YAW BBL_WebCT Digestive system_Lecture8 PDF

Dr Yasser Abdel-Wahab (Module Coordinator) WEEK 8 Introduction to Anatomy and Physiology of the Digestive System REWORD based on lecture Aims: To give an overview of the Anatomy and Physiology of the Digestive System Lecture Outlines: 1. The organisation of the digestive system 2. Overvie...

Dr Yasser Abdel-Wahab (Module Coordinator) WEEK 8 Introduction to Anatomy and Physiology of the Digestive System REWORD based on lecture Aims: To give an overview of the Anatomy and Physiology of the Digestive System Lecture Outlines: 1. The organisation of the digestive system 2. Overview of the gastrointestinal tract 3. Overview of the accessory organs of the digestive system 4. Motility in the digestive system 5. Gastrointestinal secretions and food digestion 6. Absorption of key nutrients from the gastrointestinal tract 7. Water flux and balance in the gastrointestinal tract 8. Regulation of feeding activity Intended Learning outcomes are: Describe the organs and accessory structures of the digestive system and their general function Understand the general histology of the gastrointestinal tract and the variations throughout the GIT. Understand the main functions of the gastrointestinal tract. Describe the types and function of motility of the GIT, and understand the control of the smooth muscles of the GIT. Understand the difference between endocrine and exocrine glands, and know the basic structure of an exocrine gland, including packaging and release of exocrine secretions. Outline the contents of bile and the functions of bile in the GIT. List the main secretions of the GIT, their site of secretion and their general content. Name the major nutrients and their composition. Oultine the enzymes secreted into the GIT and their substrate and products formed. Understand the general control of digestive secretions. Give an overview of the saliva, and its secretion. Understand the 3 phases of gastric secretion, and regulation of gastric secretions. Discuss the hormones of the GIT, what stimulates their release and their actions. Describe the digestion of carbohydrates, peptides and lipids and other nutrients and their absorption from intestinal lumen into the blood stream. Appreciate water flux in the GIT, the transport of water across intestinal epithelium and the regulation of water intake and secretion. Give an overview of the regulation of feeding activity and the role of leptin. 1  Dr Yasser Abdel-Wahab (Module Coordinator) ORGANS OF THE DIGESTIVE SYSTEM Digestion is the breakdown of larger food molecules into molecules which are small enough to enter the cells of the body. The digestive system refers to the organs that collectively perform the function of digestion of food, absorption of nutrients and elimination of undigested waste. There are two main organ groups of the digestive system The gastrointestinal tract (GIT) or alimentary canal which consist of: Mouth Pharynx Esophagus Stomach Small and Large intestines Rectum The function of the GIT is containing food from the time it is eaten until it is digested and absorbed or prepared for elimination. The accessory structures which include: Teeth Tongue And other organs involved in secretions aiding chemical digestion of food including: salivary glands, liver, gall bladder and pancreas General histology of GIT: The wall of the GIT from esophagus to anal canal has the same basic arrangement of tissues: Mucosa – inner lining, a mucous membrane consisting of 2  Dr Yasser Abdel-Wahab (Module Coordinator) o Epithelium (non-keratinized or simple columnar), o moistened glandular secretions o lamina propia (areolar connective tissue containing blood vessels, sensory nerve endings, lymphatic vessels, smooth muscle cells and scattered lymphoid tissue) o muscularis mucosa Submucosa – layer of dense irregular areolar connective tissue which is highly vascularised Muscularis – made up of smooth muscle cells arranged in inner circular layer and outer longitudinal layer Serosa – a serous membrane which covers the muscularis externa throughout the intestine, but not in the oral cavity, pharynx, esophagus and rectum Peritoneum The peritoneum is the largest serous membrane of the body and consists of a layer of simple squamous epithelium and underlying supporting layer of areolar connective tissue. The peritoneum lines the peritoneal cavity. Parietal peritoneum: lines