1
Q
What did the Panel convened by the WHO in August 2014 conclude regarding Ebola patients being treated with promising drugs which have not yet been evaluated for safety & efficacy in humans?
A
Concluded Ebola outbreak was exceptional and ethically acceptable to offer proven interventions but ethical standards (informed consent, fairness, autonomy) must be maintained
2
Q
What do different countries in Britain classify as “Children & young people”?
A
- <18 in England, Wales & Northern Ireland
2. <16 in Scotland
3
Q
What is the definition of “Children”?
A
People who are probably not mature enough to make important decisions themselves
4
Q
For a child who lacks capacity who makes the decision?
A
- Parents but decisions are constrained by best interests of the child
- If they are NOT seen to be making decision that promotes welfare of the child, it can be overridden
5
Q
What is the missing word regarding a child who lacks capacity:
“If ____ can be given, it should be sought”?
A
Assent
6
Q
As well as a clinical best interest, what other 6 things should you consider?
A
- Views of child/young person, including previously expressed preferences
- Views of parents
- Views of others close to child
- Cultural, religious or other beliefs and values of the child/parent
- Other healthcare professional views
- Which choice will least restrict the child’s future options
7
Q
Give an example of when doctors and parents disagree?
A
Parents were Jehovah’s Witnesses and their child had T cell leukaemia and refused to allow blood transfusing, refusal was overruled
8
Q
What is the Gillick Competence?
A
A young person under 16 with capacity to make any relevant decisions is often referred to as being “Gillick competent”
9
Q
Competence is determined if the person can do what 4 things?
A
- Understand
- Retain
- Use/weigh this information
- Communicate decision
10
Q
What is the problem with determining competence regarding a child/young person?
A
A young person who has the capacity to consent to straightforward, relatively risk-free treatment may not necessarily have the capacity to consent to complex treatment involving high risks or serious consequences
11
Q
Why is consent often more easily accepted than refusal in the mature minor?
A
Doctors only need 1 key to unlock “consent”. Potential keys:
- Mature minors
- Parents
- Courts
12
Q
What is the age restriction to organ donation in Scotland?
A
Anyone under 16 (competent or not) CANNOT be a living donor
13
Q
What is the age restriction to organ donation in England, Wales & Northern Ireland?
A
Solid organ donation by living children is permitted
14
Q
What is the BMA’s opinion on children being organ donators?
A
The were opposed, now support so long as young person is competent to give valid consent & is not under coercion
15
Q
What are the Netherlands legal rules for age restrictions in Euthanasia?
A
Legal for those over 12 (with permission of their parents)
16
Q
What has the Dutch Paediatric Association recently (June 2015) called for?
A
Age limit for Euthanasia to be lifted all together
17
Q
What is Belgium’s legal rules for age restrictions in Euthanasia?
A
Lifted all age restrictions in 2014
18
Q
What did the Nuffield Council on Bioethics report published in May 2015 say about children and clinical research?
A
- Its crutial if children themselves are to benefit from best possible treatment when ill.
- Should parents allow young children to participate if it causes minor discomfort/distress?
- Can be seen as the critically ill child’s “only hope”
19
Q
What is bioequivalence?
A
Looking at the effectiveness of one agent compared to another, it specifically relates to generic or therapeutic substitution
20
Q
What is Generic substitutions?
A
- Different formulation of the same drug is substituted (branded vs unbranded)
- They are all considered by licensing authority to be equivalent to each other & to the originator drug.
21
Q
What is therapeutic substitution?
A
- Replacement of the originally-prescribed drug with an alternative molecule with assumed equivalent therapeutic effect
- Alternative drug may be in the same class / assumed therapeutic equivalence (different beta-blockers)
22
Q
Why do oral drugs have a low bioavailability (4)?
A
- Destroyed in gut
- Not absorbed
- Destroyed by gut wall
- Destroyed by liver
23
Q
What are the pros and cons of buccal/sublingual mucosa oral route?
