Gallbladder and Pancreas Physiology - Prunuske

Question 1

What do acinar cells of the pancreas secrete?

What do centroacinar and duct cells do?

Answer 1

Acinar cells - secrete digestive enzymes

Centroacinar cells/duct cells - dilute pancreatic enzymes and add HCO3 to make them alkaline

Question 2

As the flow rate increases how do the relative concentrations of Chloride and bicarbonate change?

As the flow increases, how do the relative concentrations of Na and K change?

Answer 2

As flow increases: Chloride decreases and bicarb increases

(The lumenal side has a Cl/HCO3 exchanger)

Na and K will stay constant, independent of flow

Question 3

During high rates of flow of pancreatic juices, what happens to the pH of the juice?

Answer 3

It will increase due to the increasing amounts of bicarbonate concentration.

Question 4

90% of pancreatic cells are used for its exocrine function.

What are the exocrine functions of these cells?

Answer 4

-Secrete essential digestive enzymes and bicarbonate into the duodenum

Question 5

How are pancreatic acinar cells activated in the cephalic and gastric phases?

Answer 5

Activated by parasympathetic efferents (ACh, GRP) from vagal centers of the brain

Question 6

What activates secretion from acinar and ductal cells in the intestinal phase?

Answer 6

Protein and lipid breakdown products in the duodenum

• ->vasovagal reflex stimulates acinar cells
• ->Cause I-cells to release CCK which also stimulates acinar cells

H+ ions in the duodenum cause S cells release secretin
–>Secretin acts in duct cells to secrete HCO3-

Question 7

Monitor peptide is released during cephalic/gastric phases due to vagal stimulation.
CCK-RP is released in intestinal phase in response to AA/FA products
Monitor peptide and CCK-RP cause CCK release from I cells. CCK will cyclically upregulate CCK-RP.
So what will finally turn off CCK secretion? Why doesn’t it go on forever?

Answer 7

Pancreatic enzymes (increased by CCK release) will digest CCK-RP and Monitor Peptide, which will turn off CCK secretion

Question 8

How does CCK (the master regulator of the duodenal cluster unit) act on the:
gallbladder:
pancreas:
stomach:
Sphincter of odi:

Answer 8

gallbladder: contraction
pancreas: acinar secretion
stomach: reduced emptying
Sphincter of odi: relaxation

Also tells your brain to stop eating

Question 9

What converts trypsinogen into trypsin?

Where does this occur?

Answer 9

Enteropeptidase on the duodenal brush border

Question 10

You have a 50 year old patient on a proton pump inhibitor. Do you predict they will have increased or decreased duodenal bicarbonate secretion post-prandially?

Answer 10

Probably less.

It is the low pH in the duodenum that triggers the S-cell release of secretin. Secretin raises pH by increasing the bicarb secretion from pancreatic ducts.
A PPI is going to make the patient’s duodenum more basic already, decreasing this secretion event.

Question 11

Explain the mechanism by which secretin exerts its effects:

Answer 11

Secretin acts mostly to increase cAMP levels which opens the CFTR channel. (Cl- channel)

Cl can then feed into the Cl/HCO3 exchanger and allow HCO3 to be released into the duct!

Question 12

On the basolateral side of the duct cell, HCO3 must be brought ino the cell so that it can be exchanged with Cl at the Cl/HCO3 exchanger on the lumenal side.
What provides the power by which all this ion transport is possible?

Answer 12

Na/K ATPase on the basolateral side creates a strong intracellular Na gradient that can be used to pull HCO3 into the cell.

Question 13

Consequence of Cystic Fibrosis in regard to the ductal cells of the pancreas?

Answer 13

• Less effective at acid neutralization because there is no Cl in the duct lumen to exchange with bicarb!
• Less effective activation of digestive enzymes
• Fluid movements through pancreatic ducts will cause thicker pancreatic juice and possible pancreatitis. (Cl is responsible for some of the water movement)

Question 14

What are the main causes of pancreatitis?

Answer 14

• Cystic fibrosis
• Pancreatic duct occlusion (gallstones, neoplasm)
• Alcohol use (hyperstimulation of acinar cells results in intracellular trypsin activation and cell death)

Question 15

What are the effects of pancreatitis that are causing problems?

