Gastrointestinal system Flashcards
1
Q
What are the 6 main structures of the GI wall?
A
- Mucosal layer
- Submucosal layer
- Circular muscle layer
- Longitudinal muscle layer
- Serosa
- 2 plexuses
2
Q
What are the 2 main plexuses of the GI tract?
A
- Submucosal plexus
- Myenteric plexus
3
Q
Where is the submucosal plexus located?
A
Between the submucosa and the circular muscle layer
4
Q
Where is the myenteric plexus located?
A
Between the circular and longitudinal muscle layers
5
Q
What are the 3 elements of the mucosal layer?
A
- Epithelial cells
- Lamina propria
- Muscularis mucosae
6
Q
What is the lamina propria?
A
Thin layer of connective tissue in the mucosa also consisting of blood and lymph vessels
7
Q
What is the muscularis mucosae?
A
Layer of smooth muscle cells
8
Q
What are the 4 elements of the submucosal layer?
A
- Collagen
- Elastin
- Glands
- Blood vessels
9
Q
What is the function of elastin?
A
Expansion and recoil
10
Q
What is the difference between between the longitudinal and circular muscle layers?
A
Longitudinal layer is thinner and less densely innervated than the circular muscle layer
11
Q
What is the serosa?
A
Outer lining of the GI tract, sometimes has a mesothelium to reduce friction
12
Q
What does contraction of circular muscle cause?
A
Smaller diameter of GI tract
13
Q
What does contraction of longitudinal muscle cause?
A
Smaller segment lengths
14
Q
What is the ENS? (3)
A
- Enteric Nervous System
- Collection of nerve plexuses surrounding the GI tract
- Division of the autonomic nervous system (ANS) therefore involuntary
15
Q
What is the biliary system?
A
Liver and gall bladder (bile)
16
Q
What is the extrinsic control of the GI tract?
A
Parasympathetic and sympathetic innervation
17
Q
Which 2 parasympathetic nerves are involved in GI neural control?
A
- Vagus nerve
- Pelvic nerve
18
Q
What is the intrinsic control of the GI tract?
A
- The ENS itself, primarily via ganglia within the submucosal and myenteric plexuses
- The ENS can direct all function of the GI tract without extrinsic innervation
19
Q
How does the parasympathetic nervous system innervate the GI tract?
A
Parasympathetic ganglia relay information from PNS to smooth muscle, endocrine and secretory cells
20
Q
What kind of neurones are parasympathetic postganglionic neurones?
A
Cholinergic or peptidergic
21
Q
What do cholinergic neurones release?
A
Acetylcholine
22
Q
What do peptidergic neurones release?
A
Peptides e.g. substance P or VIP
23
Q
How does the sympathetic nervous system innervate the GI tract?
A
Afferent and efferent nerve fibres are mixed so information is relayed between the GI tract and the CNS which is coordinated by the plexuses
24
Q
What kind of neurones are sympathetic postganglionic neurones?
A
Adrinergic
25
What do adrinergic neurones release?
Norepinephrine
26
What are the 3 classes of GI signalling peptides?
- Hormones
- Paracrines
- Neurocrines
27
How do GI hormones act?
Released from GI endocrine cells and can travel to the liver via portal circulation and then re-enter systemic circulation in order to reach their target cell
28
What is an example of a GI hormone?
GIP (Gastric Inhibitory Polypeptide)
29
How do paracrines act?
Released from GI endocrine cells and act locally
30
What is an example of a GI paracrine?
Somatostatin
31
What does somatostatin do?
Inhibits the secretion of all GI hormones
32
How do neurocrines act?
Released from neurones following an action potential
33
What are some examples of neurocrines? (4)
- Nitric oxide
- GRP (Gastrin Releasing Peptide)
- Neuropeptide Y
- Substance P
34
What makes up the majority of the contractile tissue?
Unitary smooth muscle
35
What makes smooth muscle unitary?
Cells are electrically coupled via gap junctions which leads to coordinated contraction since APs can spread from cell to cell
36
What are the 2 types of contraction in the GI tract?
- Phasic
| - Tonic
37
What is phasic contraction?
- Periodic contraction and relaxations (3-12 per min)
| - Stomach has 3 contractions per minute (slowest)
38
What is tonic contraction?
Constant level of contraction (tone)
39
What are slow waves?
Periodic depolarisations and repolarisations which are subthreshold so don't cause an AP or contraction of the muscle
40
How does depolarisation occur in slow waves?
Influx of Ca2+
41
How does repolarisation occur in slow waves?
Efflux of K+
42
What is the purpose of slow waves?
- Cause weak tonic contractions
| - Phasic contractions occur at the depolarisation peaks (action potentials)
43
What is the GI pacemaker?
ICC (Interstitial Cells of Cajal)
44
What are the 6 sphincters in the GI tract?
