GI Physiology - Full summary Flashcards
1
Q
What are the 5 main regions of the stomach?
A
Cardia
Fundus
Body
Antrum
Pylorus
2
Q
What is the main function of the stomach?
A
It mixes food with gastric secretions in order to produce semi-liquid chyme
3
Q
What are the 2 forms of mechanical activity in the stomach?
A
Orad stomach - Tonic, maintained contraction
Caudad stomach - Phasic intermittent contraction
4
Q
What regions make up the orad stomach?
A
Fundus
Proximal body
5
Q
What occurs in the orad stomach?
A
During swallowing, the vagus nerve is stomaulted as the hypothalamus detects food moving towards the stomach
This causes the release of acetylcholine and nitric oxide, which allows for relaxation of the oral stomach and opening of the lower oesophageal sphincter
A prolonger, weak, tonic contraction then occurs in order to propel the food towards the caudad region
6
Q
What causes the normal rhythmic contractions of the caudad stomach?
A
Ca2+ slowly leaks into the smooth muscle, causing depolarisation
This does not reach threshold, however, and K+ then leaves the smooth muscle, therefore re-polarising the cell
7
Q
What causes the larger, intermittent contractions of the caudad stomach?
A
Acetylcholine released by the vagus nerve causes a greater depolarisation, which reaches threshold and thus allows a larger contraction to occur, which allows for the grinding and peristaltic action of the stomach
8
Q
What happens to food that does not pass into the duodenum?
A
It undergoes retropulsion, which it is forced back into the stomach and is further churned
9
Q
What factors affect the strength of antral waves and the opening of the pyloric sphincter?
A
Gastric factors
Duodenal factors
10
Q
What are the gastric factors that affect the strength of antral waves and the opening of the pyloric sphincter?
A
The volume of chyme
The consistency of chyme
Distension
11
Q
How does distension affect astral waves and opening of the pyloric sphincter?
A
Distension increases motility, as the stretch of the smooth muscle stimulates the intrinsic nerve plexuses, which increases vagus nerve activity and gastrin release
12
Q
How can duodenal factors delay emptying of the stomach?
A
The duodenum must be ready to receive chyme
The duodenum can delay emptying via neurohormonal responses or hormonal responses
13
Q
How can neurohormonal responses affect emptying of the stomach?
A
The enterogastric reflex of the duodenum decreases antral activity va signals from the intrinsic nerve plexuses and autonomic nervous system, driven by stimuli within the duodenum
14
Q
How can hormonal responses affect emptying of the stomach
A
The release of enterogastrones such as Cholecystokinin (CCK) from the duodenum inhibits stomach contraction
15
Q
What are some stimuli in the duodenum that trigger the neurohormonal and hormonal responses to prevent stomach emptying?
A
Fat - More time needed to absorb
Acid - More time required for neutralisation
Hypertonicity
Distension - Need to clear duodenum first
16
Q
What is hypertonicity and how does it occur?
A
Hypertonicity is the presence of a large water potential gradient in the intestine
This arises as the simple sugars and amino acids can draw in water from the intestines, which decreases blood plasma volume and can cause hypotension (Dumping syndrome)
17
Q
What are the 2 glandular regions of the stomach known as?
A
Oxyntic gland area
Pyloric gland area
18
Q
What is found at the entrance to all gastric pits?
A
Mucosal cells which secrete mucus and bicarbonate, which protect the stomach from hydrochloric acid by buffering
19
Q
What are the 3 main cell types of the oxyntic glands?
A
Chief cells
Enterochromaffin-like cells
Parietal cells
20
Q
What is secreted by chief cells?
A
Pepsinogen
21
Q
What is pepsinogen?
A
This is an inactive precursor to pepsin, which breaks down peptides activates more pepsinogen (autocatalytic)
22
Q
What is secreted by enterochromaffin-like cells?
A
Histamine
23
Q
What is the main function of histamine in the stomach?
A
It acts as a paracrine messenger and stimulates the release of HCl from parietal cells
24
Q
What are the 3 substances that are secreted by parietal cells?
A
Hydrochloric acid
Intrinsic factor
Gastroferrin
25
What is the function of hydrochloric acid?
Hydrochloric acid activates pepsinogen to form pepsin, denatures proteins for digestion and kills most micro-organisms
26
What is the function of intrinsic factor?
