Gastric Physiology Flashcards
(183 cards)
1
Q
Functions of the stomach
A
Store and mix food
Dissolve and continue digestion
Regulate emptying into duodenum
Kill microbes
Secrete proteases
Secrete intrinsic factor
Activate proteases
Lubrication
Mucosal protection
2
Q
Key cell types in a stomach
A
Mucous cells
Parietal cells
Chief cells
Enteroendocrine cells
3
Q
Gastric acid secretion
A
Hydrochloric acid by parietal cells
Energy dependent
Neurohumoural regulation
4
Q
Approximate production of HCl per day
A
2 litres/day
5
Q
[H+] of gastric acid secretion
A
[H+] > 150mM
6
Q
Cephalic phase stimulation
A
Parasympathetic nervous system- vagus nerve
Sight, smell, taste of food and chewing
7
Q
Cephalic phase net effect
A
Increased acid production
8
Q
Cephalic phase mechanism
A
Acetylcholine release
ACh acts directly on parietal cells
ACh triggers release of gastrin and histamine
9
Q
Purpose of intrinsic factor
A
Binds to vitamin B12
Aids absorption in terminal ileum
Moderated by same regulators of gastric acid secretion
10
Q
Gastric phase net effect
A
Increased acid production
11
Q
Gastric phase mechanism
A
Activates chemoreceptors to stimulate G cells
Gastrin release
Gastrin acts directly on parietal cells
Gastrin triggers release of histamine
Histamine acts directly on parietal cells
12
Q
Gastric phase stimulation
A
Gastric distension
Presence of peptides and amino acids
13
Q
Histamine in gastric acid secretion
A
Acts directly on parietal cells
Also mediates effects of gastrin and acetylcholine
14
Q
Gastric acid secretion
A
water (H2O) and carbon dioxide (CO2) combine within the parietal cell cytoplasm to produce carbonic acid (H2CO3), which is catalysed by carbonic anhydrase. Carbonic acid then spontaneously dissociates into a hydrogen ion (H+) and a bicarbonate ion (HCO3–).
The hydrogen ion that is formed is transported into the stomach lumen via the H+– K+ ATPase ion pump. This pump uses ATP as an energy source to exchange potassium ions into the parietal cells of the stomach with H+ ions.
The bicarbonate ion is transported out of the cell into the blood via a transporter protein called anion exchanger which transports the bicarbonate ion out the cell in exchange for a chloride ion (Cl–). This chloride ion is then transported into the stomach lumen via a chloride channel.
This results in both hydrogen and chloride ions being present within the stomach lumen. Their opposing charges leads to them associating with each other to form hydrochloric acid (HCl).
15
Q
Which nerve is stimulated in cephalic phase
A
Vagus nerve
16
Q
Gastric distension
A
Acts on stomach stretch receptors
Stimulates local and vagovagal reflexes
17
Q
Protein in the stomach
A
Direct stimulus for gastrin release
Proteins in the lumen act as a buffer, mopping up H+ ions, causing pH to rise
18
Q
Effect of rise in pH of gastric acid
A
Decreased secretion of somatostatin
More parietal cell activity (lack of inhibition)
19
Q
Inhibitin of cephalic phase
A
Lack of vagal stimulation
Result of decreased appetite and depression
20
Q
Inhibition of gastric phase
A
Low luminal pH (high [H+])
- directly inhibits gastrin secretion
- indirectly inhibits histamine release via gastrin
- stimulates somatostatin release which inhibits parietal cell activity
Negative feedback loop
21
Q
Causes of inhibition of gastric phase
A
Excessive acidity
No food in the stomach to buffer
Reduce parietal cell activity by reducing channel expression
Emotional distress: sympathetic overrides parasympathetic stimulation
22
Q
Intestinal phase of gastric acid secretion
A
Chyme in duodenum
23
Q
Inhibition of gastric secretion by intestinal phase stimulation
A
Duodenal distension
Low luminal pH
Hypertonic luminal contents
Presence of amino acids and fatty acids
24
Q