- Upper Oesophageal Sphincter
- Lower Oesophageal Sphincter
- Pyloric sphincter
- Sphincter of Oddi
- Ileocecal sphincter
- Internal and external anal sphincters
45
What does the upper oesophageal sphincter separate?
Pharynx and oesophagus
46
What does the lower oesophageal sphincter separate?
Oesophagus and stomach
47
What does the pyloric sphincter separate
Stomach and duodenum
48
What does the sphincter of Oddi separate?
Stops fluid transit from the pancreas and gall bladder
49
What does the Ileocecal sphincter separate?
Ileum (SI) and cecum (LI)
50
What is mastication?
Chewing
51
What is a bolus?
Ball-like mixture of food and saliva which forms in the mouth while chewing
52
How many salivary glands are there?
3
53
Which nerves innervate mastication muscles?
Mandibular nerve of Cranial Nerve 5
54
Is chewing voluntary?
It is an involuntary reflex but can be overridden
55
What are the 3 phases of swallowing?
- Oral
- Pharyngeal
- Oesophageal
56
What happens during the oral phase of swallowing?
- Bolus transferred into the oropharynx by the tongue
| - Somatosensory receptors in this area signal to the medulla to activate the pharyngeal phase
57
What happens during the pharyngeal phase of swallowing?
- Soft pallet pulled upwards
- Larynx opening covered by the epiglottis
- Upper oesophageal sphincter relaxes to open
58
What is the epiglottis?
Flap of tissue which covers the windpipe when eating to prevent food particles going into the lungs
59
What happens during the oesophageal phase of swallowing?
Swallowing reflex:
- Upper oesophageal sphincter closes
- Primary peristaltic wave of contraction pushes food down
60
What lines the oesophagus?
- Squamous epithelia
| - Top layer is naturally sloughed off by food action
61
What happens if food gets stuck in the oesophagus?
- Continued distention triggers secondary peristaltic wave (by ENS)
- Wave starts at the point of distention
62
What causes the lower oesophageal sphincter to open?
Release of VIP neurotransmitter from the vagus nerve
63
Which number cranial nerve is the vagus nerve?
Cranial nerve 10
64
What 3 sections can the stomach be split into?
- Fundus
- Body
- Antrum
65
What is the fundus of the stomach?
Upper part
66
What is the body of the stomach?
Middle/main part
67
What is the antrum of the stomach?
Lower part near the small intestine
68
What 2 regions can the stomach be split into?
Orad and Caudad regions
69
What is the Orad region of the stomach?
Top region (thin walled)
70
What is the Caudad region of the stomach?
Bottom region (thicker walled with 3 muscular layers)
71
What are the 3 phases to motility in the stomach?
- Relaxation in the Orad to receive food
- Contraction of 3 muscular layers in the Caudad to mix food with gastric juice forming chyme
- Gastric emptying
72
What is chyme?
Food digested in the stomach (bolus is food in the mouth)
73
What is gastric juice made of?
- HCl
- Pepsinogen
- Gastric Intrinsic factor (GIF)
- Mucus
74
What controls secretion of gastric juice from mucosal glands?
Autonomic nervous system
75
What happens during gastric emptying?
Chyme leaves slowly through the pyloric sphincter into small intestine
76
What happens during relaxation in the Orad?
- Relaxation causes a decrease in pressure so food comes in
| - Lower oesophageal sphincter closes to prevent backflow
77
What volume of food can the stomach accept in a relaxed state?
1.5 litres
78
Why is gastric emptying slow?
To allow for:
- Neutralisation of stomach acid before entering the SI
- Time for digestion and absorption further on
79
What is the purpose of HCl in the gastric juice?
- Kill pathogens
| - Optimum pH for digestive enzymes
80
What is the purpose of intrinsic factor in the gastric juice?
Important protein for the absorption of B12
81
What is the purpose of pepsinogen in the gastric juice?
Pepsinogen is cleaved into pepsin which activates other digestive enzymes
82
What is the purpose of mucus in the gastric juice?
- Protects the stomach lining
| - Lubricates the chyme
83
How does neuronal and hormonal input affect contraction of the stomach?
- Frequency of contractions don't change
| - Force of waves increase/decrease
84
What are the 3 sections of the small intestine?
- Duodenum
- Jejunum
- Ileum
85
What is the duodenum?
First section of the small intestine
86
What is the jejunum?
Middle part of the small intestine
87
What is the ileum?
The last part of the small intestine
88
What happens in the small intestine?
- Digestion and absorption of nutrients
| - Chyme is mixed with pancreatic secretions and bile
89
What are the 3 ways in which the surface area of the small intestine is increased?
- Plicae
- Villi
- Microvilli
90
What are plicae?
Muscular folds
91
What occurs in the ileum?
Absorption of B12 and bile acids which haven't already been absorbed
92
What volume of exocrine pancreatic secretion enters the duodenum per day?