the inner surfaces of body wall (abdominal cavity) Visceral peritoneum: lines organs within the peritoneal cavity Mesentery: extensions of the peritoneum which weave into the viscera and bind the organs to each other and the abdominal wall o double sheets of peritoneal membrane suspending portions of GIT with the peritoneal cavity – stabilise organs; prevent entanglement; access for blood vessels, nerves and lymphatics o during embryonic development have dorsal and ventral mesentery: ventral disappears and only remains in two places in adults (falciform ligament and lesser omentum) Falciform ligament: the peritoneal fold between liver and anterior abdomen wall; stabilises liver position binding it to the anterior abdominal wall. 3  Dr Yasser Abdel-Wahab (Module Coordinator) Lesser omentum: arises as two folds in the serosa of the stomach and duodenum suspending them from the liver; access for blood vessels and other structures entering/leaving liver Greater omentum (GO): largest peritoneal fold which forms pouch extending from stomach hanging between body wall and anterior of small intestine. It drapes over the transverse colon and coils of the small intestine; adipose tissue of GO provides insulation, protection and energy reserve Mesocolon: is an extension of the parietal peritoneum that binds the large intestine to the posterior body wall PERITONEUM ADULT Mouth (oral or buccal cavity) Formed of cheeks (lateral wall), hard and soft palate and tongue.  The lips: folds surrounding the opening of the mouth, covered externally by skin and internally by mucous membrane  Vestibule of the mouth: area between the cheeks and gums  Oral cavity proper: the space which extends from the gums/teeth to the opening between the oral cavity and the pharynx  Hard plate and soft plate Tongue (extrinsic and intrinsic muscles)  assist swallowing and chemoreception (taste buds) Salivary glands: saliva is a fluid which is continuously secreted into the mouth to keep the mucous membranes of the mouth and pharynx moist.  The buccal and minor salivary glands  Accessory (major salivary glands, 3 pairs): (a) Partid; (b) Submandibular; (c) Sublingual o Produce saliva – water, electrolytes, mucin and amylase 4  Dr Yasser Abdel-Wahab (Module Coordinator) o Dissolve food particles, moisten food, assist swallowing, and polysaccharide-digesting enzymes Teeth: these are accessory structures of the digestive system located in sockets known as gingiva.  Incisors, canines, premolars and molars o Aid chewing and mechanical digestion Esophagus The esophagus is a muscular, collapsible tube that lies behind the trachea and is about 23 – 25 cm long. Histology of the esophagus:  Mucosa  Submucosa  Muscularis  Adventitia – not serosa as the connective tissue is not covered by epithelium. The histology of the esophagus is shown in the diagram to the right Stomach The stomach is a J-shaped organ located under the diaphragm and is anatomically divided into 4 main parts:  Cardia  Fundus  Body  Pyloris Histology of the stomach:  Mucosa: contains gastric pits, gastric glands, the chief zygomatic cells and parietal (oxyntic) cells.  Submucosa  Muscularis  Serosa 5  Dr Yasser Abdel-Wahab (Module Coordinator) Pancreas The pancreas is an oblong gland, 12.5 cm long and 2.5 cm thick which has a head, body and tail region The pancreas has to histological divisions: 1. Endocrine portion (1%): Islets of Langerhans 2. Exocrine portion (99%): acinar cells which secrete their products into ducts. Liver The liver is the heaviest gland of the body, weighing about 1.4 Kg. It is located under the diaphragm and occupies most of the right hypochondrium It is divided into 2 lobes:  Right lobe (quadrate and caudate)  Left lobe Histology of the liver:  Lobules (~100,000/lobe) – liver divided up by connective tissue into hexagonal shaped lobules  Hepatic cells (hepatocytes) – adjust levels of nutrients in circulation  Sinusoids – capillaries which allow transport of all but blood cells between blood and interstitial fluid.  