Secretions of GI Tract and Pancreas Flashcards
1
Q
Rate of salivary secretion
A
1L/day
2
Q
Define secretion
A
addition of fluids, enzymes, mucus to lumen of GI tract
-saliva, gastric secretion, pancreatic secretion, bile
3
Q
Fxn of saliva
A
- initial digestion of starches and lipids by salivary enzymes
- dilution and buffering of ingested foods
- lubrication of ingested food with mucus to aid in movement through esophagus
4
Q
3 salivary glands
A
parotid
submaxillary
sublingual
5
Q
cells of parotid gland
A
serous that secrete aqueous fluid with amylase
25% saliva production
6
Q
cells of sublingual and submaxillary glands
A
serous that secrete aqueous fluid, mucous that secrete mucin glycoprotein for lubrication
75% saliva production
7
Q
Describe the structure of salivary glands
A
Acinar- blind end that produces inital saliva (water, ions, enzymes, mucus)
Intercalated duct connects acinar to striated duct and ductal cells (saliva here similar to plasma)
Striated duct has ductal cells that alter the ion concentration–> final saliva is HYPOTONIC
Myoepithelial calls line entire gland, contract and expel saliva through gland when + by neural input
8
Q
What is the composition of saliva
A
water, electrolytes, alpha amylase, lingual lipase, kallikrein, mucus
9
Q
What are the electrolyte concentrations in saliva
A
hypotonic to plasma
–> high K+ and HCO3-
–> low Na+ and Cl-
10
Q
How does primary saliva become hypotonic as it travels through the salivary gland?
A
Acinar cells secrete isotonic saliva, travels to ductal cells where exchange ions to make saliva hypotonic
—> net absorption of NaCl back into plasma
11
Q
Besides electrolyte concentration, how do ductal cells maintain salivary hypotonicity?
A
Ductal cells are impermeable to water
——-> as NaCl absorbed back into plasma, water can’t follow, so it stays in the duct and dilutes saliva
12
Q
What exchangers are on the apical side of ductal cells?
A
Na+/H+ exchanger
Cl-/HCO3- exchanger
H+/K+ exchanger
13
Q
What exchangers are on the basolateral side of ductal cells?
A
Na+/K+ ATPase
Cl- channels
14
Q
What innervates salivary glands?
A
Parasympathetic: facial or glossopharyngeal–> ganglia–> ACh on muscarinic receptors (acinar and ductal)–> produce IP3 and Ca+
Sympathetic: T1-3–>cervial ganglion–> release NE on B adrenergic receptors (acinar and ductal)–> produce cAMP
both increase saliva secretion
15
Q
Why are innervations to salivary glands special?
A
Both parasympathetic and sympathetic systems are excitatory—> stimulation produces saliva
para is dominant, though
Salivary glands exclusively under ANS control (not neural and hormonal like GI)
16
Q
What stimulates parasympathetics in saliva production?
A
conditioning: food, smell, N
17
Q
What inhibits parasympathetics in saliva production?
A
fear, sleep, dehydration
18
Q
What occurs when salivary glands are stimulated by ANS?
A
Increased saliva secretion, HCO3- and enzyme secretions, contraction of myoepithelial cells
19
Q
How do aldosterone and ADH alter saliva?
A
Decrease saliva Na+ concentrations, increase K+ concentrations
20
Q
How does Atropine affect saliva production?
A
Prevents parasympathetic pathway–> inhibits production of saliva
—————> prevents ACh from binding muscarinic receptors on acinar or ductal cells
21
Q
What secretes gastric juice
A
gastric mucosa cells
22
Q
What are the components of gastric juice
A
HCl, pepsinogen, water, mucus, intrinsic factor
23
Q
What is the only “essential” component of gastric juice
A
Intrinsic factor, how Vitamin B12 is absorbed in ileum
24
Q
Fxn of mucus in gastric juice
A
- lines stomach to protect from damage
- lubrication
- combines with HCO3- to neutralize acid and maintain neutral pH at mucosa
25
Fxn of HCl in gastric juice
- initiates protein digestion with pepsinogen
- required to convert pepsinogen to active pepsin
- kills large number of bacteria that enter stomach
26
What glands are found in the gastric mucosa?
Oxyntic glands and Pyloric glands
27
What do parietal cells of stomach produce?
HCl and intrinsic factor
28
What do chief cells of stomach produce?
Pepsinogen
29
What do G cells of stomach produce?
Gastrin into circulation (not ducts)
30
What do mucous neck cells secrete?
mucus, HCO3-, pepsinogen
31
Where are oxyntic glands found?
proximal 80% of stomach (body and fundus)
secrete acid
32
Where are pyloric glands found?
distal 20% of stomach (antrum)
synthesize and release gastrin
33
What cells are in oxyntic glands?
