Secretions of the GI tract and pancreas Flashcards
What are the functions of saliva?
- initial digestions of starches and lipids
- dilution of food
- lubrication with mucus for swallowing
What are the 3 major salivary glands?
- parotid glands
- submaxillary/submandibular glands
- sublingual glands
What are the parotid glands?
25% of salivary output, serous cells
What are submaxillary/submandibular glands?
mixed glands with serous and mucous cells
secrete fluid and mucin glycoprotein
-secrete ~75% of the daily output of saliva
What are serous cells?
secrete fluid of water, ions, and enzymes
What are mucous cells?
mucin glycoprotein
What are sublingual glands?
mixed glands with serous and mucous cells
secrete fluid and mucin glycoproteins
What is saliva?
- water
- electrolytes
- alpha amylase (ptyalin)
- lingual lipase
- kallikrein
- immunological molecules
- mucus
What enzymes help saliva lubricate and begin digestion?
amylase and lipase
Is saliva hypertonic, isotonic, or hypotonic compared to plasma?
hypotonic
What are the ions in saliva compared with plasma?
higher levels of K+ and HCO3-
lower levels of Na+ and Cl-
What are the parts of the salivary gland?
- acinus (blind end)
- myoepithelial cells
- intercalated duct
- striated duct
What is the acinus?
- blind end
- acinar cells secrete initial saliva
What are contractile/myoepithelial cells?
- have motile extensions
- when stimulated by neural input, contract to eject saliva into the mouth
What is the intercalated duct/short segment?
-saliva in the intercalated duct is similar in ionic composition to plasma
What is the striated duct?
- lined by columnar epithelial cells (ductal cells)
- ductal cells modify the initial saliva to produce the final saliva (hypotonic)
- ductal cells alter the concentration of various electrolytes
How is saliva made?
- formation of isotonic, plasma-like solution by acinar cells
- modification of the isotonic solution by the ductal cells
How is the original plasma-like solution from acinar cells modified to become the final saliva?
- absorption of Na+ and Cl-
- secretion of K+ and HCO3-
- net absorption of solute
- because ductal cells are impermeable to water and not absorbed with the solute the solution can become hypotonic
What are the transport mechanisms on the luminal/apical side of the salivary ductal cell?
Na+ in /H+ out exchange
Cl- in/HCO3- out exchange
H+ in/K+ out exchange
What are the transport mechanisms on the basolateral side of the salivary ductal cell?
Na+ out/K+ in (ATPase)
Cl- channel (out)
HCO3-/Na+ symporter (in)
What are the parasympathetic nerves for salivary glands?
- parasympathetic (dominate)
- originate in facial and glossopharyngeal nerves
- postsynaptic fibers in autonomic ganglia innervate individual glands
What are the sympathetic nerves for salivary glands?
- originate from T1-T3 and superior cervical ganglion
- postsynaptic nerve fibers extend to glands via periarterial spaces
Do parasympathetic or sympathetic nerves dominate in salivary gland innervation?
parasympathetics
Do parasympathetics or sympathetics increase salivary secretions?
BOTH
How do ADH and aldosterone modify the composition of salvia?
decrease its Na+ concentration and increase K+ concentration
What does stimulation of salivary cells result in?
- increased saliva production
- HCO3- and enzyme secretions
- contraction of myoepithelial cells
What do parasympathetics stimulate in the acinar or ductal cell?
CN VII and CN IX –> ACh
–> mAChR increases IP3, Ca2+
What do sympathetic nerves stimulate in the acinar or ductal cells?
T1-T3 –> NE –> beta AR increases cAMP
Salivary is exclusively under the control of the ___
ANS
What are the main components of gastric juice?
- HCl
- pepsinogen
- mucus
- intrinsic factor
- H2O
HCl
- what cells produce it (location)
- function
- produced from parietal cells (body)
- converts pepsinogen to pepsin to initiate protein digestion together
- kills bacteria
Pepsinogen
- what cells produce it (location)
- function
- Chief cells (body)
- inactive precursor to pepsin
Gastrin
- what cells produce it (location)
- function
- G cells (antrum)
- into circulation
Mucus
-function
- lines the wall of the stomach and protects it from damage
- lubricant
- together with HCO3- it neutralizes acid and maintains the surface of the mucosa at neutral pH
Intrinsic factor
- what cells produce it (location)
- function
- parietal cells (body)
- vitamin B12 absorption in ileum
What do parietal cells secrete?
intrinsic factor and HCl
What do chief cells secrete?
pepsinogen
What do mucous cells secrete?
mucus
pepsinogen
What do G cells secrete?
gastrin
What do mucous cells secrete?
mucus
H2O
-function in gastric juice
- medium for the action of HCl and enzymes
- solubilizes much of the ingested material
What is the gastric mucosa divided into?
oxyntic gland area and pyloric gland area
What is the oxynic gland area?
