Unit 12 - Digestive System

Identify regions of the stomach.

1. Cardiac Region 2. Fundus 3. Pyloric Region

Identify the three phases of gastric secretion and describe each.

1. Cephalic Phase: regulation of gastric function by the brain via the vagus nerve. During the cephalic phase, the brain is stimulated by the presence and smell of food, whereby the vagus nerve stimulates gastric cells to secrete pepsinogen, hydrochloric acid and histamine in preparation of food. 2. Gastric Phase: phase of digestion where food enters the stomach and gastric secretions are stimulated by distension of the stomach wall and chemical composition of chyme. End products of protein digestion, such as amino acids and smaller peptides, will further stimulate acid secretion through stimulation of parietal cells and secretion of gastrin (major effect) . This will cause further protein digestion and acid secretion (positive feedback loop). Once stomach pH falls below 2.5, gastrin is reduced and acid secretion is inhibited at pH of 1. 3. Intestinal Phase: inhibition of gastric activity caused by small intestinal digestion through neural inhibition. As chyme enters the duodenum, the distention and increase in osmolality will trigger a neural reflex to inhibit gastric activity. The presence of fat in the chyme will further inhibit gastric activity through secretion of an enterogastrone hormone (i.e. somostatin and CCK).

List the functions of the liver.

1. Detoxification of Blood 2. Carbohydrate Metabolism 3. Lipid Metabolism 4. Protein Synthesis 5. Secretion of Bile

Identify the three phases of deglutition.

1. Oral 2. Pharyngeal 3. Esophageal

Indicate the physiological functions of the stomach.

1. Storage of food 2. Mixing of food 3. Controlled gastric emptying (passage of food from stomach to small intestine)

Indicate how the autonomic nervous system impacts the interstitial cells of Cajal and its effect on motility.

Autonomic axons, located between smooth muscle cells in the intestine, release neurotransmitters that will modify the enteric nervous system, which will in turn stimulate or inhibit ICC. Acetylcholine will increase the amplitude and duration of slow waves, thus increasing motility of the small intestine.

Identify components of pancreatic juice.

Bicarbonate and about 20 enzymes including: amylase, trypsin, lipase

Describe the role of bile, micelle, emulsification, lacteals, chylomicrons in absorption of fats.

Bile: contains bile salts that will help dissolve fat into chyme by emulsifying large droplets of fat into smaller droplets of fat Micelle: help transport fatty acids/monoglycerides to intestinal epithelium; bile salts will surround lipid droplet (hydrophobic end facing inward and hydrophilic end facing the outside) Emulsification: increases surface area for enzymatic digestion by lipases Lacteals: absorbs chylomicrons into lymphatic circulatory system Chylomicrons: transport of triglycerides through lymphatic system

Trace the blood flow through the liver.

Blood enters the liver through vessels in portal triad (hepatic artery + hepatic portal vein) → hepatic sinusoids → exits via the central vein → hepatic vein

Indicate the location of the swallowing center of the brain.

Brain stem

Describe the role of cholecystokinin (CCK) on digestion and secretion.

CCK will stimulate secretion of pancreatic enzymes and trigger the contraction of gall bladder to help with digestion of fat. Inhibits gastric secretion and motility

Discuss enterohepatic circulation.

Circulation between intestine and liver is known as enterohepatic circulation. This includes the recycling of bile salts and liver secretions that are delivered to the intestine via the common bile duct. Bile salts are then reabsorbed from the small intestine and returned back to the liver via the hepatic portal vein. Enterohepatic circulation is important for the clearance of exogenous substance like drugs from where the liver will secrete these compounds into bile which will drain into intestine in order to be excreted from the body.

Define: commensal bacteria, mutualism.

Commensal bacteria is a relationship where the bacteria will benefit from the host without causing any harm, whereas mutualism is where both bacteria and the host benefit from the relationship.

Describe the crypt, villi and microvilli morphology of the small intestines and how they contribute to digestion.

