Gastrointestinal Super 7 PDF

Gastrointestinal – Super 7 1. Four layers of gastrointestinal wall: structure/function relationship (begins on p. 860- 861) • The GI tract has four layers and is usually surrounded by peritoneum • Mucosa Layer o Innermost layer, moist epithelial membrane that lines the alimentary canal from mouth to...

Gastrointestinal – Super 7 1. Four layers of gastrointestinal wall: structure/function relationship (begins on p. 860- 861) • The GI tract has four layers and is usually surrounded by peritoneum • Mucosa Layer o Innermost layer, moist epithelial membrane that lines the alimentary canal from mouth to anus o Major functions include (1) Secrete mucus, digestive enzymes and hormones (2) Absorb the end products of digestion into the blood (3) Protect against infectious disease o Has three sub-layers: a lining epithelium, a lamina propria, and a muscularis mucosae • Submucosa Layer o External to mucosa layer o Areolar connective tissue containing rich supply of blood and lymphatic vessels, lymphoid follicles, and nerve fibers which supply the surrounding GI tract wall o The elasticity of this layer always for the stomach to stretch and return to its normal size temporarily for large meals • Muscularis Externa o This surrounds the submucosa; it is also referred to as the muscularis o Responsible for segmentation and peristalsis o Has two layers: inner circular and an outer longitudinal layer of smooth muscle cells o Along the tract the circular layer thickens and forms sphincters which act as valves to control food passage and remove back flow • Serosa o The outer most layer of the intraperitoneal organs, it is the visceral peritoneum o Formed primarily of areolar connective tissue covered with mesothelium o In the esophagus the serosa is replaced by adventitia, this is dense connective tissue that binds the esophagus to surrounding structures o Retroperitoneal structures have both serosa and adventitia 2. Anatomy and function of the digestive system - Organs fall into two categories: a) Alimentary canal (GI Tract) which digests food and absorbs digested fragments into blood. This includes mouth, pharynx, esophagus, stomach, small and large intestine b) Accessory organs: teeth, tongue, gallbladder, salivary glands, liver and pancreas. - The purpose of the digestive system is to break down food and convert it to energy. There are 6 essential activities: a) Ingesting: take food in b) Propulsion: moves food through alimentary canal by swallowing and peristalsis c) Mechanical breakdown: increases surface area of food for digestive enzymes through chewing, saliva, or segmentation d) Digestion: enzymes secreted into the lumen to break down complex molecules e) Absorption: movement of end products into blood or lymph f) Defecation: eliminates waste • • • • Mouth and accessory organs o Ingestion, propulsion (swallowing), breakdown (chewing), digestion (salivary amylase in saliva) Pharynx and esophagus o Propulsion: peristalsis Stomach o Mechanical breakdown (peristalsis and gastric juice), Digestion (pepsin begins digestion of proteins), Absorption (few fat-soluble substances) Small intestines and liver/gallbladder/pancreas o • Breakdown (small intestines mixes contents, peristalsis moves food- allows time for absorption and digestion.) Digestions (enzymes from pancreas). Absorption (breakdown of carbs, protein, fat, and nucleic acid) Large Intestine o Digestion (remaining food digested by enteric bacteria). Absorption (remaining water and electrolytes). Propulsion (feces). Defecation (elimination) 3. Anatomic details of abdomen: peritoneum, mesentery, omentum (p.860) Peritoneum • • • • Surrounds the GI tract Visceral peritoneum covers the external surfaces of most digestive organs Parietal peritoneum, which is connected with the visceral peritoneum, lines the body wall Peritoneal Cavity is the space between the two peritoneum’s and contains slippery fluid that allows the organs to glide against one another without damage Mesentery • • Double layer of peritoneum, two sheets of serous membranes fused back-to-back which extend to the digestive organs from the body Provides routes for blood vessels, lymphatics and nerves to reach the digestive viscera and olds organs in place and stores fat Omentum • A fold of peritoneum connecting the stomach with other abdominal organs 4. Anatomy of intestinal blood supply and lymphatic drainage - Blood supply from splanchnic circulation Includes arteries that branch off the abdominal aorta to serve the digestive organs and the hepatic portal circulation Primary blood supply to intestines comes from 3 branches from the abdominal aorta: a) Celiac artery b) Superior mesenteric arteries- provides O2 rich blood to small intestine c) Inferior mesenteric arteries- supplies to transverse and sigmoid colon The celiac artery comes from aorta (through a space in the diaphragm called aortic hiatus) Then the celiac artery divides to 3 branches: a) Lineal artery (connects spleen) b) Left gastric artery (supplies stomach) c) Common hepatic artery/ right gastric artery • • Hepatic portal circulation collects nutrient rich venous blood