(8/17/10) - Intro to Digestion



1. List the four main functions of the digestive system: ingestion, digestion (both mechanical and chemical), absorption, elimination of wastes.

2. Identify the major organs involved with each of the four functions of the digestive system. · Ingestion: mouth/oral cavity, esophagus

· Digestion: mouth (amylase breaks down starches), stomach, small intestine (pancreatic amlyase breaks down sugars to dissacharides, dissacharidase; pancreas, gall-bladder & liver involved in secreting of enzymes/bile to aid in digestion

· Absorption: small intestine (duodenum, jejunum, ileum), large intestine (colon)

· Elimination: large intestine, anus

3. State how the anatomic position and structure of the liver allow it to absorb and metabolize lipid, protein and carbohydrate before releasing such molecules or their derivatives to the systemic circulation.

4. Identify the abdominal organs that are drained by the hepatic portal system into the liver. · Stomach, small intestine, large intestine, spleen

5. Define enterohepatic circulation.

Bile is originally created in the liver. After forming mixed micelles for lipid absorption, bile salts remain in the intestinal lumen. Protonated forms of bile salts are passively absorbed across the small intestinal mucosa. However, a majority of bile salt uptake occurs in distal ileum by Na+-dependent cotransport. Reabsorbed bile salts are then passed back to the liver. This circuit is known as enterohepatic circulation.

//Liver secretes bile into gallbladder, where it is stored until stimulation by CCK, and then is secreted into duodenum. Bile salts reduce surface tension and helps emulsify fas; form micelles & help transport lipids across intestinal mucosa. 90-95% of bile salts are re-absorbed in the ileum of the small intestion by a Na+/bile-salt co-transport system powered by the basolateral Na+/K+ ATPase. Remaining/unabsorbed bile salt is excreted.

6. Describe the role, if any, of HCl in the gastric digestion of carbohydrates, proteins, and fats.

· HCl converts pepsinogen to pepsin & creates acidic environment for pepsin

7. Define peristalsis and chyme. Describe the mechanisms by which chyme from the stomach is neutralized in the duodenum.

· Peristalsis: smooth muscle contractions by which food moves through digestive system

· Chyme: partially-digested food expelled by stomach into duodenum

· Secretin activates bicarbonate release pancreas to decrease acidity

8. Identify the cell type and anatomical location of the endocrine cells secreting gastrin, secretin, and cholecystokinin (CCK). Define the roles of the three molecules in the digestive process.

· Gastrin :

o  Secreted by G cells in antrum of stomach

o  Affected by contents in stomach (ex: amino acids of proteins activate G cells), vagus nerves, & other factors (GR, Ach)

o  Binds to parietal cells to activate secretion of HCl & intrinsic factor (important for B12)!– also activates pepsinogen secretion by chief cells

o  Acid inhibits gastrin by inhibiting G cells & releasing somatostatin (which also inhibits G cells, parietal cells & ECL cells)

· Secretin :

o  Secreted by S cells of mucosa of duodenum; stimulated by low pH

o  Acts on pancreas to release bicarbonate, which decreases acidity '

· CCK :

o  Secreted by cells in mucosa of duodenum

o  Contracts gallbladder (to release bile), relaxes sphincter of Oddi (allowing bile/pancreatic juice to flow), and increases release of zymogen granules containing digestive enzymes from pancreas

o  Secretion increased by contact of intestinal mucosa by peptides/amino acids & fatty acids

9. Briefly differentiate between apical and baso-lateral membranes of intestinal epithelia with respect to their composition and function.

· Apical membrane contains microvilli, which have a brush border to protect cells from digestive enzymes; some of these enzymes are embedded in brush border

· In small intestine/colon, apical membrane uptakes NaCl through Na+/H+& Cl-/HCO3- exchanger; baso-lateral membrane pumps out NaCl & KCl through Na+/K+ ATPase and KCC1

· In colon, sodium enters apical membrane through epithelial sodium channels (ENaC), Na+/K+ ATPase is located on baso-lateral membrane

Summary of Digestion
10. For carbohydrates, differentiate the processes of ingestion, digestion, absorption, secretion, and excretion, including the location in the GI tract where each process occurs. Repeat the analysis for proteins and fats.

