SEM2 Flashcards
(419 cards)
1
Q
What is neuropeptide Y?
A
An orexigenic factor that induces desire to eat (appetite). It’s synthesised in GABAergic neurones and is majorly expressed in interneurons
2
Q
What’s AgRP?
A
Agouti-related peptide is a neuropeptide produced in the brain by the AgRP/NPY neuron. It increases appetite and decreases metabolism and energy expenditure.
3
Q
Where is AgRP synthesised?
A
Neuropeptide Y-containing cell bodies in the ventromedial part of the arcuate nucleus in the hypothalamus
4
Q
What’s the pharmacokinetics of AgRP?
A
AgRP acts as an antagonist to MCR4 (Melanocortin 4 receptor), a G-protein-coupled receptor that binds alpha-melanocyte stimulating hormone (a-MSH)
5
Q
What receptors does neuropeptide Y bind to? (4 options)
A
Y1, Y2, Y4 or Y5
6
Q
What is POMC?
A
Proopiomelanocortin is the pituitary precursor of circulating alpha-melanocyte stimulating hormone, ACTH and ß-endorphin.
7
Q
Where is POMC synthesised?
A
In corticotrophins of the anterior pituitary (from pre-proopiomelanocortin)
8
Q
What receptors does 5HT bind to to promote metabolism of POMC?
A
5HT2C
9
Q
What happens when 5HT triggers metabolism of POMC?
A
The metabolism leads to a-MSH release onto MCR4 receptors to decrease appetite
10
Q
Name a 5HT2C agonist
A
Meta-chlorophenylpiperazine (mCPP) is a 5HT2C agonist
11
Q
What is zimeldine?
A
Zimeldine is an SSRI (selective serotonin reuptake inhibitor)
12
Q
What does zimeldine do?
A
It blocks 5HT reuptake at the serotonin reuptake pump of the neuronal membrane in the CNS, enhancing its actions on 5HT1A autoreceptors
13
Q
Where is the satiety centre?
A
The ventromedial wall of the paraventricular nuclei in the hypothalamus
14
Q
What happens when the ventromedial nuclei are stimulated?
A
It causes aphagia
15
Q
What is the feeding/hunger/thirst centre of the brain?
A
The lateral hypothalamus
16
Q
What happens when the lateral hypothalamus is stimulated?
A
Feeding/ appetite is increased
17
Q
How do opioids and growth hormone-releasing hormone affect appetite?
A
They increase appetite
18
Q
What is naltrexone?
A
An opioid antagonist that reduces the positive ‘hedonic valence’ of food, therefore decreasing appetite
19
Q
How does blood glucose concentration affect hunger?
A
High BGC stimulates gluco-receptors in the hypothalamus and cause satiety, while low BGC up-regulates hunger
20
Q
How does afferent input affect hunger?
A
Distension of the stomach inhibits appetite, while contraction of an empty stomach stimulates appetite
21
Q
How does fat ingestion affect appetite?
A
Fat in the duodenum causes CCK release from I cells, which slow gastric emptying for satiety.
22
Q
How does the amount of stored white fat affect insulin release from ß-cells?
A
With more white adipose stores, more insulin is released
23
Q
How does insulin affect appetite?
A
Some insulin released into circulation will flow through brain capillaries to the brain. Here, insulin usually reduces appetite by down-regulating NPY and AgRP in a catabolic response. Insulin can also act on POMC/CART neurons to increase food intake
24
Q
How does glucagon act as an anorexigenic agent?
A
It acts on the hindbrain via the liver to promote release of glucose and inhibition of food intake
25
Where are leptin genes expressed?
Mainly in adipocytes
26
What 3 things does leptin do?
Decrease food intake, induce weight loss and increase energy expenditure
27
How does leptin act as a lipostat?
It controls fat stores by operating a feedback mechanism between adipose tissue and the arcuate nucleus in the brain.
28
What does leptin increase the expression of?
Anorexigenic agents like POMC, cocaine- and amphetamine-regulated transcript (CART), CRH and neurotensin)
29
What does leptin inhibit to decrease appetite?
NPY
30
What is ghrelin?
A fast-acting orexin that stimulates hunger and foo intake
31
What 3 organs release ghrelin?
The pancreas, stomach and adrenal glands
32
When do circulating ghrelin levels rise and fall?
Ghrelin levels are high pre-prandially, then drop after a meal.
33
How does ghrelin generate hunger signals?
Ghrelin increases central orexin like NPY and AgRP, and suppresses the ability of leptin to stimulate anorexigenic factors
34
What can inhibit ghrelin secretion?
Leptin
35
What cells produce obestatin?
Epithelial cells of the stomach
36
What does obestatin do?
Obestatin suppresses food intake through appetite, so it antagonises ghrelin-induced foo intake and growth hormone secretion
37
What is hunger?
Discomfort caused by lack of food and by the desire to eat. A strong physiological drive for food. A sensation of emptiness of the stomach
38
What is appetite?
Physiological desire/ drive to satisfy the body's need for food
39
What is satiety?
The state of being full after eating
40
What are the 3 stages f stomach activity?
Fasting, accommodation and emptying
41
What is aphagia?
The inability or refusal to swallow
42
What is hyperphagia/polyphagia?
An abnormal desire for food (extreme unsatisfied drive to eat)
43
What 5 hypothalamic sites are involved in feeding behaviour/ food intake?
```
The lateral hypothalamus (LH)
The ventromedial nucleus (VMN)
The dorsomedial nucleus (DMN)
The paraventricular nucleus (PVN)
The arcuate nucleus
```
44
What is a microbiota?
The microorganisms of a particular site, habitat or geological period
45
What is a microbiome?
The microorganisms in a particular environment.
| The combined genetic material of the microorganisms in a particular environment
46
What are resident flora?
The normal bacteria of the body that we have for life
47
What are transient flora?
Bacteria of the body that can be modified by diet, environment, stress, hormones, age and transit time
48
What makes up around 90% of the bacteria in babies?
Bifidobacterium
49
Why is bifidobacteria so important in babies?
These bacteria utilise the oligosaccharides from breast milk, so they create the right environment for a neonate's gut
50
What is the first passage from the rectum?
Sterile meconium
51
What does normal flora shift to after weaning?
Bifidobacter is reduced, and bacteroides, clostridia and eubacteria increase
52
Roughly how many bacteria are there in the duodenum and jejunum?
Around 1000/g
53
How many bacteria are there in the ileum?
Around 10^8-10^10/g
54
What conditions can disruption of the normal flora lead to (dysbiosis)?
IBD, IBS, clostridium difficile, colon cancer, coeliac disease, diabetes
55
What is clostridium difficile?
A bacterium that can infect the bowel and cause diarrhoea, most commonly infecting people who have recently been treated with antibiotics.
56
What are the most common symptoms of C. diff?
Diarrhoea, painful abdominal cramps, nausea, dehydration, fever, loss of appetite and weight loss
57
Name 4 benefits of the presence of gut flora
Colonisation resistance- blocks pathogens
Produce metabolites of benefit to the host- vitamin K2 and B12
Normal development of immunity- tolerance nd antigenic stimulation
Gut flora aids digestion- fermentation of sugars and regulation of fat storage
58
What are the main bacteria in the duodenum and jejunum?