Kupffer’s cells – found in the sinusoidal lining, they are phagocytic cells  Bile capillaries and canaliculi Blood supply to the liver is from hepatic artery proper (1/3 of supply) and the hepatic portal vein (2/3 of supply), the latter bringing blood from most of the GIT to the liver. Gallbladder Is a hollow pear-shaped sac about 7-10 cm long, located in a fossa in the visceral surface of the liver Its stores and concentrates bile before excretion of bile into the small intestine. Histology of the gallbladder:  Mucosa (but no submucosa)  Muscular layer  Visceral peritoneum 6  Dr Yasser Abdel-Wahab (Module Coordinator) Small intestine The small intestine has 3 regions starting at the stomach and joining into the large intestine at the cecum:  Duodenum – first section of small intestine leaving stomach and is 25 cm long. Receives chyme from stomach and digestive secretions from liver, gall bladder and pancreas.  Jejunum – middle section of small intestine about 2.5 m long and the main site of digestion and nutrient absorption.  Ileum – final section, about 3.5 m long, ends at ileocecal valve (sphincter) which controls flow from small intestine into cecum of large intestine. Histology of the small intestine: Is the same as the general histology of GIT as described earlier and in addition also contain: Plicae circulares - there are approx 800 circular plicae (transverse folds) along the small intestine which increase surface area. Intestinal villi - The mucosa contains finger-like projections called villi which further increase SA Microvilli - The epithelial cells of the intestinal villi are covered in brush like projections called microvilli (cells are said to have a brush border). Lacteal – Lymphatic capillary in each villi which transport protein-lipid packages (chylomicrons) to venous circulation as they are to big to diffuse into blood stream of villi. The diagram below show the plica, villi and the microvilli 7  Dr Yasser Abdel-Wahab (Module Coordinator) Large intestine The main functions of the large intestine are (1) water reabsorption, (2) absorption of vitamins liberated by bacteria (3) compaction and storage of faeces until defecation The large intestine is about 1.5 m long and 7.5 cm wide and has 3 main regions:  Cecum – receives material from ileum. Appendix attached to posteromedial surface of cecum  Colon – wall of colon forms pouches called Haustra which allow colon to expand and elongate. Colon can be further divided into 4 sections (see diagram below): o Ascending colon o Transverse colon o Descending colon o Sigmoid colon  Rectum – expandable section of GIT about 15 cm long which stores faeces prior to defecation. o Anal canal – the last part of the rectum o Anal columns – small longitudinal fold in the anal canal o Anus – the exit of anal canal Histology is that of general GIT, however, the large intestine lack intestinal villi, and have more mucous cells to lubricate the faeces. The musclaris externa of the large intestinal has circular smooth muscle and the longitudinal smooth muscle is reduced to thin bands called the Taenia coli Physiology of the Digestive System Functions of the digestive system The digestive system carries out five basic activities: 1. Ingestion: taking food into the mouth (eating). 2. Movement of food: passage of food along the gastrointestinal tract. 3. Digestion: the breakdown of food by both chemical and mechanical processes 4. Absorption: the passage of digested food from GIT into cardiovascular and lymphatic system for distribution to cells 5. Defecation: the elimination of indigestible substance (faeces) from the GIT.  Mechanical digestion – consists of various movements of the GIT including maceration of food by teeth before swallowing and churning of food by smooth muscles of stomach and small intestines to ensure thorough mixing with enzymes.  Chemical digestion – is a series of catabolic (hydrolytic) reactions. Enzymes split the larger carbohydrate, lipid and protein molecules into small molecules that can be absorbed and used by the body cells. 8  Dr Yasser Abdel-Wahab (Module Coordinator) What is food? Food: Essential nutrients - Carbohydrates, protein, fat, vitamins, minerals, trace elements (but also includes intake of potentially toxic substances). Mouth Digestion and movement of food along the GIT begins when food enters the mouth.  The teeth aid in chewing food into small particles to increase surface area for exposure to digestive enzymes  The tongue assists in swallowing and tasting of food.  The salivary glands produce saliva, which moistens the food, digests polysaccharides and assists in swallowing. Swallowing and the Esophagus When food has been macerated and mixed with saliva it forms a bolus which can be swallowed. 