This binds to vitamin B12 and facilitates its absorption
27
What is the function of gastroferrin?
This binds to Fe2+ and facilitates its absorption
28
What are the 2 phases in which parietal cells can be in?
Active
Resting
29
What are the characteristics of parietal cells when resting?
Their proton pumps are bound to tubulovesicles in the cytoplasm
30
What are the characteristics of parietal cells when active?
Stimulatory chemicals (Gastrin, Histamine) stimulates protein kinases, which move vesicles, and thus proton pumps, to the membrane
31
What are the 2 main cell types in the pyloric gland area?
G cells
D cells
32
What is released by G cells, directly into the blood?
Gastrin
33
What is the function of gastrin?
Gastrin stimulates the secretion of HCl and increases gut motility
34
What is released by D cells, directly into the blood?
Somatostatin
35
What is the function of somatostatin?
Somatostatin inhibits HCl secretion
36
How do parietal cells produce hydrochloric acid?
Cl- moves from the blood via the chlorine bicarbonate exchanger
Chlorine is pumped into the lumen via the chlorine-potassium symporter
H+ and bicarbonate are formed from H2O + CO2
H+ is pumped out as potassium is pumped back in via the H+/K+ ATPase (Proton pump)
Cl- and H+ combine in the lumen to form hydrochloric acid
37
What stimulates the release of histamine from enterochromaffin-like cells?
Acetylcholine
38
How does histamine increase HCl levels
Histamine binds to H2 receptors on parietal cells
This activates adenylyl cylase
This then increases levels of cAMP, which increases the number of proton pumps and thus increases secretion of HCl
39
How does acetylcholine alone stimulate HCl production?
Acetylcholine binds to M3 ACh receptors
This causes activation of phospholipase C, which increases intracellular Ca2+ levels
This stimulates the production of more proton pumps, which increases secretion of HCl
40
How does gastrin increase HCl production?
Gastrin binds to cholecystokinin 2 (CCK2) receptors
This activates phospholipase C
This increases intracellular Ca2+ levels
This stimulates production of more proton pumps, which increases secretion of HCl
41
How does somatostatin decrease HCl production?
This binds to SST2R receptors on parietal cells and enterochromaffin-like cells
This prevents the release of histamine and inhibits adenylyl cyclase
This decreases cAMP levels and thus down regulates proton pump production
42
What affect do prostaglandins have on HCl production?
They decreases HCl production
43
What are the 3 phases of gastric secretion?
Cephalic phase - Before food in stomach
Gastric phase - Food in stomach
Intestinal phase - Food in small intestine
44
What occurs in the cephalic phase of gastric secretion
The hypothalamus stimulates the vagus nerve in response to food
Vagal stimulation stimulates enteric neurones
This causes the release of acetylcholine, which stimulates the release of gastrin and histamine, which all increase HCL levels
It also inhibits somatostatin production
45
What occurs in the gastric phase of gastric secretion?
There is a still a vagal tone, however, distension further activates acid secretion, which food buffers decrease somatostatin release from D cells and amino acids further stimulate G cells to produce gastrin
46
What are the 3 phases of inhibition of gastric secretion?
Cephalic phase
Gastric phase
Intestinal phae
47
What occurs in the cephalic phase of secretion inhibition?
Vagal tone is decreased due to cessation of eating and stomach emptying
This decreases HCl production via histamine, gastrin and acetylcholine
48
What are some factors that can decrease vagal tone to the stomach and thus decrease secretion?
Cessation of eating
Stomach emptying
Pain
Nausea
Negative emotions
49
What occurs during the gastric phase of inhibition of gastric secretion?
The antral pH falls as food exits the stomach due to increased buffering of gastric HCl
This stimulates the release of somatostatin and thus further decreases HCl production
The gastric mucosa also releases prostaglandin E2 which acts locally to recuse histamine levels
50
What occurs during the intestinal phase of inhibition of gastric secretion?
Enterogastrones and neuronal reflexes which reduce gastric motility begin to reduce gastric secretions
51
What is digestion?
The enzymatic conversion of complex dietary substances into a form that can be absorbed
52
What are the 3 main locations of digestion?