drainage from the digestive viscera and delivers it to the liver Receives ¼ of cardiac output 5. Digestion: definition, digestion steps in mouth and stomach Definition: the process of breaking down food by mechanical and enzymatic action in the alimentary canal into substances that can be used by the body Digestive steps in the mouth (p.869): • • • • • • • • • Ingestion only occurs at the mouth Accessory organs include: teeth, salivary glands and tongue Also called the oral cavity and buccal cavity The oral cavity is continuous with the oropharynx The walls of the mouth are lined with thick stratified squamous epithelium allowing it to be exposed to considerable friction The mouth is involved in four of the six steps in digestions (1) ingestion, (2) begin of mechanical break down by chewing, (3) initiates propulsion by swallowing, (4) starts the digestion of polysaccharides Absorption only occurs in the mouth when sublingual drugs are used Mastication (chewing): food is mixed with saliva, this is partially a voluntary and partially reflexive process Swallowing (deglutition): the pharynx and esophagus are conduits to pass food from stomach using propulsion, food is compacted into bolus and is then swallowed. There are two phases involved in swallowing, (1) buccal phase, is voluntary and occurs in the mouth when food or saliva leaves the mouth and stimulates tactile receptors initiating the next phase, (2) pharyngealesophageal phase, this involuntary phase is controlled by the swallowing center in the brain (medulla and lower pons), the vagus nerves transmit motor impulses from the swallowing center to the muscles of the pharynx and esophagus Digestive steps in the stomach (p.877): • • • • • • • • The stomach continues the demolition job that was begun by the mouth, it then delivers the product of this, chyme, into the small intestine Protein digestion is the main type of break down that occurs in the stomach Pepsin is the most important protein- digesting enzyme which is produced by the gastric mucosa Hydrochloric acid is also produced by stomach and in combination with pepsin breaks down food into chyme Children produce an enzyme called rennin, this enzyme acts on milk protein (casein) and converts it to a curdy substance Fat digestion primarily occurs in the small intestine, however, gastric and lingual lipases acting in the acidic pH of the stomach also contribute Not much is absorbed through the stomach, alcohol and aspirin are two of the main things that can be absorbed through the stomach and into the blood The stomachs only function that is essential to life is the secretion of intrinsic factor, intrinsic factor is required for intestinal absorption of vitamin B12 which is needed to produce mature erythrocytes, without this pernicious anemia results 6. • • • • • Production of hydrochloric acid by parietal cells: how? How is this regulated? Parietal cell is a type of gland cell Secrete HCL and intrinsic factor Have microvilli that provide surface area for secreting hydrogen and chloride into the stomach lumen Hydrochloric acid in the stomach is necessary to activate the protein digesting enzyme pepsin Intrinsic factor is a glycoprotein required for vitamin b12 absorption in the small intestine Regulation of Gastric Secretion Both neural and hormonal Long (vagus nerve) short (local enteric) nerves provide control Stimulation of vagus nerve = increase in secretory activity Activation of sympathetic nerves depresses activity 3 Phases of gastric secretion: A) Cephalic (reflex phase) • • • • Before food enters the stomach Sensory input from olfactory receptors and taste buds relayed to hypothalamus which stimulates vagal nuclei of medulla oblongata Sends motor impulse to enteric ganglia → stomach glands Secretory activity begins when we see or think of food B) Gastric • • • • • • • When food reaches the stomach Most important stimuli are distension (stretch receptors, local and long reflexes), peptides and low acidity ACh release stimulates output for more gastric juice G cells are secreted release secreting parietal cells, in turn releases more HCl (unless there is high acidity, below 2, gastric contents will inhibit gastrin secretion) The more protein in a meal, the greater amount of gastrin and HCl released Neural reflexes like stress and fear stimulate G cells 3 chemicals influence HCl secreting parietal cells: o Ach - from parasympathetic nerve fibres o Gastrin - secreted by G cells o Histamine All three of these must bind to parietal cell to increase HCl secretion substantially C) Intestinal 2 components: stimulatory and inhibitory - Enterogastric reflex inhibits vagal nuclei, inhibits local reflex, and activates local sympathetic fibres all causing a decline in gastric secretory activity. This releases several hormones called enterogastrones (secretin, cholecystokinin, vasoactive intestinal peptide) which all inhibit gastric secretion when stomach is active. 