Anatomy and Physiology of the Gastrointestinal Tract John P. Grant, MD, CNSP Director Nutrition...
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Transcript of Anatomy and Physiology of the Gastrointestinal Tract John P. Grant, MD, CNSP Director Nutrition...
Anatomy and Physiology of the Gastrointestinal Tract
John P. Grant, MD, CNSPDirector Nutrition Support
ServiceProfessor 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 -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 -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 -amylase degrades starch, -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 Cardia
Body
AntrumPylorus
DuodenalBulb
Incisura
Fundus
Anatomy and Physiology of Digestive System - Stomach
Hydrochloric acid from parietal cells denatures protein
Pepsinogen (Pepsin) from zymogen (chief) cells begins proteolysis
Surface Epithelial Cell
Mucous Cell
Parietal Cell
Zymogen CellLymph NoduleArgentaffine Cell
Muscularis Mucosae
SubmucosaPyloric Glands
Gastric or Fundic Glands
Anatomy and Physiology of Digestive System - Stomach
Pepsin AcidpH 1-3
pH 7 Bicarbonate / Mucus
ZymogenCell
MucousCell
ParietalCell
Gastric lumen
Mucous gellayer
Gastric mucosa
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
Jejunum Ileum
Plica circularis orValve of Kerckring
Villus
Digestion and Absorption - ???
2. The absorptive surface of the normal small intestine is equal to:
Poor question…
A. 3 tennis courts
B. 5 tennis courts
C. 1 tennis court
D. 10 tennis courts
Digestion and Absorption - ???
2. The absorptive surface of the normal small intestine is equal to:
Poor question…
A. 3 tennis courts
B. 5 tennis courts
C. 1 tennis court
D. 10 tennis courts
Digestion and Absorption - ???
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
Poor question…
Digestion and Absorption - ???
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
Poor question…
Digestion and Absorption - ???
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
It is always better to know the amount of bowel remaining following surgical resection – rather than the amount resected…Better question:
Digestion and Absorption - ???
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
It is always better to know the amount of bowel remaining following surgical resection – rather than the amount resected…Better question:
Digestion and Absorption
Wilmore, et al., Ann. Surg., 226:288-293, 1997
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
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
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
Good question…
Sites of Nutrient Absorption
5. What nutrient deficiency might be expected if 3 feet of the terminal ileum is resected?
A. IronC. Vit B-12
B. Magnesium
D. Calcium
Good question…
Sites of Nutrient Absorption
6. What nutrient deficiency might be expected if 3 feet of the terminal ileum is resected?
A. IronC. Vit B-12
B. Magnesium
D. Fat
Much harder question…
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 SulfateC. 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 SulfateC. 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 Potassiumin 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 intestinePredominates at concentrations 10 mmol/L
Active - primarily in the duodenumBelow 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 - ???
8. What mineral will be depleted if a patient has a draining T-tube in the common bile duct ?
Good question…
A. Zinc C. Magnesium
B. Sodium D. Copper
Digestion and Absorption - ???
8. What mineral will be depleted if a patient has a draining T-tube in the common bile duct ?
Good question…
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 - ???
8. What mineral will be depleted if a patient has marked diarrhea ?
Good question…
A. Zinc C. Magnesium
B. Sodium D. Copper
Digestion and Absorption - ???
8. What mineral will be depleted if a patient has marked diarrhea ?
Good question…
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 - ???
9. Even in Short Bowel Syndrome, oral iron supplementation can be effective.
Good question…
A.True
B.False
Digestion and Absorption - ???
9. Even in Short Bowel Syndrome, oral iron supplementation can be effective.
Good question…
A.True
B.False
Absorption of Iron
Iron is absorbed in duodenumferrous 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 - ???
10. The major source of carbohydrate in the diet is:
Good question…
A. Starch C. Lactose
B. Sucrose D. Fructose
Digestion and Absorption - ???
10. The major source of carbohydrate in the diet is:
Good question…
A. Starch C. Lactose
B. Sucrose D. Fructose
Average Carbohydrate Intake
PolysaccharidesStarch 200 64Glycogen 1 0.5
DisaccharidesSucrose 80 26Lactose 20 6.5
MonosaccharideFructose 10 3
Saccharides Intake (gm) % Total
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 -amylases
Cleaves starches to yield -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
GLUT5
SGLT1
GLUT2
GLUT2
GalactoseFructose
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 - ???
11. Which type of fiber can contribute to the energy needs of the colon?
Good question…
A.Cellulosic
B.Non Cellulosic
Digestion and Absorption - ???
11. Which type of fiber can contribute to the energy needs of the colon?
Good question…
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 medium-chain 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 - ???
12. Which of the following fatty acid(s) is absorbed directly into the enterocyte without micelle formation?
Good question…
A. Arachidonic acidsC. Chenodeoxycholic acids
B. Medium-chain fatty acids
D. Picric acids
Digestion and Absorption - ???
12. Which of the following fatty acid(s) is absorbed directly into the enterocyte without micelle formation?
Good question…
A. Arachidonic acidsC. 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 di- and 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 - ???
13. What is the di- and tri-peptide H+ dependent transport system in the small intestine?
Good question…
A. GLUT5 C. PepT1
B. Endopeptidase D. SGLT1
Digestion and Absorption - ???
13. What is the di- and tri-peptide H+ dependent transport system in the small intestine?
Good question…
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 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
Water Sodium Potassium Chloride Bicarbonate
100 ml4 mEq9 mEq2 mEq0 mEq
From 3/week to 3/day considered normalDiarrhea = stool weight > 200 to 500 g/24 h
Normal Stool Composition
Digestion and Absorption - ???
13. Each of the following are screening tests for intestinal absorption except:
Good question…
A.Gross inspection of stool B.Fat content of stool in random collectionC.Microscopic examination of stoolD.Lactose tolerance test
Digestion and Absorption - ???
13. Each of the following are screening tests for intestinal absorption except:
Good question…
A.Gross inspection of stool B.Fat content of stool in random collectionC.Microscopic examination of stoolD.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 !!