Lactocilli and Streptococci
59
What are the bacteria in the ileum?
There are Bacteriodes and E. coli
60
What bacteria are there I the colon?
Obligate anaerobes like Bacteriodes, Clostridia and Bifidibacter, and facultative anaerobes like E. coli
61
What's pseudomembranous colitis?
Swelling or inflammation of the large intestine due to an overgrowth of C. difficile bacteria.
62
How does pseudomembranous colitis present in mild cases?
It may appear as minimal inflammation or oedema of the colonic mucosa
63
How does pseudomembranous colitis present in more severe cases?
The mucosa is often covered with loosely adherent nodular or diffuse exudates. These raised exudative plaques are 2-5mm in size. Coalescence of these plaques generates an endoscopic appearance of yellowish pseudomembranes lining the colonic mucosa
64
What's the clinical definition of diarrhoea?
Watery or liquid stools, usually with an increase in stool weight above 200g per day and an increase in daily stool frequency and often a sense of urgency
65
What are the clinical consequences of diarrhoea?
It can lead to severe dehydration. Excessive fluid and electrolyte loss, hypovolaemia, hypokalaemia and organ failure are possible.
It can cause reduced growth.
66
What is dysentry?
Infection of the intestines resulting in severe diarrhoea with the presence of blood and mucus in the faeces
67
What are the symptoms of dysentry?
Blood and mucus in the faeces, pain, fever and abdominal cramps
68
What bacterium is the main cause of dysentry?
Shigella
69
How do enterotoxins affect the pharmacology of enterocytes?
They affect fluid and electrolyte transport by changing intracellular signalling molecules (exotoxins) or damaging endothelial cell membranes (cytotoxins)
70
What are enterocytes?
Simple columnar epithelial cells which line the inner surface of the small and large intestines, with a glycocalyx coat and microvilli on their apical surface
71
How can bacteria damage epithelium besides their toxins?
Bacteria can adhere to epithelium and damage the brush border of enterocytes by effacement of the apical membrane. This stops absorption of nutrients, resulting in anti-absorptive diarrhoea
72
What type of epithelial cells line the oesophagus?
Striated squamous epithelial cells
73
What levels does the oesophagus run from?
C6 to T12
74
What kind of muscle is in the musculo-cartilaginous structure that is the upper oesophageal sphincter?
Striated muscle
75
When does the UOS constrict?
To avoid air entering the oesophagus when you inhale
76
What muscle makes up the LOS?
Smooth muscle
77
What is the intrinsic component of the LOS?
Thick, circular, oesophageal smooth muscles under neurohormonal influence
78
What is the extrinsic component of the LOS?
The diaphragm
79
What does malfunction of the intrinsic and extrinsic components of the LOS lead to?
GORD
80
What are the 3 muscular intrinsic components of the LOS?
Thick circular smooth muscle layers
Clasp-like semi-circular smooth muscle fibres that encircle the gastrooesophageal junction medially on the right side.
Sling-like oblique gastric muscle fibres on the left lateral side that help to prevent regurgitation
81
What is the angle of His?
The oblique angle of the oesophagus as it meets the cardiac orifice of the stomach
82
What is the extrinsic component of the LOS and what's its mechanism of action?
The crural diaphragm that encircles the LOS and forms a channel
Fibres of the crural portion of the diaphragm possess a 'pinchcock-like' action and have myogenic tone
83
What creates the oesophageal hiatus?
A loop of the right crux of the diaphragm
84
What 2 neurotransmitters control contraction of the intrinsic sphincters?
ACh and substance P
85
What 2 neurotransmitters control relaxation of the intrinsic sphincters?
NO and VIP
86
What innervates the striated muscle of the upper oesophagus?
Somatic motor neurones of the vagus nerve
87
What innervates the smooth muscle of the lower oesophagus?
Visceral motor neurones of the vagus nerve
88
Where does integration of impulses to the oesophagus occur?
The NTS, nucleus ambiguous and dorsal vagal nucleus
89
What are the 2 functions of the oesophagus?
Swallowing
| Convey food and fluids from the pharynx to the stomach
90
What triggers swallowing?
Afferent impulses in the trigeminal, glossopharyngeal and vagus nerves
91
How do efferent impulses pass to the pharyngeal musculature and the tongue?
Via the trigeminal, facial and hypoglossal nerves
92
What are the voluntary and involuntary parts of swallowing?
The voluntary part is movement of food from the tongue backwards into the pharynx by skeletal muscle. Waves of involuntary contractions then push the material into the oesophagus
93
What is primary peristalsis in the oesophagus?
The ring of peristaltic waves behind the bolus at 4cm/s that move it towards the stomach
94
What is secondary peristalsis in the oesophagus?
The second wave that moves any for remnants along
95
What causes oropharyngeal dysphagia?
The inability to open the UOS or discooridnation of the timing between opening it and the pharyngeal push of the ingested bolus
96
What happens after you've swallowed something, involving the epiglottis?
The glottis opens and breathing can resume
97
Why is secondary peristalsis important for a large bolus?
A large bolus doesn't reach the stomach after the first peristaltic wave. Distension of the oesophageal lumen stimulates receptors to cause secondary peristalsis
98
What 3 things prevent reflux of the gastric contents?
The LOS closes after material has passed
The 'pinchcock' effect of the diaphragmatic sphincter on the lower oesophagus
Plug-like action of the mucosal folds in the cardia occludes the lumen of the gastrooesophageal junction
99
What is achalasia?
A disorder of motility or peristalsis of the oesophagus whereby the LOS fails to open and normal peristaltic muscle activity is reduced
100
What is GORD?
Gastro-oesophageal reflux disease caused by a weak LOS
101
What is aphagia?
Swallowing difficulty
102
What is oesophageal spasm?
Abnormal oesophageal contractions that mean food isn't effectively reaching the stomach
103
What is diffuse oesophageal spasm?
Chest pain coming from the oesophagus due to uncoordinated contractions
104
What is achalasia caused by?
It's caused by impaired LOS relaxation, which can be accompanied by impaired peristalsis. Food and liquids fail to reach the stomach, resulting in dilation of the lower oesophagus. There's a long period of sporadic dysphagia before food is regurgitated
105
What is the possible aetiology of achalasia?
Damage to the innervation of the oesophagus whereby there's degenerative lesions to the vagus nerve and loss of the myenteric plexus ganglionic cells in the oesophagus. The initiating factor is unknown, although it's thought to be autoimmune or triggered by infection
106
Give 5 symptoms of achalasia
```
Dysphagia (because the LOS fails to relax enough to allow food into the stomach)
Vomiting
Weight loss
Failure to thrive
Heartburn
```
107
After hearing the patient's description of their problems, what 2 diagnostic steps could you take?
Barium radiography
| Oesophageal manometry for absent peristalsis
108
What is bird beak deformity a sign of regarding the oesophagus?
Tapering of the lower oesophagus in achalasia
109
What is oesophageal manometry used for?
To determine the cause of non-cardiac chest pain, to evaluate the cause of GOR, and to determine the cause of dysphagia.
110
What does the oesophageal manometry test involve?