- located in the proximal 80% of the stomach (body and fundus)
- parietal cells - secretes acid
- D cells, mucous cells, ECF cells, chief cells (zymogenic cells or peptic cells)
What do D cells secrete?
somatostatin
What do ECF cells secrete?
histamine
What is the pyloric gland area?
- located in the distal 20% of the stomach (antrum)
- G cells - synthesizes and releases gastrin
- D cells, mucous cells, ECF cells
parietal cells
- function
- what forms the secretion
- secrete HCl to convert pepsinogen to pepsin
- HCl formed in villus-like membranes of canaliculi
What is the gastric pH?
1-2
lowered by HCl to convert pepsinogen to pepsin
What determines the maximal secretory rate of HCl?
of parietal cells
What is the net result of cellular mechanisms in the parietal cell?
secretion of HCl and absorption of HCO3- “alkaline tide”
What does omeprazole do?
blocks K+/H+ exchange on luminal side of parietal cells. inhibits the acid secretion.
What is the main reaction in gastric parietal cells catalyzed by?
carbonic anhydrase
Describe non-parietal gastric juice
- basal alkaline secretion of constant and low volume
- its primary constituents are Na+ and Cl-; K+ is present at the same concentration as plasma
- HCO3- is secreted at a concentration of ~30 mEq/L
Describe parietal gastric secretion
- slightly hyperosmotic
- contains 150-160 mEq H+/L and 10-20 mEq K+/L
- Cl- is the only anion
- as secretion rate increases, concentrations of electrolytes begin to approach those of pure parietal cell secretion
What does pepsinogen require?
HCl secretion from parietal cells to be converted to pepsin
What is a proteolytic enzyme?
an enzyme that converts more of itself = pepsin converts more pepsinogen to pepsin
What is the optimal pH for pepsin?
pH that pepsin is reversibly inactivated?
pH that pepsin is irreversibly inactivated?
optimal: 1.8-3.5
reversibly inactivated: >5
irreversibly inactivated: 7-8
What stimulates pepsinogen secretion?
- mainly vagus N
- H+ triggers local cholinergic reflexes that stimulate chief cells to secrete pepsinogen
What is the role of the vagus nerve on HCl secretion from parietal cells?
direct pathway: vagus N –> ACh can be blocked by atropine –> parietal cells –> HCl
indirect pathway: vagus N –> GRP –> G cells –> gastrin –> circulation –> parietal cells –> HCl
vagus N–> AChcan be blocked by atropine–> G cells –> gastrin –> circulation –> parietal cells –> HCl
What are the steps for HCl secretion from parietal cells?
- Na+ actively transported (reabsorbed) into cytoplasm
- negative charge (-40 to -70 mv) on canaliculus side
- Na+ and K+ diffuse into canaliculus
- H2O dissociates into OH- and H+ inside parietal cell
- H+ secreted into canaliculus in exchange for K+ (H+/K+ ATPase)
- Cl- is actively transported into canaliculus
- Water enters the canaliculus via osmosis
- CO2 reacts with OH- in cytoplasm to form HCO3- which is secreted into the ECF (alkaline tide)
Describe the regulation of gastrin release by somatostatin
- somatostatin acts on G cells to inhibit gastrin release
- vagal activation stimulates gastrin release by releasing GRP and inhibiting the release of somatostatin
- negative feedback regulation by gastrin (from gastrin increasing somatostatin)
- H+ in the gastric lumen stimulates release of somastatin
Describe regulation of gastrin release by ECL cells
- release histamine –> H2 receptors –> increases acid secretion
- gastrin increases acid secretion directly and potentiates ECL release of histamine
- ACh increases acid secretion directly and potentiates ECL release of histamine
- somatostatin and prostaglandings inhibit acid secretion directly and indirectly by inhibiting ECL cells
What are ECL cells activated and inhibited by?
activated by gastrin and ACh from vagus N
inhibited by somatostatin and prostaglandins
What is potentiation?
combined response to two stimulants exceeds the sum of their individual responses
-requires the presence of separate receptors on the target cell for each stimulant
What does histamine potentiate?
What does ACh potentiate?