A
- Direct absorption into blood stream
- Avoids first pass metabolism
- Not ideal surface for absorption
24
Q
What do you need the drug to have in order for it to reach the gastric mucosa?
A
Enteric coating
25
What are the pros and cons of small intestine oral route?
- Main site of drug absorption
| - Large surface area, more neutral pH
26
What are the cons of Large intestine/colon oral route?
Poor absorption, long transit times
27
What are the pros of rectal mucosa oral route
Direct to systemic circulation
28
What are the 4 ways small molecules cross cell membranes?
1. Diffusing directly through the lipid
2. Diffusing through aqueous pores
3. Transmembrane carrier proteins
4. Pinocytosis
29
What is the definition of a young person?
Those who are mature enough to make important decisions themselves
30
What percentage of bioavailability must generics have?
80-125% compared to reference product
31
What is an excipient?
Inactive substance put into drug to bulk it up
32
A weak base is _____ in acidic pH?
Ionised
33
A weak acid is _____ in acidic pH?
Unionised
34
What is the Henderson-Hasselbalch equation for a weak base?
pKa- pH = log10 [BH+]/[B]
35
What is the Henderson-Hasselbalch equation for a weak acid?
pKa- pH = log10 [AH]/[A-]
36
What do foods tend to do to the rate of gastric emptying in general?
Slows the rate
37
What is gastric emptying?
How quickly food leaves the stomach
38
What can cause decreased absorption of a drug?
- Increased intestinal motility
- Interactions with food, acids
- Presystemic metabolism
39
What can cause delayed absorption of a drug?
- Gastric emptying
| - Cmax (plasma conc.) may be decreased
40
What can cause increased absorption of a drug?
- Poorly water soluble drugs
| - Decreased presystemic metabolism
41
What is Levodopa?
- Prodrug
- Treatment of Parkinson's disease
- Precursor of dopamine
42
Where is Levodopa rapidly taken up?
Stomach & Small intestine
43
What is the active transport system for Levodopa called?
Large neutral amino acid transport carrier (LNAA)
44
Where is DOPA decarboxylase (enzyme) present?
Gastric mucosa
45
What does Antacids and proton pump inhibitors do?
Changes gastric / intestinal pH
46
What does anticholinergics do?
Decrease GI motility
47
What does vasodilators do?
Changes GI perfusion
48
What does neomycin do?
Interference with mucosal function
49
What does Charcoal do?
Decreases absorption
50
What is Diabetic Gastroparesis?
Delayed gastric emptying, slows / stops movement of food from stomach to small intestine
51
Describe the appearance of Crohn's disease (decreased drug absorption)?
- Cobblestone appearance of mucosal surface due to linear ulceration
- Abcess
- Narrowed lumen
- Thickened wall
- Then back to normal intestine
52
What are the 6 factors that affect oral absorption?
1. Particle size & formulation
2. GI motility
3. First pass metabolism
4. Physicochemical factors
5. Splanchnic blood flow
6. Efflux pumps
53
Where is first pass metabolism?
By gut wall or hepatic enzymes
54
What are the 3 Physicochemical factors which affect oral drug absorption?
1. Direct drug interactions
2. Dietary factors
3. Varying pH
55
What are the 2 Parenteral drug routes?
1. Subcutaneous - slow
| 2. Intramuscular - lipophilic drugs rapid
56
What is the rate of onset of drugs administered parenterally affected by?
- Extent of capillary perfusion
- Drug vehicle
- Affected by factors that alter perfusion
57
What are the systemic effects of inhalation of drugs?
- Lipid-soluble drugs
- Drugs of abuse
- Accidental poisoning
58
What are the local effects of inhalation of drugs?
- Modify structure
- Particulate size
- Selectivity for receptors
- Rapid breakdown in circulation
59
What are the advantages of Intranasal drug administration?
- Avoids hepatic first pass metabolism
| - Ease, convenience, safety
60
What is the main limitation of Intranasal drug administration?