Crypt: narrow pouches of epithelium at the base of the villi that face downward; contain secretory cells (goblet cells and that will release mucus and Paneth cells that release lysozyme) Villi: folding of mucosal lining of the small intestine to increases absorptive surface area. Villi are composed of columnar epithelium that is supported by the lamina propria, connective tissue with lymph nodules, blood capillaries and central lacteal (lymphatic vessel) Microvilli: microscopic folds of epithelial plasma membrane; contains digestive enzymes that will hydrolyze molecules at the cell surface just prior to absorption (i.e. enzyme is associated with brushborder and not secreted into lumen)

Differentiate between digestion and absorption.

Digestion is the process of breaking down food molecules into their monomers through hydrolysis, whereas absorption is the transport of these monomers from the lumen of the digestive tract into blood or lymph.

Describe the brush border enzymes.

Disacchridases: sucrase, maltase, lactase Peptidase - free AA and activate trypsin Phosphatase

Describe the anatomy of the small intestines and indicate relative lengths of each section.

Duodenum - 20/30cm Jejunum - 2/5ths of 3m Ileum - 3/5ths of 3m

Discuss the enteric nervous system (ENS) based on its location and autonomic regulation.

Enteric Nervous System - a complex neural network within the wall of the gut; it is intrinsic sensory neurons are not a part of the autonomic system, but acts locally within the tissues using paracrine signalling Extrinsic control of the ENS is regulated by the autonomic nervous system through sensory extrinsic afferent neurons (50,000), whereas intrinsic afferent neurons deliver sensory information to the plexuses through interneurons. Intrinsic regulation of the digestive tract is important regulator of digestive function given the large number of intrinsic afferent neurons (100 million).

Discuss the role of enterokinase and trypsin in activation of pancreatic enzymes.

Enterokinase is a brush border enzyme that will activate the zymogen trypsinogen into trypsin. Trypsin will then activate other pancreatic enzymes such as chymotrypsinogen into chymotrypsin.

Describe the digestive enzymes of the pancreas, its substrates, and products.

Enzyme ===== Substrate =====Product Trypsin--------Protein---------Amino Acid Lipase---------Tryglycerides--Fatty Acids Amylase-------Starch---------Glucose

Describe the gastroileal, ileogastric and intestino-intestinal reflexes.

Gastroileal: ↑ gastric activity, ↑ ileum motility, thus increased movement of chyme through the ileocecal valve (from ileum into cecum) Ileogastric: ↓ in ileal distention, ↓ gastric motility Intestino-intestinal reflexes: ↑ distention in a segment of intestine, relaxation of the rest of the intestine

Identify hormones that regulate appetite.

Ghrelin → stimulate appetite Peptide YY, CCK, insulin, leptin → inhibit appetite

Describe the secretion of gastric acid by parietal cells.

Hydrochloric acid is secreted by parietal cells through stimulation by gastrin, histamine and acetylcholine. 1. At the apical membrane, H+/K+ ATPase pump will transport H+ ions against its concentration gradient into the stomach in exchange for K+ 2. At the basolateral membrane, Cl- ion is transported from the blood into the parietal cell through the exchange of HCO3-. Cl- ion diffuses across the apical membrane into the stomach where it combines with H+ to form hydrochloric acid (HCl)

Discuss the role of intestinal microbiota.

In the large intestine, intestinal microbiota will ferment undigested molecules and produce short chain fatty acids that will: 1) Supply energy to intestinal enterocytes 2) Provide an energy source to the body (absorbed into bloodstream) 3) Stimulate electrolyte absorption in the large intestine (Na+, Cl-) and subsequent water absorption Microbiota will also provide B vitamins and vitamin K

Define and describe: ingestion, mastication, deglutition, bolus, peristalsis, chyme, segmentation, villi and microvilli, brushborder, plicae circulares, haustra, storage, elimination.