- histamine: ACh and gastrin
- ACh: histamine and gastrin
What do H2 receptor antagonists do?
cimetidine blocks the direct action of histamine and also blocks potentiated effects of ACh and gastrin
What do mAChR anatagonists do?
atropine blocks the direct effects of ACh and the ACh potentiated effects of histamine and gastrin
What is cimetidine used to treat?
antagonist of H2 receptors
- duodenal and gastric ulcers
- gastroesophageal reflux disease
How does the vagus N influence HCl secretion?
- release ACh which directly increases acid secretion via M3 receptors
- indirectly stimulates acid secretion by activating ECL cells to release histamine
- indirectly activatees acid secretion via GRP activating gastrin release
How do G cells influence HCl secretion?
- gastrin activates CCKB receptors to stimulate acid secretion
- gastrin also stimulates ECL cells to release histamine
- gastrin stimulates release of somatostatin
How do D cells influence HCl secretion?
- gastrin release activates somatostatin release
- inhibits acid secretion directly
- somatostatin indirectly inhibits acid secretion by inhibiting gastrin release and histamine release
What are the 3 phases of gastric HCl secretion?
- cephalic phase via vagus
- gastric phase via local nervous secretory reflexes, vagal reflexes, and gastrin-histamine stimulation
- intestinal phase via nervous mechanisms and hormonal mechanism
What stimulates and inhibits gastrin release?
stimulated by vagus N and GRP
inhibited by somatostatin
NEGATIVE FEEDBACK - gastrin increases somatostatin secretion
cephalic phase of gastric secretion
- what %
- stimuli
- mechanism
- 30% of total HCl secretion
- stimuli: smell, taste, chewing, swallowing, conditioned reflexes
- mechanisms: vagus N stimulation of parietal cells by ACh (direct), vagus N stimulation of gastrin secretion followed by stimulation of parietal cells by gastrin (indirect) from GRP
What can abolish the cephalic phase?
vagotomy
gastric phase of gastric secretion
- what %
- stimuli
- mechanism
60% of total HCl secretions
stimuli: distension of stomach; presence of products of protein breakdown - amino acids and small peptides
- mechanisms:
1. distention (mechanoreceptors in mucosa of oxyntic and pyloric glands activate both direct and indirect vagus N stimulation of parietal cells
2. distention of antrum: local reflex stimulates gastrin release
3. amino acid and small peptides stimulate gastrin release
intestinal phase of gastric secretion
- what %
- stimuli
- mechanism
10% of total HCl secretions
- stimuli: distension of SI; presence of digested protein
mechanisms:
1. digestion of SI -stimulates acid secretion (enteric NS mediated)
2. digested protein - intestinal G cells released gastrin (hormonal mediated)
How does SI inhibit acid secretion?
- reverse enterogastric reflex: distention of small intestine, presence of products of protein digesetion, acid, irritation
- release of hormones (secretin, GIP, VIP, and somastatin)
Intrinsic factor is required for ____ absorption in ileum
vitamin B12
How is vitamin B12 absorbed?
- needs intrinsic factor: mucoprotein secreted by parietal cells
- binds directly to vitamin B12
- only secretion by stomach that is essential
What happens if intrinsic factor is not secreted?
pernicious anemia - atrophic gastritis
How much B12 is stored in the liver?
enough to last several years
What is the function of gastric mucosa?
-cells involved
- secrete HCO3- and mucus
- forms tight layer of protection against HCl and pepsin
- cells:
1. mucous neck cells - mucus
2. gastric epithelial cells - HCO3-
What are protective factors that influence gastric mucosa?
- HCO3- and mucus
- prostaglandins
- blood flow
- gastrin
- growth factors
What are damaging factors that influence gastric mucosa?
- acid
- pepsin
- NSAIDs/aspirin
- H pylori
- alcohol
- bile
- stress
What are the predominant causes of peptic ulcer disease in the US?
- H pylori
- NSAIDs
Peptic ulcer disease could be the result of ____
- loss of protective mucosal barrier
- excessive H+ and pepsin secretions
- combination of both
What are the 2 types of peptic ulcer disease?
- gastric ulcer
- duodenal ulcer
Gastric ulcers
- why do they form
- major cause
- enzyme
- result
- acid secretion
- gastrin levels
- mucosal barrier is defective
- H pylori is a major causative agent
- enzyme urease allows bacteria to colonize: converts urea to NH3 - alkalinizing agent
- release cytotoxins - breakdown of mucosal barrier and underlying cells
- low acid secretion
- high gastrin levels
Duodenal ulcers
- acid secretion rate
- other influence
- inhibits what?
