Lecture 14: Secretions of GI Tract and Pancreas Flashcards
What glands produce saliva?
parotid - serous cells that release amylase
submaxillary and sublingual - serous and mucous cells that secrete mucin glycoprotein
*75% of saliva produced by the latter 2
What is the function of these parts in the salivary gland?
Acinar cells
Myoepithelial cells
Be able to label the parts of the salivary glands on the image
- secretes initial saliva (isotonic to plasma)
- has motile extensions that contract to push initial saliva into the duct
What is the difference between intercalated duct and striated duct in salivary glands?
- epithelial cells that collect initial saliva from acinar cells
- columnar/ductal cells that modify isotonic saliva to become more hypotonic (final saliva)
What is saliva composed of?
lots of K+ and HCO3- (hypotonic) and less NaCl
a-amylase, lingual lipase, kallikrein and mucus
What is exchanged on the luminal (apical) and basolateral (blood) in the salivary ductal cells and what are the respective transporters?
Be able to draw the image on the slide
Luminal:
Out (lumen/secreted): K and HCO3-
In (cell): NaCl
Transporters: Na/H, Cl/HCO3, H/K exchangers
Basolateral:
Out (blood/absorbed): NaCl
In (cell): K, HCO3-
Transporters: HCO3-/Na exchanger, Na/K ATPase (balancer)
What is the net result of the transport mechanisms in the salivary ducts?
-NaCl absorption (predominant) and KHCO3 secretion
What happens to water in the ducts and how does it affect the final saliva?
Ductal cells are impermeable to water, so it stays in the ducts = dilute (hypotonic) saliva is released
How are the salivary glands parasympathetically innervated?
How are the salivary glands sympathetically innervated?
Which one is predominant?
Medulla > CN VII & IX > synapse at ganglion by salivary gland > Ach > PLC pathway > gland (salivate)
T1-L2 > synapse at cervical ganglion > NE > PK pathway > gland (salivate)
-PNS control, SNS helps
What stimulates salivary secretion?
What inhibits salivary secretion?
- food conditioning, stimuli
- dehydration, fear, sleep
What are the roles of these substances in salivary secretion?
Atropine
ADH & aldosterone
- antagonist for mAchRs > decrease salivation
- increase Na absorption and K secretion at the ducts to make hypotonic saliva
What does the gastric mucosa secrete and what are their functions?
Hcl/H+ - acidifies the environment to activate pepsin
Pepsinogen - inactive pepsin precursor
Mucus - protects wall of stomach, acid neutralizer
Intrinsic Factor - absorbs B12 in ileum
H2O - solvent for enzymes and ingested material
What are the two types of cells in the gastric mucosa and how are they different?
Oxyntic - proximal stomach (body and fundus), secretes acid
Pyloric - distal stomach (antrum), secretes gastrin
What are the major cells of the stomach, where they are located and what they secrete:
Up to down: Parietal cells - IF, HCl Chief cells - Pepsinogen G cells - Gastrin (to circulation), stimulates HCl release if pH is low Mucus cells - Mucus, HCO3-, pepsinogen
How is HCl made?
What does the amount produced depend on?
- by parietal cells at the canaliculi (lots of MT and ATP for secretion of the acid)
- amount of HCl made depends on the number of parietal cell
What is exchanged on the luminal (apical) and basolateral (blood) in the stomach and what are the respective transporters?
Be able to draw the image on the slide
Lumen:
Out (lumen/secreted); H, Cl
In (cell): K
Transporter: K/H exchanger, Cl channels
Blood:
In (cell): Cl
Out (blood/absorbed): HCO3- (alkaline tide)
Transporter: HCO3/HCl pump, Na/K ATPase
What is omeprazole and what does it do?
-inhibits the gastric K/H exchanger resulting in decreased gastric secretions (used to treat GERD patients)
What is the difference between non-parietal and parietal gastric secretions?
Non parietal (basal/blood side) - alkaline Parietal: (gastric lumen side) - hyperosmotic, increased by food presence
What are the stimulators of H+ secretion to gastric lumen?
What are the inhibitors of H+ secretion to gastric lumen?
How is this regulated?
Be able to draw the schematic on the slide
- Ach, Gastrin, Histamine
- Somatostatin, Prostaglandins
-Negative feedback by secreted H+/low pH on simulators
What is the direct vagal pathway of stimulating HCl release?
What is the indirect vagal pathway of stimulating HCl release?
- Ach to M3 on parietal cells > Ach > release H+
- Distension of pylorus + GRP to G cells > Gastrin in circulation > parietal cells > release H+
Which vagal pathway will Atropine inhibit?
-Direct, since its a mAchR antagonist. Indirect is done via GRP and gastrin signaling
How is gastrin regulated?
Draw the schematic on the slide
- Inhibited by somatostatin (when pH is low)
- activated by CN X release of GRP to activate G cell and CN X release of Ach to inhibit somatostatin
What does potentiation mean and what are major examples?