Limited drugs suitable as it required concentrated drug
61
What are the local effects of topical drug route?
- Corticosteriods for eczema (hydrocortisone)
- Antihistaines for insect bites (mepyramine)
- Local anaesthetics (EMLA)
62
What are the systemic effects of topical drug route?
- Transdermal patches (HRT, GNT, nicotine)"
| - Accidental poisoning (AChEstrase insecticides)
63
Where does the foregut start and end?
Mouth to just distal to developing liver
64
What supplies the foregut?
| Where does the referred pain go to?
- Coeliac trunk
| - Pain to epigastrium (T7 to 9)
65
What does the foregut give rise to?
- Oesophagus
- Stomach
- Proximal duodenum
- Liver & biliary system
- Pancreas
- Spleen
66
When does the development of the stomach appear?
4th week
67
What is the movement of the Stomach during development?
- 90o clockwise around longitudinal axis so left side faces anteriorly & lesser curve to the right, while greater curve to the left (lies posterior)
- AP axis so pyloric part comes to lie on right & oesophagi-gastric junction slightly left, so greater curve faces left & inferior
68
What is the movement of the Duodenum during development?
- Initially in midline
- Rotates & swings right due to stomach
- "Falls" onto posterior abdominal wall & becomes retroperitoneal
69
What happens to the duodenum lumen during development?
Obliterated by proliferation of cells, then it is re-canalized
70
How is the liver developed?
- From endodermal bud during 3rd week
| - Penetrates ventral mesentery & septum transversum
71
What 2 things does the liver give rise to?
- Hepatic ducts
| - Gallbladder
72
How is the Pancreas developed?
- From duodenum dorsal & ventral endodermal buds
| - Rotation causes ventral bud to lie behind & fuse with dorsal bud
73
What do the fusion of dorsal & ventral buds form?
Main pancreatic duct
74
What is the accessory duct a remnant of?
Duct of dorsal bud
75
What does the ventral mesentery directly in contact with the liver become?
Liver's Visceral peritoneum
76
What are the 2 examples of times the foregut development can go wrong?
1. Part of the biliary system may duplicate
| 2. Ventral pancreas may form 2 lobes, forming an obstructive Annular Pancreas
77
What is in the free edge of the falciform ligament?
Umbilical vein
78
What is in the free edge of the lesser omentum?
- Bile duct
- Hepatic artery
- Portal vein
79
What forms within the dorsal mesentery?
Spleen
80
What is another name for the dorsal mesentery?
| And what will it become?
- Mesogastrium
| - Greater omentum
81
What lies posterior of the stomach and lesser omentum?
Lesser Sac
82
What is the opening into the lesser sac called?
Epiploic foramen
83
What are the boundaries of the Epiploic foramen?
ANTERIOR- free border of lesser omentum, with bile duct, hepatic artery proper & portal vein
POSTERIOR- IVC
SUPERIOR- caudate lobe of liver
INFERIOR- 1st part of duodenum
84
What are the boundaries of the Lesser Sac?
ANTERIOR- caudate lobe of liver, lesser omentum, stomach
POSTERIOR- pancreas
LATERAL LEFT- left kidney & adrenal gland
LATERAL RIGHT- epiploic foramen
85
How does the greater omentum end up handing off the greater curve?
Stomach rotates on AP axis & greater curve faces inferiorly, dorsal mesentery is dragged with it so the big double-layer fold (greater omentum) hangs
86
What does the the greater omentum lie in front of in the abdomen?
Lie over intestine and fuse with transverse colon
87
What is the lienorenal ligament?
The mesentery between spleen and posterior abdominal wall
88
What is the gastroleinal/gastrosplenic ligament?
The mesentery between spleen and stomach
89
What is often referred to as the "Policeman of the Abdomen"?
Greater Omentum
90
What is the start and end point of the midgut?
