GI Secretions + Hormones B&B

Question 1

which cells secrete hydrochloric acid and mucous + bicarbonate, respectively?

Answer 1

parietal cells - HCL

neck cells - mucous + bicarbonate

Question 2

describe the histological location and appearance of parietal cells vs chief cells of the stomach

Answer 2

both found in lamina propria (mucosal layer) of gastric glands

parietal cells appear eosinophilic (pink) and are more concentrated closer to the lumen (upper layers) - secrete HCl

chief cells appear basophilic (purple) and are more concentrated in basal (deeper) layers - secrete pepsin

Question 3

what are 3 ways by which the parietal cells are stimulated to secrete HCL?

Answer 3

1. gastrin (direct): hormone from G cells of antrum (distal stomach), binds CCKb receptor on parietal cells
2. gastrin (indirect): activates ECL cells (entero-chromaffin-like), which release histamine, which stimulates parietal cell secretion via H2 receptor
3. vagus nerve: releases ACh to activate M3 receptors + releases gastrin-releasing peptide (GRP) which activates G cells, which stimulate parietal cell secretion

Question 4

in the direct pathway of stimulation, gastrin is secreted from the ___ cells and binds _____ receptor on parietal cells to stimulate acid secretion

Answer 4

1. gastrin (direct): hormone from G cells of antrum (distal stomach), binds CCKb receptor on parietal cells
2. gastrin (indirect): activates ECL cells (entero-chromaffin-like), which release histamine, which stimulates parietal cell secretion via H2
3. vagus nerve: releases ACh to activate M3 receptors + releases gastrin-releasing peptide (GRP) which activates G cells, which stimulate parietal cell secretion

Question 5

in the indirect pathway of stimulation, gastrin is secreted from ___ cells and activates ECL cells, which mediate _____ release to cause acid secretion from parietal cells

Answer 5

1. gastrin (direct): hormone from G cells of antrum (distal stomach), binds CCKb receptor on parietal cells
2. gastrin (indirect): activates ECL cells (entero-chromaffin-like), which release histamine, which stimulates parietal cell secretion via H2 receptors
3. vagus nerve: releases ACh to activate M3 receptors + releases gastrin-releasing peptide (GRP) which activates G cells, which stimulate parietal cell secretion

Question 6

what are the 2 substances released from the vagus nerve that stimulate gastric acid secretion?

Answer 6

1. ACh - activates M3 receptors
2. gastrin-releasing peptide (GRP) - activates G cells (produce gastrin), which stimulate parietal cell acid secretion

Question 7

why can’t a patient with gastric ulcers be effectively treated with atropine?

Answer 7

atropine = muscarinic blocker, blunts parietal cell stimulation by ACh (secreted from vagus nerve)

however, the vagus nerve also releases gastrin-releasing peptide (GRP) which activates G cells to release gastrin

gastrin both directly (via CCKb receptor) and indirectly (via histamine release from ECL cells) stimulates acid secretion from parietal cells

Question 8

which cells release intrinsic factor, necessary for vitamin B12 absorption?

Answer 8

parietal cells - secrete HCl and intrinsic factor

Question 9

explain the cause of the “alkaline tide” that occurs after meals

Answer 9

in the basal membrane of parietal cells, carbonic anhydrase converts H2O + CO2 —> HCO3- + H+

the H+ is secreted into the lumen of the stomach via an apical H+/K+ ATPase (anti-transporter) [Cl- is secreted via a separate channel]

the HCO3- leftover is secreted into the serum via a basal HCO3-/Cl- anti-transporter (where the Cl- comes from) —> increased bicarbonate in serum causes alkaline tide

Question 10

how can urinary chloride be used to determine the cause of metabolic alkalosis?

Answer 10

will be LOW in vomiting because HCl is lost

will be HIGH in diuretic use because these drugs block NaCl reabsorption

Question 11

which 2 endogenous substances inhibit the secretion of H+ from parietal cells? what signaling pathway do the use?

Answer 11

1. somatostatin
2. prostaglandins

both decrease cAMP via Gi

Question 12

which 2nd messengers do the following stimulators and inhibitors of gastric acid secretion use?
a. ACh (via vagus)
b. gastrin (via G cells)
c. histamine (via ECL cells)
d. somatostatin
e. prostaglandins

Answer 12

via Gq —> IP3/Ca2+ (via PLC) = ACh and gastrin (both stimulators)

via Gs —> cAMP (via AC) = histamine (stimulator)

via Gi —> decrease cAMP = somatostatin and prostaglandins (both inhibitors)

[all the above are exerting effects on H+/K+ ATPase anti-transporter]

Question 13

what is the stimulus for pepsin secretion, and from which cells is it secreted?

Answer 13

stimulus for release = vagus nerve

released from chief cells as pepsinogen, activated by H+ (pH 1-3) to pepsin

function = digests proteins

Question 14

where is gastrin secreted from, and how does it reach the parietal cells?

Answer 14

produced by G cells in the mucosa (lamina propria) of the antrum of the stomach (closest to pylorus/duodenum)

secreted into portal vein, travels via bloodstream to reach parietal cells (in lamina propria of body of stomach)

Question 15

3 effects of gastrin

Answer 15

1. stimulates H+ secretion by parietal cells
2. stimulates hypertrophy/hyperplasia of gastric mucosa.
3. Increases gastric motility

Question 16

which 2 amino acids are potent stimulators of gastrin release?