Inhibition of gastric secretion by intestinal phase mechanism
A
Triggers release of entergastrones
- secretin
- Cholecystokinin
And short and long neural pathways, reducing ACh release
25
Secretin
Inhibitis gastrin release
Promotes somatostatin release
26
Stimulation of intestinal phase
Low pH
Partially digested food present
Release of intestinal gastrin
Overall effect = increased acid secretion
27
4 chemicals that regulate gastric acid secretion by second messengers
Gastrin
Acetylcholine
Histamine
Somatostatin - inhibition
28
Regulation of gastric acid secretion overview
Controlled by brain, stomach, duodenum
1 (parasympathetic) neurotransmitter (ACh +)
1 hormone (gastrin +)
2 paracrine factors (histamine +, somatostatin -)
2 key enterogastrones (secretin -, CCK -)
29
Peptic ulcers
An ulcer is a breach in a mucosal surface
Caused by action of gastric acid
30
Causes of peptic ulcers
Helicobacter pylori infection
Drugs - NSAIDS
Chemical irritants- alcohol, bile salts, dietary factors
Gastrinoma
31
How does the gastric mucosa defend itself
Alkaline mucus- bicarbonate-rich
Tight junctions between epithelial cells
Replacement of damaged cells
Feedback loops
32
Helicobacter pylori lives in…
Lives in gastric mucus
33
Helicobacter pylori mechanism
Secretes urease, splitting urea into CO2 and ammonia
Ammonia + H+ = ammonium
Ammonium, secreted proteases, phospholipases and vacuolating cytotoxic A damage gastric epithelium
Inflammatory response
Reduced mucosal defence
34
Where do peptic ulcers occur
Stomach, duodenum, oesophagus
35
NSAIDs examples
Aspirin
Ibuprofen
36
NSAIDs
Non-steroidal anti-inflammatory drugs
Mucus secretion is stimulated by prostaglandin
Cyclo-oxygenase 1 needed for prostaglandin synthesis
NSAIDs inhibit cyclo-oxygenase 1
Reduced mucosal defence
37
Peptic ulcers- bile salts
Duodeno-gastric reflux
Regurgitated bile strips away mucus layer
Reduced mucosal defence
38
Treating peptic ulcer disease- Helicobacter pylori
Eradicate the organism
Triple therapy:
1 Proton pump inhibitor
2 Antibiotics eg clarithromycin, amoxicillin, tetracycline, metronidazole
39
Treating peptic ulcer disease- NSAIDs
Prostaglandin analogues - misoprostol
Reduce acid secretion
40
Proton pump inhibitors in parietal cells
Omeprazole
Lansoprazole
Esmeprazole
41
H2 receptor (histamine) antagonists in parietal cells
Cimetidine
Ranitidine
42
What produces pepsinogen
Chief cells
43
Zymogen
Pepsinogen- Inactive form of pepsin
Synthesised by chief cells
44
What mediates pepsinogen
Input from enteric nervous system (ACh)
45
Protease secretion
Secretion parallels HCl secretion
Luminal activation
46
Protease activation
Conversion of pepsinogen to pepsin is pH dependent
Most efficient when pH<2
Positive feedback loop - pepsin also catalyses the reaction
Pepsin only active at low pH- irreversible inactivation in small intestine by HCO3 -
47
A 27 year old man presents to his General Practitioner with a three week history of worsening epigastric pain. The pain is made worse in between meals, and is relieved by antacids. The GP suspects the patient has a peptic ulcer.
Which of the following is a neurotransmitter that up-regulates the secretion of gastric acid by parietal cells?.
Acetylcholine
48
The GP prescribes the patient a drug that increases gastric mucus production. Which drug has this action?
Misoprostol
49
Which of the following is a hormone that increases gastric acid secretion by parietal cells?
Gastrin
50
Passage of chyme into the duodenum triggers a reduction in gastric acid secretion. Which of the following duodenal factors triggers the release of enterogastrones?
Presence of luminal fatty acids
51
Which of the following is an enterogastrone that causes gastric parietal cells to downregulate gastric acid secretion?