Ingestion: consumption of food material through the mouth Mastication: chewing of food into smaller pieces and mixing with saliva to form a bolus Deglutition: swallowing of food bolus from the oral cavity; the bolus travels from the mouth through the pharynx, down the esophagus and finally to the stomach Bolus: a ball-shaped mass of food that is formed in the mouth through mastication and mixing with saliva Peristalsis: wave-like rhythmic contraction of smooth muscle that propels bolus or chyme in a forward direction Chyme: pasty food material that is formed in the stomach and delivered to the small intestine Segmentation: muscular contraction of the small intestine to further mix chyme Villi: fingerlike folds in the mucosa of the intestinal lumen made of columnar epithelial cells Microvilli: folding of the apical membrane of columnar epithelial cells Brushborder: edges found on the surface of microvilli (facing the lumen of the digestive tract) Plicae circulares: large folds formed by the mucosa and submucosa in the small intestine Haustra: formed pouches on the outer surface of the large intestine Storage: capacity to temporarily store food material for further digestion and/or for controlled movement through the digestive tract Elimination: the act of removing or eliminating indigestible food material from the digestive tract

Discuss how the interstitial cells of Cajal mediate slow wave formation and their effects on smooth muscle contraction.

Interstitial cells of Cajal (ICC) are the pacemaker for contractions of smooth muscle in the small intestine. ICC have long processes and are interconnected to smooth muscle by gap junctions, which spread the depolarization originating from ICC to adjacent smooth muscle. ICC will produce graded depolarization, known as slow waves, which will cause action potentials in the smooth muscle and subsequent contraction through the following process: Slow-wave depolarization of ICC surpasses threshold → opening of voltage-gated Ca2+ channels in smooth muscle → influx of Ca2+ into muscle cell → depolarization and subsequent contraction of smooth muscle

Describe the mucosa of the stomach and indicate why it is ideal for protein digestion.

It contains gastric pits that are made up of mucous, chief and parietal cells which secrete mucus, pepsinogen and hydrochloric acid, respectively. HCl will create the low pH environment, and pepsinogen will activate and digest protein molecules, whereby the mucus will create a protective layer of gel on the gastric epithelial surface that contains bicarbonate to neutralize the acid and protect the stomach lining.

Discuss the digestion and absorption of lipids including: lipase and phospholipase A.

Lipids are digested by pancreatic lipase in the small intestine with the help of micelles (bile salts) to emulsify fat into smaller droplets, allowing access for enzymatic digestion by lipases. Lipases will hydrolyze triglycerides into three fatty acids and one glycerol molecule. Similarly, phospholipases will hydrolyze phospholipids to produce two free fatty acids and one lecithin molecule. Lipase: Tryglyceride -------> 3 free fatty acids + monoglycerides Phospholipase A: Phospholipid --------> 2 free fatty acids + lecithin Given that free fatty acids and glycerides are polar, they will associate with micelles (bile salts) to be transported to the epithelial surface. Here, they will dissociate from the micelle and be absorbed across the apical cell surface through diffusion. Once inside the enterocyte, free fatty acids and monoglycerides recombine and attach with protein to form chylomicrons. Chylomicrons will be secreted into central lymphatic lacteal via exocytosis, where it will be transported through the lymphatic circulatory system and enter the venous system through the thoracic duct.

Describe the microscopic structure of a liver lobule and indicate the functional significance of the arrangements of the central vein, sinusoids and portal triad.

Liver lobules are made up of hepatic plates that are composed of one or two hepatocytes, separated by capillary spaces called sinusoids. These spaces are very porous due to fenestrae that allow passage of large molecules such as protein. Blood will enter the liver lobule through the portal triad, located at the periphery of liver lobules. The portal triad drains blood from the hepatic portal vein and hepatic artery where they will converge and mix within the sinusoids, and both exit via the central vein located in the middle of each liver lobule. The portal triad also includes the bile ductile that carries bile away from the liver. The bile flows in the opposite direction through bile canaliculi and therefore will never mix with blood.

List and describe the anatomy of the accessory digestive organs.

Liver: located beneath the diaphragm and is the largest internal organ. Liver is connected to the digestive tract via the hepatic portal vein and the bile duct. Gallbladder: storage sac for bile that is closely associated with the liver and will release bile into the duodenum via the bile duct. Pancreas: glandular organ that is located behind the stomach, near the small intestine.

Discuss the digestion and absorption of carbohydrates including: amylase (ptyalin), maltase, sucrase and lactase.