1 litre
93
What does pancreatic secretion contain?
- HCO3- (bicarbonate ions)
| - Digestive enzymes
94
Which cells of the pancreas secrete HCO3-? (2)
- Centroacinar cells
| - Ductal cells
95
Which cells of the pancreas secrete digestive enzymes?
Acinar cells
96
What is the endocrine function of the pancreas?
Secretion of insulin and glucagon
97
What is the purpose of HCO3- in the pancreatic secretion?
Neutralise H+ being delivered from the stomach
98
Which branch of the nervous system stimulates pancreatic secretion?
Parasympathetic (rest and digest)
99
Which branch of the nervous system inhibits pancreatic secretion?
Sympathetic (fight or flight)
100
What are the 3 secretion phases of the pancreas?
- Cephalic
- Gastric
- Intestinal
101
What triggers the cephalic phase of pancreatic secretion?
Smell, taste and act of eating food
102
What triggers the gastric phase of pancreatic secretion?
- Distention of the stomach
| - Vagus nerve
103
What triggers the intestinal phase of pancreatic secretion?
Chyme entering the small intestine stimulates enteroendocrine cells which release hormones to stimulate the pancreas
104
How much of the pancreatic secretion is the intestinal phase of secretion responsible for?
80%
105
Which cells secret bile?
Hepatocytes in the liver
106
What is in bile? (4)
- Bile salts
- Pigments
- Bilirubin
- Cholesterol
107
How is bile concentrated in the gall bladder?
Epithelial cells absorb water and ions
108
What do bile salts do?
Amphipathic molecules which emulsify fat and form lipids into micelles so they can be absorbed
109
What is CCK?
- Cholecystokinin
| - Digestive hormone
110
What does CCK do?
- Secreted from the small intestine when chyme enters
- Causes the gall bladder to contract
- Causes the sphincter of Oddi to relax so bile can enter the duodenum
111
Which cells secrete CCK?
I cells in the duodenum
112
What happens to bile acids after digestion?
Recirculated to the liver via enterohepatic circulation
113
What proportion of bile acids are recycled?
95%
114
What are the 2 types of contraction in the small intestine?
- Peristaltic contractions
| - Segmentation contractions
115
What do peristaltic contractions in the small intestine do?
Propel the chyme (waves)
116
What do segmentation contractions in the small intestine do?
Split and expose chyme to secretions through coordinated actions of circular and longitudinal muscle layers
117
What is released as part of the peristaltic reflex in the small intestine?
Enterochromaffin cells release serotonin
118
What happens to material which hasn't been absorbed by the end of the small intestine?
Passes through the Ileocaecal sphincter into the caecum of the large intestine
119
What are the 3 primary functions of the large intestine?
- Absorbs water and electrolytes
- Makes and absorbs vitamins K and B
- Forms and propels faeces for excretion
120
What does aldosterone do in the large intestine?
Hormone which increases Na+ absorption
121
What is the role of bacteria in the large intestine?
- Make vitamins
| - Ferment indigestible food
122
What are the sections of the large intestine?
- Caecum
- Ascending colon
- Transverse colon
- Descending colon
- Sigmoid colon
123
What kinds of cells are in the large intestine?
- Surface columnar epithelial cells
| - Crypts
124
What is the function of surface columnar epithelial cells?
Absorption
125
What is the function of crypts?
Secretion e.g. mucus
126
What are the Taenia Coli?
3 bands of longitudinal muscle which run along the length of the large intestine
127
What is the function of the Taenia Coli?
- Propel faecal matter
| - Form Haustra
128
What are Haustra?
Pouches which form in the large intestine which form due to the Taenia Coli being shorter than the length of the LI, causing rouching
129
What are the 2 kinds of motility in the large intestine?
- Segmented contraction
| - Mass movement
130
What is segmented contraction in the large intestine?
- Occurs in caecum and proximal colon
| - Mixes the contents in the haustra
131
What is mass movement in the large intestine?
- Moving the contents from one segment of the large intestine to another
- Gastrocolic reflex
132
How many mass movements occur in the large intestine per day?
1-3
133
What is in saliva? (4)
- Alpha amylase
- Lingual lipase
- Kallikrein
- Mucus
134
What does salivary amylase target? (2)
- Amylose
| - Amylopectin
135
Why is pancreatic amylase needed?
Salivary amylase is deactivated in the acidic conditions of the stomach
136
What does lingual lipase do?
Breaks down triglycerides to diglycerides and fatty acids
137
Why is there a higher proportion of lingual lipase is infants?
Needed for digestion of breastmilk
138
Does lingual lipase continue into the stomach?
Yes
139
What is kallikrein?
Enzyme which converts kininogen to bradykinin
140
What is the purpose of mucus in saliva?
Lubricate the food
141
What is secreted in the oesophagus? (2)
- Mucus
| - HCO3-
142
Where do secretions come from in the oesophagus?