Cholecystokinin
52
To activators of pepsin activation
Low pH (HCl)
Pepsin- positive feedback loop
53
Role of pepsin in protein digestion
Not essential
Accelerates protein digestion
Normally accounts for 20% of total protein digestion
Breaks down collagen in meat - helps shred meat into smaller pieces with greater surface area for digestion
54
Gastric motility- volume of empty stomach
50mL
55
Total volume of food stomach can accommodate
1.5L with little increase in luminal pressure
Due to receptive relaxation of smooth muscle in body and fundus
56
Receptive relaxation of stomach
Mediated by parasympathetic nervous system on enteric nerve plexuses
57
Coordination of receptive relaxation
Afferent input via vagus nerve
58
What mediates receptive relaxation
Nitric oxide and serotonin released by enteric nerves
59
Peristalsis - body of stomach
Peristaltic waves begin in gastric body
Weak contraction in body (little mixing)
60
Peristalsis- gastric antrum and pylorus
More powerful contraction in gastric antrum
Pylorus closes as peristaltic wave reaches it
61
Peristalsis - retroperistalsis
Little chyme enters duodenum
Antral contents forced back towards body (mixing)
62
Pace of basic electrical rhythm of peristalsis
3/minute
63
What determines frequency of peristaltic waves
Pacemaker cells in muscularis propria
Pacemaker cells undergo slow depolarisation- repolarisation cycles
Depolarisation waves transmitted through gao junctions to adjacent smooth muscle cells
Do not cause significant contraction in empty stomach
64
Strength of peristaltic contractions varies
Excitatory neurotransmitters and hormones further depolarise membranes
Action potentials generated when threshold reached
65
Interstitial cells of Cajal
Pacemaker cells of the stomach in muscularis propria
66
Strength of peristaltic contractions increased by:
Gastrin
Gastric distension mediated by mechanoreceptors
67
Strength of peristaltic contractions decreased by:
Duodenal distension
Increased duodenal luminal fat
Increased duodenal osmolarity
Decreased duodenal luminal pH
Increased sympathetic NS action
Decreased parasympathetic NS action
68
Gastric emptying
Capacity of stomach > capacity of duodenum
69
Dumping syndrome
Overfilling of duodenum by a hypertonic solutiom
70
Dumping syndrome signs and symptoms
Vomiting
Bloating
Cramps
Diarrhoea
Dizziness
Fatigue
Weakness
Sweating
71
Gastroparesis
Delayed gastric emptying
72
Causes of gastroparesis
Idiopathic
Autonomic neuropathies (e.g. in Diabetes mellitus)
Drugs
Abdominal surgery
Parkinson’s disease
Multiple sclerosis
Scleroderma
Amyloidosis
Female gender
73
Gastrointestinal agents- gastroparesis
Aluminium hydroxide antacids
H2 receptor antagonists
Proton pump inhibitors
Sucralfate
74
Anticholinergic medications- gastroparesis
Diphenhydramine (Benadryl)
Opioid analgesics
Tricyclic antidepressants
75
Miscellaneous drugs- gastroparesis
Beta-adrenergic receptor agonists
Calcium channel blockers
Interferon alpha
Levodopa
76
Mechanisms to prevent duodenal overfilling
1. Increased acidity/fat/amino acids, hypertonicity and distension
2. Increased secretion of enterogastrones AND stimulate neural receptors
3. Decreased gastric emptying:
- increased plasma enterogastrones
- short neural reflexes via enteric neurons act on stomach directly
- long neural reflexes increases sympathetic efferents and decreases parasympathetic efferents
77
Signs and symptoms of delayed gastric emptying
Nausea
Early satiety
Vomiting undigested food
GORD
Abdominal pain and bloating
Anorexia
78
Gastric motility and emptying regulated by
Same factors that regulate HCl production
79
Which of the following cells secretes pepsin?
No cells
80
What cells produce intrinsic factor
Parietal cells
81
A 74 year old man has his stomach removed to treat a stomach cancer. He worries that he will not be able to digest food after the operation. What proportion of protein digestion normally takes place in the stomach?
20%
82
Which cells in the stomach act as pacemakers, regulating the rhythm of gastric peristalsis?
Interstitial cells of Cajal
83
Which of the following will lead to a decrease in the strength of gastric peristaltic contractions?
Increased sympathetic stimulation
84
What is cholecystokinin responsible for
Contraction of the gallbladder and release of stored bile into the duodenum
(Released in response to fatty acids in chyme)
85
Why do proteins act as a buffer
They are negatively charged so can accept H+
86
A 23 year old patient complains of stomach pains after taking a Non-steroidal anti-inflammatory analgesic (NSAID).