Luminal Enzymatic Digestion of Carbohydrates Pancreatic amylase Starch (polysaccharide) ------> maltose, maltotriose & oligosaccharide Brushborder Enzymatic Digestion of Carbohydrates MaltaseMaltose, maltotriose & oligosaccharide -------> glucose Sucrase Sucrose ---------> glucose + fructose LactaseLactose ---------> glucose + galactose

Describe the process of mastication and deglutition.

Mastication is the act of chewing food and mixing it with saliva to form a bolus. During mastication, salivary amylase will begin the process of starch digestion. Deglutition is the act of swallowing a food bolus; process is highly controlled and involves the use of 25 muscles. It is divided into three phases: 1. Oral: Mixing of food to form bolus, followed by movement of bolus to back of mouth by the tongue. 2. Pharyngeal: the presence of food bolus triggers receptors in the oropharynx, stimulating the following mechanisms: - the soft palate to lift and close the nasopharynx, preventing food from entering the nose - the epiglottis to fold over the larynx, preventing movement of bolus down the trachea - relaxation of esophageal sphincter, allowing movement of bolus into esophagus 3. Esophageal: the bolus travels down the esophagus and finally to the stomach by peristaltic contractions.

List and describe the anatomy of the organs of the alimentary canal from mouth to anus.

Mouth: located in the oral cavity; food is masticated and mixes with salivary glands to form a bolus that will be swallowed. Pharynx: cavity located between the mouth and the esophagus, posterior to the nasal cavity. The pharynx is involved in the deglutition process (swallowing). Esophagus: long muscular tube that carries food boluses from the pharynx to the stomach via peristalsis Stomach: J-shaped muscular organ that is continuous with the esophagus and will deliver food (known as chyme) to the duodenum (first section of the small intestine). Here, food is stored and mixes with acid and pancreatic juices to start the digestion process prior to moving to the small intestine. Small Intestine: long narrow tube between the stomach and large intestine. It is separated into 3 sections: the duodenum, jejunum and ileum and terminate at the ileocecal valve. The small intestine is involved in the digestion and absorption of food molecules. To increase the absorptive surface area, the mucosa of the small intestine is folded into villi, and in turn, the villi have further folds known as microvilli. Large Intestine: section of the digestive tract that runs from the ileocecal valve to the anus that is involved in water and electrolyte reabsorption. It is larger in diameter and shorter in length than the small intestine and does not contain villi. The outer surface forms haustra (pouches). It includes the cecum, the ascending colon, transverse colon, descending colon, sigmoid colon, rectum and anal colon. Rectum: last section of the large intestine where feces are passed following water and electrolyte reabsorption; it initiates the defecation reflex through increases in pressure. The rectum contains an internal and external sphincter. Anus: opening at the end of the rectum which moves feces from the rectum to the outside of the body.

Describe the four tunics of the alimentary canal and indicate their functions.

Mucosa: lining of the lumen; composed of columnar epithelium that is supported by the lamina propria (connective tissue with lymph nodules), smooth muscle layer (muscolaris mucosae) that create the folds in the villi. Submucosa: thick, vascularized connective tissue that provides blood/lymph to the mucosa. Submucosa also contains glands and the nerve plexus (Meissner's plexus). Muscularis: contains layers of smooth muscle used for movement of food through the digestive tract (segmentation and peristaltic). It includes the inner circular and external longitudinal smooth muscle. The main nervous supply, the myenteric plexus, is located between these two muscle layers. Serosa: outer protective layer of the digestive tract composed of connective tissue and simple squamous epithelium.

Identify the product each of the following cells make: mucous neck cells, parietal cells, chief (zymogenic) cells, enterochromaffin-like (ECL) cells, G cells and D cells.

Mucous neck cells: mucus Parietal cells: hydrochloric acid Chief (zymogenic) cells: pepsinogen (inactive form of pepsin) Enterochromaffin-like (ECL) cells: histamine, serotonin G cells: gastrin D cells: somatostatin

Discuss the role on digestion for the following cellular products: mucous, hydrochloric acid, pepsinogen, histamine, serotonin, gastrin and somatostatin, intrinsic factor, ghrelin.