```
Mucous neck cells--> mucus, HCO3-, pepsinogen
Chief cell--> pepsinogen
Parietal cells--> HCl, intrinsic factor
Enterochromaffin-like cell-->Histamine
D cell--> somatostatin
Enterochromaffin cell--> ANP
```
34
What cells are in pyloric glands?
Mucous neck cells--> mucus, HCO3-, pepsinogen
G cell-->gastrin
D cell-->somatostatin
35
What majority of cells are in the body of the stomach?
Parietal, chief
36
What majority of cells are in the antrum of the stomach?
Mucous, G cell
37
What determines the maximal secretory rate of HCl?
number of parietal cells
38
What is the function of low gastric pH (1-2)
convert pepsinogen to pepsin
39
Where is HCl formed?
villus-like membranes of canaliculi of parietal cells
40
Overview of HCl formation/secretion in gastric parietal cell
CO2 from aerobic metabolism combines with water--> H2CO3 via CARBONIC ANHYDRASE
--> dissociates into H+ and HCO3-
--> H+ goes out into lumen and combines with Cl-->HCl
-->bicarbonate absorbed in blood
41
What exchangers are on the apical (lumen) side of gastric parietal cells?
H+/K+ ATPase (to get H+ into lumen)
Cl- channels
42
What drug inhibits the H+/K+ ATPase on the apical side of parietal cells?
Omeprazole
43
What is the function of omeprazole
Reduce H+ secretion, treat stomach ulcers
44
What exchangers are found on the basolateral (blood) side of gastric parietal cells?
Cl-/HCO3- exchanger (to absorb bicarb into blood)
----> alkaline tide (high pH after meal)
Na+/K+ ATPase
45
What is the net absorption/secretion at gastric parietal cells?
Net secretion of HCl
| Net absorption of HCO3-
46
What secretions make up gastric juice?
Non-parietal and parietal secretions
47
Why do you need to know the composition of gastric juice?
required to treat patients with vomiting or maintained with IV
48
Describe non-parietal secretions
- basal alkaline of constant and low volume
- primarily Na+, Cl---> K+ same concentration as in plasma
- HCO3- secreted at 30 mEq/L
49
Describe parietal secretions
- hyperosmotic
- Cl- only anion
- H+ (150-160 mEq)
- K+ (10-20 mEq)
as secretion rate increases, electrolyte concentration appreaches that of pure parietal secretion
50
Describe passive feedback regulating HCl secretion
as pH falls, gastrin release is inhibited--> decreases HCl secretion
51
What stimulate H+ secretion by gastric parietal cells?
histamine, ACh, gastrin
52
What receptors does Cimetidine block?
H2 receptors, blocks histamine action
53
What parietal cell receptor does histamine bind to?
H2 receptor
54
What parietal cell receptor does ACh bind to directly?
M3 receptor
55
Describe direct ACh action on parietal cells
M3 receptor-->Gq---> IP3 and Ca++--> H+/K+ ATPase--> increase H+ secretion
56
Describe histamine action on parietal cells
H2--> Gs--> cAMP--> increase H+ secretion via H+/K+ ATPase
57
What receptor does atropine inhibit?
M3 receptor and ACh action
58
How does ACh and gastrin increase H+ secretion indirectly?
stimulate release of histamine
59
What parietal cell receptor does gastrin bind?
CCKb receptor
60
Describe action of gastrin on parietal cells
IN CIRCULATION--> CCKb receptor-->Gq--> IP3 and Ca++--> gastrin secretion from G cells and H+/K+ ATPase--> H+ secretion
61
Describe direct vagal stimulation of parietal cells
releases ACh on parietal cells--> H+ secretion
62
Describe indirect vagal stimulation of parietal cells
releases GRP to + G cells--> releases gastrin --> circulation--> acts on parietal cells to secrete H+ (via IP3, Ca++ pathway= same as ACh)
---> indirect pathway also INHIBITS somatostatin so it can't prevent gastrin release
63
What vagal pathway does atropine block?
Direct pathway (ACh)
64
Why does atropine not block indirect vagal pathway?
it won't affect neurotransmitter GRP that activates gastrin release from G cells
--------> only affects M3 receptor activated by ACh
65
How does somatostatin begin working again after indirect vagal stimulation of parietal cells?