Submucosal glands
143
What is the function of HCO3- in the oesophagus?
Protect the lining against acid reflux from the stomach
144
What is secreted in the stomach? (4)
- HCl
- Pepsinogen
- Intrinsic factor
- Mucus
145
What is secreted in the small intestine? (3)
- Mucus
- HCO3-
- Receives pancreatic secretions and bile
146
What is secreted in the large intestine? (1)
Mucus
147
How much fluid is secreted per day?
8.5 litres
148
Where do secretions in the stomach come from?
Mucosal layer
149
What cells are present in the oxyntic glands? (5)
- Enterochromaffin-like cells
- Epithelial cells
- Mucus neck cells
- Parietal cells
- Chief cells
150
What do enterochromaffin-like cells do? (2)
- Regulate parietal cells
| - Secrete histamine
151
What do epithelial cells in the oxyntic gland secrete?
HCO3-
152
Where are oxyntic glands located?
Body of the stomach (main part)
153
What is the opening of the oxyntic gland called?
Gastric pit
154
What do mucus neck cells in the oxyntic gland secrete?
Mucus
155
What is pepsinogen cleaved into?
The protease enzyme pepsin
156
What do parietal cells in the oxyntic gland secrete? (2)
- HCl
| - Intrinsic factor
157
What do chief cells in the oxyntic gland secrete?
Pepsinogen
158
What glands are present in the body of the stomach?
Oxyntic glands
159
What glands are present in the antrum of the stomach?
Pyloric glands
160
Where in the stomach are pyloric glands located?
Antrum
161
What cells are present in the pyloric glands? (4)
- G cells
- D cells
- Mucus neck cells
- Epithelial cells
162
How do pyloric glands differ from oxyntic glands?
Very similar but no parietal cells and deeper pits
163
What do G cells in the pyloric glands secrete?
Gastrin
164
What does gastrin do?
- Hormone which enters the circulation rather than the lumen of the stomach
- Stimulates the secretion of gastric acid by parietal cells
165
What do D cells in the pyloric glands secrete?
Somatostatin
166
What is the function of somatostatin?
Suppresses hormone release from the GI tract
167
What is the pH of the stomach?
- 1-2
| - Allows for conversion of pepsinogen to pepsin
168
What proteins are present in the apical membrane of the parietal cells? (2)
- H+/K+ ATPase
| - Cl- channel
169
What proteins are present in the basolateral membrane of the parietal cells? (2)
- Na+/K+ ATPase
| - HCO3-/Cl- exchanger
170
How is carbonic acid formed in intracellular fluid?
CO2 from metabolism combines with H2O
171
Which enzyme catalyses the formation of carbonic acid?
Carbonic anhydrase
172
What does carbonic acid dissociate into?
H+ and HCO3-
173
What is the formula for carbonic acid?
H2CO3
174
How is HCl secreted from parietal cells?
- H+ ions from carbonic acid enter the lumen of the stomach via the H+/K+ ATPase on the apical membrane
- Cl- follows via the Cl- channel on the apical membrane
175
What is absorbed into the blood via the basolateral membrane of the parietal cells?
- HCO3-
| - Na+
176
What is the alkaline tide?
Temporary high pH of gastric venous blood after a meal due to secretion of HCO3- into the blood from parietal cells
177
What enters parietal cells via the apical membrane?
K+
178
What enters parietal cells from the blood via the basolateral membrane?
- K+
| - Cl-
179
What happens to the HCO3- which is absorbed from parietal cells into the blood?
Later secreted back into the GI tract via the pancreas
180
What is the resulting net movement of molecules in parietal cells?
- Secretion of HCl into lumen
| - Absorption of HCO3- into blood
181
What is a secretagogue?
Substance that stimulates secretion
182
How does histamine release affect HCl secretion?
Stimulates HCl secretion
183
What kind of hormone is histamine?
Paracrine hormone
184
Which receptor on parietal cells does histamine bind to?
H2
185
Which G protein is the H2 receptor coupled to?
Gs (stimulatory)
186
How does histamine upregulate HCl secretion?
- Histamine binds to H2 receptors which activates Gs coupled protein
- Upregulates production of cAMP
- Activates protein kinase A
- Leads to secretion of HCl
187
Where is acetylcholine released from?
Vagus nerve
188
Which receptor on parietal cells does acetylcholine bind to?
M3
189
Which G protein is the M3 receptor coupled to?
Gq
190
What are the second messengers involved in acetylcholine signalling to parietal cells?
IP3 and Ca2+
191
How does acetylcholine release affect HCl secretion?
Stimulates HCl secretion
192
How does acetylcholine indirectly stimulate HCl secretion?
Stimulates enterochromaffin-like cells to secrete histamine
193
Where is gastrin released from?
G cells in the antrum of the stomach
194
Which receptor does gastrin bind to?
