Gastrointestinal Physiology
Chelsea Dawn Unruh The Basics
Functions of the GI System Ingestion, digestion, absorption, & defecation Principle Processes Motility, secretion, & membrane transport
Stages of Digestion Mechanical & Chemical Mechanical: Increasing surface area Chemical reaction of digestion: hydrolysis Anatomical Tube
2 The Basics
The gastrointestinal tract is A tube that propels a substance from one end to the other while attempting to it break down with various digestive juices, absorb as much of its digestive products as possible, & excret what is left Associated with accessory glands that produce the majority of digestive juices Controlled by both nervous and hormonal systems
3 Anatomy of GI System
The Gut Tube Accessory Glands Oral cavity Salivary glands Esophagus Pancreas Stomach Liver Duodenum Small Intestine Large Intestine Rectum Anus Which structures of the GI system are retroperitoneal? • Most of the pancreas (except tail) • Most of the duodenum (except first segment) • Ascending & Descending Colon
4 Despopoulos, Color Atlas of Physiology © 2003 Thieme GI Bloodflow
Supply Celiac a. Superior Mesenteric a. Inferior Mesenteric a. Drainage Portal Vein
Portal vein carries absorbed substances to liver
5 General GI Wall Structure
6 http://www.enel.ucalgary.ca/People/Mintchev/stomach.htm Nervous System of the GI Tract
Enteric Nervous System (ENS) Consists of about 10 −100 million nerve cells located in the ganglia of the intestinal wall. Consists of sensory neurons, interneurons, and motor neurons Some sensory signals are transmitted to the CNS ENS is modulated by the ANS Two internal nerve plexuses Auerbach’s & Meissner’s
7 Nervous System of the GI Tract Myenteric or Auerbach’s plexus Between the longitudinal and circular smooth muscle layers Coordinates the movements of muscularis externa Peristalsis, Segmentation, Propulsion, Grinding, etc. Excitatory motoneurons contract muscle by ACh to muscarinic receptors; Inhibitory use VIP and NO Sensory neurons respond to chemical or mechanical stimuli – receptors in all layers of GI tract Interneurons are involved in the many reflex arcs through GI
8 Motility
9 Nervous System of the GI Tract Submucosal or Meissner’s plexus Located in the submucosa, between the muscularis mucosae and the circular layer of muscularis externa involved in internal processing – modulates secretion and blood flow stimulatory secretomotoneurons stimulate glands and epithelium (via Ach, et al.) sensory neurons respond to chemical or mechanical stimuli to produce secretomotor reflexes submucosal vasodilator neurons dilate blood vessels in the submucosa
10 Nervous System of the GI Tract
Autonomic Control of GI Both ANS systems modulate the ENS Parasympathetic: Vagus nerve stimulates secretions and motility through distal colon Pelvic splanchnic nerves innervate distal colon & rectum Sympathetic: Innervation through splanchnic & prevertebral ganglia Reduces motility, increases sphincter tone
11 Nervous System of the GI Tract
Neurotransmitters Norepinephrine – adrenergic post-gang neurons Ach – pre- and postgang enteric fibers & post gang parasymp VIP – mediates relaxation of circular & vascular muscles Enkaphalin – intensifies contraction of sphincters GRP – mediates release of gastrin CGRP (calcitonin gene-related peptide) – stimulates release of somatostatin
12 Nervous System & GI Wall
13 Segments
14 Segments & Structure
Mouth Pharynx Esophagus Stomach Small Intestine Large Intestine Rectum Anus
15 Mouth