How do NSAIDs irritate the stomach?
inhibition of gastrointestinal mucosal cyclo-oxygenase (COX) activity
NSAIDs inhibit COX-1 and COX-2 (COX = cyclo-oxygenase).
COX-2 is the target enzyme and blockade of this will inhibit production of inflammatory and nociceptive-enhancing prostaglandins.
Inhibition of COX-1 will prevent production of gastro-protective prostaglandins.
87
The parietal cells within the stomach produce Intrinsic factor.
What is the function of Intrinsic Factor?
Intrinsic Factor is a glycoprotein produced by the parietal cells of the stomach and is essential for the absorption of Vit B12.
It binds with Vit B12 and forms a complex that resists digestion by gastric enzymes.
The Vit B12 complex then passes through the stomach where it absorbed in the terminal ileum, transported to the liver and stored.
88
The stomach contains a variety of cell types.
Which of these substances is secreted by G cells?
Gastrin
89
The porta hepatis forms part of the liver.
Which of the following structures is NOT present in the Porta Hepatis?
Hepatic vein
Porta hepatis is a fissure on the underside of the liver. It has several structures running through it, the hepatic artery proper, portal vein, hepatic bile duct, Vagus nerve branches, sympathetics and lymphatics.
90
The stomach contains a variety of cell types.
Which of these substances is secreted by Chief cells?
Pepsinogen
91
The proton pump is part of the parietal cell.
What is the function of the proton pump with regard to ion exchange across the cell membrane?
K+ into cell, H+ out of cell
92
Which of the following statements is correct regarding the function of the Vagus nerve and its action on parietal cells?
Vagus nerve is part of the parasympathetic system and releases acetylcholine onto parietal cells
93
The stomach contains a variety of cell types.
Which of these substances is secreted by D cells?
Somatostatin
94
Omeprazole is routinely prescribed for acid reflux.
What is the mechanism of action of Omeprazole on the GI tract?
Inhibition of Proton Pump to reduce acid secretion
95
Regarding the embryology of the GI tract.
Which of the following structures is classified in embryology as part of the ‘foregut’?
Pancreas, Gallbladder, proximal 2 parts of the duodenum and the lower third of the oesophagus
96
You are trying to design a drug to act on histamine receptors on parietal cells to help patients with reflux disease.
What would be the mechanism of this drug?
Inhibits Histamine 2 receptors to reduce acid secretion
97
The digestive tract has a rich blood supply.
Which of the following vessels supplies arterial blood to the Jejunum?
Superior mesenteric artery
98
The stomach contains a variety of cell types.
Which of these substances is secreted by Enterochromaffin-like (ECL) Cells
Histamine
99
A 40 year old has been diagnosed with gallstones, one of which is in the common bile duct.
Where does the Common Bile Duct drain into?
Duodenum
100
The stomach contracts to aid mixing of the ingested food.
How many layers of muscle are present in the stomach wall?
3
Longitudinal
Circular
Oblique
101
Digestion of the different dietary components occurs in different parts of the GI tract.
What is the first location that fat is acted upon by Lipase enzymes when passing through the GI tract?
Oral cavity
102
A 56 year old man has a long standing history of gastro-oesophageal reflux.
What is the change in cell-type (‘metaplasia’) seen in the lower oesophagus after prolonged reflux of acid?