Answer 15

• Autodigestion of pancreatic tissue causes upper abdominal pain
• Enzymes spill over into circulation (see elevated serum amylase and lipase)
• Fat and fat-fatsoluble vitamins are poorly absorbed (Vit A, D, E, K)
• Can cause malignancy, diabetes, infections

Question 16

Why will a person release more insulin in response to oral glucose over IV glucose?

Answer 16

Oral glucose will trigger Glucagon-Like Peptide-1 (GLP-1) from L cells and Glucose-Dependent Insulinotropic Peptide (GIP) from K cells in the intestine

They can then act along with gastrin, CCK, and ACh to release insulin from beta-cells

Question 17

There are drugs on the market that either stabilize GLP-1 or agonize it. What are these drugs used to treat?

Answer 17

diabetes.

Question 18

Which hormones act as satiety signals on the hypothalamus to decease food intake and increase energy expenditure?

Answer 18

GLP1, CCK, Insulin, Leptin

Question 19

Why might lack of sleep lead to hyperphagia?

Answer 19

lack of sleep can lower leptin levels.

This decreases satiety signaling and stimulates over-eating

Question 20

What would be the consequence of giving ghrelin prior to eating at a buffet?

Answer 20

They would probably overeat.

Ghrelin stimulates appetite.

Question 21

Where is Ghrelin produced?

Answer 21

The fundus of the stomach

Question 22

Hepatic triad. Go!

Anatomy review

Answer 22

Portal vein, hepatic artery, bile duct

Question 23

Name for macrophages surrounding hepatocytes?

Answer 23

Kupffer cells

Question 24

Which cells in the liver both produce collagen and store lipids like Vitamin A?

Answer 24

Stellate cells

Question 25

One of your chronic alcoholic patients presents with yellow sclera, a swollen belly, dysphagia, and symptoms of anemia.
What’s at the top of your differential? What is the pathological mechanism behind this problem?

Answer 25

Liver Cirrhosis
Oxidative stress caused by alcohol releases cytokines from Kupffer cells that make stellate cells deposit collagen.
Collagen deposition results in sinusoid depression. This increases resistance to blood flow leads to hepatocyte dysfunction.
Portal Hypertension results in abdominal ascites and esophageal varies
Hepatic encephalopathy can also be seen as toxins enter the blood stream.

Question 26

Do bile salts facilitate the excretion of hydrophobic or hydrophilic molecules?

Answer 26

Facilitate excretion of hydrophobic molecules (cholesterol)

Also facilitate uptake of long chain fatty acids and fast-soluble vitamins

They act as emulsifiers by adding a polar group which interacts with the aqueous environment

Question 27

What occurs in order to convert bile acids into bile salts?

Answer 27

Bile acids are conjugated to amino acids - increasing their aqueous solubility

Question 28

Why in the canals of Hering are are glucose and amino acids actively removed from the bile while IgA and mucus are added?

Answer 28

Prevents overgrowth of bacteria which would cause deconjugation

Question 29

Between meals, NO/VIP stimulation allows the gallbladder to relax and fill along with high pressure at the sphincter of Oddi.
Explain what happens during intestinal phase after a meal? I want details!

Answer 29

1) Nutrients in the duodenum activates CCK release
2a) The dorsal vagal complex is stimulated by CCK and goes on to stimulate ACh to contract the gallbladder and NO/VIP to relax the sphincter of Oddi
2b) CCK also stimulates the gallbladder directly
3) Bile is secreted!

Question 30

What is the mechanism by which the gallbladder concentrates bile?

Answer 30

• Actively pumps Na to the basolateral side followed by Cl

- Water follows these ions, and the bile in the lumen becomes more concentrated

Question 31

What are 3 big causes of cholestasis?

Answer 31

Primary Biliary Cirhosis (cholangiocyte destruction)
Primary Sclerosing Cholangitis (bile duct inflammation)
Pregnancy (progesterone reduces gallbladder muscle tone)

Question 32

What are the negative effects of cholestasis?

Answer 32

Bile accumulates in liver causing metabolic dysfunction
Bile regurgitates into the plasma causing itching
Hypercholesterolemia
Deficiency in fat-soluble vitamins

Question 33

Im confused. What is the connection between Cholelithiasis and a bleeding disorder?

Answer 33

Gallstones can block bile release.
Cause jaundice
Steatorrhea
Bleeding disorder (Fat-soluble vitamin K cannot be absorbed and person becomes deficient)