Ingestion & Digestion Mechanical Mastication (chewing, cutting & grinding with teeth), mixing with tongue Chemical Salivary glands: Parotid, Sublingual, Submandibular Secretions (1.5L/day) Mostly salt & water but also includes amylase, lingual lipase, lysozyme, peroxidase, R-binder
(important protein for Vit B12 metabolism), IgA, glycoproteins
16 http://medical-dictionary.thefreedictionary.com/ Functions of Saliva
Moistens, cleans, & protects enamel Lubricant aiding in speech, chewing, & swallowing (mucins) Dissolves food – allows for taste Acts as a bonding agent to form bolus Alkaline secretions neutralize regurgitated gastric acid Enzymes (amylase & lipase) begin digestion Immunological: Lysozyme, IgA, & lactoferrin
17 Salivary secretion
18 Salivary Reflexes
Conditioned
Unconditioned
19 Pharynx
Circular muscles Superior, middle ,and inferior pharyngeal constrictors force food down esophagus while swallowing Other muscles Close off oral cavity, nasopharynx, and trachea during swallowing
20 http://www.home-speech-home.com/dysphagia.html Esophagus
Straight muscular tube Propels food bolus from pharynx to stomach 1/3 composed of striated muscle, 2/3 smooth muscle LES – physiological sphincter at cardiac orifice
Clinical: Correlation Achalasia – inability of the LES to relax causing dysphagia, regurgitation, and chest 21 pain. Causes: cancer, Chagas disease Deglutition
Coordinated by swallowing center in medulla oblongata & pons ≥ 22 muscles involved 2 stages Buccal - voluntary Pharyngeal/esophageal - involuntary
22 Deglutition
23 Stomach
24 Stomach J-shaped muscular sack for food storage & digestion located in upper abdomen, directly below diaphragm Empty volume 50 mL, may hold up to 4 L Structures 4 regions: Cardia, fundus, body, and pylorus/antrum 2 sphincters: Lower esophageal/cardiac, pyloric Rugae Innervation ENS, PNS (vagal), SNS Circulation Supplied by celiac artery Drains to hepatic portal circulation
25 Stomach Wall
Mucus Only
26 Stomach
Secretory Cells Secretory Products - Surface mucous & mucous Mucus, HCO 3 neck cells Oxyntic (Parietal) cells HCl, intrinsic factor
Chief (Peptic) cells Pepsinogen, gastric lipase, rennin/chymosin (infancy?) Neurendocrine cells Peptide Hormones G cells Gastrin D cells Somatostatin
27 Gastric Protection
H. pylori • Gram negative microaerophilic rod • Flagella to bury itself in the protective mucus NSAIDs • • Urease breaks down urea toCO and ammonia COX inhibitors 2 • (neutralizes) ↓ PGs ↑ acid
•Treatment: Triple Therapy 28 Regulation of Gastric Function
Cephalic Phase Stimulated by sight, smell, or thought of food (1/3 of secretion) Medicated by vagus nerve, secretions begin before food arrives Gastric Phase Stimulated by food in the stomach (2/3 of gastric secretion) Ingested food stretches and raises the pH activating mechanical and chemical receptors Gastric secretion stimulated by ACh, histamine, and gastrin Intestinal Phase Stimulated by chyme entering the duodenum Enterogastric reflexes reduce gastric motility and secretions
29 Gastric Acid Basal Acid Output: <10 mmol/hr Maximum Acid Output: <50 mmol/hr ↑ c c d d a c i -E is Sy . ↓ va t my ici s a mia
Gastric HCl has pH ~1.0, Activates pepsin, dissolves food, disinfects, & stimulates duodenum to secrete secretin Gastric Enzymes Pepsin – cleaves protein into smaller peptides Lipase – digests fats, of little importance except with pancreatic insufficiency Gastric juices (pH 1.5 −2, about 2 −3 liters/day) 30 31 Mechanism of HCl secretion by gastric parietal cells.
