[image courtesy of erica newon zelfand]
this unit focused on pancreatic secretions and their role in carbohydrate and protein digestion in the intestine. each day, the pancreas secretes 1L of pancreatic enzymes, among which are enzymes that break down carbohydrates into monosaccharides, enzymes that break down proteins into peptides, lipases which break down triacylglycerols into fatty acids. these digestive enzymes are secreted by the "acinar" cells of the pancreatic ducts, while water and electrolytes such as bicarbonate are secreted by duct cells (a similar strategy to salivary and gastric secretion). the bicarbonate from duct cells comes from carbonic acid, which is formed in duct cells by carbonic anhydrase. bicarbonate is transported into the duct lumen in exchange for a chloride ion by the CFTR transporter. the acinar cells can be stimulated to produce more secretion either directly by vagal stimulation or by different neuropeptides such as CCK, GRP, SubP, VIP. duct cells are stimulated to increase water and bicarbonate production mainly by secretin (which functions to reduce acidity in the intestine and as such also inhibits gastric secretion and emptying).
as with gastric secretion, pancreatic secretions can be divided into three phases (refer to comparison chart), cephalic, gastric, and intestinal. in the cephalic phase, thoughts or sensation of food causes increase of pancreatic secretion via vagal stimulation. in the gastric phase, gastric distention triggers vagal stimulation of pancreatic secretion. the most important phase for pancreatic secretion is the intestinal phase, where intestinal distention, high acid levels, or other digestive products trigger hormonal release that modify pancreatic secretion. CCK is released from I cells in response to fat and proteins, which stimulates acinar cells to increase enzymatic secretion. secretin is released from S cells in response to acid and fat, which stimulates bicarbonate and water secretion from pancreatic duct cells.
carbohydrate digestion, already initiated with salivary alpha amylase, continues with the secretion of pancreatic alpha amylase into the intestinal lumen. polysaccharides are cleaved into smaller di and tri saccharides, and then further digested by the brush border enzymes (see the biochem chapter for a much more detailed description). different sugars are absorbed into the enterocyte and bloodstream by different transporters: for example, glucose and galactose are absorbed into the enterocyte by SGLT1, a sodium co-transporter, while fructose is facilitatively absorbed by GLUT 5. the pancreas also secretes enzymes that digest proteins, all of which are activated by enterokinase, which activates trypsinogen into trypsin, which activates the other zymogens procarboxypeptidase, chymotrypsinogen, proelastase (see the biochem protein digestion chapter).
an interesting note about the role of tight junctions: most absorption of nutrients occurs through the membrane of the enterocyte, or transcellularly. however, in the case of macromolecules that are too large to be absorbed transcellularly, paracellular transport can occur via modulation of the tight junctions between enterocytes, which can occur reversibly via the molecule zonulin. paracellular transport can also occur in "leaky gut", hyperpermeability of the tight junctions, caused by excess glucose levels, alcohol abuse, NSAID/steroidal use,food allergies, crohn's disease. there is a distinct but underexplored relationship between tight junctino permeability and autoimmune disease; people with dysregulation of tight junction permeability have a higher susceptibility for autoimmune diseases.
questions
1. enzymes digest carbohydrates, fats, proteins by what type of reaction?
2. what is SGLT1 and what does it do?
describe the absorption of these substances from the intestinal lumen into the enterocyte, and from there into the blood stream:
3. glucose
4. lactose
5. fructose
6. glycogen
7. sodium
tight junctions...
8. describe the absorptive pathway from the intestinal lumen to the mucosal capillary.
9. what is a function of tight junctions in intestinal epithelium that is not commonly discussed?
10. what is the relationship of tight junctions and the immune system?
11. what are tight junctions made of?
12. what is "leaky gut" and what are some factors that cause it?
13. what is zonulin and what does it do?
14. what is lactulose and how is related to leaky gut?
pancreas...
15. where is the pancreas?
16. how much liquid does the pancreas secrete per day?
17. what do the acinar and duct cells secrete?
18. what are the electrolytes that are secreted by duct cells?
19. describe the secretion of bicarbonate by duct cells.
20. what are the enzymes that are secreted by the pancreas that digest proteins?
21. how are the protein digestion enzymes activated?
22. what does pancreatic amylase do?
23. what are the pancreatic enzymes that digest lipids?
24. what are the different ways in which pancreatic acinar cells are stimulated?
25. what are the actions of secretin?
pancreatic phases...
26. what are the three phases of pancreatic secretion?
27. describe the cephalic phase of pancreatic secretion.
28. describe the gastric phase of pancreatic secretion.
29. describe the intestinal phase of pancreatic secretion.
30. describe the secretion and actions of CCK.
31. describe the secretion and actions of secretin.
32. how does enzymatic secretion adapt to different dietary compositions?
carbohydrate digestion...
33. what are the approximate proportions of the different types of carbohydrates ingested?
34. pancreatic and salivary amylase digests starch into...
35. how are di and trisaccharides digested into monosaccharides?
36. what are the two ways that glucose and galactose can be transported into the intestinal epithelium?
37. compare the absorption of glucose and fructose.
38. describe the negative feedback that can occur in carbohydrate digestion.
39. how can malfunctioning carbohydrate digestion cause diarrhea?
40. what is the hydrogen breath test?
41. what effect does celiac disease has on the intestinal lining?
protein digestion and absorption...
42. how are proteins digested in the stomach?
43. how are proteins digested in the intestine?
44. how are polypeptides digested and absorbed in the intestine?
pancreatic tests...