Lumen (Luminal)
Brush border (Membrane)
Cytoplasm (Cytoplasmic)
53
What are the 2 membranes of digestion in enterocytes known as?
Apical membrane (Lumen)
Basal membrane (Blood)
54
What are the 3 main types of carbohydrates?
Monosaccharides
Oligosaccharides
Polysaccharides
55
What are some examples of monosaccharides?
Glucose
Fructose
56
What are some examples of oligosaccharides?
Sucrose
Lactose
57
What are some examples of polysaccharides?
Amylose
Amylopectin
Glycogen
58
What monomers form sucrose?
Glucose + Fructose
59
What monomers form lactose?
Glucose + Galactose
60
Where in the GI tract are carbohydrates first digested?
Oral cavity - Salivary amylase
Duodenum - Pancreatic amylase
61
What is the function of salivary and pancreatic amylase?
They break down polysaccharides into oligosaccharides (e.g. Starch into maltase)
62
How are oligosaccharides digested?
Oligosaccharides are broken down into monosaccharides by enzymes on the brush border
63
What are some examples of oligosaccharases?
Lactase
Maltase
Sucrase
Isomaltase
64
What is the function of lactase?
It hydrolyses lactose into glucose and galactose
65
What is the function of maltase?
Maltase hydrolyses 1,4 glycosidic bonds in straight chains
66
What is the function of sucrase?
It hydrolyses sucrose into glucose and fructose
67
What is the function of isomaltase?
It is the only enzyme that hydrolyses branching 1,6 glycosidic bonds
68
What is the function of alpha-amylase?
This is an end-enzyme which breaks down linear alpha-1,4 glycosidic bonds
69
Where in the GI tract does absorption of monosaccharides occur?
Duodenum and jejunum
70
How are glucose and galactose absorbed into the blood?
They are moved into the enterocytes via SGLT1 secondary active transporters, with Na+
They then move out of the cell via facilitated diffusion through GLUT2 channels
The Na+ gradient is maintained by the Na+/K+ ATPase which pumps Na+ back out, into the blood
71
How is fructose absorbed into the blood?
It is transported into the cell by the GLUT5 channel and then moves out via the GLUT2 channel
72
Where are proteins first broken down?
In the stomach
73
What effect does HCl have on proteins?
HCl denatures proteins in the stomach
74
What effect does pepsin have on proteins?
Pepsin cleaves proteins into peptides in the stomach
75
What is the optimum pH for pepsin?
1.8 - 3.5 and it becomes denatured in the alkaline conditions of the duodenum
76
What are the different ways in which proteins can be broken down and absorbed?
Proteins in the stomach can either be broken down into peptides or amino acids
Amino acids can be directly absorbed
Peptides can either be hydrolysed by membrane enzymes into amino acids before being absorbed, or they can be absorbed first and then hydrolysed by cytoplasmic enzymes
77
What is the calculation for BMI?
BMI = Weight (Kg) ÷ Height^2 (m)
78
What is the BMI range for being overweight?
25 - 29
79
What is the BMI range for being obese?
30 - 39.9
80
What is the BMI range for being morbidly obese?
≥40
81
Why do obese people find it hard to lose weight?
Obesity causes chemical changes within the brain, which cause the increased fat storage to be viewed as advantageous, and so any attempts to lose this excess fat will be counteracted by physiological mechanisms
82
What 3 systems control body weight and energy expenditure?
Autonomic nervous system
Neuroendocrine system
Behavioural system
83
What is the main site of integration for the control mechanisms of body weight?
The hypothalamus, which then determines feeding behaviour
84
What are the 3 basic stimuli that determine feeding behaviours and body weight?
Satiety signalling
Adiposity negative feedback signalling
Food reward
85
What is satiation?
The sensation of fullness generated during a meal
86
What is satiety?
The period of time between termination of one meal and the initiation of the next
87
What is meant by adiposity?
The state of being obesity
88
What are some examples of satiation signals?
Cholecystokinin (CCK)
Peptide YY (3-36)
Glucagon-lie peptide 1 (GLP-1)
Oxyntomodulin
Obestatin
89
Where is cholecystokinin released from?
The entero-endocrine cells in the duodenum and jejunum
90
What stimulates the release of cholecystokinin?
Lipids and proteins in meals that reach the small intestine
91
What are the actions of Cholecystokinin (CCK)?