1. The food bolus is pushed against the hard palate of the mouth, the tongue retracts forcing the food bolus into the pharynx and pushing soft palate up to close of nasopharynx (buccal phase of swallowing). 2. The larynx elevates and the epiglottis folds over to close the glottis (prevents the food entering the trachea). The pharyngeal muscle contracts and pushes the food into the esophagus (pharyngeal phase) 3. Esophageal phase: The food bolus enters the esophagus and is moved towards the stomach by PERISTALSIS. Travelling wave of contraction of circular muscle and relaxation of longitudinal muscle. When the food bolus approaches stomach the lower esopahgeal sphincter opens allowing the food to enter the stomach. 9  Dr Yasser Abdel-Wahab (Module Coordinator) Stomach The stomach has 4 main functions: 1. The storage of ingested food 2. Mechanical mixing/churning and breakdown of food 3. Dissolving food by breakdown of chemical bonds by acids and enzymes (pepsin) in the stomach 4. Production of intrinsic factor which aids vitamin B12 absorption The epithelial lining of the stomach contains numerous shallow depressions called gastric pits which communicate with several gastric glands in the body and fundus of the stomach.  Gastric gland Mucous o Mucous cells – secrete alkaline mucous Gastric pit cells o Parietal cells – secrete intrinsic factor which aid absorption of Vit B12 across intestinal lining, and secrete HCl as H+ and Cl- ions. o Chief cells – secrete inactive pepsinogen, Parietal cells Gastric which is converted to active pepsin gland Chief (proteolytic enzyme) by acid and pepsin cells aids protein digestion G cells o G cells (enteroendocrine cell) – produce gastrin which stimulates secretion by parietal and chief cells and contraction of gastric wall to mix/stir stomach contents. Parietal cells and chief cells secrete ~ 1500 ml of gastric juice per day and keep stomach contents at an acidic pH of 1.5 – 2.0. The food and acid/enzyme mix which is churned in the stomach is known as chyme. Gastric secretions are initiated by the thought, taste, smell or sight of food by actions of the CNS via the vagus nerve. 10  Dr Yasser Abdel-Wahab (Module Coordinator) Movement of food from stomach to the small intestine (duodenum) After 3-4 h of mixing and digestion in the stomach the chyme moves into the small intestine following relaxation of the pyloric sphincter. The stomach performs peristaltic contractions along the length of the stomach to squeeze small amounts of chyme into the small intestine (duodenum). Only small amounts of chyme enter the duodenum at a time to allow neutralisation of the acidic chyme which would otherwise interfere with digestion and absorption within the small intestine. In the small intestine the chyme is neutralised and mixed with digestive juices, bile, and pancreatic juice which enable breakdown of the food molecules for absorption As discussed in the anatomy of the small intestine, the small intestine has a large surface area due to the presence of numerous finger-like projections into the lumen called intestinal villi. The intestinal villi are covered in microvilli (said to give the villi a brush like appearance) known as the brush border of the epithelial cells of the villi, and these increase the surface area of the absorptive surface. These microvilli project out of the cell membrane of the epithelial cells and contain actin filaments. Theses microvilli are covered in hair like glycocalyx which are carbohydrate portions of protein structures in the plasma membrane. Motility of the gastrointestinal tract Motility of the GIT is controlled by the contraction of the smooth muscle layers of the mucosa muscularis and muscularis externa.  This motility aids mechanical mixing of food with digestive enzymes/juices.  Increases exposure of the digested food to absorptive surfaces.  