Adv Pathophysiology Unit 9: GI Page 1 of 22

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1 Adv Pathophysiology Unit 9: GI Page 1 of 22 Learning objectives for this file: 1. Review the functional anatomy of the gut and neurologic control of function 2. Review gut reflexes, hormones of gut function, types of gut movements 3. Review blood supply to gut, vessel anatomy in villus, adaptive benefit of hepatic portal system 4. Proceed down the gut and review functions of the sequential sections of the gut (starting with the mouth) and related selected clinical pathologies

2 Adv Pathophysiology Unit 9: GI Page 2 of 22 OVERVIEW: Alimentary tract provides water, nutrients, electrolytes. Our bodies are a tube within a tube (the gut is the inner tube ) AND there are accessory structures (accessory organs) of digestion hanging off the gut. Food: source of energy & essential nutrients & fluid Must be moved down the GI tract (alimentary canal) digested (requires secretion of digestive juices) absorbed carried away from digestive tract by blood stream ENTIRE process must be regulated (controlled) by hormones & nervous system Digestion: to break down food, both grossly (mechanically) and then chemically. food is mixed and moved broken down physically & microscopically WHY? to expose more surface area (SA) of food to digestive juices. Alimentary canal: Our body is a tube within a tube (the GI tract is the inner tube ) gut activity is within the gut lumen the enterocytes make up the gut wall. GI tract includes: o mouth o esophagus o stomach o small intestine o large intestine o anus o & accessory organs of digestion (gallbladder, exocrine pancreas, liver)

3 Adv Pathophysiology Unit 9: GI Page 3 of 22 MOTILITY: A. FUNCTIONAL ANATOMY: GI tract is a tube. Sometimes our bodies are described as a tube within a tube because the contents of the intestine are never seen by the rest of the body 1. Intestinal wall: (going from the outside of the tube inwards) serosa longitudinal muscle circular muscle submucosa mucosa (which also contains sparse muscle fibers called muscularis mucosae). 2. Smooth muscle of gut and special electrical activity: tunica muscularis is composed of two layers of smooth muscle o inner circular layer, outer longitudinal layer o specialized circular muscles are sphincters acts as syncytium so that there is coordination of activity Continual slow electrical activity resulting in slow waves o rhythmic contractions due to changes in resting membrane potential o not true action potentials -- cause unknown. Also generate spike potentials (action potentials) Also has tonic contractions (regular ongoing tone)

4 Adv Pathophysiology Unit 9: GI Page 4 of 22 B. CONTROL OF MOTILITY: 1. Intrinsic in GUT from Enteric NS: the gut's own nervous system, from esophagus to anus. Plexus of enteric NS: Two plexuses (plexi) Outer myenteric (Auerbach's) between muscle layers for muscle control; o excitement causes peristalsis o inhibitory action (via vasoactive intestinal polypeptide, VIP) relaxes muscle sphincters (relaxation of pyloric & ileocecal sphincters) Inner (Meissner's) in submucosa o for secretory (secretions) o AND vasomotor (blood vessel) control. Neurotransmitter used a hormone: 5HT (serotonin) made by gut enterochromaffin cells (EC cells) stimulate gut function & motility by acting on 5HT receptors in gut smooth muscle & gland promote motility & secretions, coordination of gut function Serotonin (5-HT) Normalizes Gut Function Peristalsis & Receptive Relaxation Proximal Segment Distal Segment Interneurons in the myenteric plexus Movement of Gut Contents Orad motor neurons (contraction) Ach / SP CGRP Sensory neuron Caudad Motor neurons (relaxation) VIP / NO 5-HT 4 Receptors 5-HT Enterochromaffin cells release 5-HT Adapted from Grider et al, Gastroenterology 1998; 115:370. Proximal contraction Distal relaxation Coordination of peristalsis with proximal contraction and distal relaxation accomplished by gut neural plexi and endogenous gut hormones such as 5HT (serotonin).