Stimulates satiation via sensory nerves to the NTS of the hindbrain
Stimulates contraction of the gallbladder to release bile
Stimulates release of pancreatic juices
92
Where is peptide YY released from?
The endocrine mucosal L-cells of the GI tract
93
What is the action of peptide YY?
This is secreted post-prandially and inhibits gastric motility, slowing emptying of the stomach and reducing food intake via the hypothalamus, causing satiation and increased water absorption
94
Where is glucagon-like peptide released from?
This is formed by the pro-glucagon gene and is released from L-cells of the GI mucosa in response to food ingestion
95
What is the action of glucagon-like peptide 1?
It inhibits gastric emptying and reduces food intake via the hypothalamus and NTS, causing satiation
96
Where is oxyntomodulin released from?
The oxyntic cells and L-cells of the small intestine post-prandially
97
What is the action of oxyntomodulin?
The mechanism unknown but it is known to suppress appetite
98
Where is obestatin released from?
The cells lining the stomach and small intestine
99
What is the action of obestatin?
It is thought to reduce food intake and may antagonise the actions of ghrelin
100
How does the amount of body fat get communicated to the brain?
Via 2 hormones, produced in the peripheral tissues, which act on the hypothalamic neurones
101
What 2 hormones communicate body fat levels from the adipose tissue to the brain?
Leptin
Insulin
102
Where is leptin made and released?
It is made and released from adipocytes
103
What is the main action of leptin?
As more fat is stored, more leptin is produced and released into the blood
This leptin then binds to leptin receptors on the hypothalamus, which is thought to decrease food intake and thus body weight
104
What is ghrelin?
Ghrelin is a hunger signal, an octanoylated peptide produced by oxyntic cells in the stomach
105
What are the actions of ghrelin?
Ghrelin is released before a meal and stimulates food intake, decreases energy expenditure and decreases fat utilisation, and thus increases body weight
It also triggers storage of nutrients as fat
It finally causes contraction of the stoamch and small intestines, causing stomach rumbling
106
Why is leptin infusion not an effective therapy in obesity?
A majority of those with obesity have a resistance to leptin due to decreased numbers of leptin receptors, caused by chronic high levels in the blood
107
What is orlistat?
An OTC anti-obesity drug
108
How does orlistat work?
This inhibits pancreatic lipases, therefore decreasing triglyceride absorption by around 30% and thus causing a decrease in body fat levels
109
What are some management options in obesity?
Lifestyle changes
Cognitive Behavioural Therapy
Bariatric surgery
Limited therapeutic management (Orlistat)
110
What are some side effects associated with orlistat?
Cramping
Bloating
Diarrhoea
Flatulence
Abdominal pain
Vitamin deficiency
111
What vitamin supplements are required in those who take orlistat?
Vitamin A, D and E
112
What is contrave?
Contrave is a combination drug of buproprion (Dopamine re-uptake inhibitor) and naltrexone (Opiod antagonist)
113
Where is contrave available?
It is available on private prescription or online under the name Mysimba in the UK
114
How can liraglutide (Victoza) cause weight loss?
Despite being a treatment for type II diabetes, it also acts as a glucagon-like peptide 1 agonist and so can increase satiation and inhibits gastric emptying
115
What are some risks of victoza use?
Increased risk of pancreatic cancer and thyroid cancer
116
What occurs during bariatric surgery?
This is a gastric bypass surgery, which induces malabsorption and decreased calorie intake, and this produces substantial weight loss
It is used in those who are morbidly obese
117
Where in the body is brown adipose tissue found?
In the neck, clavicle and spinal cord
118
How does brown adipose tissue increase energy expenditure?
Brown adipose tissue increases expenditure by uncoupling oxidative metabolism from ATP production
This is via a fatty acid activated protein, uncoupling protein 1 (UCP1) , which short circuits the proton gradient in mitochondria and accelerates fuel oxidation, therefore causing heat
119
How does 2,4-Dinitrophenol work?
This irreversibly converts white adipose tissue to brown adipose tissue via exposure to cold
This therefore increases energy expenditure and stimulates increased thermogenesis
120
Why is 2,4-Dinitrophenol not given in obesity?
It acts as a metabolic poison and causes extreme hyperthermia, due to the large amount of thermogenesis, which can almost cook the person from the inside
121
What are the 2 action types of the pancreas?
