Lecture 16/17: Secretions of the GI Tract and Pancreas Flashcards
Factors that increase salivary secretions
PNS (d/t conditioning, food, nausea)
SNS
Factors that decrease salivary secretions
Inhbition of PNS (d/t sleep, dehydration, fear, and anticholinergic drugs)
Inhibition of SNS
Factors that increase gastric secretions
Vagal stimulation via ACh
Gastrin
Histamine
Factors that decrease gastric secretions
Negative feedback mechanisms inhibit secretion of H+ by parietal cells
[low pH, somatostatin, prostaglandins]
Factors that increase pancreatic secretions
Secretin
CCK
ACh (via vagovagal reflexes)
Factors that decrease pancreatic secretions
Cystic fibrosis
3 major salivary glands and type of secretions
Parotid = serous (water, ions, enzymes)
Submandibular = mixed serous and mucous (fluid, mucin glycoprotein)
Sublingual = mixed serous and mucous (fluid, mucin glycoprotein)
2 major enzymes of saliva
Alpha amylase
Lingual lipase
Structural elements of saliva glands include acinus, striated ducts, contractile elements, and short segments. What are their functions?
Acinus (acinar cells) = produce initial saliva
Striated duct (ductal cells) = modify saliva to produce final hypotonic product
Contractile (myoepithelial cells) = contract to eject saliva based on neuron input
Short segment = intercalated ducts
Primary secretion product of saliva is hypotonic, containing ptyalin (amylase), mucus, and ECF. What changes occur throughout the fine-tuning process to create this hypotonic product?
Na+ active absorption
Cl- passive absorption
K+ active secretion
HCO3- secretion
Saliva is not just an ultrafiltrate of plasma. What are its components?
Water Electrolytes Alpha-amylase (ptyalin) Lingual lipase Kallikrein Mucous
What is the purpose of kallikrein in saliva?
Helps make bradykinin —> vasodilation
Saliva is hypotonic compared to plasma, with higher levels of ____ and _____, and lower levels of _____ and ______
K+; HCO3-
Na+; Cl-
Which channels are present on the luminal vs. basolateral side of salivary ductal cells?
Luminal:
Na+/H+ exchanger
Cl-/HCO3- exchanger
H+/K+ exchanger
Basolateral:
Na/K ATPase
Cl Channels
HCO3/Na exchanger
The overall effect of saliva formation is _______ of Na and Cl (lower compared to plasma), and _______ of K and HCO3 (higher compared to plasma)
Absorption
Secretion
Why is there net absorption of solute during formation of saliva?
Because ductal cells are impermeable to water, so water remains in lumen and saliva becomes hypotonic
What is unique about autonomic control of salivary glands?
Both parasympathetic and sympathetic systems increase salivary secretions (usually these oppose each other)
Note that parasympathetic is dominant
Autonomic control of salivary glands via PNS originates in ____ and ____ nerves, which synapse at _______ receptors with ____ NT
Autonomic control of salivary glands via SNS originates from _____ and ________. Postsynaptic fibers extend to glands via periarterial spaces and synapse at ______ receptors with ___ NT
Facial; glossopharyngeal; muscarinic; ACh
T1-T3; superior cervical ganglion; b-adrenergic; NE
Major components of gastric secretions
HCl Pepsinogen IF Mucus Water
Location and secreton of parietal cells
Body of stomach; HCl and intrinsic factor
Location and secretion of chief cells
Body of stomach; pepsinogen
Location and secretion of G cells
Pyloric antrum; gastrin
Location and secretion of mucous cells
Primarily pyloric antrum (although they are everywhere); mucus, pepsinogen
Significance of IF contained in gastric secretions
Required for vitamin B12 absorption in the ileum
Gastric mucosal cells are basically located in which 2 types of glands? Which regions of the stomach are these found?
Oxyntic - primarily fundus and body
Pyloric - primarily antrum
_____ cells are the primary cell type in oxyntic glands of gastric mucosa. They secrete ______
Also found in oxyntic glands are D cells, mucous cells, ECF cells, and chief cells
Parietal; acid (HCl)
_____ cells are the primary cell type in pyloric glands of gastric mucosa. They secrete ______ which is released to _____
Also found in oxyntic glands are D cells, mucous cells, and ECF cells
G; gastrin; circulation
Within parietal cells, HCl is formed in canaliculi. it lowers the gastric pH to 1-2. HCl is responsible for converting _____ to ______. The more parietal cells present, the _____ the maximal secretory rate of HCl.