Stratified squamous to columnar
103
Function of D cells
Release somatostatin
104
Function of G cells
Release gastrin, HCl
105
Function of enterochromaffin-like cells
Release histamine
106
Function of chief cells
Produce pepsinogen
107
Function of parietal cells
Produce gastric acid and intrinsic factor
108
Function of mucous cells
produce mucous at entrance to gland
Forms a barrier between the gastric acid and gastric mucosa
Rich in HCO3 - (bicarbonate)
109
Stimulation of Cephalic phase
Vagus
110
Stimulation of gastric phase
Local nervous secretory reflexes
Vagal reflexes
Gastrin-histamine stimulation
111
Stimulation of intestinal phase
Nervous mechanisms
Hormonal mechanisms
112
Luminal secretion of lower oesophageal sphincter and stomach cardia
Mucus
HCO3 -
113
Luminal secretion of Fundus and body of stomach
H+
Intrinsic factor
Mucus
HCO3 -
Pepsinogens
Lipase
114
Luminal secretion of antrum and pylorus of stomach
Mucus
HCO3 -
115
Motility of lower oesophageal sphincter and cardia of stomach
Prevention of reflux
Entry of food
Regulating of belching
116
Motility of Fundus and body of stomach
Reservoir
Tonic force during emptying
117
Motility of antrum and pylorus of stomach
Mixing
Grinding
Sieving
Regulation of emptying
118
Function of gastric acid
Activates pepsin
Kills bacteria
119
Function of intrinsic factor
Complexes with vitamin B12 to permit absorption
120
Function of histamine
Stimulate gastric acid secretion
121
Function of somatostatin
Inhibits gastric acid secretion
122
APUD cells
Amine precursor uptake decarboxylation cells
Dispersed amongst epithelial cells
123
Superficial to deep order of cells in stomach lining
Mucus neck cells
Parietal cells
Enterochromaffin-like cells
Chief cells
D cells
G cells
124
What neurotransmitter activates parietal and chief cells to initiate receptive relaxation
ACh
125
Inhibition of Cephalic phase
Lack of vagal stimulation
Result of decreased appetite and depression
126
Cephalic phase direct effect
On parietal cells
Increases channel expression
127
Cephalic phase indirect phase
On G cells and ECL cells
Increase release of gastrin and histamine which act on parietal cells to increase the number of H/K ATPase on the apical membrane
128
Why do proteins and amino acids stimulate an increase in gastrin
Molecules act as a buffer for H+ therefore pH rises
129
Inhibition of gastric phase
Excessive acidity inhibits gastrin secretion and increases somatostatin secretion
Can occur when there is no food in the stomach to buffer
Reduce parietal cell activity by reducing channel expression
Emotional distress
130
Parasympathetic neurotransmitter stomach physiology
ACh
131
Hormone stomach physiology
Gastrin
132
Paracrine stomach physiology
Histamine
Somatostatin
133
Enterogastrins stomach physiology
Secretion
Cholecystokinin (CCK)
134
Stimulation of intestinal phase
Low pH
Partially digested food present
Release of intestinal gastrin
135
Inhibition of intestinal phase
Duodenal distention
Hypertonic solutions
Presence of amino acids and fatty acids
Leads to entero-gastric reflex
Release of intestinal hormones
Secretin inhibits gastrin release and promotes somatostatin release
136
Function of secretin
Inhibits gastrin release
Promotes somatostatin release
137
Stomach lining damage- chemical irritants
Alcohol and bile salts
Duodenal-gastric reflux- bile enters the stomach
Alkaline bile strips away gastric mucosal layer resulting in reduced defence
138
Zollinger-Ellison Syndrome/ gastrinoma
Rare tumour of G cells
Excessive gastrin release
Increased attack on the gastric mucosa leading to ulcers
139
Duodenal absorption occurs by
Simple diffusion
Facilitated diffusion
Active transport
Endocytosis
Paracellular transport
140
Small intestine digestion
In lumen by secreted enzymes
Cell surface of enterocytes by membrane bound enzymes
141
3 ways that peptides modulate GI tract function
Endocrine
Paracrine
Neurocrine
142
Which cells release secretin
Duodenal S cells
143
Primary effects of secretin
Increasing secretion of:
Bile from the liver and gall bladder
Secretion of HCO3- and enzymes from the oancreas
144
Secondary effects of secretin
Reducing gastric motility
Reducing gastric secretory rates
145
Primary effects of Gastric inhibitory peptide (GIP)
Inhibits gastric activity
Increases insulin release
146
Secondary effects of Gastric inhibitory peptide (GIP)
Stimulating duodenal gland activity
Stimulating lipase synthesis
Increasing glucose use by skeletal muscle
147
Which cells release cholecystokinin