PROTEIN DIGESTION
· Digestion: In stomach, G cells release gastrin in stomach, which stimulates H+ (and intrinsic factor) release from parietal cells and pepsinogen release from chief cells. Pepsinogen is activated by H+ and converts to pepsin (pepsin then auto-catalyzes). Pepsin breaks down peptides. Duodenal endocrine cells secrete secretin and CCK. Secretin stimulates HCO3- release, which increases pH. CCK stimulates release of pancreatic zymogens from pancreatic acinar cells and enteropeptidase, aminopeptidase , and dipeptidase from intestinal epithelial cells. Enteropeptidase activates trypsin (from trypsinogen). Trypsin converts chymotrypsinogenàchymotrypsin, proelastaseàelastase, procarboxypeptidaseàcarboxpeptidase. Exopeptidases (amino, carboxy) vs. endopeptidases.

· Absorption: occurs in enterocytes. Single amino acids are taken up via active co-transporter (Na+/aa), while di/tri-peptides are taken up by PEPT1 (H+co-transporter). Na/K ATPase helps maintain Na+ gradient. Di/tri-peptidase are digested to amino acids intracellularly. Amino acid transport to capillaries occurs via facilitated diffusion.

LIPID DIGESTION
Lipids enter the duodenum after minor digestion in the mouth by lingual lipase and in the stomach by gastric lipase (which do not require bile acids or colipase to function optimally). Pancreatic cells secrete pancreatic lipase into the duodenum. Colipase (cleaved by trypsin from procolipase) is a coenzyme that allows pancreatic lipase to work. Bile salts are secreted by the liver into the gallbladder where they help emulsify lipids into droplets, allowing the water-soluble lipases access to the lipids. Triglycerides are hydrolyzed into FAs and 2-monoacylglycerol, and these are incorporated into micelles. Micelles form due to the amphpathic nature of the bile acids. Monoglycerides, cholesterol, fat-soluble vitamins, and short/medium chain FAs cross the apical and basolateral membranes of the enterocytes and pass directly to the bloodstream. Long chain FAs are transported across the microvillus membrane and repackaged into chylomicrons. These chylomicrons are exocytosed and enter lacteals (lymphatic capillaries), which collect at the thoracic duct. The thoracic duct empties into the subclavian vein, and this point serves as the entrance to the bloodstream.

CARBOHYDRATE DIGESTION
· gestion: in mouth, salivary amylase breaks down starch a1,4 bonds. In SI, duodenal endocrine cells release secretin, which causes HCO3- release by pancreas, neutralizing acid. CCK causes release of pancreatic amylase by pancreatic acinar cells. Starch breakdown of pancreatic amylases (a1,4) produces free glucose, maltotriose, maltose & a-limit dextrins (containing a1,6 bonds). Isomaltase (a1,6), maltases, and glucoamylases break down remainder of starch. Disaccharidases, located on pancreatic brush border, break down sugars to monosaccharides.

o  Sucrose—(sucrase)àglucose+fructose (a1,2)  *hydration: water added to cleave sugar

o  Lacrose –(lactase)àglucose+galactose (b1,4)

o  Maltose—(maltase)àglucose (a1,4)

o  Cellulose: b1,4 cannot be cleaved and passes through body as fiber

11. Describe the initial digestive process that occurs in the mouth (chemical and mechanical). State the substrates and digestion products of salivary amylase (ptyalin).

12. State the stimuli for pepsinogen release and the mechanism for activating pepsinogen, and describe the digestion products of pepsin activity.

13. Describe the mechanism by which pancreatic zymogens are activated in the small intestine.

Secretin triggers release of pancreatic zymogens. Among these is trypsinogen, which is activated to trypsin by enteropeptidase (kinase secreted by duodenal epithelial cells). Trypsin then cleaves and activates the other pancreatic zymogens.