32 Agents that stimulate and inhibit H + secretion by gastric parietal cells.
33 Gastric Motility Migrating Motor Complexes (MMC) – 90 min cycle Pacemaker cells (Interstitial cells of Cajal) create 3 phases Phase I – no contractions Phase II – 6 min, irregular contractions Phase III – 3 min, regular contractions (gastric 3 per min, duodenal 11 per min) Receptive reflex: Relaxes stomach to allow entry of food, modulated by swallowing center (vagus) Enterogastric reflexes: (act on motility & secretion) Hormonal signaling from intestines slows gastric emptying and reduces motility Neural reflex: hyperosmolar chyme & mechanical distention
34 Gastric Motility When receptive reflex is activated, MMC is replaced with peristaltic actions Mechanical churning for digestion Emptying time usually ~4hrs Sympathetic System can prolong emptying Antrum holds ~30mL of chyme and releases ~3mL into duodenum with each peristaltic wave
35 36 Small & Large Intestines
37 Small Intestine
In the small intestine (duodenum, jejunum, ileum), contractile activity serves to mix the chyme with the alkaline exocrine secretions of the intestine, pancreas, and liver. These secretions contain a number of digestive enzymes, including proteases, amylases, and lipases. Protein, lipids, carbohydrate, vitamins, water, and electrolytes are absorbed primarily in the small intestine 3 parts Duodenum (25cm) Jejunum (2.5 m) Ileum (3.5m) and ends at ileocecal junction
38 Small Intestine
39 Small Intestine: Duodenum
Segment between pylorus of stomach and jejunum 4 segments: only 1 st segment (duodenal cap) is intraperitoneal Submucosal Brunner’s glands Produce alkaline mucus to neutralize stomach acid (pepsin is inactivated by the elevated pH and pancreatic enzymes take over the job of chemical digestion) Receives pancreatic digestive juices and bile juices from liver Ampulla of Vater (major duodenal papilla), sphincter of Oddi Primary site for Fe 2+ absorption
40 Small Intestine: Jejunum & Ileum
Major site of digestion: brush border contains numerous digestive enzymes 90% absorption – specialized transporters, simple diffusion, facilitated diffusion, active/passive transport Protection against infection – Peyer’s patches, M cells Hormone secretion – CCK, Secretin, Somatostatin, etc Intestinal juice secretion – isotonic fluid (w/ enzymes) secreted by crypts of Lieberkuhn, mucus from goblet cells
41 Small Intestine Motility
42 Large Intestine
In the large intestine (cecum, colon, rectum, anal canal), colonic contractile activity transports chyme slowly and mixes it thoroughly, exposing it to the absorptive surface where most of the remaining fluid is absorbed. Anatomy Colon Parts: Cecum, ascending, transverse, descending, sigmoid Ileocecal valve, Haustra, teniae coli, epiploic appendages Retroperitoneal sections: Ascending & Descending Colon
43 44 Large Intestine
No further chemical digestion occurs Most nutrients have already been absorbed Volume of contents is reduced as liquid is absorbed Dense population of many species of bacteria = bacterial flora. Ferment cellulose and other undigested carbohydrates Synthesize B vitamins and vitamin K
45 Large Intestine Motility
Basal Electric Rhythm 9 waves /min @ ileocecal valve Up to16 waves/min @ sigmoid
Haustral Shuttling – kneading of mass to ↑H2O absorption Segmental propulsion – from one haustra to next Mass movements (systolic multi-haustral propulsion) - stronger contractions, moving mass towards rectum 2-5 cm/min. Occur infrequently or as gastrocolic reflex.
46 Large Intestine
Transit Time Can take ≥ 12 hours to pass through large intestine Rectum can hold ≤ 3 days ↑ fiber = ↓ transit time
Reflexes Defecation – spinal reflex Distention of rectum causes internal sphincter to relax (pressure of 18-55mmHg manifests the urge to deficate) Gastrocolic – Mass contraction of colon caused by distention of stomach. Very obvious in infants and children.