Mucous: protects stomach mucosa from acidity of gastric juices Hydrochloric acid: lowers the pH of gastric juice to initiate protein digestion and kill bacteria Pepsinogen: precursor to pepsin (enzyme for protein digestion) Histamine: stimulates parietal cells to release HCl Serotonin: paracrine regulator; used to control intestinal movements by activating motor neurons through the myenteric plexus. Gastrin: stimulate parietal cells to release hydrochloric acid + simulation of ECL cells to release histamine Somatostatin: inhibit secretion of gastrin from G cells, which in turn, reduce secretion of HCL from parietal cells Intrinsic factor: required for the absorption of B12 vitamin in the ileum. Ghrelin: may help regulate hunger

Identify the 2 plexuses that compose the ENS.

Myenteric Plexus (Auerbach's plexus) Meissner's Plexus

Discuss the regenerative capabilities of the intestinal mucosa.

New epithelial cells are formed in intestinal crypts and will migrate from the crypt to the top of the villi, where cells will eventually be shed into the intestinal lumen. 4-5 day turnover

Discuss how fats are transported in the blood.

Once in the blood, chylomicrons dissociate. Free fatty acids will attach to albumin in blood plasma, whereas the cholesterol travels to the liver where it will combine with apolipoproteins and triglycerides and secreted in the blood as VLDL (very- low-density lipoprotein) and LDL (low-density lipoprotein)

Differentiate between exocrine and endocrine pancreas.

Pancreas has an endocrine function by secreting the hormones insulin and glucagon into the blood by a group of cells known islets of Langerhans. The pancreas is also an exocrine gland since it secretes pancreatic juice which contains digestive enzymes into the duodenum through the pancreatic duct.

Discuss zymogens and their activation.

Pancreatic enzymes are in their inactive form (i.e. zymogens) while they are stored in the pancreas to prevent digestion of the pancreas. Once pancreatic juice is delivered to the duodenum, a brush border enzyme will activate zymogens into their active form by cleaving off a polypeptide sequence.

Discuss the process of peristalsis and how it moves food throughout the alimentary canal.

Peristalsis is a wave-like muscular contraction that propels food in a forward direction. It involves the contraction of both circular and longitudinal smooth muscle. Contraction of circular smooth muscle behind the bolus will push the bolus forward (smooth muscle in front of the bolus is relaxed). This is followed by contraction of the longitudinal smooth muscle that shortens the tube, further propelling it forward.

Discuss the digestion and absorption of proteins including: pepsin, trypsin, chemotrypsin, elastase and carboxypeptidase.

Protein digestion begins in the stomach where pepsin begins to cleave peptide bonds to form short-chain polypeptides. The majority of protein digestion takes place in the duodenum and jejunum where pancreatic enzymes will cleave internal peptide bonds; these enzymes are known as endopeptidases and include trypsin, chymotrypsin and elastase. Exopeptidase is another group of enzymes that will cleave peptide bonds at the end of polypeptide chain at the amino and carboxyl terminal end and are known as carboxypeptidase and aminopeptidase, respectively. Pepsin: Protein --------> shorter polypeptides Trypsin, chemotrypsin, elastase, carboxypeptidase: Shorter Polypeptide --------> amino acids, dipeptides, tripeptides Free amino acids are absorbed across the apical membrane by secondary active transport (coupled with Na+). Di and tripeptides will also cross the apical membrane through secondary active transport using an H+ gradient. Once inside the enterocyte cell, di and tripeptides will be hydrolyzed into individual amino acids by dipeptidase and tripeptidases, respectively. Free amino acids can then freely cross the basolateral membrane into interstitial fluid and into blood capillaries.

Discuss the role of salivary glands in deglutition and digestion of carbohydrates.

Salivary glands release saliva that moistens food to help form the bolus that is subsequently swallowed. Saliva also contains salivary amylase to begin the digestion of starch (carbohydrates).

Describe the role of secretin on digestion and secretion

Secretin stimulates water and bicarbonate release from the pancreas to help neutralize the acidity of chyme that is leaving the stomach. This will raise the pH in the duodenum to allow digestive enzymes to function. Secretin will further promote secretion of pancreatic enzymes along with CCK.

Identify regulators of pancreatic juice and bile secretion.

