Anatomy and Physiology of the Gastrointestinal Tract John P. Grant, MD, CNSP Director Nutrition Support Service Professor of Surgery Duke University Medical Center Durham, NC Specialty Examination Rule of thirds: 1/3 of questions are simple – no study needed. 1/3 of questions you will answer from experience. 1/3 of questions you will not know, studying will not help (with combination of studying and experience you can make an educated guess in 1/3). What are the Functions of the Gut? Digestion… Process by which large molecules in diet are broken down into smaller ones, which are acceptable to the enterocytes for absorption. What are the Functions of the Gut? Absorption… Process by which contents of the small bowel enter the mucosal epithelial cells, and eventually the portal vein or lymphatics. What are the Functions of the Gut? Protection… Barrier to entry of pathogens and toxins Digestion and Absorption - ??? 1. What digestive process does not occur in the oropharynx? A. Micelles are formed with fat B. Salivary a-amylase degrades starch C. Pharyngeal lipase hydrolyzes triglycerides to diglycerides and fatty acids D. Food particles are mechanically broken up Digestion and Absorption - ??? 1. What digestive process does not occur in the oropharynx? A. Micelles are formed with fat B. Salivary a-amylase degrades starch C. Pharyngeal lipase hydrolyzes triglycerides to diglycerides and fatty acids D. Food particles are mechanically broken up Anatomy and Physiology of Digestive System - Mouth Mouth - Digestive Action Food mechanically broken down Saliva - normally about 25 ml/hr is secreted, increases up to 300 ml per hour with eating Salivary a-amylase degrades starch, a-amylase is deactivated by gastric acid Anatomy and Physiology of Digestive System - Mouth Mouth - Protective Action Preventive bacteria in the mouth are important for defense against invading microorganisms Contains specific antimicrobial proteins like lysozyme, lactoferrin and lactoperoxidase, but also mucin, IgA, and nitric oxide-donating substances such as nitrates Mucus covers food and follows it to colon. It can attach to mucosal surfaces and forms protective barrier Anatomy and Physiology of Digestive System - Mouth Inhibition of Saliva Anticholinergics, analgesics, antispasmodics, antidiarrheals, antidepressants, antihistamines, antihypertensives, antipsychotics, and diuretics Stimulation of Saliva Pilocarpine 5mg po tid Anatomy and Physiology of Digestive System - Esophagus Esophagus Transports food to stomach Pharyngeal lipase hydrolyzes triglycerides to diglycerides and fatty acids Anatomy and Physiology of Digestive System - Stomach Stomach: Stores, mixes, and grinds food to form an emulsion Gastroesophageal Junction Incisura Pylorus Duodenal Bulb Cardia Body Antrum F u n d u s Anatomy and Physiology of Digestive System - Stomach Hydrochloric acid from parietal cells denatures protein Surface Epithelial Cell Mucous Cell Pepsinogen (Pepsin) from zymogen (chief) cells begins proteolysis Parietal Cell Zymogen Cell Lymph Nodule Argentaffine Cell Muscularis Mucosae Pyloric Glands Submucosa Gastric or Fundic Glands Anatomy and Physiology of Digestive System - Stomach Pepsin Acid pH 1-3 Mucous gel layer Bicarbonate / Mucus pH 7 Gastric lumen Gastric mucosa Zymogen Cell Mucous Cell Parietal Cell Anatomy and Physiology of Digestive System - Small Bowel Small Intestine - averages around 5 meters in length Duodenum: ~10” long, 2” in diameter Jejunum: ~ 2/5 length of rest of small bowel, 1 ½ to 1 ¼” in diameter, thick, many blood vessels. Ileum: ~3/5 length, 1 ¼ to 1” diameter, thin wall, large Peyer’s patches Anatomy and Physiology of Digestive System - Small Bowel Small Intestine Major organ for nutrient absorption Absorptive surface enhanced by plicae circulares, foldings called villi with surface projections called microvilli Final surface area about 1.7 m cm2 About 800 cm2 to absorb 1 Kcal (100-200 cm2/Kcal minimum) Anatomy and Physiology of Digestive System - Small Bowel Plica circularis or Valve of Kerckring Villus Jejunum Ileum Digestion and Absorption - ??? Poor question… 2. The absorptive surface of the normal small intestine is equal to: A. B. C. D. 3 tennis courts 5 tennis courts 1 tennis court 10 tennis courts Digestion and Absorption - ??? Poor question… 2. The absorptive surface of the normal small intestine is equal to: A. B. C. D. 3 tennis courts 5 tennis courts 1 tennis court 10 tennis courts Digestion and Absorption - ??? Poor question… 3. How much small intestine can be removed before a patient will develop short bowel syndrome? A. 1/3 C. 2/3 B. 1/2 D. 3/4 Digestion and Absorption - ??? Poor question… 3. How much small intestine can be removed before a patient will develop short bowel syndrome? A. 1/3 C. 2/3 B. 1/2 D. 3/4 Digestion and Absorption - ??? It is always better to know the amount of bowel remaining following surgical resection – rather than the amount resected…Better question: A patient is likely to, but not always, require HTPN if only the following amount of small bowel can be saved at the time of surgery: A. 10 feet C. 3 feet B. 5 feet D. 1 foot Digestion and Absorption - ??? It is always better to know the amount of bowel remaining following surgical resection – rather than the amount resected…Better question: A patient is likely to, but not always, require HTPN if only the following amount of small bowel can be saved at the time of surgery: A. 10 feet C. 3 feet B. 5 feet D. 1 foot Digestion and Absorption There is a high probability of transitioning patients off HTPN if the ratio of remaining intestinal length to body weight is: > 0.5 cm/kg ie: > 40 cm for an 80 kg patient Wilmore, et al., Ann. Surg., 226:288-293, 1997 Anatomy and Physiology of Digestive System - Colon Absorbs water and electrolytes Stores waste “Organ within an Organ” Colonic microflora ferment malabsorbed nutrients and soluble fiber to a form the colonic mucosa can absorb Nutrient Absorption Sites of Nutrient Absorption Sites of Nutrient Absorption Good question… 5. What nutrient deficiency might be expected if 3 feet of the terminal ileum is resected? A. Iron C. Vit B-12 B. Magnesium D. Calcium Sites of Nutrient Absorption Good question… 5. What nutrient deficiency might be expected if 3 feet of the terminal ileum is resected? A. Iron C. Vit B-12 B. Magnesium D. Calcium Sites of Nutrient Absorption Much harder question… 6. What nutrient deficiency might be expected if 3 feet of the terminal ileum is resected? A. Iron C. Vit B-12 B. Magnesium D. Fat Absorption of Water 8 L/day fluid reaches the small intestine of which about 2 L is dietary in origin Small bowel absorbs about 7 L/d, mainly in jejunum, colon absorbs 1 to 1.5 L/d (can increase absorption up to 4 L/d) Digestion and Absorption - ??? 7. Water absorption by the small bowel may be enhanced by adding the following to the enteral formula: A. Zinc Sulfate C. Magnesium Chloride B. Sodium Chloride D.Medium-Chain Fat Digestion and Absorption - ??? 7. Water absorption by the small bowel may be enhanced by adding the following to the enteral formula: A. Zinc Sulfate C. Magnesium Chloride B. Sodium Chloride D.Medium-Chain Fat Absorption of Water Water absorption is entirely passive - follows absorption of solutes (can move in either direction, depending on osmotic gradients) Particularly true of the solute Na+ High sodium enteral diets enhance water absorption Low sodium diets predispose to diarrhea Absorption of Sodium and Chloride - Small Bowel Sodium absorption is directly coupled to absorption of organic solutes such as glucose, amino acids, water-soluble vitamins, and bile salts Absorption of Sodium and Chloride - Small Bowel Once inside cell, sodium is extruded against chemical and electrical gradient via a basolateral membrane-associated Na+-K+-ATPase Absorption of Sodium and Chloride - Small Bowel Chloride passively follows absorption of sodium Absorption of Sodium and Chloride – Distal Ileum and Colon Neutral NaCl co-transport, Na+ for H+ and Cl for HC03 Absorption of Potassium in Small Bowel Overall K+ movement is result of solvent drag and is potential-dependent K+ actively secreted in colon Rectosigmoid colon has active K+ absorption - exchanges K+ for H+ Absorption of Calcium Passive - throughout the small intestine Predominates at concentrations 10 mmol/L Active - primarily in the duodenum Below 10 mmol/L, active transport occurs with 1,25 dihydroxy vitamin D3 Absorption of Calcium Absorption of Magnesium Absorbed from distal small intestine and all of colon by passive diffusion Digestion and Absorption - ??? Good question… 8. What mineral will be depleted if a patient has a draining T-tube in the common bile duct ? A. Zinc C. Magnesium B. Sodium D. Copper Digestion and Absorption - ??? Good question… 8. What mineral will be depleted if a patient has a draining T-tube in the common bile duct ? A. Zinc C. Magnesium B. Sodium D. Copper Absorption of Copper Dietary copper is absorbed in stomach and duodenum Active process requires energy and involves absorption of complexes of copper and amino acids Copper is excreted by bile urine losses = ~1-2% of intake Digestion and Absorption - ??? Good question… 8. What mineral will be depleted if a patient has marked diarrhea ? A. Zinc C. Magnesium B. Sodium