7. Basic concepts of gastrointestinal neurophysiology: role of autonomic nervous system (p. 877) • Neural controls consist of both long (vagus nerve-mediated) and short (local enteric) nerve reflexes • In each of the above cases acetylcholine (Ach) is released, stimulating the output of gastric juices • When vagus nerves are stimulated and all of the glands are stimulated • Enteric Nervous System o The in-house nerve supply of the alimentary canal o Staffed by the enteric neurons that communicate widely with one another to regulate digestive system activity o Semiautonomous enteric neurons o Two major intrinsic nerve plexuses are found in the walls of the alimentary canal; the submucosal and myenteric nerve impulses o There are both long and short reflex arcs ▪ Short reflexes: mediated entirely by enteric nervous system plexuses in response to stimuli within the GI tract ▪ Long reflexes: CNS integration centers and extrinsic autonomic nerves are involved, information is sent to the CNS via afferent visceral fivers, these can be aroused by stimulants inside or outside the GI tract Gastrointestinal Absorption 1. Exocrine pancreatic functions Exocrine Function: The pancreas contains exocrine glands that produce enzymes important to digestion. These enzymes include trypsin and chymotrypsin to digest proteins; amylase for the digestion of carbohydrates; and lipase to break down fats. When food enters the stomach, these pancreatic juices are released into a system of ducts that culminate in the main pancreatic duct. The pancreatic duct joins the common bile duct to form the ampulla of Vater which is located at the first portion of the small intestine, called the duodenum. The common bile duct originates in the liver and the gallbladder and produces another important digestive juice called bile. The pancreatic juices and bile that are released into the duodenum, help the body to digest fats, carbohydrates, and proteins. Acinar cells are the exocrine (exo = outward) cells of the pancreas that produce and transport enzymes that are passed into the duodenum where they assist in the digestion of food. Pancreatic juice is composed of two secretory products critical to proper digestion: digestive enzymes and bicarbonate. The enzymes are synthesized and secreted from the exocrine acinar cells, whereas bicarbonate is secreted from the epithelial cells lining small pancreatic ducts. Digestive Enzymes The 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: 1. Proteases Digestion 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 the inactive proenzyme’s trypsinogen and chymotrypsin. As you might anticipate, proteases are rather dangerous enzymes to have in cells, and packaging of an inactive precursoris 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 on the surface of small intestinal epithelial cells. More on this later. 2. Pancreatic Lipase A major component 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. 3. Amylase The major dietary carbohydrate for many species is starch, a storage form of glucose in plants. Amylase (technically alpha-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 Enzymes In addition to the proteases, lipase and amylase, the pancreas produces a host of other digestive enzymes, including ribonuclease, deoxyribonuclease, gelatinase and elastase. Bicarbonate and Water Epithelial cells in pancreatic ducts are the source of the bicarbonate and water secreted by the pancreas. Bicarbonate is a base and critical to neutralizing the acid coming into the small intestine from the stomach. 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. 4. Colon: function, peristalsis (definition and role of intrinsic/extrinsic neurons) and defecation/gastro colic reflexes What Is the Function of the Colon? Responsible for the final stages of the digestive process, the colon’s function is threefold: to absorb the remaining water and electrolytes from indigestible food matter; to accept and stores food remains that were not digested in the small intestine; and to eliminate solid waste (feces) from the body. The colon works to maintain the body’s fluid balance. It absorbs certain vitamins, and processes indigestible material (such as fiber), and stores waste before it is eliminated. Within the colon, the mixture of fiber, small amounts of water, and vitamins, etc., mix with mucus and the bacteria that live in the large intestine, beginning the formation of feces. As the feces makes its way through the colon, the lining absorbs most of the water as well as some of the vitamins and minerals present. Bacteria within the colon feed on the fiber, breaking it down in order to produce nutrients that will nourish the cells that line the colon. This is why fiber is such a vital part of a diet geared toward the colon’s long-term health. Feces is moved along until the walls of the sigmoid colon contract, causing waste to move into the rectum. Known as peristaltic action, this wave-like motion encourages feces to move closer to the rectum and, finally, be expelled through the anus. Physiology of Peristalsis Peristalsis is a distinctive pattern of smooth muscle contractions that propels foodstuffs distally through the esophagus and intestines. It was first described by Bayliss and Starling (J Physio (Lond) 24:99 -143, 1899) as a type of motility in which there is contraction