47 Major Accessory Glands
Liver & Pancreas
48 Liver
49 50 Liver & Bile Secretion
Clinical: Cholecystitis Cholelithiasis Primary biliary cirrhosis Etc…
51 Bile
Constituents: bile salts (taurocholate & glycocholate), bile pigments (bilirubin & biliverdin), lipids (cholesterol, lecithin, fatty acids, and triglycerides), and electrolytes. Cholesterol usually between 60-170mg/L High concentrations predispose to gall stones. - Bile juice has ↑ HCO 3 content, much higher than plasma Alkaline (pH = 7,0-7,4) Bile salts are the only important factor for digestion Amphipathic molecules – steroid nucleus (hydrophobic) + polar (hydrophilic) groups—enhance intestinal absorption of lipids
52 Enterohepatic circulation
The total bile pool (2–4 g) recirculates about 6–10 times a day 20–30 g of bile salts are required for daily fat absorption
53 Enterohepatic circulation
85% of bilirubin formed from breakdown of hemoglobin in RBCs Stercobilin gives stools brown color
Jaundice: Prehepatic – excessive bilirubin formed, i.e. ↑h m ysis. E vat d i di ct bi i bi . Intrahepatic – liver dysfunction Posthepatic – impairment of flow, i.e. stone or tumor. Elevated direct bilirubin & grey stools. 54 Secretion, Digestion & Absorption
55 Fluid Balance
Inflow/Secretions: Saliva 1-2 L/day Gastric juices 2-3 L/day Exocrine pancreas 1.2-1.5 L/day Bile juices 0.5-1 L/day Small Intestine 1-2 L/day Total ~ 8.5 L/day secretions Only 2 L delivered to colon, and only 0.1-0.2 L/day in feces
56 Electrolyte Absorption
57 Absorption
58 Carbohydrates
Carbohydrates provide ½ - ⅔ of the energy requirement.
≥50% of dietary carbohydrates consist of starch (amylose and amylopectin), a polysaccharide Other important dietary carbohydrates are cane sugar (saccharose = sucrose) and milk sugar (lactose).
Total of about 350 to 450 grams of carbohydrates per day.
59 Carbohydrate Digestion
Begins in mouth with salivary amylase. Resumes in duodenum with pancreatic enzymes Finishes at brush border with disaccharidases
60 Faller, The Human Body © 2004 Thieme Carbohydrate Digestion & Absorption
61 Carbohydrate Absorption
α-Amylase breaks α-1,4 bonds of non-terminal sugars (endoenzymes) Creates maltriose, maltose, and α-limit dextrins α-Amylase cannot cut: Terminal α-1,4 link Adjacent α-1,4 link α-1,6 link (branching)
62 Carbohydrate Absorption
Brush border oligosaccharidases continue Lactase deficiency digestion Lactose cannot be broken down and absorbed Lactase = Glc + Gal unless sufficient lactase is available. Lactase deficiencies lead to diarrhea 1) because water is Both taken up by SGLT1 retained in the intestinal lumen due to osmotic Maltase = Glc + Glc mechanisms, and 2) because intestinal bacteria convert the lactose into toxic substances. Taken up by SGLT1 Surcase-isomaltase Actually 2 enzymes capalble of hydrolyzing sucrose, maltose, maltotriose, and and α-limit dextrins
63 Carbohydrate Absorption
Secondary active transport – SGLT1 uses Na + gradient to drive Glc into cell SGLT1 & GLUT5 are found on apical membrane GLUT5 & GLUT2 allow for facilitated diffusion across membranes
64 Fiber
Fiber = Unavailable carbohydrates, indigestible oligosaccharides (eg, raffinose) dietary fiber (cellulose and hemicellulose)
These carbohydrates are not digested in the small intestine. They pass to the colon, where they are fermented by bacterial enzymes.
Fiber decreases transit time, adds bulk to feces, and allows for easier defecation
65 Lipids
The average intake of fats (butter, oil, margarine, milk, meat, sausages, eggs, nuts etc.) is roughly 60–100 g/day, but there is a wide range of individual variation (10–250 g/day). Most fats in the diet (90%) are neutral fats or triacylglycerols (triglycerides). The rest are phospholipids, cholesterol esters, and fatsoluble vitamins (vitamins A, D, E and K). Over 95% of the lipids are normally absorbed in the small intestine. •Deficiency: •Vitamin A - night blindness •Vitamin D – rickets •Vitamin K – clotting factor deficiencies •Excess 66 •Toxicity - hypervitaminosis Lipid Digestion
Begins in the mouth with lingual lipase Continues activity in the stomach Emulsification in duodenum by bile salts, formation of micelles
67 Faller, The Human Body © 2004 Thieme Lipid Absorption
68 69 Cholesterol
Cholesterol is an important constituent of cell membranes. Precursor for bile salts, vitamin D, and steroid hormones
Clinical: Familial hypercholesterolemia Atherosclerosis Dyslipidemias
70 Protein Digestion
Begins in the stomach with pepsins, continues with pancreatic enzymes Polypeptides cleaved into oligopeptides and amino acids
71 Faller, The Human Body © 2004 Thieme Protein Digestion
72 73 Protein Absorption
Peptidase activity: brush borders within the cytoplasm of intestinal mucosa cells. Aminopeptides must be absorbed by specific amino acid and peptide transport systems. Intracellular peptidases hydrolyze absorbed peptides. Basolateral transport: many different AA transporters.