Result is a net secretion of HCl and absorption of _____
Pepsinogen; pepsin; Greater
HCO3
G cells secrete gastrin. They are stimulated by the _____ nerve, which can increase secretion of gastrin directly via _____ release or decrease secretion of gastrin indirectly via ______ release
Vagus; GRP; somatostatin
What effect does somatostatin have on G cells? What cells secrete somatostatin?
Somatostatin from D cells acts on G cells to inhibit gastrin release
What effect does gastrin have on somatostatin secretion?
Gastrin increases somatostatin secretion via negative feedback
[H+ in gastric lumen also stimulates somatostatin secretion]
Pepsinogen is secreted by _____ and by mucous cells in the _____ glands of the stomach
Its activation requires H+ secretion from ______ cells to lower the pH of gastric contents
Chief cells; oxyntic
Parietal
What is the most important stimulus for pepsinogen secretion from chief cells and mucous cells?
Vagus nerve stimulation
What effect does H+ secretion have on pepsinogen secretion?
H+ triggers local cholinergic reflexes that stimulate chief cells to secrete pepsinogen
What effect does Omeprazole have on HCl secretion from parietal cells? What is its MOA?
Inhibits the H/K-ATPase of parietal cells to reduce HCl secretion
Effect and MOA of Cimetidine medication
H2 receptor antagonist that treats GERD, duodenal, and gastric ulcers by reducing H+ secretion
[H2 receptor is what histamine acts on to increase H+ secretion via cAMP]
Vagus nerve stimulation resulting in ACh binding its muscarinic receptor on parietal cell would result in GPCR activation and _____ and ____ second messengers leading to _____ H+ secretion
IP3; Ca2+; increased
[gastrin acts at CCK-b receptor in the same way with same result]
Effects of somatostatin and prostaglandins on H+ secretion
Both decrease H+ secretion via Gi GPCR which inhibits cAMP
NSAID effect on H+ secretion
Since NSAIDs reduce prostaglandin production, which indirectly causes an increase in H+ secretion (since it is going uninhibited), may lead to damage to mucosal lining
Effect of atropine on HCl secretion
Atropine decreases H+ production by inhibiting communication between ACh and M3 receptor (PNS via vagus n)
How does the PNS indirectly influence parietal cells to secrete HCl?
By inducing gastrin release
GRP acts directly on G cells, distension acts on G cells via ACh
Potentiation involves the combined response of 2 stimulants that exceed their summed response; requires separate receptors for each stimulant
Examples include histamine and ACh, what do these signals potentiate?
Histamine potentiates ACh and gastrin responses
ACh potentiates actions of histamine and gastrin
Pharmacological implications of H2 receptor antagonists (e.g., cimetidine) — What do they block?
Direct action of histamine and potentiated effects of ACh and gastrin
Pharmacological implications of muscarinic receptor antagonists (e.g., atropine) — What do they block?
Direct action of ACh and potentiated effects of histamine and gastrin
What are the 3 phases of gastric HCl secretion
Cephalic
Gastric
Intestinal
The cephalic phase is responsible for 30% of total HCl secretion. What are the stimuli and mechanisms?
Stimuli = smell, taste, chewing, swallowing, and conditioned reflexes
Mechanisms = vagus nerve stim of parietal cells (direct); vagus nerve stimulation of gastrin secretion, followed by stimulation of parietal cells by gastrin (indirect)
What phase is responsible for the majority of gastric HCl secretion?
Gastric phase at 60%
Stimuli and mechanisms of gastric phase of gastric HCl secretion
Stimuli = distension, presence of protein breakdown products (amino acids and small peptides)
Mechanisms = distension activates both direct and indirect stimulation from vagus nerves on parietal cells, distension of antrum as a local pyloropyloric reflex, amino acids and small peptides stimulate gastrin release
The intestinal phase is responsible for 10% of total HCl secretions. What are the stimuli and mechanisms of the intestinal phase?
Stimuli = distension of small intestine; presence of digested protein
Mechanisms = distension of small intestine stimulates acid secretion, digested protein acts on intestinal G cells which then release gastrin
Gastric juice can be seen as a mixture of what 2 separate secretions?
