the wall of the gut) Digestive Tract Physiology • Process begins with ingestion of foodstuffs and mastication (chewing) à chewing mechanically digests food but also mixes it with saliva containing salivary amylase (carbohydrate digestion) From Mouth to Stomach • Overall: peristaltic contractions of the esophagus deliver food to the stomach, which secretes very acidic gastric juice that is mixed with the food by gastric contractions – proteins in the resulting mixture (called chyme) are partially digested by the enzyme pepsin • Deglutination – swallowing, following mastication o Three phases: oral, pharyngeal and esophageal § Oral phase is under voluntary control via somatic motor neurons • Muscles in the mouth and tongue mix the food with saliva and create a bolus – the mass to be swallowed – that the tongue moves toward the oropharynx • Receptors in the oral cavity and oropharynx stimulate the pharyngeal phase § Pharyngeal and esophageal phases are automatic and controlled by the swallowing center in the brain stem via autonomic neurons • Pharyngeal phase moves the bolus from the oral cavity to the esophagus • Complex activities in the pharyngeal phase: soft palate lifts to close off nasopharynx (so food does not go into nose), vocal cords close off the opening to the larynx, epiglottis covers the vocal cords, larynx is moved away from the pathway of the bolus toward the esophagus (prevents choking) o All activities only take a total of ~1 second • Esophageal phase moves the bolus of food by peristaltic contractions toward the stomach o ~5-‐6 seconds • Once in the stomach, ingested material is churned and mixed with HCl and pepsin (protein digesting enzyme) o Mixture is pushed via muscular contractions past the pyloric sphincter § Pyloric sphincter guards entry of small intestine from stomach Esophagus • Portion of the GI tract that connects the pharynx to the stomach • Esophageal hiatus – opening in the diaphragm allowing the esophagus to pass through before entry into the stomach • Walls of esophagus contain either skeletal or smooth muscle o Upper portion is only skeletal muscle o Middle portion is skeletal and smooth muscle o Lower portion is only smooth muscle • Gastroesophageal sphincter – slightly narrow terminal portion of the esophagus at the entrance to the stomach due to thickening of the circular muscle fibers in its wall o Sphincter contracts after bolus enters stomach to prevent regurgitation o Not a true sphincter in humans, allowing us to regurgitate o Heartburn is produced if stomach acid reaches the esophagus Stomach • Most distensible part of the GI tract • Functions: store food, initiate digestion of proteins, to kill bacteria with the strong acidity of the gastric juice and to move the food into the small intestine as a pasty material called chyme • Contractions of the stomach churn the chyme – mixes it more thoroughly with the gastric secretions o These contractions also push partially digested food from the antrum through the pyloric sphincter and into the first part of the small intestine • Rugae: long folds on the inner surface of the stomach • Gastric pits: openings of these folds into the stomach lumen • Exocrine gastric glands: formed by cells that line the folds – secrete various products into the stomach o Mucous neck cells: secrete mucus o Parietal cells: secrete HCl § Used in small intestine for absorption of vitamin B12 o Chief cells: secrete pepsinogen (inactive form of pepsin) o ECL cells: secrete histamine and serotonin à paracrine regulators o G cells: secrete the hormone gastrin into the blood o D cells: secrete the hormone somatostatin • Intrinsic factor: polypeptide secreted by the gastric mucosa required for intestinal absorption of Vitamin B12 o Vitamin B12 is necessary for the production of red blood cells in the bone marrow • Ghrelin: hormone secreted by the stomach o Secretion rises before meals and falls after – serves as a signal from the stomach to the brain to regulate hunger • Gastric juice: highly acidic solution formed by a large amount of water and the exocrine secretions of the gastric cells • Enteroendocrine cells: individual cells that produce hormones like gastrin Secretion of Acid in the Stomach • Parietal cells at the apical membrane secrete H+ into the gastric lumen via primary active transport (ATPase) o H+/K+ ATPase pumps transport H+ uphill against a million-‐to-‐one concentration gradient into the lumen of the stomach o Transport K+ in the opposite direction o Potassium recycling: the K inside the parietal cell leaks out through K channels to prevent depletion of Kin the gastric lumen o Parietal