GI Physio | Secretions II (Exopancreatic, Hepatic)

Question 1

What channel is responsible for the low levels of Cl- and the high levels of HCO3- in pancreatic secretion fluid?

Answer 1

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride channel that lowers Cl- by bringing it back into pancreatic ductal cells in exchange for HCO3- in fluid.

Question 2

Secretin stimulates ____ channel and the translocation of ______ ATPase to the basolateral membrane through cAMP activity.

Answer 2

Secretin promotes CFTR activation and movement of H-K+ ATPase to the basolateral side through cAMP.

Question 3

What factors enhance secretin release and how do they do it?

Answer 3

CCK and ACh potentiate secretin by enhancing the K+ channel via Ca2+ influx. Intra-luminal acid (H+) can also activate secretin release.

Question 4

What are the main mediators of pancreatic secretion in the intestinal phase? What percentage of daily secretion does this account for?

Answer 4

CCK (fats and peptides), Vagal tone and secretin (H+) are main mediators for pancreatic secretion of the intestinal phase. This accounts for 70% of daily secretions.

Question 5

Pertaining to pancreatic secretions, ____ mediates release of enzymes; meanwhile, ____ induces the aqueous (fluid) component.

Answer 5

CCK mediates enzyme secretion in presence of fats, peptides and AAs. Secretin induces the aqueous component that is potentiated by CCK and ACh.

Question 6

Intestinal secretions are highly _____. On average these are released at ____ ml/day. Diarrhea from a cholera infection can bring this up to more than _____ ml/day.

Answer 6

Intestinal secretions are highly INDUCIBLE. Averages at 1,500 mL/day but can jump to >10,000 mL/day.

Question 7

What channel accounts for the duodenum being rich in HCO3- as compared to the neutral Jejunum and ileum?

Answer 7

The Cl/HCO3- exchanger present in the duodenum makes it rich in HCO3-, as compared to the distal small intestines where it’s absent.

Question 8

Describe the pathway that activates CFTR activity in the cells of the small intestine.

Answer 8

Intraluminal acid (H+) stimulates secretin to activate cAMP pathways. This results in “PKA-mediated Phosphorylation” that activates CFTR activity to SECRETE CHLORIDE ions.

Question 9

What effects do an entero-toxins have on CFTR? How can one treat this condition?

Answer 9

Toxins in the GI tract can CONSTITUTIVELY activate CFTR channels resulting in XS chloride secretion, diarrhea and dehydration. To treat this issue, stimulate the SGLT channel to restore lost fluid balance. This dramatically reduces diarrheal death.

Question 10

Describe the normal external fluid circuit in the lumen of the small intestine.

Answer 10

Water, Na and Cl are secreted @ the bottom of the intestinal crypt via CFTR channel. At the top (closer to the lumen), these same molecules are absorbed into the blood stream.

Question 11

How can we treat infection-induced secretory diarrhea from over-activation of CFTR channel?

Answer 11

Activate the SGLT channel at the top of the enterocyte to reabsorb glucose and Na+. this restores fluid/osmotic balance and reduces diarrheal death.

Question 12

What organic substances produced by the liver help maintain cholesterol levels in the body? Where would an excess of cholesterol be stored?

Answer 12

Phospholipids (22%) and bile salts (67%) maintain cholesterol in body solution. Too much cholesterol would be stored in the gallbladder or biliary ducts.

Question 13

Bile acids are converted into ___ ___ before they can be secreted to be stored in the _____ or released into the ______.

Answer 13

Bile salts (BS) are sent for storage in the gallbladder or released into the intestines to emulsify fats.

Question 14

Why do we only secrete bile salts? How does the conversion work?

Answer 14

We secrete bile salts (instead of bile acids) to form micelles that solubilize lipids in water. Conjugate the BAs with hydrophilic amino acids (Glycine or taurine) to have them ionize better in plasma.

Question 15

What is the molecular feature of bile salts that distinguishes them from bile acids?

Answer 15

Bile salts (BS) are AMPHIPATHIC that enables them to effectively form micelles and emulsify lipids as long as they exceed critical concentration.

Question 16

Bile salts are secreted through _____ transporters. This explains why BAs cannot be secreted without ______.

Answer 16

BS secreted via ACTIVE transporters on hepatocytes. BAs cannot be secreted without CONJUGATION.

Question 17

The Sphincter of Oddi is closed during what 2 conditions? What would a prolonged closure of this result in?

Answer 17

The Sphincter of Oddi is closed at night or during the interdigestive period. Constant secretion of bile from liver + prolonged closure of the sphincter = increased risk of gallstones (fasting, high-fat foods)

Question 18

Most of the Bile salts are ______ by bacteria and reabsorbed into the _______. The 10% that is lost daily is _____ by the liver.

Answer 18

BS are “de-conjugated” by gut bacteria to be absorbed into the portal vein. The liver replenishes 10% BS lost daily via de novo synthesis.

Question 19

What are the respective roles of CCK and Secretin in bile synthesis and transport?

Answer 19

CCK relaxes the sphincter of Oddi and causes contraction of gallbladder SM to release bile into the duct. Secretin dilutes the bile by increasing HCO3- secretion via activation of ductal cells.

Question 20

During the digestive period, we see a high amount of _____ and recycled _____. This results in a reduction of _____.

Answer 20

Digestive period sees a high amount of lipids in intestines and recycled BAs in circulation, thus reducing de novo synthesis of BS.

Question 21

During the interdigestive period, the sphincter of oddi is ____ and bile is _____ until the next meal.

Answer 21

During the Interdigestive period, the Sphincter of Oddi is closed and bile is stored in the gallbladder until the next meal, hopefully during breakfast time.

Question 22

How is de novo bile acid biosynthesis affected in people without an ileum as compared to within intact people?

Answer 22

In people with a removed ileum, there is less reabsorption (recycling) of bile salts in the portal vein. This results in a condition closer to the interdigestive period where de novo BA biosynthesis is INCREASED (faster kinetics).

Question 23

What are the 2 main secretions form hepatocytes? What are some substances excreted by the liver?

Answer 23

Major hepatocyte secretions are organic substances (bile-acid dependent), water and electrolytes (plasma-like). Some major excretory components are cholesterol, metals and bilirubin (0.3% of secreted bile).