Answer 16

1. phenylalanine
2. tryptophan

Question 17

where do gastrinomas occur? (2)

Answer 17

gastrin secreting tumors occurring in duodenum or pancreas (G cells found in fetal pancreas)

—> excessive acid secretion + hypertrophy/hyperplasia of mucosa
—> Zollinger-Ellison Syndrome: abdominal pain + chronic diarrhea

Question 18

what are the symptoms of Zollinger-Ellison Syndrome? (4)

Answer 18

occurs with gastrinomas (occur in duodenum or pancreas)

1. abdominal pain (acidity)
2. chronic diarrhea - acidity activates pancreatic enzymes and inhibits Na/H2O absorption in small intestines
3. ulcers in distal duodenum (unusual location) - refractory to PPI therapy
4. heartburn

Question 19

how can a secretin test be used to dx a gastrinoma?

Answer 19

normal G cells inhibited by secretin (hormone) - however, gastrinomas are stimulated by secretin, so gastrin levels will rise after administration

helps differentiate gastrinomas from other causes of high gastrin levels

Question 20

how are gastrinomas treated? (3)

Answer 20

1. high dose PPI - omeprazole, lansoprazole, pantoprazole
2. octreotide (somatostatin)
3. surgical excision

Question 21

why does pernicious anemia cause a rise in gastrin levels?

Answer 21

pernicious anemia = autoimmune gastritis, loss of parietal cells which are responsible for absorption of vitamin B12 (intrinsic factor)

G cells produce gastrin to stimulate parietal cells —> Gastrin levels increase in an attempt to stimulate parietal cells to increase absorption of vitamin B12

Question 22

what are 4 effects of cholecystokinin?

Answer 22

1. gallbladder contraction
2. Pancreatic enzymes secretion from the I cells of the duodenum + jejunum
3. relaxation of sphincter of Oddi
4. inhibits gastric emptying (time for enzymes to work)

Question 23

what is the mechanism by which cholecystokinin stimulates the secretion of pancreatic enzymes?

Answer 23

Indirectly – there are CCK receptors on the vagus nerve, which releases acetylcholine —> stimulates pancreatic secretion

Question 24

What molecules stimulate the release of cholecystokinin? (2)

Answer 24

1. fatty acids + monoglycerides (NOT triglycerides)
2. amino acids

[CCK stimulates contraction of gallbladder + secretion of pancreatic enzymes]

Question 25

what stimulates the release of secretin and what is its role?

Answer 25

Released by **S cells of duodenum** in response to *acid and fatty acids* and duodenum —> raises pH in small intestine via **bicarb secretion from pancreatic duct cells** also inhibits gastric acid secretion, increases bio production, and promotes pancreatic flow (water secreted with bicarbonate)

Question 26

What pharmalogical agent is used to treat bleeding varices before surgery?

Answer 26

varices = blood vessel in esophagus or stomach that occur with portal HTN or liver disease; bleeding can be fatal **octreotide** (somatostatin) is administered to reduce splanchnic blood flow [inhibitory hormone to digestion] to decrease bleeding (then ultimately treated with surgery)

Question 27

what are four clinical uses for octreotide?

Answer 27

Octreotide = somatostatin 1. **Carcinoid syndrome** - somatostatin receptors found on carcinoid tumors (release serotonin), can improve flushing and diarrhea 2. **Acromegaly** - inhibits growth hormone secretion 3. **Gastrinoma/glucagonoma** - inhibits hormone release 4. **Bleeding varices** - decreases splanchnic blood flow

Question 28

What stimulates the release of GIP (GI hormone) and what are its effects?

Answer 28

GIP = glucose-dependent insulinotropic peptide —> **stimulates insulin release** from pancreas (also blunts H+ secretion) released by **K cells** of duodenum/jejunum in response to **glucose, fatty acids, and amino acids** (only hormone stimulated in response to fats, proteins, and carbs)

Question 29

explain why oral glucose is metabolized faster than IV glucose

Answer 29

oral glucose stimulates the release of **GIP** (glucose dependent insulinotropic peptide), which **stimulates insulin release** from the pancreas [IV glucose does not stimulate GIP release]

Question 30

what is the role of VIP (vasoactive intestinal peptide)?

Answer 30

**neurocrine** that causes relaxation of smooth muscle - important for *relaxation of lower esophageal sphincter* also raises pH by stimulating pancreatic bicarb secretion (water follows, increasing flow in GI tract)

Question 31

what are the symptoms of a VIPoma (3), and why do these occur?

Answer 31

VIP (vasoactive intestinal peptide) relaxes smooth muscle and increases bicarb secretion from pancreas + inhibits gastric acid secretion 1. **watery (secretory) diarrhea** - water follows bicarb, causes *tea-colored, odorless diarrhea* resembling cholera 2. **hypokalemia** - from high volume diarrhea 3. **achlorhydria** - absence of gastric acid

Question 32

Pt is a 44yo M presenting with complain of chronic, tea-colored, odorless diarrhea. They have also been having difficulty digesting food despite trying different diets. Labs show hypokalemia and endoscopic sample shows a high pH in the stomach. What is the dx?

Answer 32

dx = **VIPoma** —> VIP (vasoactive intestinal peptide) relaxes smooth muscle and increases bicarb secretion from pancreas + inhibits gastric acid secretion 1. **watery (secretory) diarrhea** - water follows bicarb, causes *tea-colored, odorless diarrhea* resembling cholera 2. **hypokalemia** - from high volume diarrhea 3. **achlorhydria** - absence of gastric acid

Question 33

which antibiotic can treat a “frozen stomach” by binding/activating motilin receptors?

Answer 33

**erythromycin** gastroparesis (frozen stomach/intestine) often occurs in diabetics