cells at the apical surface have many microvilli with a high surface area to allow the insertion of a large number of H/K pumps • Parietal cells at the basolateral membrane take in Cl-‐ against its electrochemical gradient by coupling its transport to the downhill movement of bicarbonate o Bicarbonate is produced within the parietal cells by the dissociation of carbonic acid o Carbonic acid = CO2 + H2O via carbonic anhydrase o Therefore, Cl-‐ is secreted by facultative diffusion, as well as H+ into the gastric juice while bicarbonate is secreted into the blood o The secretion of Cl-‐ and K+ recycling is necessary for continues activity of the H/K pumps • Secretion of HCl by the parietal cells is stimulated by gastrin, histamine, and ACh o Gastrin enters general circulation and can stimulate the parietal cells directly by binding to receptors on the parietal cell basolateral membrane o Gastrin stimulation is mostly indirect – gastrin stimulates ECL cells to secrete histamine à histamine acts as a paracrine regulator to stimulate parietal cells to secrete HCl § Histamine stimulation of parietal cells is mediated by the H2 type of histamine receptor – different from H1 type involved in allergic reactions • Parasympathetic neurons of the vagus nerve stimulate both parietal and ECL cells – stimulation of ECL cells is most important effect • High concentration of HCl from the parietal cells makes gastric juice very acidic – pH <2 o Strong acidity serves 3 functions: § Ingested proteins are denatured at low pH – become more digestible § Under acidic conditions, weak pepsinogen enzymes partially digest each other à frees the fully active pepsin enzyme as small inhibitory fragments are removed § Pepsin is more active under acidic conditions à catalyzes the hydrolysis of peptide bonds in the ingested protein • Thus, cooperative activites of pepsin and HCl permit the partial digestion of food protein in the stomach • Since the strong acid and pepsin could damage the lining of the stomach, defense mechanisms are necessary o Adherent layer of mucus – first line of defense § Stable gel of mucus that is stuck to the gastric epithelial surface § Contains alkaline bicarbonate – results in a nearly neutral pH at the epithelial surface § Major barrier to potential damage to the stomach caused by pepsin by slowing its diffusion so that it doesn’t normally reach the epithelial cells o Other important protective mechanisms: § Tight junctions between epithelial cells – prevent acid and pepsin from leaking past the barrier § Rapid rate of epithelial cell division replaces the entire epithelium every 3 days – damaged cells can be rapidly replaced Digestion and Absorption • Proteins are only partially digestion in stomach • Carbohydrates and fats are not digested at all by pepsin – almost all products of digestion are absorbed through the wall of the small intestine o Alcohol and aspirin can be absorbed across stomach wall due to lipid solubility – promotes damage to gastric mucosa • Peptic ulcers – erosions of the mucosa of the stomach (produced by the action of HCl) that penetrate through the Muscularis mucosa o Zollinger-‐Ellison Syndrome: ulcers in the duodenum produced by excess gastric acid resulting from very high levels of gastrin – released by a gastrin-‐secreting tumor § Shows that excessive gastric acid can cause ulcers in the duodenum o Stomach ulcers are due to mechanisms that reduce the barriers of the gastric mucosa to self-‐digestion § Ulcers are produced by Helicobacter pylori bacteria – have adaptations that allow them to survive in high acidic environments o Can be treated with a drug regimen consisting of a proton pump inhibitor combined with 2 antibiotics § Ulcers can also be caused by NSAIDs (Nonsteroid Anti-‐Inflammatory Drugs) – aspirin and ibuprofen o Damage the gastric mucosa because NSAIDs inhibit prostaglandin synthesis – prostaglandin contributes to the mucosa barrier by stimulating mucus and bicarbonate production § Acute gastritis: inflammation that occurs when gastric barriers are broken down and acid can leak through the mucosa to the submucosa o Causes direct damage and stimulates inflammation o Histamine released in response will stimulate further acid secretion – causing further damage à why drugs that block H2 histamine receptors may be used to treat gastritis § Duodenum is normally protected from gastric acid by a number of defenses o Adherent layer of mucus – surrounding epithelium normally exposed to a neutral pH o Bicarbonate secretion by the Brunner’s glands in the submucosa – glands unique to the duodenum o Acidic chyme is neutralized by