- gastrin level
- H+ secretion rate is a little higher than normal
- H pylori has indirect influence
- inhibits somatostatin secretion from D cells
- gastric H pylori infection spreads to duodenum and inhibits HCO3 secretion
- high gastrin level in response to ingestion of food
Which is more common: gastric ulcers or duodenal ulcers?
duodenal ulcers
Zollinger-Ellison syndrome
- H+ secretion
- gastrin secretion
- H+ secretory rates highest
- tumor (often in pancreas) secretes large amounts of gastrin
- increased H+ by parietal cells
- trophic effect on parietal cells
- excessive delivery of H+ to duodenum -acidified duodenum despite HCO3-
- inactivation of pancreatic lipases due to suboptimal pH
- treatment: cimetidine, omeprazole, surgery
What are common causes of pernicious anemia?
- atrophic gastritis - chronic inflammation of the stomach mucosa that leads to loss of parietal cells
- autoimmune metaplastic atrophic gastritis - immune system attacks IF protein or gastric parietal cells
What are symptoms of Zollinger-Ellison syndrome?
- diarrhea
- N/V
- peptic ulcer disease
- increased resting gastrin level
- weight loss
- epigastric pain
- GERD
- hematemesis
- hematochezia
- melena
- ulcers in unusual location such as the proximal jejunum
What is teh test to confirm Zollinger-Ellison syndrome?
secretin stimulation test
- secretin administration normally inhibits gastrin release
- in gastrinomas, injection of secretin causes a paradoxical increase in gastrin release
What are pancreas secretions?
- HCO3- to neutralize H+ from stomach
2. enzyme secretions to digest CHO, protein, lipids
Describe the organization of pancreatic glands
acinus - acinar cells secrete enzymes
ducts - ductal epithelial cells; connects to acinus by centroacinar cells: secrete aqueous solution with HCO3-
Describe enzymatic secretions (acinar cells) of the exocrine pancreas
- pancreatic amylases and lipases - active enzymes
- pancreatic proteases - secreted as inactive molecules, that are converted in lumen of duodenum to active forms
- trypsin inhibitor helps keep trypsin inactive
Describe aqueous secretion (centroacinar and ductal cells) of the exocrine pancreas
- initial isotonic solution with Na+, K+, Cl-, and HCO3-
- modified as passes through ductal regions
What is the net reaction of pancreatic ductal cells?
secretion of HCO3- and absorption of H+
- CO2 diffuses into ductal cells, CA forms H2CO3 which dissociates to HCO3- and H+
- HCO3- exchanged into lumen for Cl-
- H+ exchanged for Na+ on basolateral side, Na+ secreted into lumen
- water into lumen
What is the relationship between CFTR mutations and pancreas secretion
- regulated Cl- channel on apical surface of ductal cells
- pancreas fails early in CF
- some CFTR mutations associated with loss of HCO3- secretion –> acute and chronic pancreatitis
What are the phases of pancreatic secretion?
- cephalic
- gastric
- intestinal
cephalic phase of pancreatic secretion
- %
- initiated by
- produces
10-15%
- initiated via vagus N by smell, taste, and conditioning
- produces mainly enzymatic secretions
gastric phase of pancreatic secretion
- %
- initiated by
- produces
5-10%
- initiated via vagus N by distention of stomach
- produces enzymatic secretions
intestinal phase of pancreatic secretion
- %
- driven by
- stimulates
80%
- driven by secretin
- stimulates enzymatic and aqueous secretion
Describe innervation of the pancreas
- sympathetic -postganglionic nerves from celiac and superior mesenteric plexuses: inhibitory
- parasympathetic - vagus N: stimulatory; preganglionic fibers synapse in ENS; postganglionic fibers synapse on exocrine pancreas
Describe hormonal pancreatic secretions
- cells of duodenum that secrete CCK and secretin
- secretin: secreted by S cells as prosecretin and converted to secretin in response to pH < 5.0 in duodenum
- CCK: secreted by I cells in response to fats and protein digestion byproducts in duodenum and jejunum
secretions of SI
- mucous glands secrete mucus from Brunner’s glands
- mucus is alkaline and helps neutralize and protect duodenum
- crypts of Lieberkhuhn contain goblet cells and enterocytes
- enterocytes secrete almost pure ECF and have brush border enzymes (not secreted) — intestinal lipase and lactose
secretions of LI
-crypts of lieberkhum - mucus secretions only