Aids in solubilisation of food molecules. The mechanical mixing and solubilisation caused by 11  Dr Yasser Abdel-Wahab (Module Coordinator) contracting and relaxing of the circular smooth muscle is known as segmentation. Peristalsis is the movement of food along the GIT caused by waves of muscular contraction of the muscularis externa. The circular muscles behind the food bolus contract and those in front relax while the longitudinal muscles in front of the bolus contract to shorten the segment of intestine. The diagram to the right shows the movement of food bolus by peristalsis Control of circular and longitudinal smooth muscles 1. Smooth muscle of the GIT is myogenic: it can contract without external stimulation. Some of the smooth muscle cells contract periodically and the contraction spreads from cell to cell. 2. The contractions causing peristalsis and motility are also controlled by reflexes coordinated at the mysenteric plexus. Sensory receptors (e.g. stretch receptors) send signal to mysenteric plexus were signals are relayed back to the muscle to cause contraction. Higher levels of control such as large peristaltic movements can also be controlled by the CNS. 3. Hormones secreted from enteroendocrine cells in response to nutrients in the intestine can also regulate gastrointestinal motility. Gastrointestinal secretions  The GIT tract and associated organs contain both endocrine (hormone producing) and exocrine (secretory products) glands.  The exocrine glands and their secretions enter the GIT were they mix with food to aid solubility, digestion and absorption.  The aqueous secretions contain a mixture of enzymes, electrolytes and mucus.  Nutrients and other factors can stimulate endocrine hormone release and these hormones have numerous biological functions as discussed later. 12  Dr Yasser Abdel-Wahab (Module Coordinator) Exocrine cells Exocrine glands of the GIT (salivary glands, pancreas and liver/gall bladder) release their secretory products into ducts, which carry the secretions to the lumen of the duodenum of the GIT (or mouth in terms of salivary glands).  A single chamber (Acinus) of an exocrine gland is lined by exocrine acinar cells.  Acinar cells package their secretory products (zymogens) in Zymogen granules until release into the lumen of the chamber and ducts by exocytosis. Many of the zymogens are inactive enzymes, which only become active in the lumen of the GIT, e.g. trypsinogen (in pancreatic juice) is converted to trypsin by the enterokinase enzyme located on the microvilli of the small intestine. Bile and bile salts  Bile is produced (~ 1 L/day) in the liver and either secreted into the duodenum or is stored in the gall blabber.  Bile contains mostly water, and some ions, cholesterol, lipids and bile salts (derivatives of cholesterol with both hydrophobic and hydrophilic regions) but also biliverdin/bilirubin which give it its distinctive colour (bile pigments)  If the hepatopancreatic sphincter is closed, bile from the hepatic duct cannot enter the bile duct but is transported to the gall bladder via the cystic duct.  Water is absorbed from bile in the gallbladder to make it more concentrated.  Release of bile into the duodenum via the hepatopancreatic sphincter is controlled by the intestinal hormone cholecystokinin (CCK).  Bile neutralizes the acidic chyme, aids in dispersion (emulsification) of fat into smaller emulsion droplets to increase surface area for lipases, and aid the elimination of water insoluble waste. 13  Dr Yasser Abdel-Wahab (Module Coordinator) The table below summarizes the secretions from the different regions of the GIT. The enzymes secreted in the small intestine continue to work in the large intestine but are not secreted in the large intestine. Site Secretion Contents Composition of major nutrients The major nutrients found in food are carbohydrates, protein and fat, but also essential are minor amounts of vitamins and minerals. These major nutrients must be digested into smaller fragments which can be absorbed into the circulation and carried to the cells for use. These nutrients are digested by the action of enzymes in saliva, gastric secretions and pancreatic juice. Enzymes of the GIT, their site of secretion and action and their digestive function are highlighted below. These enzymes digest food into smaller fragments which can be absorbed.  Mouth & stomach 14  Dr Yasser Abdel-Wahab (Module Coordinator)  Small intestine & pancreas  Small intestine Control of digestive secretions The flow chart below summarizes how digestive secretions are controlled by both neural (nerves) and hormonal (endocrine hormones such as gastrin, CCK) actions. 