the buffering action of bicarbonate in alkaline pancreatic juice – released into duodenum upon arrival of acidic chyme Small Intestine • The portion of the GI tract between the pyloric sphincter of the stomach and the ileocecal valve opening into the large intestine • Small diameter but longest part of the GI tract • Main site of digestion and absorption of liberated nutrients • Portions: o Duodenum – initial section extending from the pyloric sphincter o Jejunum – next 2/5 of the small intestine o Ileum – last 3/5 of the small intestine – empties through the ileocecal valve • Products of digestion are absorbed across the epithelial lining of the interstitial mucosa at a rapid rate due to extensive foldings of mucosa o Absorption of carbohydrates, lipids, amino acids, calcium and iron occurs primarily in the duodenum and jejunum o Absorption of bile salts, vitamin B12, water, and electrolytes occurs primarily in the ileum • Plicae circulares – large folds formed by the mucosa and submucosa o Cause content to spiral through to ensure that there is a mixing with secretions from the lumen of the small intestine o Allows us to bring enzymes into contact with material we are digesting o Villi – microscopic folds of mucosa further increasing surface area o Microvilli – foldings on the plasma membrane of the cells that line these villi § Used interchangeable with brush border • Villus: fingerlike fold of mucosa that projects into intestinal lumen o Covered with columnar epithelial cells – including mucus-‐secreting goblet cells o Lamina propria: forms the connective tissue core of each villus § Contains lymphocytes, blood capillaries and central lacteal (lymphatic vessel) – absorbed monosaccharides and amino acids enter the blood capillaries and fat enters the lacteal o Intestinal crypts: narrow pouches that open through pores into the intestinal lumen – formed from invaginations of the epithelium at the base of the villi § Paneth cells – secrete antibacterial lysozyme and bactericidal peptides (defensins) • Found at the bottom of the intestinal crypts – only in small intestine, not large • Secretions help maintain intestinal stem cells § Intestinal stem cells – found with Paneth cells • Divide mitotically to replenish and produce specialized cells of the intestinal mucosa o Intestinal epithelium is renewed every 5-‐7 days § Mitosis at the base of the villi in the crypts occurs once a day § Mitosis at the top of the crypts stop and cells differentiate into secretory cells (Paneth cells, goblet cells and endocrine cells) and enterocytes (intestinal epithelial cells) § The new cells migrate to the top of the villi and those previously at the top undergo apoptosis Intestinal Enzymes • Brush border enzymes – digestive enzymes in the plasma membrane of the microvilli that hydrolyze disaccharides, polypeptides and other substrates o Remain attached to plasma membrane – not secreted into lumen o Enterokinase: required for activation of the protein-‐digesting enzyme trypsin Intestinal Contractions and Motility • 2 types of contractile movement o Peristalsis § Weak in small intestine § Important in esophagus and stomach § Stretch and chemical changes in a bolus are relayed to the enteric nervous system – directs excitation and smooth muscle contraction behind bolus and inhibition and relaxation ahead of it § Intestinal motility is slow for proper absorption o Segmentation – serves to mix chyme with luminal fluids; major contractile event in the small intestine § Localized event of contractions and relaxations § One section with be contracted and segment after it is relaxed • Contractions of the intestinal smooth muscle: o Occur automatically in response to endogenous pacemaker activity o Slow waves – rhythm of contraction paced by graded depolarizations § Interstitial cells of Cajal: unique pacemaker cells that produce slow waves – neither neurons nor smooth muscle cells • Long projections that join them to each other and smooth muscle cells through gap junctions • Gap junctions conduct depolarization along cells – allows entire muscularis to work as a functional syncytium • Serve to depolarize adjacent smooth muscle cells § Can only spread a short distance and must be regenerated by next region of cells – produces segmentation • Autonomic nerves modify the automatic contractions by influencing the enteric nervous system Large Intestine • Absorbs water, electrolytes and vitamins – little to no digestive function • Extends from the ileocecal valve to the anus • Chyme from ileum of small intestine is passed to large intestine into the cecum • Waste passes from ascending colon