Exocrine
Endocrine
122
What are some of the hormones produced by the endocrine pancreas?
Insulin
Glucagon
Somatostatin
123
What are some of the secretions of the exocrine pancreas?
Digestive enzymes
Sodium bicarbonate
124
What stimulates the release of insulin?
Increased blood glucose levels
125
From which cells is inulin released?
ß-cells of the Islets of Langerhan's
126
What are the 3 cells in which glucose is stored due to insulin production?
Muscle cells
Adipocytes
Hepatocytes
127
In what form is glucose stored in hepatocytes?
Glycogen
128
What stimulates the release of glucagon?
Decreased blood glucose levels
129
Where is glucagon released from?
Alpha cells of the Islets of Langerhan's
130
How does increased blood glucose levels stimulate insulin production?
Increased levels causes intake of glucose into ß-cells via GLUT2
Glucokinase phosphorylates tis to form G6P and then glycogen
This yields ATP, which causes closure of K+ ion channels
K+ ATPase closure depolarises the cell
This stimulates activation of voltage gated Ca2+ channels
Intracellular Ca2+ causes exocytosis of insulin
131
What are the 2 types of diabetes mellitus?
Type I - Insulin dependant
Type II - Non-insulin dependant
132
What causes Type I diabetes?
An autoimmune reaction to ß-cells, resulting in a failure to produce insulin
133
What are some causes of Type II diabetes?
Insulin resistance in hepatocytes
Secretion of abnormal insulin
Inappropriate liver gluconeogenesis (Increased glucose release)
Obesity (age demand placed on pancreas)
134
What are 2 common drugs in diabetes control?
Metformin
Sulfonylureas (e.g. gliclazide)
135
What is the action of metformin?
Metforin stimulates AMP activated protein kinases, which reduces hepatic gluconeogenesis and triggers GLP-1 production, which enhances the release insulin
136
What is the action of sulfonylureas (e.g. gliclazide)
They cause closure of the K+ ATPase in ß-cells, therefore triggering depolarisation and exocytosis of insulin
137
What are some 3 main classes of peptidase?
Aminopeptidase
Carboxypeptidase
Endopeptidase
138
What is the function of aminopeptidases?
Hydrolyses proteins at the terminal amino end
139
What is the function of the carboxypeptidases?
Hydrolyses proteins at the terminal carboxyl end
140
What is the function of the endopeptidases?
Hydrolyses linear non terminal bonds
141
What are some examples of endopeptidases?
Trypsin
Chymotrypsin
Elastase
142
What are some examples of carboxypeptidases?
Carboxypeptidase A
Carboxypeptidase B
143
How many mechanisms of protein absorption are there?
7: 5 Na+ dependant and 2 Na+ indépendant
144
Describe the absorption of amino acids via a Na+ dependant mechanism
K+ is pumped in while Na+ is pumped out via the sodium potassium pump
This creates a gradient for Na+ to move in with amino acids via an Na+ dependant transporter
145
How are lipids emulsified in the body?
Mastication
Gastric churning
Peristalsis
Biliary secretions
146
How are lipids absorbed by bile salts?
Bile salts form a multi-lamelar vesicle around the lipids, which is then compressed into a single layer micelle, allowing the lipids to be dissolved
147
What are the products of triacyglycerol breakdown?
Diacyglycerol
Free fatty acid
148
What hydrolyses triacylglycerol in the GI tract?
Gastric lipases
149
What stimulates the release of gastric lipases?
Gastrin stimulates the release of gastric lipases from chief cells
150
What breaks down medium and short chain fatty acids in the GI tract?
Pancreatic lipases
151
What stimulates the release of pancreatic lipases from the pancreas?
Cholecystokinin
152
What happens to fatty acids and monoglycerides when they enter the enterocyte?
They are released from the micelle and resynthesised to form a chylomicron in the endoplasmic reticulum, which is then exocytosed into the central lacteal
153
How is cholesterol absorbed?
It is transported by endocytosis in clatherin coated pits by the Niemann-Pick C1 like protein
154
What is the mechanism of action of ezetimibe?
This binds to the Niemann-Pick C1-like protein and prevents the endocytosis of cholesterol
155
What is the use of ezetimibe?