A thin, pressure-sensitive tube is passed through the nose, along the pharynx, through the oesophagus into the stomach. When you swallow, the pressure-sensitive tube monitors the strength and coordination of muscle contractions and of relaxation of the LOS
111
What does low LOS pressure suggest from oesophageal manometry?
GORD
112
What is normal LOS pressure?
<26mmHg
113
What LOS pressure is considered achalasia?
>100mmHg
114
What LOS pressure is considered nutcracker achalasia?
> 200mmHg
115
What does the patient do once the pressure-sensitive catheter is in place?
Take a deep breath and swallow water
116
What are the 2 most common types of oesophageal cancer?
Oesophageal adenocarcinoma
| Squamous carcinoma
117
Where does oesophageal adenocarcinoma begin?
The mucus-secreting glands, usually in the lower oesophagus
118
Where does oesophageal squamous carcinoma most often occur?
In the upper and middle portions of the oesophagus
119
How are young people with low surgical risk treated for achalasia?
Laparoscopic Heller's myotomy
120
How are older patients with low surgical risk treated for achalasia?
Pneumatic dilation
121
How are patients with high surgical risk treated for achalasia?
Botulinum toxin injection or Ca2+ blockers if this fails
122
Describe GORD
The retrograde movement of gastric contents into the oesophagus due to relaxation of the LOS
123
Why does gastro-oesophageal reflux usually stimulate salivation?
Saliva is an effective natural antacid, so it dilutes and neutralises refluxed gastric contents to decrease damage caused
124
What are around 98% of reflux events in normal individuals associated with?
Transient spontaneous relaxation of the LOS
125
What happens when the resting LOS pressure is too weak to resist the pressure within the stomach?
Sudden relaxation of the LOS that isn't induced by swallowing
126
What are 3 factors that contribute to GORD severity?
Weak or uncontrolled oesophageal contractions
Length of time the oesophagus is exposed to gastric acid
Amount of pressure placed on the anti-reflux barrier
127
Name some lifestyle factors associated with GORD
Pregnancy, obesity, fatty food, coffee, alcohol, large meals, orange juice, onions, cigarettes and certain drugs
128
How can GORD lead to basal cell hyperplasia?
Desquamation of the oesophageal squamous mucosal cells from acid reflux and resulting cell loss
129
What can excessive desquamation of oesophageal mucosal cells lead to?
Ulceration
130
What is Barrett's oesophagus?
Where stratified squamous epithelium of the oesophagus changes to simple columnar epithelium with interspersed goblet cells. This change is considered premalignant, as it's associated with increased incidence of oesophageal adenocarcinoma
131
What are the pathophysiological and clinical features of GORD?
Low or absent resting LOS tone
LOS tone fails to increase when lying flat or during pregnancy
Poor oesophageal peristalsis leads to decreased acid clearance
132
How can a hiatus hernia affect LOS function?
A hiatal hernia can impair the function of the LOS and diaphragmatic closing mechanisms, giving symptoms similar to GORD
133
Give 3 symptoms of GORD
Heart burn and acid regurgitation
Nocturnal awakenings
Dysphagia
134
What is the first line of investigation of GORD?
Low dose proton pump inhibitor challenge
135
What are further steps for investigation of GORD?
Upper GI endoscopy, manometry or 24-hour ambulatory pH monitoring
136
How does pregnancy affect or induce GORD?
A foetus increases the pressure on the abdominal contents, pushing terminal segments of the oesophagus into the thoracic cavity. The last trimester of pregnancy is associated with increased abdominal pressure that forces gastric contents into the oesophagus. Heartburn subsides in the last months as the uterus descends into the pelvis
137
What causes heartburn in the absence of pregnancy?
Less efficient LOS that allows gastric contents to episodically reflux into the oesophagus.
138
Name 6 potential long-term effects of GORD
```
Oesohpagitis
Oesophageal strictures
Squamous cell carcinoma
Barrett's oesophagus
Oesophageal adenocarcinoma
Oesophageal ulcers
```
139
Name some lifestyle changes for someone with GORD
```
Raise the head of the bed for better sleep.
Lose weight
Decrease intake of trigger foods
Avoid large meals
Avoid lying down after meals
```
140
What is Nissen fundoplication?
Surgery in which doctors wrap the funds around the LOS so that it strengthens the valve mechanism
141
What drugs can someone with GORD take?
Antacids
H2 receptor antagonists and proton pump inhibitors.
Metoclopramide/ domperidone to enhance peristalsis and aid clearance of gastric acid
142
What do antacids do in treatment of GORD?
Neutrlise gastric acid and increase the pH of the gastric lumen.
Inhibit peptic activity and stop acid secretion
143
What do magnesium salts cause?
Diarrhoea
144
What do aluminium salts cause?
Constipation
145
What cells synthesise bile?
Hepatocytes
146
What is the pathway of bile into the duodenum?
Bile drains through the left and right hepatic ducts into the cystic duct and into the gallbladder. It's then secreted into the duodenal lumen via the common bile duct and the ampulla of Vater
147
What is the function of the gallbladder?
Storage and secretion of bile
148
What do pancreatic juices contain?
Bile salts, bile pigments and dissolved substances in alkaline electrolytes. This is due to joining of the pancreatic duct to the common bile duct prior to entry into the duodenum
149
What are bile canaliculi?
Small, thin, capillary-like tubes that collect bile secreted by hepatocytes. They empty into a series of progressively larger bile ductules and ducts
150
What do terminal bile ducts merge to form?
The left and right hepatic ducts, which merge to for the common bile duct
151
What are cholangiocytes?
Epithelial cells that line the bile ducts
152
What is glutathione?
GSH is an antioxidant capable of preventing damage to important cellular components that's caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides and heavy metals
153
What do bile ductules secrete in response to secretin in the postprandial period?
Ductules secrete IgA for mucosal protection, HCO3- and H2O
154
What 2 cell types secrete the components of bile?
Hepatocytes produce cholesterol, lecithin, bile acids and bile pigments. Epithelial cells of bile ducts produce bicarbonate-rich salt solution
155
What are 3 bile pigments?
Bilirubin, biliverdin and urobilin
156
When is bile secretion at its greatest?
During and after a meal
157
When does the sphincter of Oddi contract?
During periods of fasting
158
When does the sphincter of Oddi relax?
During and after meals
159
What substances are secreted across the bile canalicular membrane?
Bile acids, phosphatidylcholine, conjugated bilirubin, cholesterol and xenobiotics
160
Describe the composition of hepatic bile
97% water, then fractional cholesterol, lecithin, bile acids and bile pigments etc.
161
Describe the composition of gallbladder bile
89% water, then the rest is HCO3-, Cl-, Ca2+, Mg2+, Na2+, cholesterol, bilirubin, bile salts etc.
162
Where is bile concentrated?
In the gallbladder, where NaCl and H2O loss leads to increased solid content
163
What are bile acids made from?
Cholesterol
164
What are bile acids conjugated to once secreted into bile in the liver?
Glycine or taurine
165
Why are bile acids conjugated?
To help increase the ability of bile acids to be secreted and to decrease their cytotoxicity
166
What does bile acid conjugated with glycine form?
Glycocholic acid
167
What does bile acid conjugated with taurine form?
Taurochenodeoxycholic acid
168
What are the 4 major bile acids in humans?