45. what is the stool chymotrypsin test?
46. what is the pancreatic elastase test and why might it be more reliable than the stool chymotrypsin test?
answers
1. hydrolysis reactions.
2. it is a sodium / glucose co-transporter, facilitating absorption of glucose, galactose
3. glucose is transported into the enterocyte via SGLT1, then into the blood via GLUT2.
4. lactose is broken down into glucose and galactose via the brush border enzyme lactase, and glucose and galactose are absorbed and transported in the same way as question 3.
5. fructose is transported into enterocytes via GLUT5, and absorbed into blood via GLUT2.
6. glycogen is broken down into oligsaccharides and alpha limit dextrins by alpha amylase, and then broken down further into monosaccharides by brush border enzymes and absorbed the same way as in question 3.
7. sodium is transported along with glucose or galactose via the SGLT1 co-transporter.
8. intestinal lumen -> unstirred layer of fluid -> glycocalxces on microvilli of enterocytes -> cell membranes and cytoplasm -> basement membrane -> capillary
9. tight junctions can facilitate absorption of macromolecules, nutrients that are too big to be absorbed directly into enterocytes.
10. when tight junction regulation of macromolecule absorption is dysregulated, this can sometimes lead to intestinal and extraintestinal autoimmune disorders.
11. occludins, claudin family of proteins, junctional adhesion molecules.
12. hyperpermeability of the intestinal epithelium. caused by alcohol abuse, high sugar intake, food allergies, NSAIDS/steroid drugs, celiac disease and crohn's disease.
13. a molecules that facilitates the permeability of tight junctions and as such is involved in the absorption of fluid and macromolecules across the intestinal barrier, and also protect the intestine from being colonized by microorganisms.
14. a macromolecule that can only be absorbed paracellularly; its presence in the blood as compared to mannose (which is absorbed transcellularly) is a good indicator of leaky gut.
15. the body of the pancreas lies deep to the stomach and the tail extends to the spleen.
16. 1L per day
17. acinar cells secrete enzymes, duct cells secrete water and electrolytes.
18. bicarbonate and sodium.
19. bicarbonate is formed from carbonic acid which is formed by carbonic anhydrase and CO2. H+ is absorbed into blood, and bicarbonate is transported into the lumen by the transmembrane regulator CFTR (cystic fibrosis transmembrane regulator) which exchanges a chloride ion for a bicarbonate ion.
20. trypsinogen, proelastase, chymotrypsinogen, procarboxypeptidase.
21. trypsinogen is activated by the brush border protease enterokinase, forming trypsin, which activates the other enzymes.
22. an endoglucosidase that hydrolyzes carbohydrates into di and tri-saccharides.
23. pancreatic lipase, cholesterol esterase, phospholipase.
24. directly via the vagus nerve, or indirectly via stimulation of the vagus nerve by CCK, VIP, GRP, SubP.
25. stimulates duct cells to release bicarbonate, inhibits gastric secretion and emptying- overall effect is to raise pH.
26. cephalic, gastric, intestinal
27. stimulated by thoughts or sensation of food, vagus nerve stimulates pancreas secretion.
28. gastric distention causes vagal stimulation, which causes pancreas secretion.
29. the most important phase for pancreatic secretion; digestive products or low pH trigger release of hormones that control secretion.
30. CCK is secreted from I cells in the intestinal epithelium in response to proteins or fats. chief among its many effects is to stimulate pancreatic acinar secretion of enzymes.
31. secretin is released from S cells in the intestine in response to acid or fat-- its main effect is to increase water and bicarbonate secretion by pancreatic duct cells, thereby raising the pH of the intestinal lumen. it also decreases gastric motility and emptying.
32. CCK can up or downregulate the protein digesting proteases and the carbohydrate digesting amylases depending on the ratio of protein to carbohydrates in the diet.
33. 50% starch, 20% sucrose, 6% lactose, 1-2% maltose.
34. di and trisaccharides.
35. by the brush border enzymes.
36. transcellularly via the SGLT1 Na+ cotransporter or paracellularly with water with high glucose concentrations (see section on tight junctions)
37. fructose absorption is slower and uses a facilitated transporter rather than a co-transporter. (see question 5)
38. chemo and osmotic receptors sense high glucose levels in the duodenum and jejunum and trigger the vasovagal reflex, which decreases gastric motility and emptying.
39. in the case of lactose intolerance, lactose remains undigested and cause a hyperosmolar intestinal lumen from excess sugar as well as products from bacterial processing of these sugars; causing water to accumulate in the lumen and cause diarrhea.
40. a test which measures amount of hydrogen in breath, which is produced from bacteria that metabolize lactose in the intestine in lactose intolerant people.
41. destroys villi.
42. gastric pepsinogen is secreted and converted to pepsin by the low pH environment of the stomach. it cleaves proteins into smaller polypeptides.
43. in the intestine, proteins are digested by different pancreatic enzymes: trypsin, chymotrypsin, carboxypeptidase, elastase. trypsin activates the other three enzymes, which cleave large polypeptides into small polypeptides.
44. small polypeptides are cleaved further into smaller polypeptides and amino acids, which are then transported into the enterocyte and then absorbed into the blood by carrier proteins.
45. a marker for pancreatic output; normal is >9U/g stool, low is <>200 mcg/g stool, low is <100>
46. another test for pancreatic output, which might be more accurate because elastase is only produced by human pancreatic cells. normal is >200 mcg/g stool, low is <100>
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