Starts distal to entrance of bile duct into duodenum, ends 2/3 along transverse colon
91
What supplies the midgut?
| Where does the referred pain go to?
- Superior Mesenteric Artery
| - Peri-umbilical region (T10)
92
What happens to the midgut by the 5th week?
Suspended from dorsal abdominal wall as primary intestinal loop by mesentery
93
What connects the midgut to the yolk sac?
Vitelline duct
94
What happens to the primary intestinal loop?
- Cranial limb of loop grows to become much of jejunum & ileum.
- Loop rotates counter clockwise by 90o & 180o as loop drops back into abdomen at 70 days (10 weeks)
95
What is the position of caecum at 70days compared to the end?
As intestine drops back into abdomen caecum is up in right hypochondrium, then migrates with appendix inferiorly to right iliac fossa
96
What are the possible congenital abnormalities related to midgut development?
- Partial/Abnormal rotation
- Vitelline duct fistula/patent (faecal discharge at umbilicus)
- Vitelline cyst
97
What can failure of recanalisation lead to?
Narrowing/complete obstruction of GI tract at any point
98
What does the hindgut give rise to?
- Distal end of transverse colon (1/3)
- Descending colon
- Sigmoid colon
- Rectum
- Upper 2/3 anal canal
99
What supplies the hindgut?
| Where does the referred pain go to?
- Inferior mesenteric artery
| - Suprapubic region (T12)
100
Where is the most inferior part of the hindgut developed from?
Cloaca
101
What does the Cloaca develop into?
ANTERIORLY- urogenital system
| POSTERIORLY- anorectal canal
102
When does the distal membrane of the cloaca break down?
8 weeks
103
What does the pectinate line mark?
Lies between proximal 2/3 of anal canal derived from hindgut endoderm & distal 1/3 from ectoderm
104
What can the common origin of anal canal and urogenital organs mean?
Fistulae between can occur
105
What is it called when the anal membrane isn't broken down?
Imperforate anus
106
What is Hirchsprung disease?
Problem with colon innervation leading to constricted, ganglionic segment of bowel with an expanded segment proximally (innervation normal)
107
What is the definition of Psychosomatic disorders?
Disorders where emotional / psychological factors can impact on the symptoms
108
Give 5 examples of psychosomatic disorders?
1. Asthma
2. Atopic dermatitis
3. Tension-type headaches
4. Chronic fatigue syndrome
5. Irritable bowel syndrome
109
What is the definition of Irritable Bowel Syndrome (IBS)?
Common digestive condition, your GP may be able to identify IBS based on symptoms, although blood tests may be needed to rule out other conditions
110
List the many symptoms/signs of Irritable Bowel Syndrome?
- Abdominal pain & cramping, may be relieved by defecation
- Change in bowel habits (diarrhoea, constipation, both)
- Bloating/swelling of stomach
- Excessive wind
- Occasionally experiencing an urgent need to go to the toilet
- Feeling you haven't emptied bowels after going
- Passing mucus
111
What is the occurrence of irritable bowel syndrome?
- 20-30yrs old
- More common in women
- 10-20% of population
112
What is the Rome III Criteria for diagnosing Irritable bowel syndrome?
Last 3 months, symptom onset at least 6months prior to diagnosis the individual experiences recurrent abdominal pain at least 3 days per month in last 3 months associated with 2/+ of:
- Improvement with defecation
- Change in frequency
- Change in form
113
What is the criteria for diagnosis in the UK for Irritable bowel syndrome?
Rome III criteria & 2+ of the following:
- Change in how you pass stools
- Bloating, hardness/tension in abdomen
- Symptoms worse after eating
- Passing mucus from rectum
114
What conditions can blood tests rule out?
- Coeliac
| - Ulcerative Colitis
115
What conditions can stool samples rule out?
Calprotectin (IBD)
116
What does HRQoL stand for?
Health Related Quality of Life
117
What are the putative causes of Irritable bowel syndrome?