Cholic acid, chenodeoxycholic acid
Deoxycholic acid
Lithocholic acid
169
What are the major 5 functions of bile?
Elimination of cholesterol to bile acids
Reduction of precipitation of cholesterol in the gallbladder
Facilitate the absorption of fat-soluble vitamins (ADEK)
Regulate their own transport and metabolism via enterohepatic circulation
Facilitate the digestion of triglycerides
170
What are the 3 phases of contraction of the gallbladder?
The cephalic phase, gastric phase and intestinal phase
171
What is the cephalic phase of gallbladder contraction?
Taste, smell and the presence of food in the mouth generates impulses via the vagus nerve
172
What is the gastric phase of gallbladder contractions?
Distension of the stomach generates impulses in the vagus nerve
173
What is the intestinal phase of gallbladder contraction?
A major period of gallbladder emptying. Key mediators are CCK and secretin, in response to lipids and hyperacidity, respectively
174
How does CCK affect bile secretion?
CCK directly and indirectly triggers contraction of the gallbladder and relaxation of the sphincter of Oddi
175
What neurotransmitters relax the sphincter of Oddi?
NO and VIP (NANC neurones)
176
How does secretin affect bile secretion?
Secretin stimulates duct cells in the liver to produce bile
177
What effects do CCK and secretin have on the pancreas?
CCK induces enzyme-rich pancreatic juice secretion. Secretin causes secretion of HCO3- rich pancreatic juice
178
Where are bile salts and lecithin synthesised?
The liver
179
How are most bile salts reabsorbed?
Na+ bile salt coupled transporters
180
What's enterohepatic circulation?
Circulation of bile acids, bilirubin, drugs or other substances from the liver to bile, into the small intestine, being absorbed by enterocytes and transported back to the liver
181
What causes cholesterol gallstones?
Excessive secretion of cholesterol from the liver and reabsorption of salt and water, giving increased cholesterol, which crystallises into stones
182
What are the 2 types of gallstones?
Cholesterol gallstones
| Calcium gallstones
183
What are 3 causes of cholesterol gallstones?
Obesity
Decreased bile acids
Decreased phospholipids
184
What causes calcium gallstones?
Increased conjugated bilirubin
185
What are factors of gallstone formation?
Sequestered bile salts in the gallbladder
Decreased bile acids due to malabsorption or bile production problems
Chronic infection by bacteria that aid pigment stone formation
Super-Saturation of bile with cholesterol
Presence of nucleation factors or glycoprotein
186
Where may large gallstones lodge?
The opening of the gallbladder
187
What can happen when gallstones lodge in the ampulla of Vater?
Stoppage of bile and pancreatic secretions, so pressure builds up and causes decreased bile secretion, resulting in jaundice and possible nutritional deficiency
188
How can gallstones be diagnosed?
Visualisation, either via ultrasonography or CT scanning of the right upper quadrant
189
What is cholescintigraphy?
Administration of technetium-99m-labelled derivative of iminodiacetic acid to image the gall bladder and ducts
190
What is endoscope retrograde cholangiopancreotography (ERCP)?
A technique used to visualise the biliary tree by injecting contrast media from an endoscope channel
191
What proportion of gallstone cases are asymptomatic?
Around 85%
192
What are possible symptoms of gallstones?
Acute cholecystitis
Cholestatic jaundice
Cholangitis
193
What does gallstone in the cystic bile duct cause?
Painful gallbladder contractions
194
What does gallstone blocking the common bile duct cause?
Pain and nausea, as well as lack of bile release and jaundice
195
What does gallstone blocking the duodenal papilla cause?
Inappropriate activation of pancreatic zymogens
| Acute pancreatitis
196
What cations are found in gastric juice?
Na+, K+, Mg2+, H+
197
What anions are found in gastric juice?
Cl-, HPO4 2-, SO4 2-
198
What is the pH of gastric juice?
3.0
199
What volume of gastric juice is secreted each day?
Around 2.5L
200
What 3 things do the fundus and body of the stomach secrete?
Mucus, HCl and pepsinogen
201
What is secreted less in the antrum and what is secreted more?
Less HCl is secreted, but more gastrin is secreted to stimulate HCl secretion in the fundus and body
202
What are the cells that line the wall of the stomach and was do they secrete?
Parietal cells secrete HCl and intrinsic factor
203
What do ECL cells secrete?
Enterochromaffin-like cells secrete paracrine agents such as histamine for local effects
204
What cranial nerve is very important to acid secretion?
The vagus nerve
205
How is gastric acid made in the stomach lumen?
HCO3- is exchanged for Cl- in the blood, decreasing acidity of venous blood from the stomach. Excess Cl- diffuses out into the stomach through Cl- channels as the H+ is pumped into the stomach lumen by K+ H+ ATPase pumps. The net effect is flow of HCl out of parietal cells into the stomach lumen
206
What do non-parietal cells secrete?
Resting juice, which is similar to plasma, with a pH of 7.4
207
What is mucus high in?
HCO3-, so it's alkaline
208
What's the function of mucus secreted into the stomach?
It forms water-insoluble gel on the epithelial surface to protect against H+
209
What is the function of rennin?
Rennin is an enzyme that curdles milk into a casein clot in some animals
210
What does intrinsic factor prevent?
Pernicious anaemia, by aiding absorption of vitamin B12
211
What are the 3 functions of stomach HCl?
Kill bacteria
Acid denaturation of digested food
Activate pepsinogen into pepsin
212
What are the 3 phases of gastric secretion?
The cephalic phase, gastric phase and intestinal phase
213
What regulates HCl secretion?
Neuronal pathways and duodenal hormones
214
How are gastric secretions mediated in the cephalic phase?
The vagus nerve stimulates acid production and pepsin activation
215
How are gastric secretions mediated in the gastric phase?
Local nervous secretory reflexes, vagal reflexes and gastrin-histamine stimulation
216
What elicits HCl secretion in the cephalic phase?
ACh release stimulates histamine release from ECL cells, as well as acting directly on parietal cells
217
How does the gastric phase cause HCl secretion?
Distension of the stomach activates neural reflexes, causing ACh release from enteric neurons onto parietal cells. Peptides cause G cells to secrete gastrin that triggers histamine release from ECL cells and HCl release from parietal cells.
218
What hormone inhibits gastrin, histamine and HCl secretion?
Somatostatin from D cells
219
Why can excessive protein in the diet lead to stomach ulcers?
Hyperacidity. Proteins remove the inhibitory powers of HCl on gastrin secretion and hence acid secretion, so they increase gastrin-mediated acid secretion
220
In the intestinal phase, what does high acidity of the duodenal contents cause?
An inhibitory reflex on acid secretion to prevent chyme from becoming too acidic
221
What 4 things inhibit acid secretion in the intestinal phase?
```
Distension of the duodenum
Hypertonic solution
Amino acids
Fatty acids
(Therefore the composition and volume of chyme)
```
222
What causes the release of enterogastrones?
Acidity, distension, changes in osmolarity and presence of fats in the duodenum
223
What are enterogastrones?
CCK, secretin, glucagon-like peptide-1 (GLP1) and gastrin-inhibiting peptide (GIP)
224
What receptors does gastrin bind to on parietal cells and ECL cells?