5 Adv Pathophysiology Unit 9: GI Page 5 of Extrinsic Autonomic NS efferent control: also affects gut peristalsis & secretions Cranio-sacral parasympathetics excitatory: CN X (vagus nerve) controls esophagus, stomach, small intestine, pancreas, first half of large intestine. Sacral via pelvic nerves to second half of large intestine. Neurotransmitter: acetylcholine excites gut activity (peristalsis & secretions) Sympathetics inhibitory: pre-ganglionic outflow to thoraco-lumbar to celiac ganglion & mesenteric ganglia, postganglionic to gut. Neurotransmitters: catecholamines (NE & EP) slow down gut activity. C. GUT REFLEXES: 1. Gut afferents to CNS: Impulses: o irritation of gut mucosa o distension of gut o presence of chemical mediators in gut. Travel both to dorsal spinal cord and/or via vagus afferent nerve trunk. This is a vasovagal reflex loop. 2. Gut reflexes: exist because of afferent efferent loop Gut activity is monitored with afferents Gut activity is controlled with efferents

6 Adv Pathophysiology Unit 9: GI Page 6 of 22 D. HORMONAL CONTROL OF MOTILITY MAJOR GUT HORMONES: (MORE ON THESE LATER) Cholecystokinin (CCK): o secreted by "I" cells in duodenal/jejunal mucosa in response to fat breakdown products o causes gallbladder contraction to release bile for emulsification of these substances o also slows gastric emptying. Secretin: o secreted by "S" cells in duodenal mucosa in response to acidic gastric juice o inhibits gut motility. Gastric inhibitory peptide (GIP): o secreted by upper small intestine in response to presence of fat, amino acid & carbohydrate breakdown products o slows gastric emptying. Other chemicals acting as neurotransmitters in gut: o dopamine, substance P, vasoactive intestinal polypeptide (VIP), somatostatin, leuenkephalin, met-enkephalin, bombesin. E. TYPES OF MOVEMENTS: Propulsive (Peristalsis): coordination!! with gut distension, mucosal irritation, or parasympathetic stimulation a contractile ring appears and moves down the gut tube -- movement of food or fecal bolus this is proximal contraction Distal from this ring the myenteric plexus causes relaxation of the portion of the gut that will receive the bolus, called receptive relaxation. Peristalsis is coordinated movement of bolus down the gut tube Proximal contraction is met by distal relaxation Mixing: both peristalsis + local constrictive movements. Proximal contraction Distal relaxation

7 Adv Pathophysiology Unit 9: GI Page 7 of 22 BLOOD FLOW: A. SPLANCHNIC ARTERIAL CIRCULATION: this is a PORTAL SYSTEM Remember: normally, arterial blood goes into a tissue bed and is drained by a vein the vein then carries the blood to the right heart BUT in a portal system, the arterial blood goes to the tissue bed (the GUT) and is drained by a portal vein that carries blood to a SECOND tissue bed this second tissue bed is the LIVER then, the blood is drained by veins that go to the heart for the gut, this is the type of blood supply o EXCEPT in the lower 1/3 of the anus o EXCEPT chylomicrons that are absorbed by the lacteals and go to the thoracic duct thus, all ingested substances (food, herbs, drugs, toxins, etc.) go to the LIVER first, before going to the body s cells (in pharmacology, called the first-pass effect ) more below 1. Superior & inferior mesenteric arteries: supply blood to small & large intestine by the mesenteric web system, celiac artery supplies the stomach. Blood flows through gut, liver, pancreas, & spleen

8 Adv Pathophysiology Unit 9: GI Page 8 of Vasomotor control of splanchnic circulation: locally produced GI hormones (cholecystokinin, VIP, gastrin, secretin, kallidin, bradykinin) plus the ANS. Autoregulation of gut blood flow: Decreased O2 in the gut also increases blood flow via local release of adenosine. Neurogenic control of blood flow: some influence as well Parasympathetic: dilatation. Sympathetic vascoconstriction: (e.g. with heavy exercise, shock) of both arteries and veins. This means that blood can't get in, and blood is forced out of venous capacitance vessels into systemic circulation for use. Really empties the gut of blood!! Don t swim a mile after you ve just eaten lunch! Ischemic bowel pain will result!