It is used in those with high blood cholesterol levels who cannot tolerate statins
156
What regulates the absorption of Ca2+?
1,25-Dihydroxycholecalciferol D3 (Calcitriol)
Parathyroid hormone (Increases calcitriol synthesis)
157
What is the main form of iron in food?
Fe2+ as inorganic iron, ahem or ferritin
158
How is Fe2+ absorbed into the enterocytes?
Via divalent metal transporters (e.g. DMT1) with H+
159
What happens to Fe2+ when it enters the enterocytes?
Moved by chaperone proteins to the basal membrane-bound ferroportin 1 and pumped into the blood
or
Combined with cytoplasmic apoferin to form ferritin for storage
160
What happens to Fe2+ when it pumped out of the enterocyte?
It is oxidised to form Fe3+ by hephaestin and is transported to tissues bound to transferrin, which can bind to transferrin receptors on cells such as erythroblasts
161
How is haem absorbed in the GI tract?
It is transported into the cell by haem carrier protein 1 where it is metabolised to release Fe2+ and biliverdin
162
What are some molecules that can reduce ingested Fe3+?
Duodenal cytochrome B
HCl
Vitamin C
Gastroferrin
163
What will cause increased expression of divalent metal transporter 1?
Blood loss
164
What will cause a decreased expression of divalent metal transporter 1?
Human haemochromatosis protein
165
What will decrease expression of ferroprotein 1 and thus decrease release of iron into the blood?
Hepcidin hormone which is released by the liver if iron levels are too high
166
Describe the absorption of vitamin B12 (Cobalamin)
Vitamin B12 is ingested in foods, bound to proteins
Saliva contains haptocorin, which binds to vitamin B12 and the protein
The protein is then released by the stomach acid, leaving just haptocorin bound to vitamin B12
Pancreatic proteases digest haptocorin in the small intestine, and so releases vitamin B12
Intrinsic factor then binds to vitamin B12, allowing it to be absorbed by endocytosis in the terminal ileum
167
Which vitamins are fat soluble?
Vitamin A (Retinoic acid)
Vitamin D
Vitamin E
Vitamin K
168
Which vitamins are water soluble?
B complex vitamins (Not 12)
Vitamin C (Ascorbate)
Vitamin H (Biotin)
169
How are fat soluble vitamins absorbed?
Absorption of fat soluble vitamins required adequate bile secretion and an intact intestinal mucosa
This is because fat soluble vitamins are incorporated into mixed micelles and are passively transported into enterocytes
Here, they are incorporated into chylomicrons or VLDLs where they exit the cell and are distributed into the intestinal lymphatics
170
How are water soluble vitamins absorbed?
Transport of water soluble vitamins are similar to that of monosaccharides and amino acids, meaning there are Na+ dependent and Na+ independent pathways
Examples include:
- Vitamin B9 (Folic acid) → Na+ Independant folate trasnporter 1 (FOLT)
- Vitamin C → Na+ dependent vitamin C transporters (SVCT1 & SVCT2)
- Vitamin H → Na+ dependant multivitamin transporter (SMVT)
171
What are the main mechanisms of ion transport that allow movement of water in the GI tract?
- Na+/Glucose co-transport
- Na+/AA co-transport
- Na+/H+ exchange
- Parallel Na+/H+ and Cl-/HCO3- exchange
- Epithelial Na+ channels (ENaC)
172
How do the Na+/Glucose and Na+/Amino acid transporters allow for the movement of water?
They are both examples of secondary active transporters and are electrogenic, meaning they create a transepithelial potential, in which the lumen has a negative charge, which drives the absorption of Cl-
The movement of Na+ into the cells decreases the water potential of the cell, and thus creates an osmotic gradient into the cell, via which water moves in, from the lumen
173
Where does Na+/H+ exchange mostly occur in the GI tract?
Jejunum
174
What are the 3 main forms of Na+/H+ transporter?
- NHE 1 - Basolateral membrane
- NHE 2 - Apical membrane
- NHE 3 - Apical membrane
175
Describe the role of Na+/H+ transporters and pancreatic bicarbonate in the movement of water
Bicarbonate from the pancreas causes an alkaline environment in the jejunum
This drives the movement of H+ into the lumen and Na+ into the cell
As Na+ moves into the cell, it decreases the water potential and thus creates an osmotic gradient for water into the cell
176
Where does parallel exchange of Na+/H+ and Cl-/HCO3- occur?