CCKB (AKA CCK2)
225
What receptors does ACh act on in the gut?
M3
226
What receptors does histamine act on on parietal cells?
H2 receptors
227
What type of receptor are H2 receptors?
Gs-mediated receptors that activate the A pathway
228
What kind of receptors are somatostatin and prostaglandin receptors?
Gi-mediated receptors that inhibit the A pathway
229
What 3 effects do prostaglandins have on the gut?
They inhibit parietal cell activity, promote bicarbonate secretion and promote mucus secretion
230
What does HCl concentration depend on?
Rate of secretion, amount of buffering, composition of ingested food, rate of gastric emptying and amount of diffusion back into mucosa
231
What is hypochlorhydria/achlorhydria?
Absence of or low HCl production in gastric secretions which causes failure of protein digestion
232
What are possible causes of hypochlorhydria?
Age, stress, medications, bacterial infection, zinc deficiency, or surgical procedures like gastric bypass
233
Give symptoms of hypochlorhydria
```
Presence of undigested food in stool
Flatulence
Bloating
Diarrhoea
Heartburn
Hair loss
Nausea
Nutrient deficiencies
```
234
How can hypochlorhyria be treated?
Antibiotics for H. pylori infection or a change to current medications.
235
What factors increase HCl secretion?
Histamine, ACh, gastrin, caffeine, alcohol, NSAIDs, nicotine, H. pylori, Zollinger-Ellison syndrome, hyperparathyroidism and stress
236
What cells secrete pepsin?
Chief cells secrete pepsin in the form of pepsinogen, an inactive zymogen
237
How does acidity activate pepsinogen?
Shape is altered by high acidity, which exposes its active site in an autocatalytic feedback process
238
What stimulates pepsinogen secretion?
Nerve inputs to chief cells
239
How do NSAIDs cause topical irritation to the gut?
They impair the barrier properties of the mucosa and suppress gastric prostaglandin synthesis. They decrease gastric mucosal flow, interfere with repair of superficial injury and inhibit platelet aggregation.
240
How does the liver contribute to lowering blood glucose levels?
By regulating the flux into the pathways that remove free glucose
241
Name 2 serum proteins of which the liver is the major site of synthesis?
Albumin and clotting factors
242
What does the liver convert glucogenic amino acids to?
Sugars
243
What does the liver convert ketogenic amino acids to?
Ketone bodies
244
What processes is the liver the major site for regarding amino acid metabolism and urea metabolism?
Transamination and deamination of amino acids.
| Detoxification of ammonia
245
What 3 processes involving lipids does the liver play a central role in?
Synthesis, transport and metabolism
246
What percentage of endogenous cholesterol does the liver make?
Around 50%
247
What is cholesterol made from?
Acetyl CoA
248
What is the key enzyme to cholesterol synthesis?
HMG-CoA reductase
249
What's cholesterol transported from the liver as?
VLDL
250
What system disposes of cholesterol?
The biliary system
251
What are the 2 routes to the metabolism of ethanol by the liver?
Oxidation through the activity of alcohol dehydrogenase (80-90%)
Microsomal oxidation using cytochrome P450 (10-20%)
252
What is the first reaction in the metabolism of ethanol?
The conversion of ethanol to acetaldehyde in a process requiring alcohol dehydrogenase and NAD+, which gets protonated
253
What mass of alcohol is metabolised per hour?
Around 10g
254
What is methanol metabolised to?
Formaldehyde
| This is very toxic and associated with blindness, paralysis and loss of consciousness
255
What is the second reaction in metabolism of ethanol, once it's become acetaldehyde?
Conversion of acetaldehyde to acetate, which requires aldehyde dehydrogenase and NAD+ + H2O, which forms NADH and 2H+
256
Caucasians have 2 isoforms of acetaldehyde dehydrogenase. What are they?
ALDH-1 and ALDH-2
257
What is the main isoform of acetaldehyde dehydrogenase?
ALDH-2, which is mitochondrial with a low km
258
Around 40% of east-asians are intolerant to ethanol. What are the symptoms?
Vasodilation, facial flush, tachycardia and nausea
259
What converts acetate to acetyl CoA?
Acetyl CoA synthase
260
Why are large quantities of acetyl CoA, NADH and ATP formed from alcohol?
Oxidation of alcohol takes precedence over other nutrients and there's no negative feedback for its metabolism
261
How do acetyl CoA, NADH and ATP formed from alcohol metabolism affect glucose metabolism?
They inhibit glucose metabolism by inhibiting PFK and pyruvate dehydrogenase
262
How do NADH and acetyl CoA affect the TCA cycle?
NADH inhibits the cycle, and acetyl CoA inhibits it further
263
What does acetyl CoA production from alcohol lead to?
Ketone body formation and the stimulation of fatty acid synthesis. Fatty acids are esterified to TG for export as VLDL
264
What is the second route of ethanol metabolism?
The microsomal ethanol-oxidising system
265
What does the microsomal ethanol-oxidising system involve?
The oxidation of ethanol by members of the cytochrome P450 family of enzymes, using NADPH, which is required for the synthesis of the antioxidant glutathione
266
What highly reactive substance can accumulate with excessive ethanol intake?
Acetaldehyde
267
How can acetaldehyde accumulation affect the body?
Acetaldehyde can inhibit enzyme function. In the liver, this can lead to reduction in the secretion of both serum protein and VLDL. It can also enhance free-radical production, leading to tissue damage such as inflammation and necrosis
268
What are the 3 stages of alcohol liver damage?
Stage 1- fatty liver
Stage 2- alcoholic hepatitis (groups of cells die, resulting in inflammation)
Stage 3- cirrhosis, which includes fibrosis, scarring and cell death
269
What happens in a cirrhotic liver?
Ammonia accumulates, resulting in neurotoxicity, coma and possibly death.
270
What proportion of cirrhosis is due to alcohol?
75% of cases
271
What proportion of alcoholics get cirrhosis?
Around 25%
272
What are xenobiotics?
Compounds not naturally produced in the body that have no nutritional value
273
Name some xenobiotics
Plant metabolites, synthetic compounds, food additives, agrochemicals, cosmetics, drugs
274
The liver plays a major role in xenobiotic metabolism. What's its aim?
To make xenobiotics harmless and more readily disposed of by the kidney in urine or the gut in faeces
275
What are the 3 phases of metabolism of xenobiotics?
Phase 1- oxidation
Phase 2- conjugation
Phase 3- elimination
276
What other modifications of xenobiotics are possible besides oxidation?
Hydroxylation and reduction
277
What is the point of the modification in phase 1?
To increase solubility of the xenobiotic by introducing functional groups that enable participation in further reactions promoted by cytochrome P450
278
Where is cytochrome P450 mostly found?
In the liver and cells of the intestine
279
What happens in conjugation of xenobiotics (phase 2)?
Xenobiotics are modified by addition of groups such as glutathione, glucuronic acid and sulphate to increase solubility and target the xenobiotics for excretion
280
Why is xenobiotic metabolism a potential clinical hinderance?
The body does't distinguish between harmful compounds and beneficial compounds such as therapeutic drugs. Oral drugs pass through the liver first, and modification made can significantly reduce the effectiveness of the drug
281
How do statins work?