Indirect vagal inhibits somatostatin
--> gastrin itself has negative feedback on somatostatin, so it increases somatostatin release along with H+ in gastric lumen
66
Describe HCl potentiation
Histamine potentiates actions of ACh and gastrin
ACh potentiates actions of histamine and gastrin
67
Define potentiation
sum of 2 stimulants exceeds the sum of their individual responses
-----> requires separate receptors on target cell
68
How does cimetidine affect HCl potentiation?
Since it is an antagonist of H2 receptor, it blocks DIRECT action of histamine and POTENTIATION effects of ACh and gastrin
69
How does atropine affect HCl potentiation?
since it is an antagonist of M3, it blocks DIRECT effects of ACh and POTENTIATION effects of histamine and gastrin
70
What is cimetidine used to treat?
duodenal and gastric ulcers, GERD
71
What is omeprazole used to treat?
ulcers via reduced H+ secretion
72
What are the 3 phases of gastric HCl secretion?
Cephalic
Gastric
Intestinal
73
What controls cephalic phase of gastric HCl secretion?
Vagus N
74
What controls gastric phase of HCl secretion?
- Local nervous secretory reflexes
- Vagal reflexes
- Gastrin-histamine stimulation
75
What controls intestinal phase of HCl secretion?
Nervous mechanisms
| Hormonal mechanisms
76
What HCl secretion phase does a vagotomy abolish?
cephalic phase
77
What stimuli activate the cephalic phase?
smelling, tasting, chewing, swallowing, conditioned reflexes
78
What phase accounts for 30% of total HCl secretion in response to a meal?
cephalic phase
79
What are the mechanisms behind the cephalic phase?
Vagus nerve releases ACh on parietal cells
Vagus nerve releases GRP-->gastrin--> circulation--> parietal cell
BOTH direct and indirect vagal mechanisms
80
What phase accounts for 60% of total HCl secretion in response to a meal?
Gastric phase
81
What stimuli activate the gastric phase?
distension of stomach, presence of breakdown of proteins, AA and small peptides
82
What are the mechanisms of the gastric phase?
- Distension + mechanoreceptors in mucosa of oxyntic and pyloric glands
- --> vagus nerve releases ACh on parietal cell
- ---> vagus nerve releases gastrin--circulation--parietal cell
- Distension of antrum
- ---> local reflexes release ACh on parietal and G cells (GASTRIN)
- Amino acids and small peptides
- -----> activate GASTRIN--circulation--parietal cell and chief cell (pepsin)
83
What food/drink can also stimulate gastric HCl secretion?
coffee
| alcohol
84
What phase accounts for 5-10% of total HCl secreted in response to a meal?
Intestinal phase
85
What are the mechanisms behind the intestinal phase?
Distention of small intestine + acid secretion
Digested protein + acid secretion via DIRECT effect on parietal cells and GASTRIN on parietal cells
86
What stimulus activate the intestinal phase?
products of protein digestion
87
When is pepsinogen secreted?
Only when gastric pH is acidic enough to convert it to pepsin (<5)
88
What secretes pepsinogen?
chief cells and mucus cells in oxyntic glands
| ------> needs H+ secretion from parietal cells to lower pH in stomach
89
What is the most important stimulus for pepsinogen secretion?
Vagus N
90
What role does H+ play in pepsinogen secretion?
triggers local cholinergic reflexes--> stimulate chief cells to secrete pepsinogen
91
What allows more conversion of pepsinogen to pepsin?
Pepsin
92
What is the fxn of pepsin?
converts more pepsinogen to pepsin
degrades food proteins into peptides
93
What is the optimal pH for pepsin?
1.8-3.5
94
What pH makes irreversible inactivation of pepsin?
over 7-8
-->reversible if between 3.5 and 5
95
Where is intrinsic factor synthesized?
parietal cells
96
What is the fxn of intrinsic factor?
binds to vitamin B12 for absorption in ileum
97
What is the only secretion required in the stomach?
intrinsic factor
98
What is associated with failure to secrete intrinsic factor?
achlorhydria, absence of parietal cells
99
What occurs when stomach does not produce enough intrinsic factor?
decreased absorption of vitamin B12
100
What occurs when there is a failure to secrete intrinsic factor?
pernicious anemia
101
Causes of pernicious anemia
atrophic gastritis (chronic inflammation of stomach mucosa--> loss of parietal cells)
autoimmune metaplastic atrophic gastritis (immune system attacks intrinsic factor protein or gastric parietal cells)
102
What is a consequence of gastrectomy?
loss of parietal cells, therefore instrinsic factor
103
What occurs with a gastric bypass
exclusion of the stomach, duodenum and proximal jejunum---> alters absorption of vitamin B12
104
What is the fxn of the gastric mucosal barrier?
protect mucosal epithelium against HCl and pepsin
105
What is the gastric mucosal barrier composed of?