D. Copper Digestion and Absorption - ??? Good question… 8. What mineral will be depleted if a patient has marked diarrhea ? A. Zinc C. Magnesium B. Sodium D. Copper Absorption of Zinc Major loss of zinc is in the feces - during intravenous nutrition it is suggested to give: 2 mg Zn + 17.1 mg Zn/kg stool lost + 12.2 mg Zn/kg of gastric/duodenal/or jejunal fluid lost Absorption of Zinc Zinc is absorbed primarily in jejunum Binds to a ligand in lumen – transports to mucosa Transferred to binding site on cell Active process requiring energy, oxygen, and Na+ Absorption stimulated by glucose Digestion and Absorption - ??? Good question… 9. Even in Short Bowel Syndrome, oral iron supplementation can be effective. A. True B. False Digestion and Absorption - ??? Good question… 9. Even in Short Bowel Syndrome, oral iron supplementation can be effective. A. True B. False Absorption of Iron Iron is absorbed in duodenum ferrous salt > ferric salt At brush border, ferrous ion oxidized to ferric and transported by various brush border carrier proteins - regulated by body’s need for iron At pharmacologic doses, passive diffusion occurs Digestion and Absorption - ??? Good question… 10. The major source of carbohydrate in the diet is: A. Starch C. Lactose B. Sucrose D. Fructose Digestion and Absorption - ??? Good question… 10. The major source of carbohydrate in the diet is: A. Starch C. Lactose B. Sucrose D. Fructose Average Carbohydrate Intake Saccharides Intake (gm) % Total Polysaccharides Starch 200 64 Glycogen 1 0.5 Disaccharides Sucrose 80 26 Lactose 20 6.5 Monosaccharide Fructose 10 3 Carbohydrate Digestion and Absorption Primarily absorbed in duodenum and proximal jejunum (75% in first 70 cm of jejunum) Carbohydrate intolerance is nearly always related to a defect in intestinal surface digestion of a polysaccharide or disaccharide Carbohydrate Digestion and Absorption Luminal phase Hydrolysis of starch by salivary and pancreatic a-amylases Cleaves starches to yield a-limit dextrans, maltotriose, and maltose Carbohydrate Digestion and Absorption Brush-border phase Hydrolysis by glycosidases to monosaccharides: glucose, galactose, and fructose Carbohydrate Digestion and Absorption Cellular phase - transport to venous system Glucose and galactose transported via SGLT1 Na+-linked active transporter Fructose via GLUT5 facilitated diffusion Carbohydrate Digestion and Absorption SGLT1 GLUT2 Galactose Fructose GLUT5 GLUT2 SGLT1 Glucose Fiber Digestion and Absorption Non-starch carbohydrate of plant origin that escapes enzymatic digestion in the small intestine Two types Cellulosic: high molecular weight, non-soluble (cellulose, wheat bran) Noncellulosic: soluble (hemicelluloses, pectin, gums, mucilages) Digestion and Absorption - ??? Good question… 11. Which type of fiber can contribute to the energy needs of the colon? A. Cellulosic B. Non Cellulosic Digestion and Absorption - ??? Good question… 11. Which type of fiber can contribute to the energy needs of the colon? A. Cellulosic B. Non Cellulosic Fiber Digestion and Absorption Non Cellulosic fiber is degraded rapidly by anaerobic microflora of cecum and colon (fermentation) to give short-chain fatty acids: Acetate, Propionate, N-butyrate Fiber Digestion and Absorption Non Cellulosic fiber Enhances colonic blood flow Serves as fuel for colonocyte (70% ) Increases colonocyte proliferation Enhances Na+ absorption Preserves colonic mucosal barrier Fiber Digestion and Absorption Cellulosic fiber Contributes to fecal mass and water content Reduces mean stool transit time Fat Digestion and Absorption 96% of ingested fat is absorbed daily 90% of ingested fat is triglycerides, 10% is cholesterol, phospholipids, and plant sterols Triglycerides Majority of triglycerides contain long-chain fatty acids (16 -18 C) A few dietary triglycerides contain mediumchain fatty acids (8 -12 C) Lipid Absorption Lipids in diet are emulsified in the stomach by mechanical grinding Pancreatic lipase in duodenum digests to free fatty acids and 2-monoglycerides Bile acids form water soluble micelles which diffuse easily across the unstirred water layer Fat Digestion and Absorption Digestion and Absorption - ??? Good question… 12. Which of the following fatty acid(s) is absorbed directly into the enterocyte without micelle formation? A. Arachidonic acids C. Chenodeoxycholic acids B. Medium-chain fatty acids D. Picric acids Digestion and Absorption - ??? Good question… 12. Which of the following fatty acid(s) is absorbed directly into the enterocyte without micelle formation? A. Arachidonic acids C. Chenodeoxycholic acids B. Medium-chain fatty acids D. Picric acids