Statins inhibit HMG-CoA reductase, which is crucial to cholesterol biosynthesis
282
What degrades statins?
CYP3A4, which can be inhibited by components of grapefruit juice
283
What is aflatoxin B1?
A very potent carcinogen produced by the fungus Aspergilus flavus, which is activated bt P450 isoenzymes, leading to epoxide formation and hepatocarcinogenesis
284
How does the liver metabolise paracetamol?
The liver first conjugates it with glucoronate to produce a soluble molecule that's readily excreted by the kidney, or sulphated for similar effects. There is a small amount of metabolism by P450 to form NADPQL, which is metabolised with the aid of glutathione to form a soluble molecule excreted in urine
285
What is the mechanism of peptic ulcer formation?
Breakage of the mucosal barrier- imbalance between protective and damaging factors. Then tissues are exposed to the erosive effects of HCl and pepsin, leading to ulcers
286
Where are the 3 commonly affected sites for ulcers?
The oesophagus, stomach and duodenum
287
Name 7 factors that prevent infection of the gastric mucosa?
```
HCl
Peyer's patches
Mucus production
IgA secretion at mucosal surfaces
Peristalsis and fluid movement
Fast cell turnover
Seamless epithelium with tight junctions
```
288
What protective factors prevent auto digestion of the stomach?
Secretion of alkaline mucus and HCO3-
Protein content in food
Presence of tight junctions between epithelial cells and the fibrin coat
Replacement of damaged cells within the gastric pits
Prostaglandins inhibit acid secretion and enhance blood flow
289
Describe H. pylori
Gram-negative, aerobic spirochete bacteria that can be coccoid
290
Describe how H. pylori infects the gut
H. pylori penetrates the gastric mucosa via flagella that enable 'corkscrew motility' towards the gut epithelium
291
What are 5 virulence factors of H. pylori?
Motility- it moves closer to the epithelium where pH is favourable
Uses mucinase activity to digest the protective mucus layer
Produces urease to form ammonia that buffers gastric acid
Cytotoxin-associated antigen (CagA) inserts pathogenicity islands and confers ulcer-forming potential
Vacuolating toxin A (VacA) alters the trafficking of intracellular protein in gastric cells
292
What does H. pylori infection positively dysregulate?
Gastrin secretion
293
What is the basic description of the cause of peptic ulcers?
Increase gastric acid secretions that lead to mucosal breakdown
294
Name aggravators of peptic ulcers
Regurgitated bile acids, NSAIDs, genetics, smoking, alcohol, spicy food, chronic gastritis and H. pylori infection
295
What does mucinase released from H. pylori do?
Breaks down the protective alkaline mucus layer of the gut
296
What does urease released from H. pylori do?
Urease converts urea to ammonia, which buffers gastric acid and produces CO2
297
What 4 specific locations are common sites of peptic ulcers?
The first part of the duodenal cap
The junction of the body and antrum of the stomach
The distal oesophagus, especially in Barrett's oesophagus
Meckel's diverticulum in the small intestine
298
What are 2 options for diagnostic tests for a suspected peptic ulcer?
Endoscopy (oesophagogastroduodenoscopy)
| Histological examination and staining of an EGD biopsy
299
What are 2 tests for the presence of H pylori?
Stool antigen test
| Evaluation of urease activity via a urea breath test
300
What are symptoms of a peptic ulcer?
Anaemia, black, tarry stools, nausea, dyspepsia, anorexia, vomiting, haematemesis, epigastric pain, chest discomfort, weight loss
301
Where does chronic peptic ulcer occur?
The upper GIT
302
Name 5 complications of peptic ulcers
Haemorrhage
Perforation (peritonitis)
Penetration, which may lead to leakage of luminal contents
Narrowing of the pyloric canal or oesophageal stricture
Malignant changes (3-6 times more likely with H. pylori infections)
303
Name 4 H2 receptor antagonists
Cimetidine, ranitidine, famotidine and nizartidine
304
What is the clinical use of H2 receptor antagonists?
Treatment of peptic ulcers and reflex oesophagitis
305
How do H2 receptor antagonists work?
They inhibit histamine action on parietal cells, reducing gastric acid secretion and pepsin secretion. They can decrease basal and food-stimulated acid secretion by around 90%
306
What are the side effects of H2 receptor antagonists (although rare)?
Diarrhoea, muscle cramps, hypergastrinaemia and transient rashes
307
What can cimetidine rarely cause in men?
Gynaecomastia, which decreases sexual function
308
How does cimetidine affect drug metabolism?
Cimetidine inhibits P450 enzymes, which decreases metabolism of anticoagulants and tricyclic antidepressants like imipramine, dosulepin and amitriptyline
309
Which drug has a lower IC50, ranitidine or cimetidine?
Ranitidine
310
Name 4 proton pump inibitors
Omeprazole, lansoprazole, pantoprazole and rabeprazole
311
What are the (3) clinical uses of proton pump inhibitors?
Treatment of peptic ulcers and reflux oesophagitis and of Zollinger-Ellison syndrome
312
What is the mechanism of action of proton pump inhibitors?
They are weka bases that are inactive at neutral pH and irreversibly inhibit the K+ H+ ATPase pump. They decrease basal and food-stimulated gastric acid secretion
313
What are the side-effects of proton pump inhibitors?
Headache, diarrhoea, mental confusion, rashes, somnolence, impotence, gynaecomastia and dizziness
314
What drugs are gastroprotective?
Prostaglandins (PGE2 and PGI1)
315
What is misoprostol?
A stable analogue of PGE1 that works by inhibiting basal and food-stimulated gastric acid secretion and inhibiting histamine- and caffeine-induced gastric acid secretion. It increases mucosal blood flow and can augment the secretion of HCO3- and mucus
316
What are pancreatic acini?
Clusters of cells that produce digestive enzymes and secretions and make up the bulk of the pancreas
317
What is meant by 'the pancreas is a dual organ'?
It has exocrine and endocrine portions
318
What do acing cells contain?
Zymogen granules
319
What are acing cells surrounded by?
A basal lamina
320
What cells form an intercalated duct?
Centroacinar cells
321
What part of the pancreas do acini form?
The exocrine part, as they secrete digestive enzymes
322
What extend from the apical side of acinar cells?
Microvilli
323
How much fluid does the exocrine pancreas secrete per day?
1.5L
324
What does the pancreas secrete?
HCO3- and sodium-rich juice containing albumin, globulin and digestive enzymes
325
What is significant about the enzymes secreted in pancreatic juice?
They are inactive forms to prevent auto digestion, and they activate in the duodenum at the brush border
326
How is composition of pancreatic juice modified as it travels through the duct?
Cl- is actively exchanged for HCO3- by the epithelial cells. H+ is actively eliminated, so more CO2 and HCO3- is produced in blood. H+ is exchanged for K+ and Na+, and neutralises HCO3- to form H2CO3. CO2 diffuses in and forms H2CO3 with H2O
327
What 3 major types of enzymes does the pancreas secrete?
Proteolytic enzymes
Amylase
Lipase
328
What are the 3 proteolytic enzymes secreted by the pancreas?
Trypsin, chymotrypsin and carboxypeptidase
329
What's trypsin secreted by the pancreas as?
Trypsinogen, which is activated by enteropeptidase and by trypsin itself
330
What activates pancreatic alpha-amylase?
