Anatomy and Physiology of the Gastrointestinal Tract John P. Grant, MD, CNSP Director Nutrition...

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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 !!