9 Adv Pathophysiology Unit 9: GI Page 9 of 22 B. PORTAL VENOUS CIRCULATION: A portal system means that the veins that drain the tissue bed don t go directly back to the right heart but instead to to ANOTHER tissue bed In this case, the blood drained from the gut goes FIRST to the liver (second tissue bed) and THEN goes to the right circulation Pathway: Systemic blood gut & accessory organs portal vein drains gut liver (2nd tissue bed) venous system to right heart. MPS cells in liver lining the liver sinusoids remove bacteria & other particulate matter Hepatic cells absorb & process nutrients Villus in small intestine drainage: Villus means finger and there are AV anastamoses between the villus arteriole and the venule Portal vein drainage from venule of the villus Other drainage from the villus lacteal thoracic duct right circulation o Chylomicrons drain into the lacteal and goes to thoracic duct (right heart) o A very fatty meal sends chylomicrons directly into your bloodstream (accelerate atherosclerotic processes)

10 Adv Pathophysiology Unit 9: GI Page 10 of 22 ADAPTIVE BENEFIT OF HAVING A HEPATIC PORTAL SYSTEM: First pass (biotransformation, detoxification) -- hepatic portal system: If there are any INGESTED toxins, first pass elimination (detoxification) is done by a variety of liver enzymes (multiple cytochrome enzyme chains, or the CYP-450 system)(cyp). Also how body rids itself of old hormones, endogenous chemicals of any type. Protective benefit of allowing your liver to see what has been digested & absorbed before it gets to your body s systemic circulation From the anatomy lab at Ohio University -- cadaver with hepatic portal vein The liver sees everything FIRST! o EXCEPT blood drained by the lower 1/3 of the anus o EXCEPT chylomicrons that go into the lacteals and then into the thoracic duct

11 Adv Pathophysiology Unit 9: GI Page 11 of 22 Pharmacology correlate rectal absorption of drugs: the lower 1/2 2/3 of the rectum does NOT drain via the portal vein o absorption through the lower half of the rectum drains to IVC o therefore has its absorption directly into systemic blood (no first pass effects) o but usually rectally administered drugs via suppository slip upward and absorption is into the portal circulation via superior hemorrhoidal vein (& then to liver) with the usual first pass effects) o overall, the usual effect on rectally administered drugs (due to anastomoses of veins) causes only a 50% first pass biotransformation effect the upper 1/3 1/2 of the rectum DOES drain via the portal vein o in this case all the biotransformation issues apply o drugs are altered by the liver before they are brought into the body

12 Adv Pathophysiology Unit 9: GI Page 12 of 22 C. MICROVASCULATURE IN VILLUS: built to increase surface area for absorption of digested foodstuffs. The food must be digested to the basic building blocks (glucose and other monosaccharides, fatty acids and triglyceride, chlolesterol, amino acids). 1. Villus: means finger functional unit of the small intestine finger-like projection of the mucosa with a covering of microvilli, made up of specialized secretory cells (increased surface area) inside the villus is the blood & lymphatic supply whenever you see a similar anatomy -- it is designed to increase the surface area available for absorption Think of trees along the mountain ridge soaking up the sunlight.

13 Adv Pathophysiology Unit 9: GI Page 13 of Special blood flow in villus: The artery-vein system forms a hairpin loop inside the villus o artery & vein running side by side along the length of the villus o AV anastamoses allow plenty of time to absorb & carry away digested nutrients from gut lumen o absorbed foodstuffs go to the hepatic portal vein to the liver o oxygen transport is efficient by the time the artery reaches the villus tip, most O2 has already diffused out (the villus gets as much oxygen as possible) Clinical correlate: o If blood flow is diminished, this results in ischemic anatomical blunting and reduced function of the villus seen especially with advanced age What is the lacteal o special blind vessel (like the lymphatics) that drains the gut of chyle after a fatty meal o the chylomicrons that are the only type of free-flowing fats not complexed as lipoproteins o these are sent straight to the thoracic duct (right circulation) and NOT to the hepatic portal vein to liver

14 Adv Pathophysiology Unit 9: GI Page 14 of 22 FOOD MOVES DOWN THE ALIMENTARY TRACT: A. INGESTION (mouth, pharynx & esophagus): hunger response causes ingestion metabolic & nutritional needs of the body are met with desire for foodstuffs. 1. Mastication: actions of teeth, jaw, tongue mechanical breakdown of food. Omnivore teeth: incisors cut canines tear (MEATS) molars grind (PLANTS) 2. Chewing reflex: food is placed in the mouth the jaw drops causing reflex jaw closure. then the action is repeated (this is chewing).