Cl-
331
What activates elastase?
Trypsin activates elastase to digest elastin
332
What activates phospholipase A2?
Trypsin activates phospholipase A2 to digest phospholipids
333
What are chymotrypsins secreted sand what do they do?
Chymotrypsin is secreted as chymotrypsinogen and activated by trypsin to digest proteins and polypeptides
334
What do carboxypeptidase A and B digest?
They're activated by trypsin to digest proteins and polypeptides
335
What causes enterokinase secretion?
CCK
336
Whta is enterokinase?
A brush border enzyme that converts trypsinogen to trypsin.
337
What are Kazal inhibitor, enzyme Y, chymotrypsin C and caldecrin?
Autodigestion inhibitors
338
What happens in acute pancreatitis?
Trypsin activates phospholipase A2 in the pancreatic duct. PLA2 converts lecithin to isolecithin. Isolecithin disrupts pancreatic tissue, causing membrane damage and necrosis
339
What are symptoms of pancreatic lipase insufficiency?
Malabsorption and steatorrhea
340
What are the 4 mediators of pancreatic secretions?
Neurocrine signals
Vagal parasympathetic stimulation (enhances rate of secretion)
Sympathetic stimulation (inhibits secretion)
Secretin and CCK stimulate secretion
341
What happens in the cephalic phase involving the pancreas?
Vagal stimulation of gastrin release from the antrum via ACh and VIP leads to secretion of some protein-rich pancreatic juice
342
What happens in the gastric phase regarding pancreatic secretions?
Distension and the vagal reflex on the fundus or antrum, and amino aicd- and peptide-stimulated gastrin secretion leads to release of enzyme-rich pancreatic juice
343
What happens in the intestinal phase with regards to pancreatic secretions?
Chyme in the duodenum and jejunum induces secretion of pancreatic juice via CCK and secretin
344
What effect does secretin from the duodenum and jejunum have on the pancreas?
Secretin acts at duct cells to induce HCO3- rich pancreatic juice secretion
345
What effect does CCK from the duodenum and jejunum have on the pancreas?
CCK stimulates pancreatic acing cells to synthesis and release enzyme-rich pancreatic juice. CCK also potentiates the effects of secretin
346
What does cystic fibrosis affect?
The sinuses, lungs, skin, liver, pancreas, intestines and reproductive organs. It can block the pancreatic ducts
347
What's the direct pathway of gastric acid secretion?
ACh, gastrin and histamine all stimulate the parietal cells and trigger secretion of H+ into the lumen
348
Where in the GIT is gastrin secreted?
The gastric mucosa and duodenum
349
What effects do milk and Ca2+ have on gastrin secretion?
They stimulate gastrin release
350
What effects does metoclopramide have on gastric motility and emptying?
Metoclopramide inhibits pre- and post-synaptic dopamine receptors (D2) as well as 5-HT3 receptors in the CNS to inhibit vomiting. It stimulates various 5-HT receptors in the ENS for pro kinetic effects, and also stimulates inhibitory nitrergic neurons for coordinated gastric motility
351
How does dopamine affect the gut?
Dopamine inhibits release of ACh from intrinsic myenteric cholinergic neurons by activating prejunctional D2 receptors. Dopamine has relaxant effects on the LOS and fundus and antrum by activating D2 receptors. Dopamine can induce contraction in the proximal intestine but relaxation in the distal intestines
352
What type of drug is metoclopramide?
A D2 receptor antagonist
353
How does metoclopramide affect gastric motility?
It increases release of ACh and increases intragastric pressure by increasing LOS tone and tone of gastric contractions. These improve antroduodenal coordination, which accelerates gastric emptying and relaxes the pyloric sphincter
354
Through additional pro kinetic effects, how does metoclopramide cause coordinated gastric motility?
Metoclopramide stimulates presynaptic excitatory 5-HT receptors and inhibitory nitrergic neurons
355
How does metoclopramide elicit antiemetic effects?
Metoclopramide inhibits central pre- and post-synaptic D2 receptors and 5-HT receptors to inhibit vomiting
356
What is metoclopramide used for? (5)
```
Symptoms of gastroparesis
Promotes gastric emptying
Anti-emetic effects via CNS
GORD
Nausea due to surgery ir cancer
```
357
What is metoclopramide useless for?
Paralytic ileus, because it causes moderate to diffuse abdominal discomfort
358
Which serotonin receptors does metoclopramide stimulate?
5-HT4
359
What do antispasmodic agents do?
Decrease spasm in the bowel by relaxing smooth muscle.
360
What type of drug is propantheline?
An antimuscarinic agent (inhibits parasympathetic activity)
361
What is propantheline used for?
Irritable bowel syndrome and diverticular disease
362
What are the goals of pharmacological intervention in gastric ulcers? (3)
Reduce acid secretion with H2 receptor antagonists
Neutralise secreted acid with antacids
Attempt to eradicate H. pylori
363
What's the general mechanism of action of antacids?
Neutralise the acid
| Increase the pH of gastric acid, as peptic activity stops at pH 5
364
Name an antacid with cytoprotective effects
Bismuth chelate
365
How does bismuth chelate work?
It protects the gastric mucosa by forming a coat over the crater of the ulcer, absorbing pepsin and increasing HCO3- and PG secretion
366
What are signs of bismuth chelate use?
It blackens the stool and the tongue. It can cause nausea and vomiting
367
How can NSAIDs cause gastric bleeding?
They inhibit PG synthesis
368
Name 2 selective COX-2 inhibitors that decrease gastric bleeding
Celecoxib and rofecoxib
369
How does bismuth chelate affect H. pylori?
It has toxic effects, preventing the adherence of H. pylori to the mucosa or inhibiting its proteolytic activity
370
What may happen to plasma bismuth chelate concentration in someone with renal impairment?
Plasma bismuth chelate concentration may rise dangerously high and cause encephalopathy
371
What can't you do if you're taking metronidazole for H. pylori infection?
Drink alcohol, as disulfiram-like reactions result
372
Why can't you drink alcohol while taking metronidazole for H. pylori infection?
Disulfiram inhibits acetaldehyde dehydrogenase, leading to acetaldehyde build-up and unpleasant flushing and nausea
373
What are consequences of constipation as a result of rectal distension?
Headache, loss of appetite, nausea and abdominal distension and pain
374
What does holding of faecal matter lead to?
Increased water loss and drier faeces, leading to more painful, difficult defecation
375
What causes constipation?
Diet, or decreased motility of the large intestine due to age, disease, drugs or enteric NS damage
376
What are alarm signs in patients with constipation?
```
Acute onset constipation in elderly patients
Weight loss >10lb
Haematochezia
Anaemia
Family history of colon cancer or IBD
```
377
What are possible causes of haematochezia?
Diverticular disease, anal fissure, colitis, angiodysplasia, peptic ulcers, polyps and colorectal cancer
378
How do purgatives like laxatives, faecal softeners and stimulant purgatives help constipation?
They retain water in the gut lumen to promote peristalsis
379
How does lactulose, a laxative work?
It reaches the colon unchanged. Here, bacteria break it down into short-chain fatty acids. Osmotic pressure and biomass increase, leading to softening of the faeces and increased stool volume. Peristalsis is stimulated and colonic transit time is shortened
380
What causes diarrhoea?