-targeting a substance, is indirectly targeting other substances
- if Cimetidine (H2 antagonist) blocks Histamine action, it also blocks Ach/and gastrin (and vice versa if stimulating)
- if Atropine blocks Ach action, it also blocks histamine and gastrin (and vice versa if stimulating)
Draw the cephalic phase of gastric acid secretion
Ok
Draw the Gastric phase of gastric acid secretion
Ok
What exogenous substance will stimulate the gastric phase of gastric acid secretion?
Coffee, stimulates HCl secretion
Draw the Intestine phase of gastric acid secretion
Ok
Which gastric secretion phase does vagotomy abolish?
Cephalic
What is required for pepsinogen secretion?
Be able to draw the pathway for pepsinogen release
low pH so it can be converted to pepsin
What are the characteristics of pepsin?
pH ranges of activity?
-proteolytic, converts more pepsinogen to pepsin once present
-optimal pH is 1.8 - 3.5,
reversibly inactivated > 3.5 -5
irreversible inactivated >7-8
What is the importance of Intrinsic factor?
What is IF deficiency associated with?
- important for B12 absorption in the ileum
- achlorydria or reduced/absent parietal cells that make it
Draw the pathway of B12 absorption
Ok
What is pernicious anemia?
What are the common causes?
-not enough IF, thus not enough B12 for RBC maturation
atrophic gastritis (chronic inflammation of mucosa leading to loss of parietal cells) Autoimmune metaplastic atrophic gastritis (immune system attacks IF protein or gastric parietal cells)
How does gastrectomy or gastric bypass disrupt B12 absorption?
-both mess up the stomach anatomy > lose cells that are critical to B12 absorption
How is the gastric wall protected from acidic secretions?
-Gastric epithelium secretes HCO3- (from surface epithelial cells) and mucus (from mucous cells) to form protective barrier
What substances damage the gastric wall?
acid, pepsin, NSAIDs, H. pylori, smoking, alcohol, bile, stress
Zollinger Ellison syndrome
Cause
Clinical
- increased gastrin usually due to gastrinoma (increased Hcl secretion, parietal cell mass), water and Na not reabsorbed = secretory diarrhea
- ulcer as HCO3- buffer is overwhelmed with acid, malabsorption of lipids = steatorrhea
What is a secretin stimulation test and what is it used for?
- secretin inhibits gastrin
- pt’s with gastrinoma have gastrin secreting tumors that don’t respond to secretin so gastrin levels are still elevated despite injection of secretin
Peptic ulcer disease
Cause:
Clinical:
- H. pylori and NSAIDs leading to mucosa damage and/or excessive H+ and pepsin
- gastric and duodenal ulcers
What is the role of H. Pylori in development of peptic ulcer disease?
Urease breaks down urea to NH3 + H+ > NH4+ = alkalanized gastric mucosa allowing H. pylori to colonize it = damage
What is the difference between gastric and duodenal ulcers?
Gastric ulcer - in the stomach, likely due to mucosa damage
Characterized by: low H+ secretion since the cells that produce them are damaged, high Gastrin to try and stimulate H+ release
Duodenal ulcer: small intestine, likely due to increased H+ secretion causing damage
What is the composition of pancreatic juice?
HCO3- for acid neutralization of stomach secretions
How is the exocrine pancreas sympathetically innervated?
How is the exocrine pancreas pancreas parasympathetically innervated?
SNS: via celiac and superior mesenteric plexus > exocrine pancreas > inhibit secretion
PNS: Vagus > ENS > Exocrine pancreas > stimulate secretion
What is the function of these parts in the exocrine pancreas
Acinar cells
Ductal cells
- enzymatic secretion (active amylase and lipase, inactive protease and converted in duodenum)
- secrete HCO3- aqueous solution to alkalinize the acinar secretions > pancreatic secretion is isotonic
What is exchanged on the luminal (apical) and basolateral (blood) in the pancreatic ducts and what are the respective transporters?
Be able to draw the image on the slide
Luminal:
In (cell): Cl
Out (lumen/secreted): HCO3-
Transporter: HCO3/Cl exchanger, CTFR
Blood:
In (cell): Na
Out (blood/absorbed): H+
Transporter: Na/H transporter, Na/K ATPase (balancer)
How does cystic fibrosis affect the pancreas?
CTFR channel that replenishes Cl in the lumen to exchange for HCO3- is mutated = no HCO3- secretion = acidic lumen = enzymes are activated there = pancreatitis
What are the roles of …
CCK
Secretin
… on pancreatic secretion?
- increases pancreatic enzyme release at the acinus
- increases HCO3- release from pancreas into duodenum
How does Phe, Met, Trp, small peptides and FA stimulate pancreatic enzyme release?
Be able to draw this pathway
Phe, Met, Trp, small peptides and FA > I cells > CCK > acinar cells (via IP2) > enzyme release
*Acinar cell action potentiated by Ach
How does H+ stimulate aqueous secretion of Na and HCO3- by the pancreas?
Be able to draw this pathway
H+ > S cells > secretin > ductal cells (via cAMP) > aqueous secretion
*ductal cell action potentiated by Ach, CCK