Nonparietal = basal alkaline secretion of constant and low volume; primary constituents of Na and Cl, some K and HCO3
Parietal = slightly hyperosmotic, Cl is only anion present, as secretion rate is increased, concentration of electrolytes begins to approach those of pure parietal cell secretion
T/F it is important to understand the composition of gastric juice in the treatment of patients suffering ionic loss d/t vomiting
True
______ is required for vitamin B12 absorption in the ileum
Intrinsic factor
Intrinsic factor is a mucoprotein secreted by _____ cells and it binds directly to vitamin B12. Failure to secrete IF results in _________; however, the _____ stores enough vitamin B12 to last most individuals for several years
Parietal; pernicious anemia; liver
What does the gastric mucosa secrete to form a protective layer against HCl and pepsin? What cells are present?
HCO3 and mucous
Cells present = mucous neck cells secrete mucous and gastric epithelial cells secrete HCO3
Protective factors that influence gastric mucosa
HCO3 and mucous Prostaglandins Blood flow Gastrin Growth factors
Damaging factors that influence gastric mucosa
Acid Pepsin NSAIDs/aspirin H pylori Alcohol Bile Stress
Gastrinomas are commonly associated with what syndrome?
Zollinger-Ellison syndrome
A 55-year-old man is admitted to the hospital because of hematemesis. Measurement fasting serum gastrin levels show the to be 8-fold higher compared with a normal individual and an upper
gastrointestinal endoscopy shows multiple ulcers in the duodenum. A multiple endocrine neoplasia
type 1 (MEN 1) is suspected.
Administration of which of the following substances will most likely confirm the diagnosis?
A. CCK B. GIP C. Motilin D. Pentagastrin E. Secretin
E. Secretin
Why is secretin used in the dx of gastrinomas or other gastrin secreting tumors?
Under normal conditions, secretin administration inhibits gastrin release
In gastrinomas, injection of secretin causes a paradoxical increase in gastrin release
2 predominant causes of PUD in the US
H pylori and NSAID use
Peptic ulcer diseases could be the result of what conditions? What are the 2 types of PUDs?
Could be the result of:
- loss of protective mucosal barrier
- excessive H+ and pepsin secretions
- combination of the 2 above
2 types:
- gastric ulcers
- duodenal ulcers
Which type is more common - gastric or duodenal ulcers?
Duodenal
The major causative agent of gastric ulcers is H pylori. What is its MOA?
H. Pylori secretes urease which converts urea to NH3, an alkalinizing agent
Release of cytotoxins also causes mucosal breakdown
Describe formation of duodenal ulcers in terms of H+ production and the role of H pylori
H+ secretion rates are a little higher than normal
H pylori has an indirect influence (inhibits somatostatin secretion from D cells and spreads and inhibits HCO secretion)
In which of the following are H+ secretory rates the highest?
A. Gastric ulcers B. Duodenal ulcers C. Pancreatic ulcers D. Zollinger-Ellison syndrome E. None of the above
D. Zollinger-Ellison syndrome
With Zollinger-Ellison syndrome, a tumor often found in the ______ secretes large amounts of _______.
There is increased H+ secretion by _____ cells which has a _____ effect on those cells
Pancreas; gastrin
Parietal; trophic
[excess delivery of H+ to duodenum acidifies it despite HCO3; inactivation of pancreatic lipases due to suboptimal pH; tx options include cimetidine, omeprazole, and surgery]
2 main components of exocrine pancreatic secretions
- Aqueous solution with HCO3
2. Enzymatic secretion to digest CHO, proteins, and lipids
Organization of pancreatic glands
Acinus - acinar cells secrete enzymes
Ducts - ductal epithelial cells; connects to acinus by centroacinar cells. Secrete aquaous solution with HCO3
When saliva is secreted from ductal epithelial cells of salivary glands, it is hypotonic. How does this compare to secretions of secretions from ductal epithelial cells in the exocrine pancreas?