74 Hartnup disease affecting the absorption of nonpolar amino acids, particularly tryptophan that can be, in turn, converted into serotonin, melatonin and niacin
75 Absorption of whole proteins
Normal cells can endocytose proteins and degrade them (90%) M cells endocytose fewer intact proteins but 50% emerge for presentation to immuno cells
76 Regulation of the GI Tract
Hormonal and neuronal controls
77 Gastrin Family of hormones
78 Gastrin Secreted by the G cells Gastric antrum & duodenum Zollinger Ellison Syndrome A non–beta islet cell, gastrin-secreting Gastrin is released by G cells after:tumor of the pancreas (seen in MEN-1) vagal stimulation (via GRP) causing over secretion of HCl and resulting distention of the stomach in peptic ulcers presence of protein digestion products in the stomach
Release is inhibited by Somatostatin, PGE 2, or when gastric/duodenal lumen pH <3.5 Stimulates acid secretion and gastric mucosal growth Gastrin is the only GI hormone known to be released by direct neural stimulation
79 CCK (Cholecystokinin)
Produced throughout small intestinal mucosa (I cells) Release stimulated by presence of long-chain fatty acids, AA, and oligopeptides in lumen Actions: gall bladder contraction ↑ motility of SI & LI Secretion of enzyme-rich Trophic effect on pancreas pancreatic juice ↑secretion of enterokinase Potentiates secretin on Stimulates insulin & pancreas glucagon release Inhibits gastric emptying Produces satiety
80 Parietal Cell Control
Neural Control (Vagus) ACh (+) Indirect - stimulates ECL to release Histamine which stimulates Parietal cells Direct - stimulates Parietal cells GRP (Gastrin Releasing Peptide) (+) Hormonal Control Gastrin (+) Histamine (+) Somatostatin (-)
PGE 2(-) Secretin-Glucagon Family
82 Secretin
Produced in duodenum (S cells) Release stimulated by acidic chyme & presence of protein digestion products Actions Stimulates pancreatic ↑ hepatic secretion of bile bicarbonate secretion ↓gastric acid Potentiates CCK effect on ↑tone of pyloric sphincter pancreas ↓glucagon secretion
83 GIP (Gastric Inhibitory Peptide)
Part of Incretin family (with GLP-1) Produced in duodenum & intestinal mucosa (K cells) Release stimulated by protein, fat & carbohydrate fragments in lumen
Actions Inhibits acid secretion & gastric motility Stimulates insulin release Incretins
Causes an ↑i i s i s c . M cha ism is s d by GLP-1 a a s t i c as i s i s c ti i diab tic ati ts 84 Others VIP (Vasoactive Intestinal Peptide) Dilates blood vessels & relaxes intestinal smooth muscle ↑ watery secretions VIPoma Inhibits gastric acid Seen in MEN-1, causes secretory Peptide YY diarrhea leading to metabolic alkalosis Inhibitor of gastrin -mediated acid secretion Release from jejunal mucosa stimulated by fats in lumen Motilin Released by neurons in the small intestine and regulates digestive motility Paracrine transmitters: Histamine, Somatostatin, and prostaglandin are the main paracrine transmitters in the GI tract.
85 86 tmc acesLvrG Gt Brain Gut GB Liver Pancreas Stomach
Despopoulos, Color Atlas of Physiology © 2003 Thieme