Fat Digestion and Absorption Medium-chain triglycerides, which are more water soluble, may be absorbed intact with direct transport to the portal system as free fatty acids Protein Digestion and Absorption Derived from animal and vegetable sources and make up to 11 to 14% of average caloric intake (70 to 100 gm/day) Primarily absorbed in the duodenum and proximal jejunum, yet some does pass into and is absorbed by the colon Protein Digestion and Absorption Luminal gastric digestion Acid denaturation makes protein susceptible to proteolysis by pepsin resulting in large soluble oligopeptides, peptones, and some amino acids Protein Digestion and Absorption Luminal duodenal phase Three pancreatic endopeptidases and two pancreatic exopeptidases reduce oligopeptides to free amino acids and diand tripeptides Protein Digestion and Absorption Luminal enterocyte phase Enterocyte brush border membrane hydrolase produces amino acids, dipeptides and tripeptides Protein Digestion and Absorption There are 4 major Na+ dependent, group specific, active transport systems Neutral amino acids Glycine, proline, hydroxyproline Dibasic amino acids and cystine Dicarboxylic amino acids Digestion and Absorption - ??? Good question… 13. What is the di- and tri-peptide H+ dependent transport system in the small intestine? A. GLUT5 C. PepT1 B. Endopeptidase D. SGLT1 Digestion and Absorption - ??? Good question… 13. What is the di- and tri-peptide H+ dependent transport system in the small intestine? A. GLUT5 C. PepT1 B. Endopeptidase D. SGLT1 Protein Digestion and Absorption There is a H+ dependent di- and tripeptide transport system (PepT1 Transporter) Cephalosporin antibiotics, containing a peptide bond, share the same transport system Protein Digestion and Absorption Amino acids absorbed by either route efflux from the basolateral membrane via transporters whose kinetic characteristics are sensitive to circulating amino acid concentrations Protein Digestion and Absorption Mucosal uptake of peptides has an important role in protein absorption - absorption of a-amino nitrogen is greater during perfusion of di- and tripeptides Yet have less effect on Na+ and water uptake than free amino acids or complex proteins (diarrhea) Protein Digestion and Absorption Although theoretical advantages may exist for enteral products containing peptides vs intact protein or free amino acids, little experimental data exists to support their advantage. Any advantage would be more apparent with increased “protein load” as during cyclical feedings Malabsorption Clinical symptoms include unexplained weight loss, steatorrhea, diarrhea, anemia, tetany, bone pain, pathologic fractures, bleeding, dermatitis, neuropathy, glossitis, and edema Malabsorption Normal Stool Composition Water 100 ml Sodium 4 mEq Potassium 9 mEq Chloride 2 mEq Bicarbonate 0 mEq From 3/week to 3/day considered normal Diarrhea = stool weight > 200 to 500 g/24 h Digestion and Absorption - ??? Good question… 13. Each of the following are screening tests for intestinal absorption except: A. Gross inspection of stool B. Fat content of stool in random collection C. Microscopic examination of stool D. Lactose tolerance test Digestion and Absorption - ??? Good question… 13. Each of the following are screening tests for intestinal absorption except: A. Gross inspection of stool B. Fat content of stool in random collection C. Microscopic examination of stool D. Lactose tolerance test Malabsorption - Screening Tests Gross inspection of stool Microscopic examination of stool Fat content of stool in random collection Protein content of stool in random collection Malabsorption - Screening Tests Serum carotene D-xylose absorption Radiologic evaluation of transit time, motility, mucosal diseases, fistulas, strictures/obstructions Malabsorption - Specific Tests Lactose tolerance test (Lactase deficiency, short gut, mucosal disease) Schilling test (B12 absorption, tests terminal ileum and gastric production of intrinsic factor) Malabsorption - Specific Tests Small bowel biopsy (celiac disease, tropical sprue, Whipple’s disease, etc.) Radioactive compounds (iron, calcium, amino acids, folic acid, pyridoxine, vit D, bile salts, and others) Malabsorption - Balance Tests 3-5 day timed stool collection for quantitative fat absorption (standard fat intake = 100 g/d) Usually less than 5% lost in stool Malabsorption - Balance Tests Radioactive tracer studies 14C-triolein and 13C-trioctanion breath tests for neutral fat absorption 131I-albumin, 51Cr-albumin given IV with stool measurement of radioactivity for protein-losing enteropathies Specialty Examination Good Luck !!