Infectious agents, toxins, anxiety, and drugs like amitryptiline, doxepin, clonidine, codeine, tramadol and methadone
381
What are the therapeutic strategies to diarrhoea treatment?
Maintain fluid and electrolyte balance via oral rehydration therapy. Use anti-infectives. Use anti-motility drugs- adsorbents that modify fluid and electrolyte transport
382
What is the main cause of gastroenteritis?
Campylobaceter sp
383
What is loperamide (Imodium)?
An anti-diarrhoea medication that can treat diarrhoea or IBS. It's also used for longer lasting diarrhoea from bowel problems like Crohn's disease, ulcerative colitis and short bowel syndrome
384
What's the mechanism of action of loperamide?
Loperamide is an opioid receptor agonist that exerts its effects on the µ-opioid receptor of the myenteric plexus of the large intestine, inhibiting gastric emptying by increasing sphincter tone. This induces stationary motor patterns and blocks peristalsis
385
Does loperamide have central effects?
No, as it doesn't cross the BBB
386
What's the daily fluid intake breakdown in the average adult?
2550ml
Liquids: 1200ml
Food: 100ml
Metabolically produced: 350ml
387
What's the daily fluid output breakdown in the average adult?
```
2550ml
Insensible loss via skin and lungs: 900ml
Sweat: 50ml
Faeces: 100ml
Urine: 1500ml
```
388
What's the daily NaCl intake in an average adult?
10.5g
389
What classifies as diarrhoea (frequency-wise)?
>3 unformed stools per 24 hour period
390
What are 3 causes of decreased absorption of water and the type of diarrhoea that accompany them?
Increased number of osmotic particles (osmotic diarrhoea)
Increased rate of flow of intestinal contents (deranged motility diarrhoea)
Abnormal increase in secretion of the GIT (secretory diarrhoea)
391
What 2 situations cause osmotic diarrhoea?
1) Ingestion of poorly absorbed substrate- usually a carbohydrate or divalent ion (mannitol, sorbitol, Epson salt, antacid)
2) Malabsorption- inability to absorb certain carbohydrates most commonly. (A common cause example is lactose intolerance)
These situation cause decreased absorption of electrolytes and nutrients
392
How does lactose intolerance work?
A moderate quantity of lactose is consumed, but the intestinal epithelium is deficient in lactase, and lactose cannot be effectively hydrolysed into glucose and galactose for absorption. Osmotically-active lactose is retained in the intestinal lumen, where it 'holds' water. Lactose passes into the large intestine and is fermented by colonic bacteria, resulting in excessive flatulence
393
When does osmotic diarrhoea stop?
When the patient fasts or stops consuming the poorly absorbed solute
394
How does secretory diarrhoea work?
ACh, substance P and neurotensin act via increased Ca2+ concentration to increase rate of intestinal secretions. Diarrhoea occurs when secretion of water into the intestinal lumen exceeds absorption
395
What can cause uncontrolled water secretion from crypt enterocytes?
Bacterial toxins that strongly activate adenylate cyclase, causing a prolonged increase in intracellular [cAMP] within crypt enterocytes. This results in prolonged opening of Cl- channels
396
Besides bacterial toxins, what other agents can cause secretory diarrhoea?
Some laxatives, hormones (e.g. VIP) secreted by certain tumours, certain drugs, or certain meals, organic toxins and plant products
397
What diarrhoea does IBD cause?
Chronic exudative diarrhoea
398
How does deranged motility diarrhoea occur?
Lack of absorption, so some agents may promote secretion as well as motility.
399
How may GI stasis promote diarrhoea?
It may stimulate bacterial overgrowth
400
Name 2 parasites that cause diarrhoea
Entamoeba histolytica and Giardia lamblia
401
Describe entamoeba histolytica infection
It can be asymptomatic or cause amoebic dysentry. Onset is gradual and gives systemic symptoms like anorexia and headaches
402
Describe Giardia lamblia infection
Causes steatorrhoea and abdominal pain. Causes maldigestion and malabsorption of lipids, CHOs, vitamin A and B12, and folic acid
403
What 3 causes are there for bloody diarrhoea?
Chronic disease
Ulcerative colitis
Neoplasm
404
What are the 2 major consequences of severe diarrhoea?
Hypovolaemia
| Metabolic acidosis due to loss of HCO3-
405
Briefly describe vomiting
Retrograde giant contractions that lead to oral expulsion of the upper GI contents and bile
406
What sympathetic effects occur from vomiting?
Sweating, salivation and heart rate incresae
407
What controls vomiting?
The central trigger zone in the area postrema of the medulla oblongata in the brainstem
408
What inputs can initiate vomiting?
Distension of the stomach or small intestine
Action of some substances on chemoreceptors in the brain or intestines
Increased intracranial pressure
Motion sickness
Intense pain
Tactile stimulus to the back of the throat
Sight, smell and emotional circumstances
409
What are the consequences of excessive vomiting?
```
Increased salt and water loss
Severe dehydration
Circulatory problems (hypovolaemia)
Metabolic alkalosis due to loss of H+
Nutritional deficit and failure to thrive
Death
```
410
What is lost in vomit?
Food, mucus with Na+, K+, Cl- and HCO3-, gastric acid, upper GI contents e.g. bile, and possibly blood
411
What are the consequences of fluid loss form the GI tract?
```
Hypovolaemia
Haemoconcentration/ polycythaemia
Dehydration
Ionic imbalance and poor perfusion of tissues
Malnutrition and increased mortality
```
412
What are the circulatory consequences of hypovolaemia?
```
Decreased venous return
Arterial hypotension
Myocardial dysfunction
Increased anaerobic metabolism and acidosis
Multi-Organ failure
```
413
What are symptoms of dehydration?
```
Nausea
Headache
Irrationality
Cramps
Increased temperature
Dizziness
Decreased skin turgor
Heat shock
Fainting
Blood clotting
Constipation
Acid reflux
Indigestion
```
414
How does the body respond to water loss?
Cardiovascular adaptation and renal adaptation
415
What's the renal adaptation to profuse sweating?
Hypoosmotic salt solution is lost, so plasma volume decreases. This stimulates increase in GFR and plasma aldosterone, both of which decrease Na+ excretion. Increase in plasma osmolarity from water loss increases plasma vasopressin to decrease H2O excretion
416
What happens when the macula dense senses low NaCl concentration?
Renin release is increased and resistance to blood flow in the afferent arterioles is decreased by vasodilation
417
How does ADH work?
ADH inserts aquaporin-2 channels into the membrane of the collecting duct of the kidney, which increases the permeability of the collecting ducts to H2O, resulting in concentrated urine of low volume
418
What factors regulate ADH release?
```
Large decrease in blood volume detected by baroreceptors
Severe dehydration
Intake of copious amounts of water
Hyperventilation
Vomiting/ diarrhoea
Fever, heavy sweating or burns
```
419
What's the problem with diarrhoea-induced hypercalcaemia?
It gives increased risk of kidney stones, kidney failure and arrhythmia. Symptoms include nausea, vomiting, loss of appetite, constipation, abdominal pain, excessive thirst, fatigue, muscle weakness and joint pain