à transverse colon à descending colon à sigmoid colon à rectum à anal canal • Intestinal microbiota: microorganisms of the large intestine o Necessary because they provide Vitamin B, Vitamin K and folic acid o Produce short-‐fatty acid chains by bacterial fermentation that stimulate active Na and Cl absorption – results in secretion of water Accessory digestive organs o Liver, gallbladder and pancreas o Important digestive organs – provide majority of digestive enzymes for small intestine as well as buffering substances to adjust acidic chyme coming from stomach Pancreas • Soft, glandular organ that has both exocrine and endocrine functions o Endocrine function: performed by pancreatic islets that secrete insulin and glucagon into the blood o Exocrine function: secretes pancreatic juice into duodenum § Acini – exocrine secretory units • Pancreatic juice: product of Acinar cells and epithelial cells o Contains bicarbonate (produced by epithelial cells) and digestive enzymes (produced by Acinar cells) § Amylase – digests starch § Trypsin – digests protein § Lipase – digests triglycerides § Note: complete digestion by the small intestine requires both enzymes from the pancreatic juice and brush border o The enzymes are produced in an inactive form (zynogens) – must be activated once they get to the small intestine § Activated by trypsin which is converted from trypsinogen by enterokinase § Must be inactive in pancreas so they don’t break down the walls of the pancreas o Acini absorb Cl and secrete bicarbonate so pancreatic juice has much more bicarbonate than Cl-‐ § CFTR (cystic fibrosis trans-‐membrane conductance regulator) transports Cl-‐ back into lumen § Dissociation of carbonic acid produces this bicarbonate and H+, which is secreted into the blood Liver • Hepatocytes: liver cells the form hepatic that are separated from each other by sinusoids – discontinuous capillaries with fenestrations o Hepatic sinusoids are much more permeable than other capillaries due to their lack of a diaphragm or basement membrane § Kupffer cells: phagocytic cells in the sinusoids o Fenestrations, lack of basement membrane and plate structure allow intimate contact between hepatocytes and blood • Hepatic Portal System: unique pattern of blood circulation o Capillaries in digestive tract drain into the hepatic portal veinà capillaries in the liver à hepatic vein o Hepatic portal vein: brings in deoxygenated blood that is nutrient rich into the liver o Hepatic vein: returns blood to general circulation to the inferior vena cava o Hepatic artery: brings oxygenated blood to liver § Accounts for the rest of the blood to the liver (75% delivered via hepatic portal vein) § Adjusted to compensate for changes in blood flow through the hepatic portal vein à allows a relatively constant blood flow needed to maintain hepatic clearance • Liver lobules: functional units of the hepatic plates o Branches of the hepatic portal vein and hepatic are in the periphery surrounding a middle central veins o Arterial and venous blood mix and migrate from periphery to central vein § Central veins of different lobules converge to form the hepatic vein o Bile canaliculi: channels within each hepatic plate – bile produced by hepatocytes is secreted into the canaliculi § Drained at the periphery of lobules by bile ducts à then drained into hepatic ducts that carry bile away from the liver § Blood and bile do not mix in the liver because blood travels in the sinusoid in the opposite direction o Portal triad: branch of bile duct, hepatic portal vein and hepatic artery • Functions of the liver: o Blood detoxification via § Phagocytosis by Kupffer cells § Chemical alteration of biologically active molecules (hormones and drugs) § Production of urea, uric acid and other molecules that are less toxic than parent compounds § Excretion of molecules in bile o Carbohydrate metabolism via § Conversion of blood glucose to glycogen and fat § Production of glucose from liver glycogen and from other molecules by glycogenesis § Secretion of glucose into the blood o Lipid metabolism via § Synthesis of triglycerides and cholesterol § Excretion of cholesterol in bile § Production of ketone bodies from fatty acids o Protein synthesis via § Production of albumin § Production of plasma transport proteins § Production of clotting factors (fibrinogen, prothrombin, etc.) o Secretion of bile via § Synthesis of bile salts § Conjugation and excretion of bile pigment (bilirubin) Enterohepatic Circulation • Some compounds absorbed by small intestine and enter hepatic circulation are re-‐circulated between liver and small intestine o