CCKb receptors
195
Which signalling pathway does gastrin act by?
Same pathway as acetylcholine
196
How does gastrin release affect HCl secretion?
Stimulates HCl secretion
197
How does gastrin indirectly stimulate HCl secretion?
Stimulates enterochromaffin-like cells to secrete histamine
198
Which molecules stimulate HCl secretion from parietal cells? (3)
- Histamine
- Acetylcholine
- Gastrin
199
Which molecules/conditions inhibit HCl secretion from parietal cells? (3)
- Low pH
- Somatostatin
- Prostaglandins
200
How does low pH inhibit HCl secretion?
Inhibits gastrin secretion from G cells
201
Where is somatostatin secreted from?
D cells
202
Which G protein is the somatostatin receptor coupled to?
Gi (inhibitory)
203
How does somatostatin affect HCl secretion?
Inhibits HCl secretion
204
Which pathway does somatostatin act via?
Same as histamine but has an inhibitory effect of cAMP instead of a stimulatory effect
205
How do prostaglandins inhibit HCl secretion?
Same pathway as somatostatin
206
Which cells absorb fluids in the small intestine?
Villus cells
207
Where do the enzymes in the small intestine come from?
- Embedded in the brush border
| - From the accessory organs
208
Where do secretions in the intestines come from?
Epithelial cells in the Crypts of Lieberkuhn
209
What do the intestines secrete?
- Intestinal fluid
| - Electrolytes
210
What is the purpose of intestinal secretions?
To protect against bacteria/toxins in the lumen
211
How do epithelial cells in the intestines protect against harmful substances in the lumen?
- Polar- have apical and basolateral membranes separated by tight junctions
- Tight junctions determine whether transport can be trans/paracellular
212
What proteins are present in the apical membrane of epithelial cells in the crypts of the intestines?
Cl- channels
213
What proteins are present in the basolateral membrane of epithelial cells in the crypts of the intestines? (2)
- Na+/K+/2Cl- transporter
| - Na+/K+ ATPase
214
Which direction does Cl- travel across epithelial cells of crypts in the intestines?
From blood to lumen through basolateral Na+/K+/2Cl- transporters and apical Cl- channels
215
How are apical Cl- channels in epithelial cells of crypts controlled?
- Hormones/neurotransmitters bind to receptors on the basolateral membrane
- Activates adenylyl cyclase which makes cAMP from ATP
- cAMP causes opening of Cl- channels
216
Which hormones/neurotransmitters control Cl- in intestinal epithelial cells?
- Acetylcholine
| - Vasoactive Intestinal Peptide (VIP)
217
Which enzyme catalyses formation of cAMP from ATP?
Adenylyl cyclase
218
What happens when apical Cl- channels in epithelial cells of crypts are opened?
- Cl- enters the lumen of the intestines
| - Na+ and H2O follow via paracellular transport
219
How does cholera toxin cause diarrhoea?
- Overstimulates adenylyl cyclase in intestinal epithelial cells
- Cl- channels open and too much Cl- is secreted which is followed by Na+ and H2O
- The secretions are too much for the villus cells to absorb
220
What proteins are present in the apical membrane of villi epithelial cells in the jejunum?
- Na+/sugar or amino acid co-transporter
| - Na+/H+ exchanger
221
What proteins are present in the basolateral membrane of villi epithelial cells in the jejunum?
- Na+/K+ ATPase
- Sugar and amino acid transport proteins
- HCO3- transport protein
222
What proteins are present in the apical membrane of villi epithelial cells in the ileum?
- Na+/sugar or amino acid co-transporter
- Na+/H+ exchanger
- HCO3-/Cl- exchanger
223
What proteins are present in the basolateral membrane of villi epithelial cells in the ileum?
- Na+/K+ ATPase
- Sugar and amino acid transport proteins
- Cl- channels
224
What is the net absorption in the ileum?
NaCl
225
What is the net absorption in the jejunum?
NaHCO3
226
How is bicarbonate formed intracellularly?
- CO2 and H2O from metabolism form carbonic acid (H2CO3) via carbonic anhydrase enzyme
- Carbonic acid dissociates into H+ and HCO3-
227
What does the pancreas secrete?
- Enzymes
| - Bicarbonate ions (HCO3-)
228
Which pancreatic enzymes are released in active forms? (2)
Pancreatic lipase and amylase
229
Which pancreatic enzyme is released in its inactive form?
Pancreatic protease
| Cleaved, pepsinogen to pepsin
230
Which receptors does CCK act on?
Receptors on acinar cells in the pancreas
231
What protein is present in the apical membrane of the ductal cells in the pancreas?
Cl-/HCO3- exchanger
| HCO3 secreted into pancreatic juice
232
What proteins are present in the basolateral membrane of the ductal cells in the pancreas?
- Na+/K+ ATPase
| - Na+/H+ exchanger
233
What causes acidification of pancreatic venous blood?