15  Dr Yasser Abdel-Wahab (Module Coordinator) Secretion of Saliva Saliva is a watery secretion from the saliva glands, which contain water, mucin (lubricates food and protects lining of mouth from abrasion), amylase (digests starch and glycogen), lysozyme (digest bacteria preventing tooth decay) and electrolytes Secretion of saliva from the salivary glands is controlled by both sympathetic and parasympathetic neurons of the autonomic nervous system. In the absence of food, watery saliva is slowly secreted to maintain moisture of the lining of the mouth and pharynx. The presence of food in the mouth stimulates chemoreceptors (taste buds) in the mouth which send signals to the salivary center of the medulla oblongata. This activates the parasympathetic nervous system to increase secretion of saliva. The sight/smell and thought of food can also send signal from the cerebral cortex to the salivary center of the medulla oblongata, again causing increased secretion of saliva. Activation of the sympathetic nerves innervating the salivary glands causes secretion of minute amounts of protein rich, thick saliva. Modification of saliva Saliva can be either watery or concentrated. The initial saliva secretion from the acinar cells into the duct can be modified as the saliva flows through the duct towards the GIT. Epithelial cells lining the duct can secrete or absorb ions and water into or from the saliva to concentrate or dilute the saliva. Gastric secretions There are 3 phases of gastric secretion as shown in this chart. 1. Cephalic phase: The sight, smell, taste, chewing, and swallowing of food stimulate parasympathetic neurons of the vagus nerves (which originates in the medulla oblongata) to the stomach which increase the release of pepsinogen from chief cells and HCl from parietal cells. G cells are also stimulated to by these neurons to secrete the hormone gastrin, which enter the circulation, and act to enhance secretion of pepsin and HCl from the chief cells 16  Dr Yasser Abdel-Wahab (Module Coordinator) and parietal cells. Histamine also acts as a paracrine agent to increase secretion of pepsinogen and HCl. 2. Gastric phase: The presence of food in the stomach activates stretch receptors while protein and protein digestion products (polypeptides and peptides) in the stomach activate chemoreceptors. These receptors send nerve signals via short and long reflexes which enhance Gastrin release from G cells, thus enhancing pepsinogen and HCl release. The proteins also directly stimulates gastrin secretion from G cells. 3. Intestinal phase: As the food leaves the stomach and enters the small intestine (duodenum), the contents of the duodenum become more acidic, have increased fat content and the osmolarity of the contents of the duodenum are raised. The duodenum also becomes stretched as more chyme enters. These stimulate osmoreceptors, chemoreceptors and stretch receptors in the duodenum which send short and long reflex signals to chief cells and parietal cells to decrease pepsinogen and HCl release. Endocrine cells of the small intestine also respond to nutrients to increase secretion of secretin, GIP, VIP to reduce pepsinogen and HCl release, slow gastric emptying, and increase release of bicarbonate rich pancreatic juice to neutralize the acid chyme. Control of gastric acid secretion As discussed above gastric acid (HCl) is secreted from the parietal cells of the stomach. Secretion of HCl from these cells is regulated by the cephalic phase (see above) through direct stimulation by the vagus nerve and by increased release of gastrin from G cells, increasing plasma gastrin which acts to increase secretion of HCl. Histamine release also increases HCl secretion from parietal cells. Endocrine hormones secreted from the small intestine, include GIP, CCK and somatostatin. CCk increased secretion of HCl, while GIP and somatostatin inhibit HCl secretion from parietal cells. Furthermore, the presence of increased HCl in the stomach (e.g. following exit of chyme into duodenum, resulting in less acid buffering proteins in stomach) inhibits the release of gastrin from G cells directly. Gastric secretions & gut hormones The hormone Gastrin is secreted by the G-cell of stomach in response to undigested proteins. CCK, Secretin, VIP, GIP, Motilin, GLP-1 and other hormones are secreted by the presence of other nutrients in the small intestine. The stimulus and effects of these hormones are summarized in the figure below. 17  Dr Yasser Abdel-Wahab (Module Coordinator) The diagram below summarizes the different hormones of the GIT, the digestion products or stimuli which increase their secretion and their function on regulation of GIT activity Absorption of a carbohydrate meal  Starch (a polysaccharide) is digested by amylase in saliva and pancreatic juice into smaller disaccharides (such as maltose), maltotriose or -dextrins.  