above and relaxation below a segment being stimulated. Peristalsis is not affected to any degree by vagotomy or sympathectomy, indicating its mediation by the intestine's local, intrinsic nervous system. Peristalsis is a manifestation of two major reflexes within the enteric nervous system that are stimulated by a bolus of foodstuff in the lumen. Mechanical distension and perhaps mucosal irritation stimulate afferent enteric neurons. These sensory neurons synapse with two sets of cholinergic interneurons, which lead to two distinct effects: One group of interneurons activates excitatory motor neurons above the bolus - these neurons, which contain acetylcholine and substance P, stimulate contraction of smooth muscle above the bolus. Another group of interneurons activates inhibitory motor neurons that stimulate relaxation of smooth muscle below the bolus. These inhibitor neurons appear to use nitric oxide, vasoactive intestinal peptide and ATP as neurotransmitters. Defecation The defecation reflex is an involuntary response of the lower bowels to various stimuli thereby promoting or even inhibiting a bowel movement. These reflexes are under the control of the autonomic system and play an integral role in the defecation process along with the somatic system that is responsible for voluntary control of defecation. The two main defecation reflexes are known as the intrinsic myenteric defecation reflex and parasympathetic defecation reflex. Intrinsic Myenteric Defecation Reflex The entry of feces into the rectum causes the distention of the rectal wall. This stretching triggers signals to the descending and sigmoid colon via the myenteric plexus to increase peristalsis. The myenteric plexus is part of the enteric nervous system which is the gut’s own internal neural network as discussed under stomach nerves. The peristaltic waves extend all the way to the rectum an anus. In this manner, fecal matter is moved closer to the anus. When the wave reaches the anus, it causes the internal anal sphincter, which is always constricted, to relax. This is achieved by inhibitory signals via the myenteric plexus to reduce sphincter constriction. Parasympathetic Defecation Reflex The parasympathetic defecation reflex works in essentially the same way as the intrinsic myenteric defecation reflex but involves parasympathetic nerve fibers in the pelvic nerves. It triggers peristaltic waves in the descending and sigmoid colon as well as the rectum. It also causes relaxation of the external anal sphincter. The difference is that the parasympathetic defecation reflex enhances this process and makes the intrinsic reflex much more powerful. If sufficiently stimulated, it may even cause the sigmoid colon to completely empty all of its contents in the rectum rapidly. The force triggered by the parasympathetic defecation reflex can be powerful enough to result in defecation, despite conscious efforts to keep the external anal sphincter constricted. Other Defecation Reflexes Gastrocolic reflex – distention of the stomach while eating or immediately after a meal triggers mass movements in the colon. Gastrolienal reflex – distention of the stomach while eating or immediately after eating triggers the relaxation of the ileocecal sphincter and speeds up peristalsis in the ileum (end portion of the small intestine). This causes the contents of the ileum to rapidly empty into the colon. Enterogastric reflex – distention and/or acidic chyme in the duodenum slows stomach emptying and reduces peristalsis. Duodenocolic reflex – distention of the duodenum a short while after eating triggers mass movements in the colon. Irritation within the stomach or duodenum can stimulate or even inhibit the defecation reflexes. In addition to these gastrointestinal reflexes, there are other reflexes involving the peritoneum, kidney and bladder that can affect the defecation process. This includes the: Peritoneointestinal reflex involving the peritoneum and intestines Renointestinal reflex involving the kidney and intestines Vesicointestinal reflex involving the bladder and intestines. 4. Anatomy and physiology of liver and bile (composition, secretion, regulation) Gross Anatomy • • • • • • • Largest gland in the body located in R. hypochondriac, epigastric region almost entirely within ribcage 4 lobes: right, left, caudate, and quadrate Falciform ligament separates right from left and attaches liver to diaphragm and anterior abdominal wall Round ligament/ligamentum teres – remnant of umbilical vein Bare area – not covered by a visceral peritoneum, touches diaphragm Blood supply – hepatic artery and portal vein – enter at porta hepatis (gateway to liver) Bile leaves liver through right/left hepatic ducts becoming common hepatic duct>cystic duct>bile duct (See diagrams page 883) Microscopic Anatomy • • • • Liver cells are called hepatocytes They form liver lobules – 6-sided structure with hepatocytes arranged in plates Central vein – runs long ways with the hepatocytes coming out in layers Portal triad – at each of the 6 corners of the liver lobule, has 3 parts o branch of hepatic artery – supplies oxygen rich blood o