HCO3- (surface epithelial cells)
Mucus (mucous cells)
Both form gel-like barrier over gastric mucosa
106
What protects the gastric mucosa?
- HCO3-
- mucus
- prostaglandins (misoprostol)
- mucosal blood flow
- gastrin
- growth factors
107
What damages the gastric mucosa?
- acid
- pepsin
- NSAIDs
- Helicobacter pylori
- alcohol
- bile
- stress
- smoking
108
Describe Zollinger-Ellison syndrome
large secretion of gastrin by duodenal or pancreatic gastrinomas
- --> increases parietal cell mass
- --> H+ secretory rate high
**** inhibits absorption of Na+ and H20 by SI= secretory diarrhea
109
How do you get an ulcer with Zollinger-Ellison syndrome?
excessive H+ arrives in duodenum and overwhelmes capacity of HCO3- in pancreatic juice
110
Describe the consequences of low intestinal pH in Zollinger-Ellison syndrome
- inactivation of pancreatic digestive enzymes
- interferes with emulsification of fat via bile acid
- damages intestinal epithelial cells and villi
- leads to maldigestion and malabsorption--> steatorrhea
111
Describe the secretin stimulation test
Injection of secritin causes paradoxical increase in gastrin release in gastrinomas
--> secretin used to dx gastrin-secreting tumors given the fact that it inhibits gastrin release normally
112
Mechanical causes of Peptic ulcer disease
H. pylori infection and NSAIDs
113
Functional causes of peptic ulcer disease
- loss of protective mucosal barrier
- excessive H+ and pepsin secretions
OR combination
114
What are the types of peptic ulcer disease?
duodenal ulcers
gastric ulcers
115
How does H pylori damage the gastric mucosa?
H pylori releases cytotoxins that breakdown mucosal barrier and damage the underlying epithelial cells
116
What enzyme allows bacteria (H pylori) to colonize gastric mucosa?
urease
117
What is the major cause of cytotoxicity in ulcer disease?
Ammonium
urease converts urea--> ammonia--> ammonium (damages epithelial cells after breaks barrier)
118
Why do gastric ulcers form?
defective gastric mucosal barrier--> form ulcers that line stomach
119
Why do duodenal ulcers form?
more common than gastric due to high H+ secretion rates
-->usually not malignant
120
What ulcesr have increased gastrin levels?
- gastric ulcer due to decreased H+ secretion
- duodenal ulcer due to gastrin response to ingestion of food
- zollinger-ellison syndrome (way higher gastrin c/t others)
121
What ulcer has increased parietal cell mass due to increased gastrin levels?
duodenal ulcer
122
What sympathetics innervate the exocrine pancreas?
postganglionic nerves via celiac and superior mesenteric plexuses
123
What is the exocrine pancreas organized like?
salivary glands
124
What cells of the exocrine pancreas secrete aqueous solution containing HCO3-?
ductal and centroacinar cells
125
What are the two components of pancreatic secretions?
- enzymatic secretion by acinar cells
- ------> amylases and lipases
- ------> proteases secreted in inactive form, converted to active in lumen of DUODENUM
- aqueous secretion by centroacinar and ductal cells
- ---------> secrete HCO3- rich fluid (alkalinizes and hydrates acinar cell)
- ----------> initial secretion modified by transport processes in ductal epithelial cells
126
What is the net result of pancreatic secretions by ductal cells?
Secretion of HCO3- into ductal lumen
Absorption of H+ into blood
127
Cystic fibrosis and the pancreas
mutations in transmembrane conductance regulator (CFTR)
128
What organ is the first to fail in cystic fibrosis?
pancreas
129
What is the function of CFTR in cystic fibrosis
regulated Cl- channel in the apical surface of ductal cell
130
What is associated with CFTR mutations?
loss of HCO3- secretion, chronic or acute pancreatitis
131
What phases are pancreatic secretions divided into?
cephalic
gastric
intestinal
132
What is the different between gastric and pancreatic phases?
pancreas secretes mainly enzymatic secretions (aqueous in intestinal)
****intestinal is majority of secretion
133
What induces pancreatic enzyme release into duodenal lumen?
CCK
134
What induces secretion of HCO3- from pancreatic cells into duodenum?
Secretin
135
What stimulates pancreatic intestinal phase?
Phe, Met, Trp, small peptides, fatty acids
--> I cells--> CCK--> IP3 and Ca++--> enzyme release
H+--> S cells--> Secretin--> cAMP--> aqueous secretion (Na+, HCO3-)
136
What potentiates the pancreatic intestinal phase?
ACh and CCK