Secretions are isotonic
Enzymatic secretions from acinar cells in exocrine pancreas
Pancreatic amylases and lipases - active enzymes
Pancreatic proteases - inactive forms conerted in lumen of duodenum
The net reaction at the ductal cells of the pancreas includes secretion of HCO3, coupled with the exchange of ____. There is also a net absorption of _____
Cl; H
3 phases of pancreatic secretion
Cephalic
Gastric
Intestinal
Cephalic phase of pancreatic secretion initiated by _____ nerve by smell, taste, and conditioning
Produces mainly _______________
Vagus
Enzymatic secretions
Gastric phase of pancreatic secretion initiated by ____ nerve by distension of the stomach
Produces mainly ____________
Vagus; enzymatic secretions
Intestinal phase of pancreatic secretion is responsible for the majority of pancreatic secretion.
Produces _______
Enzymatic and aqueous secretions
Effect of sympathetic stimulation on pancreas
Inhibitory via postganglionic nn from celiac and superior mesenteric plexuses
Effect of parasympathetic stimulation of pancreas
Stimulatory via vagus nerve (preganglionic fibers synapse in ENS; postganglionic fibers synapse on exocrine pancreas)
Regulation of pancreatic secretion depends on cells of the duodenum that secrete CCK and secretin.
_____ cells secrete CCK
______ cells secrete secretin
I
S
In terms of regulating pancreatic secretion, phenylalanine, methionine, tryptophan, small peptides, and fatty acids stimulate I cells to produce ______, this along with the potentiation of ACh acts on acinar cells to initiate second messenger response of _______ to produce pancreatic enzymes
CCK; IP3; Ca++
In terms of regulating pancreatic secretion, H+ stimulates S cells to produce ______, which is potentiated by the action of ACh and CCK to act on ductal cells which then produce second messenger _______ to promote aqueous secretion with Na and HCO3
Secretin; cAMP
_____ = regulated Cl channel on apical surface of ductal cell in pancreas, thus the pancreas fails early in ____ ______
CFTR; cystic fibrosis
[some CFTR mutations are associated with loss of HCO3 secretion leading to acute and chronic bouts of pancreatitis]
A 39 y/o woman with a hx of hemiplegic migraines presented for evaluation of recurrent left sided submandibular swelling and pain that she first noticed 2 weeks ago. X ray reveals submandibular sialolithiasis. Patient reports taking topamax for migraines, which is a carbonic anhydrase inhibitor. How might usage of this drug contribute to the development of the salivary gland stone?
A. Reduced HCO3 secretion into salivary ducts
B. Reduced H+ secretion into salivary ducts
C. Increased Ca concentration in saliva
D. Increased pH of saliva
E. Reduced Cl secretion in saliva
A. Reduced HCO secretion into salivary ducts
Autoimmune destruction of which of the following cell types of the salivary glands would result in saliva remaining normotonic to plasma, rather than hypotoninc?
A. Acinar cells B. Ductal cells C. Myoepithelial cells D. Squamous epithelial cells E. Beta cells
B. Ductal cells
Blockade of which of the following receptor families would result in dry mouth?
A. Muscarinic and beta adrenergic B. Alpha adrenergic and nicotinic C. Beta adrenergic and nicotinic D. Muscarinic and alpha adrenergic E. Muscarinic only
A. Muscarinic and beta adrenergic
A 3 month old female infant born prematurely has been maintained on parenteral nutrition since a length of her bowel was resected secondary to necrotizing enterocolitis when she was 2 weeks old. The removed bowel included the ascending colon, ileum, and distal portion of jejunum. She’s unable to thrive on enteral feeding alone. After resection of the ileum, which specific vitamin will likely be malabsorbed?
A. Vitamin C B. Vitamin B12 C. Vitamin B3 D. Niacin E. Vitamin B6
B. Vitamin B12
GRP has additionally been described to play a role in tumor maintenance as it is secreted by many tumors and has angiogenic properties. Thus, GRP inhibitors have been used experimentally to inhibit GRP secretion from these tumors. Which of the following would be an expected side effect of the use of a GRP inhibitor should early experiments begin to move towards a clinical project?
A. Increased somatostatin secretion B. Activation of D cells of stomach C. Activation of parietal cells of stomach D. Decreased somatostatin secretion E. Increased gastrin release
D. Decreased somatostatin secretion
A physician makes the diagnosis of adenocarcinoma of the terminal duodenum and surgical resection of the entire duodenum is performed. An increase in which of the following is most likely seen in this patient compared to pre-op levels?
A. Absorption of lipids B. CCK secretion C. Gallbladder contraction D. Gastric acid secretion E. Secretin secretion
D. Gastric acid secretion