Ileum and proximal colon
177
How does parallel exchange of Na+/H+ and Cl-/HCO3- affect water movement?
Reduced Na+ and Cl- absorption decreases the osmotic gradient for water into the cell, and so more water remains in the lumen, thus causing diarrhoea
178
What are some factors that reduce absorption of Cl- and Na+ and thus increase luminal water levels?
cAMP
cGMP
Ca2+
179
How does E.coli cause diarrhoea?
E.coli produces a heat stable enterotoxin which activates adenylyl cylase, which converts AMP into cAMP
This cAMP can then reduce NaCl movement into the cell and thus can cause diarrhoea
180
What is ENaC?
Epithelial Na+ channels
181
How does aldosterone increase water intake from the GI tract?
ENaC mediates electrogenic Na+ absorption in the distal large intestine
This absorption is increased by aldosterone, which opens ENaC, increases the number of ENaC in the membrane, and increases synthesis of ENaC
182
Describe the absorption of Cl- in the GI tract
Absorption of Cl- can occur passively via trans-cellular or para-cellular routes
The passive absorption of Cl- occurs due to electrogenic movement or via the Cl-/HCO3- exchanger
This electrogenic gradient in the small inetstine is created by the transport of Na+ via the Na+/Glucose and Na+/Amino Acid symporters
The electrogenic gradient in the large intestine is created by the transport of Na+ through ENaC
183
Where in the GI tract does secretion of Cl- occur?
Crypt cells
184
What are the 3 basolateral processes of Cl- secretion?
- Na+/K+ exchange → Na+/K+ ATPase
- Na+/K+/2Cl- co-transport → NKCC1
- K+ transport → IK1 and BK
185
Describe the secretion of Cl- in the GI tract
Na+/K+ ATPase pumps Na+ out of the cell and K+ in
NKCC1 pumps Na+, K+ and 2Cl- into the cell
K+ is pumped back out of the cell by IK1 and BK
This maintains a K+ and Na+ gradient into the cell
This creates a high concentration of Cl- in the cell
This can then move out of the cell and into the lumen via CFTR channels
CFTR channels are usually inactive, so there is usually little Cl- secretion
These CFTR channels can be activated by a number of factors, which increases secretion
186
What are some factors that increase secretion of Cl- in the GI tract?
- Bacterial endotoxins
- Hormones
- Neurotransmitters
- Immune cell products
- Laxatives
187
How does Cl- secretion affect water movement?
Movement of Cl- into the lumen causes the movement of Na+ into the lumen down an electrical gradient, therefore causing water to remain in the lumen
188
What is diarrhoea?
Diarrhoea is defined as a loss of fluid and solutes from the GI tract in excess of 500ml per day
This is diagnosed as >3 loose stools in 24 hours
189
What are some possible consequences of diarrhoea?
Dehydration
Metabolic acidosis
Hypokalaemia
190
What are some treatment options in diarrhoea?
Fluid maintenance
Electrolyte replacement
Anti-infective agents if appropriate
Anti-diarrhoeal drugs
191
What are some types of causes of diarrhoea?
Impaired absorption of NaCl
Poorly absorbable solutes
Hyper-motility
Excessive secretion
192
What are some causes of impaired absorption of NaCl, leading to diarrhoea?
E.coli
Cholidorrhoea
193
What is cholidorrhoea?
This is a congenital defect resulting in the absence of Cl-/HCO3- exchanger, inflammation and excess bile production
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What is an example of a condition that will lead to poorly absorbed solutes in the lumen?
Lactose intolerance in which lactose is not broken down and decreases water potential in the lumen, therefore causing diarrhoea
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How does vibrio cholerae cause watery diarrhoea?
Vibrio cholerae bacteria release cholera toxin (CTX) which enters the enterocytes
Here, it inhibits GTPase and action of Gsa
This increases the activity of adenylate cyclase, which converts AMP to cAMP
cAMP stimulates CFTR and reduces NaCl transport
This causes hypersecretion of Cl, thus causing the movement of Na+ out of the cell, which reduces the water potential and causes more water to remain in the lumen
This causes diarrhoea