branch of portal vein – carrying venous blood with nutrients from digestion o bile duct ▪ Liver sinusoids – between hepatocyte plates, fenestrated to pass blood from portal triad to central vein ▪ From central vein > hepatic veins > inferior vena cava ▪ Walls of liver sinusoid are formed by stellate(hepatic) macrophages ▪ Stellate Macrophages remove bacteria and worn-out blood cells ▪ Bile canaliculi run between hepatocytes toward bile duct branches in portal triads Hepatocytes • • • • • • • Hepatocytes have large amounts of rough and smooth ER, golgi apparatus, peroxisomes, mitochondria Secrete 900mL of bile / day Store glucose as glycogen Use amino acids to make plasma proteins Store fat soluble vitamins Detoxify Turn blood ammonia into urea (See Diagrams page 885) Bile • • • • Alkaline Yellow/green colour Contains bile salts, bile pigments, cholesterol, triglycerides, phospholipids, electrolytes *Only the bile salts and phospholipids aid the digestive process Bile Salts • • • • Cholesterol derivatives Digest and absorb fats Substances secreted in bile leave the body in feces, bile salts do not Enterohepatic circulation conserves bile salts Enterohepatic circulation • • • Bile salts are reabsorbed into the ileum Returned to the liver via the hepatic portal Resected in newly formed bile; 95% of secreted salts are recycled Bilirubin • • • Chief bile pigment – yellow Waste product of heme of hemoglobin from broken down erythrocytes Absorbed from blood by liver cells>excreted into bile>metabolized by bacteria in sm. Intestine 5. Protein absorption: how does meat get absorbed (beginning to end!)? See page 903 • • • Proteins include dietary protein (125g/day) and protein from used mucosal cells (15 -25g/day) Protein is digested down to its amino acid monomers Begins in the stomach with pepsin Pepsin • • • • • Chief cells secrete pepsinogen which is activated to pepsin Functions best from pH1.5-2.5 (stomach environment) It prefers tyrosine and phenylalanine ands reduces them to free amino acids Pepsin hydrolyzes 10-15% of ingested protein It is inactivated once reaching the duodenum Protein Digestion Summary (see diagram page 903) • • • • • • • • Pancreatic proteases break down protein pieces In the small intestine, protolytic enzymes, trypsin and chymotrypsin break them down more Carboxypeptidase split off one amino acid at a time from the chain Brush border enzymes also break amino acids off the end of chains Dipeptidases break pairs of amino acids in two Teamwork like this speeds up the process Amino acids are cotransported across apical membrane of the absorptive epithelial cell Amino acids exit across the basolateral membrane via facilitated diffusion 6. Fat absorption and portal circulation: how do we process butter? • • • Triglycerides are the most abundant fats in the diet Primarily digested in the small intestine Pancreas is the major source of fat-digesting enzymes (lipases) Fat Digestion Summary Emulsification • • • • • Fats need pre-treatment with bile salts because they are not soluble in water Bile salts break large globules of fat into small bits increasing the surface area exposed to pancreatic lipases Bile salt non-polar end (hydrophobic) cling to fat molecules Polar end (hydrophilic) interacts with water Emulsification does not break bonds it reduces attraction between fat molecules and disperse them Digestion • Pancreatic lipases hydrolyze triglycerides making monoglycerides and free fatty acids Micelle Formation • • • Bile salts also essential in the absorption of the end product of fat digestion Also, hydrophilic/hydrophobic ‘jackets’ on fat molecules but 500 X smaller than emulsion It allows fat to be absorbed by epithelial cells Diffusion • Upon reaching the epithelial cells the substances leave the micelles and move through the plasm membrane by simple diffusion Chylomicron Formation • • • Free fatty acids and monoglycerides enter the epithelial cells and smooth ER converts them back into triglycerides They are combined with lecithin, phospholipids, cholesterol, and a skin of protein Now called chylomicrons Chylomicron Transport • • • • • Chylomicrons are too big to pass into the capillary They are extruded by exocytosis through the basolateral membrane Most fat enters the lymphatic system for distribution by the lymph Then emptied into the venous blood of the thoracic duct In the bloodstream, chylomicrons are 7. Carbohydrate absorption (see page 902) • • • 60% of digestible carbohydrate is starch Digestion of starch begins in the mouth Salivary amylase in saliva splits starch into smaller fragments until inactivated by the stomach Carbohydrate digestion summary • • • • • • Starch that escapes being broken down by salivary amylase is acted on by pancreatic amylase in the stomach It is entirely converted within 10 min. Brush border enzymes further digest these products into monosaccharides Most important brush border enzymes are dextrinase, glucoamylase, maltase, sucrose, lactase Monosaccharides are cotransported across the apical membrane of the absorptive epithelial cell Monosaccharides exit across the basolateral membrane by facilitated diffusion