Absorption of H+ into the blood via Na+/H+ exchanger on the basolateral membrane of ductal cells
(H+ from dissociation of carbonic acid)
234
What proteins are present in the apical membrane of epithelial cells in the colon?
- Na+ channel (in)
| - K+ channel (out)
235
What proteins are present in the basolateral membrane of epithelial cells in the colon?
- Na+/K+ ATPase
| - K+ channel
236
What does aldosterone do in the colon?
Induces synthesis of Na+ channels in the apical membrane of epithelial cells in the colon which causes an increase in Na+ absorption and K+ secretion
237
In which sections of the small intestine are digestion products absorbed?
Jejunum and ileum
238
What carbohydrases are present in the GI tract? (6)
- Alpha amylase
- Alpha dextrinase
- Maltase
- Sucrase
- Trehelase
- Lactase
239
Where are the products of carbohydrase digestion absorbed?
Into villus blood in the small intestine
240
What proteases are present in the GI tract? (5)
- Pepsin
- Trypsin
- Chymotrypsin
- Elastase
- Carboxypeptidases
241
Where are the products of protease digestion absorbed?
Into villus blood in the small intestine
242
Where are the products of lipase and bile salt digestion absorbed?
Into the lacteals within villi
243
What are lacteals?
Lymphatic vessels inside the villi of the small intestine which absorb digested fats.
244
What are the 3 end products of carbohydrate digestion?
- Glucose
- Galactose
- Fructose
245
What does SGLT1 mean?
Sodium Glucose Transporter
246
How are glucose and galactose absorbed into epithelial villus cells?
- Enter via SGLT1 with Na+ across the apical membrane against an electrochemical gradient
- Na+ travels from a high to low concentration from the lumen into the cell and brings glucose/galactose with it
- Basolateral Na+/K+ ATPase sets up driving force for Na+ entry
247
How is fructose absorbed into epithelial villus cells?
Facilitated diffusion through GLUT5 on the apical membrane
248
How do glucose, galactose and fructose enter the blood once inside the intestinal epithelial cells?
Facilitated diffusion through GLUT2
249
What are the 3 end products of protein digestion?
- Amino acids
- Dipeptides
- Tripeptides
250
Where does most protein digestion take place?
Stomach
251
How are amino acids absorbed into epithelial villus cells?
Sodium/amino transporter on the apical membrane
252
How do amino acids enter the blood once inside intestinal epithelial cells?
Facilitated diffusion
253
How are dipeptides and tripeptides absorbed into epithelial villus cells?
- H+ dependent co-transport across the apical membrane
| - Low intracellular H+ set up by Na+/H+ exchanger on apical membrane
254
How do dipeptides and tripeptides enter the blood once inside intestinal epithelial cells?
- Hydrolysed into amino acids by peptidases
| - Absorbed same way as amino acids
255
Where does lipid hydrolysis occur?
Duodenum and jejunum
256
What are the end products of lipid digestion which are solubilised in micelles?
- Cholesterol
- Lysophospholipids
- Monoglycerides
- Fatty acids
257
Which end product of lipid digestion is water soluble?
Glycerol
258
What lipases are present in the GI tract? (4)
- Pancreatic lipase
- Colipase
- Milk lipase
- Other esterases
(Aided by bile salts)
259
What is an enterocyte?
A cell of the intestinal lining
260
How are products of lipid digestion absorbed?
- Micelle exterior is lined with amphipathic bile salts so can enter enterocyte across the luminal cell membrane
- Products are modified and absorbed into lacteal in the form of chylomicrons
261
How do fatty acids leave micelles?
- Alkaline gel mucus layer protecting cell lining, acidic layer underneath caused by Na+/H+ exchanger
- Fatty acids become protonated in the acidic layer and leave the micelle
262
Which 3 ways can fatty acids enter enterocytes?
- Simple diffusion
- Incorporated into enterocyte membrane
- Carrier-mediated transport
263
Which 3 carrier proteins can fatty acids use to enter enterocytes via carrier-mediated transport?
- FAT
- FABP
- FATP
264
What does FAT stand for?
Fatty Acid Translocase
265
What does FABP stand for?
Fatty Acid Binding Protein?
266
What does FATP stand for?
Fatty Acid Transport Protein
267
Where are bile salts absorbed?
- Distal ileum
| - 95% recycled because body couldn't cope with demand for making new bile salts if they were lost in faeces
268
What happens to products of lipid digestion once inside enteroctyes?
- Converted back into triglycerides, phospholipids, esters, cholesterol in the SER
- Associate with apolipoproteins from RER and form chylomicrons
- Chylomicrons packaged into secretory vesicles at the Golgi and leave via exocytosis across basolateral membrane
269
How do chylomicrons enter the blood stream?