I cells in duodenum, Jejunum and less so from the ileum
148
Pancreatic effects of cholecystokinin
Accelerates release of enzymes
Increases HCO3- secretions
149
Liver and gallbladder effects of cholecystokinin
Sphincter of Oddi relaxation
Gallbladder contraction
Increasing secretions
150
High CCK levels
Inhibit gastric activity
Feeds to CNS to reduce sensation of hunger
151
Vasoactive intestinal peptide
Stimulated the secretion of intestinal glands
Dilates regional capillaries
Inhibits acid production in the stomach
Dilation of capillaries allows more efficient absorption
152
Direct causes of release of duodenal regulators
Nervous input from the brain or luminal contents eg acid
153
Indirect causes of release of duodenal regulators
Distention of the gut
Release of another hormone
154
Negative feedback loop in duodenal digestion
Acid activates D cells which release somatostatin and this acts to reduce the further release of acid
Inhibits G cells production of gastrin
Inhibits enterchromaffin-like cells release of histamine
Directly inhibits the release of acid from parietal cells
Stops the chief cells production of pepsinogen
155
Which hormone inhibits gastrin
GIP
156
What is mainly responsible for gastric-inhibitory peptide (GIP) secretion
Presence of glucose in duodenum
157
What cells are found at the bottom of the Crypt of Lieberkuhn in intestinal mucosa
Proliferating stem cells
158
What causes Zollinger-Ellison syndrome
A gastrin secreting tumour- leading to excessive gastric acid secretion
159
Which hormone delays gastric emptying to prevent unabsorbed nutrients entering the lower ileum
Gastric inhibitory peptide
160
What reduces gastric acid production
Somatostatin
Enterogastric reflex
Cholecystokinin
Secretin
161
What effect does initiation of the Cephalic phase have on gastric secretion
Directly: chief cells and parietal cells
Indirectly: G cells
162
Where are S cells found
Mainly in duodenum and partially in Jejunum
163
What stimulates gastric acid release
Gastrin
Acetylcholine
Enterochromaffin-like cells (secrete histamine)
164
Which neurotransmitters cause contraction of smooth muscle above a food bolus during peristalsis
Acetylcholine and substance P
165
During vagal stimulation of G cells, which neurotransmitter triggers release of gastrin from G cells
Gastrin releasing peptide
166
What are the main functions of motilin
Increases gastrointestinal motility
Promotes gastric emptying
167
Which hormone is produced in excess in Zollinger-Ellison syndrome
Gastrin
168
How is procolipase activated
By trypsin in the small intestine
169
Where are glucagon-like peptide-1 and glucagon-like peptide-2 hormones released from
Enteroendocrine L cells in the ileum and colon
170
Risk factors of GORD
Pregnancy
Hiatus hernia
Smoking and alcohol
Stress and anxiety
171
Histological change associated with GORD
Barrett’s oesophagus
Stratified squamous —> simple columnar
172
Forms of mucosal defence
Alkaline secretions
Tight junctions
Rapid cell replacement
Feedback loop for gastric acid secretion
173
Where is vitamin b12 absorbed and how
Terminal ileum bound to intrinsic factor
174
Function of vitamin b12
DNA synthesis
Brain development
Erythrocytes formation
175
Macroscopic differences between small and large bowel
Smaller / larger
Longitudinal muscle layer is continuous/ not continuous but is 3 muscles called tense coli
No appendices epiploe/has
Wall smooth/sacculated (haustrations)
Villi/no villi
176
A 22 year old medical student develops profuse watery diarrhoea whilst on his elective in Bangladesh. Although he is drinking approximately 2 litres of fluid per day, he is passing 8-10 litres of liquid stools per day. He sees a doctor, who diagnoses cholera infection. Which part of the gastrointestinal tract normally absorbs the most fluid?
Jejunum
177
A dietician is prescribing total parenteral nutrition for a severely malnourished patient. Which of the following vitamins is fat-soluble?
Biotin
Folic acid
Retinol
Riboflavin
Niacin
Retinol
178
What nutrients are absorbed in the stomach
Water
Copper
Iodide
Fluoride
179
What nutrients are absorbed in the duodenum
Iron
Fat-soluble vitamins
Calcium
Magnesium
180
What nutrients are absorbed in the Jejunum
Thiamine
Riboflavin
Calcium
Phosphorus
Iron
181
What nutrients are absorbed in the ileum
Vitamin C
Vitamin B12
Votamin D
Folate
Vitamin K
182
What nutrients are absorbed in the colon
Water
Vitamin K
Biotin
Sodium
Chloride
Potassium
183
Which vitamin can only be found in meat products
Vitamins B12