Can be retaken up, put back in liver and go through bile then repeat • Variety of exogenous compounds excreted by liver in bile – thus liver can “clear” blood of particular compounds, which are eliminated in feces • Drugs are processed in liver – detoxified, broken down and eliminated from the body • Bile salts are recycled o Bilirubin – broken down part of heme § Broken down by bacteria § Gives coloration to feces § Can be converted into urobilinogen – can be recycled too but can be picked up by the kidneys and then is responsible for coloration in urine Lipid Transport and Utilization • Lipoproteins: lipid-‐protein complexes that solubilize the hydrophobic lipids as well as providing signals that regulate lipid entry/exit at target cells • Emulsification: process in which bile salt miscelles are secreted into the duodenum and act as detergents to break up the fat droplets into tiny emulsification droplets of triglycerides o Is not chemical digestion – bonds are not hydrolyzed o Aids digestion because the small droplets present a greater surface area • Pancreatic lipase: fat-‐digesting enzyme aided by colipase o Colipase: protein secreted by liver that coats the droplets and anchors the lipase enzyme to them o Lipase hydrolyzes two of the three fatty acids into free fatty acids and monoglycerides • Phospholipase A: digests phospholipids further after the removal of the first two fatty acids into fatty acids and lysolecithin • The free fatty acids, monoglycerides and lysolecithin are more polar in this form – quickly enter micelles of bile salts à move to the brush border for absorption o They can leave the micelles and enter the intestinal epithelial cells – used to resynthesize triglycerides and phospholipids o Triglycerides, phospholipids and cholesterol are combined with protein inside the epithelial cells to form small particles – chylomicrons, which are secreted by exocytosis into the central lacteal • ApoE: protein constituent the chylomicrons acquire once in the blood – allows chylomicrons to bind to receptor to be hydrolyzed to release free fatty acids • VLDL (very low density lipoproteins): cholesterols and triglycerides combined with other apolipoproteins secreted into the blood to deliver triglycerides to other organs • LDL (low density lipoproteins): new particle formed when triglycerides are removed from VDLD – transports cholesterol • HDLP (high density lipoproteins); returns excess cholesterol to the liver Neural and Endocrine Regulation of the Digestive System • Modify the activity of the GI tract • GI tract serves as both an endocrine gland and target for various hormones • Gastric function: divided into 3 phases o Cephalic phase: control by the brain via the vagus nerve § Stimulated by sight smell and thought of food § Stimulates chief cells to secrete pepsinogen and parietal cells to secrete HCl § Major mechanism is indirect – vagus nerve stimulates G-‐cells to secrete gastrin à stimulates ECL cells to secrete histamine àstimulates paracrine cells to secrete HCl o Gastric Phase: stimulated by arrival of food in the stomach § Stimulated in response to distention of the stomach (by amount of chyme) and chemical nature of the chyme – act primarily via the secretion of gastrin § Partially digested proteins stimulate gastrin secretion § Gastrin stimulates pepsinogen secretion from chief cells and HCl from parietal cells (indirectly) § Positive feedback loop develops: as more HCl and pepsinogen are secreted, more partially digested proteins are released à stimulates additional secretion of gastrin à additional secretion of HCl and pepsinogen § Negative feedback loop: as the pH drops, D cells secrete somatostatin à inhibits gastrin secretion from G cells à inhibits HCl secretion from parietal cells o Intestinal Phase: inhibition of gastric activity as chyme enters small intestine § As duodenal distention and osmolality increase, gastric motility and secretion are inhibited § Enterogastrone: gastric inhibitory hormone stimulated by the presence of fat in the chyme § Hormones • Secretin: buffers acidic of chyme coming from the stomach into the small intestine • CCK – cholecystokinin: produced in presence of fat and protein • GIP – glucose-‐dependent insulinotropic peptide: stimulates beta cells in pancreas to release insulin in response to glucose in food • Pancreatic juice and bile regulation: o Arrival of chyme into small intestine also stimulates secretion of pancreatic juice and bile § Secretin: stimulates live to secrete bile after a meal § CCK: increases the blow of bile into the duodenum
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