15 Adv Pathophysiology Unit 9: GI Page 15 of Deglutition (swallowing): can start as a voluntary action (tongue rolls food back as bolus) becomes involuntary once bolus reaches posterior mouth/pharynx. Afferent impulses from posterior mouth & pharynx to medulla trigger the reflex reflex loop back via medulla & lower pons (swallowing center) interrupts breathing (medulla) almost never initiated by higher centers takes about 2 seconds. Involuntary swallowing (deglutition) reflex: soft palate goes up to prevent food into nasal passages palatopharyngeal folds come together & forms a narrow sagittal (vertical) slit only allows small pieces of food into esophagus Vocal cords and larynx move & cause sliding of the epiglottis backward over the opening of the larynx food not allowed into the trachea The upper esophageal sphincter relaxes, pharyngeal muscles contract to push bolus down This excitation-contraction is spread down the esophagus as the primary peristaltic wave. Control of deglutition: upper 1/3 of esophagus is striated muscle under both glossopharyngeal (CN IX) & vagus (CN X) control lower esophagus only vagus (involuntary)

16 Adv Pathophysiology Unit 9: GI Page 16 of Esophageal movement & receptive relaxation: Primary peristaltic wave: o excitation-contraction spreads down esophagus due to pharyngeal muscles contracting during last phase of swallowing. Secondary peristaltic wave: o bolus of food distends the esophagus o the esophageal distension sets up a vasovagal reflex loop (vagus afferent/efferent) o contraction Vagus denervation: o if vagus cut, after a few days, bolus distension excites myenteric plexus to peristalsis o intrinsic activity of the myenteric plexus (enteric nervous system) o even with vagus denervation, you regain your ability to eat Receptive relaxation of sphincter: o there is coordination of peristalsis with proximal contraction and receptive relaxation o the lower esophageal (gastroesophageal) sphincter also relaxes Clinical correlate: o if sphincter doesn't relax = achalasia. 5. Reflux prevention: Reflux (backwards flow of chyme from the stomach) should normally NOT occur Coordination of peristalsis in stomach & duodenum with proximal contraction and receptive relaxation lower esophagus has tonic contraction & a "pseudo-valve" closure to prevent reflux of food back from stomach to esophagus This area is called the Lower Esophageal Sphincter.

17 Adv Pathophysiology Unit 9: GI Page 17 of 22 Gastroesophageal Reflux Disease (GER)(GERD): (MORE ON THIS LATER FILE) Incompetence of the valve creates reflux The lining of the esophagus does not have protective mechanisms to protect it against acid (like the stomach does) GASTROESOPHAGEAL REFLUX DISEASE (GERD) o GERD leads to many complications o erosive esophagitis o pulmonary aspiration o reflex bronchoconstriction (wheezes could have esophagitis) o Hiatal Hernia may contribute to the reflux syndrome o Longstanding esophagitis can cause bleeding, stricture, and cancer Normal esophagus Erosive esophagitis from reflux disease -- on endoscopy -- note the tears and erosions of the mucosa the esophagus does not have the protective coating that is found inside the stomach, and thus exposure to stomach acid is EROSIVE

18 Adv Pathophysiology Unit 9: GI Page 18 of 22 B. STOMACH: mixes food with gastric juice to form chyme. bolus (portion) of chyme passes on down the gut. Receptive relaxation: mediated by a vagovagal reflex (vagus afferent & efferent loop) when food enters. Contraction ring: propels food, mixing contractions mix food. Anatomy: fundus, body, antrum; lesser & greater curvature. Gastric glands line stomach (except along lesser curvature). Endoscopic view of stomach -- note the rugae Emptying & Gastric Motility: intestinal activity slows gastric motility Antral contractions cause pyloric sphincter receptive relaxation for emptying. Emptying of stomach is inhibited when food enters duodenum o Through nervous system & hormonal feedback Mechanism hormonal: o fats cause release from intestine of CCK that travels to stomach o other hormones include secretin & gastric inhibitory peptide (GIP) More food = higher rate of emptying due to activity of gastrin (in response to digestive products of food breakdown, esp. protein) Empty stomach: o Hunger contractions occur when stomach empty for several hours or when you have hypoglycemia. o Hunger pangs hrs after last meal, worse by 3-4 days, then weaken.