14. List the chemical classes of the carbohydrates entering the duodenum from the stomach, and identify mechanisms mediating further digestion and absorption across the apical and basolateral membranes of the intestinal epithelia. Include pancreatic secretions and brush-border enzymes.

15. Predict the small intestine and colonic consequence of a deficiency in the enzyme lactase, and identify ethnic/age groups who commonly exhibit this deficiency.

Unabsorbed lactose is osmotically active, drawing water followed by ions into the intestinal lumen. Colon bacteria metabolize lactose to galactose, glucose, CO2, and H2 gas (thus causing gas). Asian, African, and Native Americans most commonly exhibit this deficiency.

16. Summarize in a single sentence each the etiology of celiac and tropical sprue.

17. List the chemical classes of the proteins entering the duodenum from the stomach, and identify mechanisms mediating further digestion and absorption across the apical and basolateral membranes of the intestinal epithelia. Include pancreatic secretions and brush-border enzymes.

18. Contrast the secondary active transport of amino acids with that of di- and tri-peptides, including the ion used as the energy source.

19. Summarize in a single sentence each the etiology of Kwashiorkor, marasmus, Hartnup’s Disease and cystinuria.

Hartnup's disease: a congential defect in the mechanism that transports neutral amino acids in the intestine and renal tubules.

Cystinuria: A congenital defect in the transport of basic amino acids.

Marasmus: a form of severe protein-energy malnutrition characterized by energy deficiency.

Kwashiorkor: an acute form of childhood protein malnutrition characterized by edema, irritability, anorexia, ulcerating dermatoses, and an enlarged liver with fatty infiltrates.

20. List the chemical classes of the lipids entering the duodenum from the stomach, and identify mechanisms mediating further digestion and absorption across the apical and basolateral membranes of the intestinal epithelia. Include the roles of pancreatic lipase, colipase, and micelles.

21. Contrast the physical state of an emulsion with a micellar solution, and explain the conditions for the formation of emulsifications and micelles in the duodenum.

22. Summarize in a single sentence the role of the endoplasmic reticulum in processing lipids absorbed across the apical membrane of enterocytes. (Note this is covered in 'some detail in Week 6; should be addressed only briefly here.)

23. Briefly describe the composition and formation of chylomicrons, their movement across the enterocyte basolateral membrane, and the route of entry into thecardiovascular system''. (Note this is covered in some detail in Week 6; should be addressed only briefly here.)''


 * Large lipids are processed by Golgi and ER and processed into chylomicrons and exocytosed into the lymphatic system. The lymphatic system enters the bloodstream through the thoracic duct. Chylomicrons contain protein and fat and are send off to adipose cells and other targets. Hence: the lipoproteins of LDL and HDL. Low density ones have more cholesterol, sat fats, while HDLs have more protein and tell cells to take up cholesterol from the bloodstream and send it back to the liver.

24. Define steatorrhea, and predict the effects of steatorrhea on the absorption of fatsoluble vitamins.

Steatorrhea: fatty, bulky, clay-colored stools due to the impaired digestion and absorption of fat. The undigested fats dissolve lipid-soluble vitamins such as A,D,E and K, along with carotenoids. Fat soluble nutrients are therefore excreted along with the undigested fat molecules.

25. Explain how Olestra functions as a non-digestible artificial fat used in commercial foodstuffs.

Olestra is synthesized from a sucrose backbone (not glycerol) it can bond with six, seven, or eight fatty acids. The resulting radial arrangement is too large and irregular to move through the intestinal wall and be absorbed. Olestra has the same taste and mouthfeel as fat, but it passes through the gastrointestinal tract undigested without contributing calories or nutritive value to the diet.

26. Describe the amphipathic structure of bile acids, and predict how this property assists the digestion of fats. (Note this is covered in some detail in Week 6; should be addressed only briefly here.)

27. Identify substrates and products of colonic bacterial metabolism, and predict the impact of metabolites on the rate and composition of intestinal gas formation (flatus).