- Too large to go straight into capillaries
- Enter the lacteal, lymphatic circulation carries chylomicrons to the thoracic duct where lymph fluid is emptied into the bloodstream
270
How is glycerol absorbed?
Enters the bloodstream straight away
271
How much of the pancreas is endocrine tissue?
1-2%
272
What is the pancreatic endocrine tissue called?
Islets of Langerhans
| Embedded within exocrine tissue
273
What are the 3 main secretory cells of the Islets of Langerhans?
- Alpha cells (α)
- Beta cells (β)
- Delta cells (δ)
274
What proportion of the Islets of Langerhans is beta cells?
65% (main cells)
275
What proportion of the Islets of Langerhans is alpha cells?
20%
276
What proportion of the Islets of Langerhans is delta cells?
10%
277
What are the 3 other endocrine cells scattered in the Islets of Langerhans?
- F cells
- Epsilon (ε) cells
- Enterochromaffin cells
278
How richly perfused with blood are the Islets of Langerhans?
5x the cardiovascular system
279
What do beta cells produce? (4)
- Insulin
- Proinsulin
- C-peptide
- Amylin (IAPP)
280
What do alpha cells produce?
Glucagon
281
What is proinsulin?
Pre-cursor for insulin
282
How is insulin formed from proinsulin?
Proinsulin is cleaved into C-peptide and insulin
283
What is the function of amylin? (3)
Co-secreted with insulin after a meal to:
- Locally prevent glucagon release
- Slow gastric emptying to prevent spikes in blood glucose
- Promotes satiety
284
What do delta cells produce?
Somatostatin
285
What is the function of somatostatin?
Regulates production of other hormones
286
What do F cells produce?
Pancreatic polypeptide
287
What is the function of pancreatic polypeptide?
Suppresses exocrine pancreatic secretion
288
What do ε cells produce?
Ghrelin protein
289
What is the function of Ghrelin protein?
Stimulates hunger
290
What do enterochromaffin cells produce?
Substance P
291
What are fenestrated capillaries?
'Leaky' capillaries with pores
292
What are the features of the blood supply of the Islets of Langerhans?
- Fenestrated capillaries
- Venous blood of one cell type bathes others around it so signalling molecules can have paracrine and endocrine function
293
How do alpha and beta cells in the Islets of Langerhans communicate?
Gap junctions
294
How do delta and beta cells in the Islets of Langerhans communicate?
Delta cells send out dendrite-like processes to beta cells
295
Which 3 types of neurons are the Islets of Langerhans innervated by?
- Adrenergic
- Cholinergic
- Peptidergic
296
How is insulin secretion regulated by blood glucose?
- High blood glucose detected by receptors on beta cells stimulates insulin synthesis and secretion
- Low blood glucose inhibits synthesis and secretion
297
Which receptors on beta cells increase insulin secretion when stimulated by the sympathetic nervous system?
Beta adrenergic receptor stimulation
298
Which receptors on beta cells inhibit insulin secretion when stimulated by the sympathetic nervous system?
Alpha adrenergic receptor stimulation
299
What neurotransmitter does the vagus nerve release?
Acetylcholine
300
Which branch of the nervous system is the vagus nerve part of?
Parasympathetic
301
How does parasympathetic innervation of the beta cells affect insulin secretion?
Release of ACh from the vagus nerve increases insulin secretion
302
Which 3 humoral factors have an effect on insulin secretion?
- GIP
- Amylin
- Somatostatin
303
What is does GIP stand for?
Glucose-dependent insulinotropic peptide
304
What is does GIP stand for?
Glucose-dependent Insulinotropic Peptide
305
What is the function of GIP?
- Released by the small intestine in response to a meal
| - Causes insulin release
306
What is the most potent activator of insulin secretion by beta cells?
Glucose
307
How does glucose affect insulin secretion from beta cells?
- Glucose enters beta cell via GLUT2 channel by facilitated diffusion
- Glucose metabolised with glucokinase to form ATP
- Closes ATP dependent K+ channels
- Induces depolarisation
- Depolarisation opens voltage gated Ca2+ channels
- Increase in intracellular Ca2+ causes exocytosis of vesicles containing insulin
308
How do ACh and CCK affect insulin secretion in beta cells?
- Bind to Gq coupled protein receptors
- Activates intracellular intermediate PKC (Protein Kinase C)
- Causes exocytosis of vesicles containing insulin
309
How do beta adrenergic agonists affect insulin secretion in beta cells?
- Bind to beta adrenergic receptors (Gs protein coupled receptors)
- Causes conversion of ATP to cAMP via adenylyl cyclase
- Activates PKA (Protein Kinase A) which causes exocytosis of vesicles containing insulin
310
How do somatostatin and alpha adrenergic agonists affect insulin secretion in beta cells?
- Bind to Gi coupled protein receptors
- Down regulates adenylyl cyclase
- Down regulates formation of cAMP
- No secretion of insulin
311
How does glucagon affect insulin secretion in beta cells?