19 Adv Pathophysiology Unit 9: GI Page 19 of 22 C. SMALL INTESTINE: 1. Anatomy: duodenum, jejunum & ileum. From outside in Surface serosa longitudinal muscle layer circular muscle layer mucosa with villi & their specialized digestive cells. 2. Function: combination of mixing contractions & propulsive movements. Mixing contractions: slow waves of intrinsic electrical activity that are alterations in resting membrane potential. Propulsive movements (peristalsis): peristalsis, initiated by food entering duodenum & also by gastroenteric reflex of food entering duodenum. Peristaltic rush: o Irritation of intestinal mucosa causes a peristaltic rush mediated by CNS reflex loop & myenteric plexus reflexes o Seen in infectious diarrhea 3. Hormonal Regulation: Hormones enhancing motility here are gastrin, CCK, insulin, serotonin Hormones inhibiting motility here are secretin & glucagon. 4. Movement into colon: an empty cecum allows relaxation of sphincter & emptying of small intestine. If cecum is distended or irritated, increased ileocecal sphincter tone prevents emptying. Clinical: o appendicitis as irritation of vestigial part of cecum prevents small intestinal emptying o causes an ileus (inhibition of peristalsis, bowel dilates due to gases and secretions) and also lack of appetite

20 Adv Pathophysiology Unit 9: GI Page 20 of 22 D. COLON: 1. Anatomy: longitudinal muscle is grouped into 3 strips (teniae coli) muscle strips contract in powerful rings (haustral contractions) and cause the noncontracting colon to bulge out (haustrations). Transit of food & feces: o it takes 8-15 hours for chyme bolus to reach transverse colon o here the chyme becomes feces. Cecum

21 Adv Pathophysiology Unit 9: GI Page 21 of Control of movements: enteric nervous system local production of neurotransmitter serotonin (5-HT) acting on various subtypes of 5- HT receptors (see IBS) and some ANS innervation 3. Mass movement & colonic reflexes: a full stomach/duodenum causes a large portion of colon to strongly contract (gastrocolic & duodenocolic reflexes). at transverse colon, mass movement occurs 1-3 times daily, especially after eating breakfast. Hyperactive: o Colon irritation has frequent almost continuous mass movement contractions o Seen in ulcerative colitis Inhibition: o peritonitis, nephritis, ureteritis, abdominal skin irritation all inhibit colon activity o These are all inflammations OUTSIDE the colon 4. Receptive relaxation: the rectum is empty most of the time due to the presence of a weak sphincter located about 20 cm from anus this sphincter is at the sigmoid/rectum junction. 5. Defecation: Mass movement into rectum causes distal relaxation of anal sphincter & contraction of rectum. reflex mediated with afferent feedback loop to spinal cord & efferent loop of parasympathetic pelvic nerves. accompanied by deep breath, glottal closure, & abdominal contractions (Valsalva maneuver). Anal sphincter relaxation plus above reflex pulls outward on anal ring and evaginates the feces (the lips of the anus pouch outward and the contents of the anal canal are extruded).

22 Adv Pathophysiology Unit 9: GI Page 22 of Anal sphincter control: allows for toilet training once peripheral myelination is complete o this myelination complete by age 2 yo o toilet training not really effective before this age o excessively early toilet training can lead to encopresis (soiling) o sometimes the encopresis is watery retained stool becomes inspissated (dehydrated) and the watery stool from above flows around it o common reason for office visit!! Involuntary: o Internal anal sphincter (smooth muscle) Voluntary: o external anal sphincter (striated muscle) o can be consciously controlled thus we have toilet training!!