Enzymes of the brush border finalise digestion of these products to monosaccharides. o Maltase converts maltose to two glucose molecules o Lactase converts lactose (milk sugar) to glucose and galactose o Sucrase converts sucrose (sugar) to glucose and fructose. o Dextrinases digest the branched polysaccharide -dextrin The digestion of these products at the brush border into monosaccharides is the rate limiting (RL) step of carbohydrate absorption  The monosaccharides glucose and galactose are then transported into the epithelial cells of the small intestine by active transport with sodium ions (Na+).  Fructose enters the epithelial cells by facilitated diffusion  At the basolateral membrane of the epithelial cells, these monosaccharides move into the interstitial fluid by facilitated diffusion, from here they diffuse into the capillaries to enter the circulation The carbohydrate cellulose, from plant material is undigestible by humans and passes through the GIT. Cellulose (or dietary fibre) aids gastrointestinal motility. 18  Dr Yasser Abdel-Wahab (Module Coordinator) Active transport of amino acids/sugars Amino acids (the products of protein digestion) are also absorbed from the intestinal lumen into the epithelial cells by active transport with sodium ions. This diagram show how monosaccharides (S) or amino acids are transported into the cell with Na+ The GIT lumen contents are usually rich in Na+ and their concentration will be higher in the lumen than the epithelial cells. Thus they are co-transported (with glucose, galactose or amino acids) by a carrier protein into the epithelial cells. The concentrations in the cells are kept low by the transport actions of the Na+/K+ pump which requires ATP. This pumps Na+ out of the cells at the basolateral membrane and into the interstitial fluid in exchange for K+. This ensures that Na+ continues to enter the epithelial cells from the GIT lumen Absorption of amino acids Proteins are made up of polymers of amino acids. Protein digestion starts in the stomach with pepsin. Several pancreatic enzymes further digest the proteins into amino acids in the lumen of the small intestine. These enzymes include trypsin, chymotrypsin, but also carboxypeptidase and aminopeptidase (a brush border enzyme). Carboxypeptidase and aminopeptidase are endopeptidases as they cleave amino acids of the carboxy of amino terminal of peptide chains. The amino acids have 4 Co-transport systems involving Na+ which are based on the properties of the amino acid: 1. 15 Neutral amino acids 2. Dibasic amino acids (Arginine, Lysine, Histidine) 3. Diacidic amino acids (Glutamate, Aspartate) 4. Glycine, Proline, Hydroxyproline 5. System for dipeptides (2 aa) / tripeptides (3 aa) is via distinct transporters. The dipeptides and tripeptides which are transported into the cell are then cleaved to single amino acids by protease enzymes within the epithelial cells. Amino acids enter the interstitial fluid by facilitated diffusion and then diffuse into the surrounding blood capillaries. 19  Dr Yasser Abdel-Wahab (Module Coordinator) Absorption of fats Fat digestion mainly occurs in the small intestine, when bile salts aid in the breakdown of fat into smaller droplets (emulsification) increasing surface area for exposure to action of lipases. Triglycerides (TG, three fatty acids attached to a glycerol molecule) account for approx 90% of dietary fat intake. Lipases break triglycerides into a monoglyceride (glycerol with free fatty acid attached) and 2 free fatty acids. Some of these are absorbed into the epithelial cells, other remain in the lumen and combine with bile salts to form small lipid-bile salt particles called micelles. Micelles release the fatty acids and monoglycerides and they diffuse into the epithelial cells. Micelles usually disappear by the time the chyme reaches the terminal ileum due to absorption of the fatty acids, monoglycerides and bile salts across the epithelium. Inside the epithelial cells the monoglycerides and free fatty acids are resynthesised into TG in the endoplasmic reticulum (ER). The TG and other lipids (phospholipids/cholesterol) enter the Golgi apparatus of the cells were they are packaged into large particles with a protein coating called Chylomicrons. The chylomicrons are secreted into the interstitial fluid inside the intestinal villi by exocytosis from the epithelial cells. Most of the chylomicrons pass into the lacteals (lymphatic system) of the villi were they are transported to the subclavian vein were they enter the bloodstream. Absorption of other nutrients Vitamins do not undergo digestion. Vitamins A, D, E and K are fat soluble and are absorbed into micelles and are transported into the cells with the lipids. They can enter chylomicrons to be carried to the circulation and cells. The other vitamins are water soluble and are absorbed by either passive diffusion or by carrier mediated transport. 