- Bind to beta adrenergic receptors (Gs protein coupled receptors)
- Causes conversion of ATP to cAMP via adenylyl cyclase
- Activates PKA (Protein Kinase A) which causes exocytosis of vesicles containing insulin
312
What is the structure of the insulin receptor?
- Heterotetramer
- 2 extracellular alpha chains
- 2 membrane-spanning beta chains
- Intracellular tyrosin kinase domain
- Intracellular phosphorylation sites
313
What does activation of the insulin receptor cause?
- Insulin binds to activate
- Autophosphorylates to downregulate the receptor itself
- Phosphorylates other substrates to cause various downstream effects
314
What substances can the insulin receptor phosphorylate to cause downstream effects? (4)
- PKC
- Phosphatases
- Phospholipases
- G proteins
315
What downstream signalling effects can insulin cause by binding to insulin receptors? (4)
- Cell growth
- Cell proliferation
- Gene expression
- Synthesis of glycogen, lipids, proteins
316
How does insulin trigger glucose uptake in target cells?
- Insulin binds to insulin receptors
- Triggers signal transduction cascade
- Causes exocytosis of vesicles containing GLUT4 channels
- Channels embed in the membrane which increases glucose uptake into the cell
317
What are the 5 functions of insulin?
- Increases uptake of glucose by muscle and fat cells
- Promotes glycogenesis in liver and muscle cells
- Excess glucose is converted to fat (lipogenesis)
- Inhibits glycogenolysis
- Inhibits gluconeogenesis (reducing blood glucose)
318
What is glycogenesis?
Conversion of glucose to glycogen
319
What is lipogenesis?
Conversion of glucose to fat
320
Which enzymes does insulin upregulate transcription of to promote glycogenesis in the liver?
- Glucokinase
- Hexokinase
- Glycogen synthase
321
What is glycogenolysis?
Breakdown of glycogen to glucose
322
What is gluconeogenesis?
Production of glucose from non-carbohydrates
323
What are the 4 major effects of insulin on hepatocytes?
- Promotes glycogenesis by upregulating glucokinase
- Promotes glucose metabolism
- Promotes lipogenesis
- Promotes protein synthesis
324
What are the 4 major effects of insulin on muscle cells?
- Promotes glucose uptake by embedding GLUT4 in the membranes
- Promotes glycogenesis by upregulating hexokinase
- Promotes glucose metabolism
- Promotes protein synthesis
325
What are the 4 major effects of insulin on adipocytes?
- Upregulates expression of GLUT4 in the membrane
- Glucose converted into fatty acids and stored as triglycerides
- Inhibits breakdown of lipids
- Increases synthesis of lipoprotein lipase which frees fatty acids for triglyceride synthesis
326
What is the effect of insulin on Na+/K+ ATPase?
Promotes K+ uptake into cells by increasing activity of Na+/K+ ATPase
327
What is the effect of insulin of the hypothalamic satiety centre?
Causes feeling of being full
328
What is Diabetes Mellitus?
- High blood sugar over prolonged periods
| - Type 1 or 2
329
What is Type 1 Diabetes Mellitus?
- 'Insulin dependent'
- Autoimmune destruction of pancreatic Islets of Langerhans (alpha and beta cells)
- No insulin or glucagon produced
330
What is Type 2 Diabetes Mellitus?
- 'Non-insulin dependent'
- Low insulin production
- Peripheral insulin resistance
- Linked to obesity
331
What are the effects of Type 1 Diabetes Mellitus? (7)
- Hyperglycaemia
- Increased blood fatty acid and ketoacid concentration
- Increased blood amino acid concentration
- Osmotic diuresis
- Polyuria
- Hypotension
- Hyperkalaemia due to K+ moving out of cells
332
What are the symptoms of Type 1 Diabetes Mellitus? (7)
- Increased thirst and urination
- Hunger
- Weight loss
- Fatigue
- Irritability
- Fruity smelling breath (DKA)
- Blurred vision
333
What is the treatment for Type 1 Diabetes Mellitus?
Insulin replacement therapy
334
What are the effects of Type 2 Diabetes Mellitus? (2)
- Downregulation of insulin receptors in target tissues causing insulin resistance
- Elevated blood glucose even at normal insulin levels
335
What are the symptoms of Type 2 Diabetes Mellitus? (7)
- Thirst
- Hunger
- Frequent urination
- Weight loss
- Fatigue
- Blurred vision
- Headaches
336
What are the treatment options for Type 2 Diabetes Mellitus?
- Sulphonylurea drugs which stimulate insulin secretion
- Biguanide drugs which upregulate receptors on target tissues
- Calorie restriction
337
What is an example of a sulphonylurea drug for Type 2 Diabetes treatment?
Tolbutamide
338
What is an example of a biguanide drug for Type 2 Diabetes treatment?
Metformin