Secretion of Pancreatic Juice: - Acetylcholine (vagus nerve) - CCK, secreted by duodenum due to the stimulus of protein and fat in chyme; secretion of digestive enzymes from pancreas - Secretin, secreted by duodenum due to low pH; secretion of bicarbonate from pancreas Secretion of Bile: - presence of a meal (sends signal to liver via the enterohepatic circulation) - secretin stimulates bile ducts to secrete bicarbonate, increasing volume of bile - CCK due to presence of fat stimulates contraction of gall bladder and delivery of more bile to the duodenum - presence of chyme stimulates a neural reflex which in turn stimulates contraction of gall bladder.

Identify components of gastric juice.

Secretions from gastric cells (i.e. pepsin, hydrocholoric acid, etc.) and water.

Describe segmentation and indicate its digestive function.

Segmentation is a type of contraction where circular smooth muscle will contract in multiple locations at the same time. This serves to move chyme back and forth to thoroughly mix it with digestive juices and mucus.

List the functions of the gall bladder and describe its connection to the alimentary canal and liver.

The gall bladder stores and concentrates bile from the liver. Bile is delivered to the gallbladder via bile ducts, hepatic duct and cystic ducts when the sphincter of Oddi, located at the end of the common bile duct, is closed (preventing bile delivery to the duodenum). Upon contraction, the gall bladder will drain bile into the duodenum via the common bile duct.

Describe the fluid and electrolyte absorptive capabilities of the large intestine.

The large intestine absorb roughly 90% of the 2L of fluid that pass through it each day This largely takes place through passive diffusion/osmosis of water down its concentration gradient created by Na+/K+ pumps located in the basolateral membrane.

Describe the anatomy of the large intestine and indicate relative lengths of each section.

The large intestine is the distal part of the digestive tract originating from the ileocecal valve to the anus. It is shorter in length but larger in diameter compared to the small intestine and does not contain villi. It includes the ascending colon, transverse colon, descending colon, sigmoid colon, rectum and anal canal.

Describe the anatomy of the liver, gall bladder and the hepatic portal circulation.

The liver is made up of hepatic plates that are composed of one or two hepatocytes, separated by capillary spaces called sinusoids. These spaces are very porous due to fenestrae that have a single endothelial lining allowing passage of large molecules such as protein. Gall Bladder is a pear-shaped organ attached to the liver that stores bile produced by liver hepatocytes. Bile is transported to the gall bladder from the liver via the cystic duct. The common bile duct and cystic duct will deliver bile to the duodenum. Hepatic Portal Circulation is the unique system of vessels that carry blood from the digestive tract to the liver for processing and back to systemic circulation. Capillaries carry blood to the liver via the hepatic portal vein where it is distributed across liver lobules through capillaries (hepatic sinusoids) and returned to systemic circulation via the hepatic vein.

Describe the lower esophageal sphincter and indicate its function.

The lower esophageal sphincter is a thickening of smooth muscle at the distal end of the esophagus, between the esophagus and the stomach. It prevents the regurgitation of food from the stomach back into the esophagus.

Describe the anatomy of the pancreas.

The pancreas is a glandular organ that is located behind the stomach, near the small intestine. The pancreas includes an endocrine and exocrine portion, each with specialized cells. The exocrine pancreatic acini contain a layer of acinar cells where zymogens are produced, stored and secreted into the surrounding lumen before entering the pancreatic duct. The pancreas is connected to the duodenum via the pancreatic duct through which pancreatic juice is delivered. The endocrine pancreas consists of a group of cells known as pancreatic islets of Langerhans that produce and secrete insulin and glucagon into the blood.

Describe the muscular composition of the esophagus on the effects on deglutition.

Upper 1/3 - skeletal muscle Middle 1/3 - mix of skeletal and smooth Lower 1/3 - smooth muscle

Discuss the defecation reflex.

When rectal pressures rise to a particular level that is etermined by habit. External sphincters relax to allow feces into the anal canal.

Discuss why low pH of gastric juices is ideal for digestion.

i. Denatures proteins ii. Pepsinogen partial degrade each other, forming pepsin iii Pepsin activity is increased in low pH