20  Dr Yasser Abdel-Wahab (Module Coordinator) Vitamin B12 must be bound to intrinsic factor if it is to be absorbed. Intrinsic factor is secreted by the parietal cells of the stomach. Nucleic acids are broken down by nucleases (pancreatic juice) into nucleotides, free nitrogenous bases and monosaccharides which are absorbed by active transport. Water fluxes in the GIT  Usually only about 2 L of water is consumed by food and drink each day.  Secretion of the GIT including saliva, gastric secretions in the stomach, bile from the liver, pancreatic juice, and mucosal secretions of the cells lining the small intestine account for about and extra 7 L of water entering the GIT.  The majority of this water is reabsorbed in the small intestine (~7.8 L)  The rest of the fluid is reabsorbed in the colon such that only 150 ml is eliminated in the faeces each day. This water is absorbed by passive diffusion from the lumen into the interstitial fluid, were it enter circulation. Water transport in intestine  As mentioned earlier, Na+ is co-transported along with sugars and amino acids from the GIT lumen into the epithelial cells.  The concentration of Na+ at the tip of the villi increases, this draw water into the cells by osmosis.  At the basolateral membrane of the epithelial cells Na+ is pumped into the interstitial fluid, increasing concentration of Na+ in interstitial fluid compared to that within the epithelial cell.  This causes passive diffusion of water from the epithelial cells into the interstitial fluid due to the differences in osmotic pressure. Water balance There need to be a delicate balance between water intake and excretion in order to maintain plasma volume. 21  Dr Yasser Abdel-Wahab (Module Coordinator) If plasma volume is decreased:  then water excretion needs to be decreased and water intake increased.  Osmolarity of plasma increases and stimulates hypothalamic osmoreceptors to signal posterior pituitary gland to release more ADH.  Blood pressure increases stimulating atrial baroreceptors, which stimulates increased ADH release.  ADH increases water reabsorption back into the blood from the kidney tubules  Signals are sent to the hypothalamus to increase thirst prompting intake of fluids. Regulation of feeding activity This diagram summarizes the factors which regulate feeding activity via the hypothalamus. For example, when the environmental temperature is very hot, appetite can be suppresse; the distension of the stomach and small intestine as well as release of hormones following a meal will send signals to the hypothalamus to increase satiety (feeling of fullness) which will reduce or stop feeding activity. Leptin The peptide hormone leptin was discovered in the early 1990’s in a strain of obese mice (ob/ob mice). These mice had a defective leptin gene, and had low concentrations or no leptin When these mice were treated with leptin they lost weight and became like normal lean mice. Leptin is produced and secreted by white adipose tissue during the synthesis of TG following nutrient absorption and transport to the cells. 22  Dr Yasser Abdel-Wahab (Module Coordinator) Leptin acts on brown adipose tissue to increase thermogenesis, thus increasing energy expenditure. Leptin also acts on appetite-control centers in the hypothalamus to suppress appetite (i.e. increase satiety). Reading List:  Martini FH & Nath JL, Fundamentals of Anatomy and Physiology, San Francisco, Pearson Benjamin Cummings. Martini’s Fundamentals of Anatomy and Physiology was specially selected for this module on the basis of the quality of the textbook, the inclusion of the valuable Fundamentals of Anatomy and Physiology. It comes with Interactive CD-ROM and supporting WWW site (freely accessible to students purchasing this text). 23