- Emotional stress
- Psychological disorders
- Hyper-reactivity in the brain-gut interface
- Infection
- Food intolerance
- Abnormal muscle contraction
- Serotonin receptors
118
What are the health messages in the common sense model of IBS?
Abdominal pain, disturbed bowel habit affected by GI infections, food intolerance, abnormal gut physiology
119
What are emotional reactions in the common sense model of IBS affected by?
- Life events
- Chronic stressors
- Psychological disorders
120
How can you manage IBS?
- Diet/lifestyle (physical activity) changes
- Drug treatments
- Psychological approach
- Complementary therapies approach
121
What are the 1st line drug treatments for IBS?
- Antidiarrhoeal
- Laxatives
- Antispasmodics
122
What are the 2nd line drug treatments for IBS?
- Laxatives
- Antidepressants
- Tricyclic antidepressants (TCA's) if 1st line ineffective
- Selective serotonin reuptake inhibitors (SSRI's) if TCA's ineffective
123
What are the complementary therapies for managing IBS?
- Nutraceuticals
- Chinese herbal medicine
- Probiotics
124
What are the different psychological approaches (after 12 months) used to manage IBS?
- Cognitive behavioural therapy
- Hypnotherapy
- Psychological therapy
125
What are the targets for a doctor trying to treat an IBS patient?
- Reduce disability
- Improve coping
- Reduce dependence on healthcare
126
What are arthritic osteophytes?
Indent the oesophagus & cause pain on swallowing
127
Describe the superior 1/3 of the oesophagus?
- Begins C6
- Supplied by inferior thyroid arteries
- Drainage to brachiocephalic veins
- Supplied by branches of Vagus (recurrent laryngeal nerves)
- Drain to deep cervical lymph nodes
128
Describe the middle (thoracic) 1/3 of the oesophagus?
- Supplied by thoracic aorta & bronchial arteries
- Drainage to azygos system
- Supplied by oesophageal plexus (vagus & sympathetic)
- Drain to tracheobronchial lymph nodes
129
Describe the inferior (abdominal) 1/3 of the oesophagus?
- Supplied by gastric artery
- Drainage to left gastric veins & portal vein
- Supplied by branches of oesophageal plexus (vagus & sympathetic)
- Drain to left gastric & coeliac lymph nodes
130
How can the oesophageal constrictions be shown?
Normal barium swallow through endoscope
131
What are the 4 oesophageal constrictions?
1. Upper oesophageal sphincher 17cm
2. Arch of aorta
3. Left main bronchus 28cm
4. Diaphragm (lower oesophageal sphincter) 43cm
132
What structure causes an indentation on the oesophagus?
Left atrium
133
What lies anterior to the oesophagus?
- Trachea
- Right pulmonary artery
- Left main bronchus
- Left atrium
- Diaphragm
134
What lies posterior of the oesophagus?
- Vertebral bodies (C6-T12)
- Thoracic duct
- Thoracic aorta
135
What is the epithelium and lining of the oesophagus?
Stratified squamous epithelium with submucosal mucous glands and has smooth muscle walls
136
Where does the oesophagus pass through to exit the thorax and enter the abdomen?
Right crus of diaphragm at T10 just left of the midline
137
How can Cirrhotic liver disease cause oesophageal varies?
Disease raises portal venous pressure (portal hypertension) & blood escapes via submucosal veins in oesophagus, veins become dilated & tortuous. Can cause fatal haemorrhage
138
What are the 3 components of the "physiological" cardiac sphincter which prevents gastric reflux?
1. Contraction of right crus of diaphragm
2. Tonic contraction of circular layer of smooth muscle in lower oesophagus
3. "Valvular" effect of oblique entry of oesophagus into stomach, augmented by oblique muscle layer
139
What controls closure of the "physiological" cardiac sphincter?
Vagal control
140
What does the Z-line represent?
Transition from stratified squamous (oesophageal) to columnar (gastric) epithelium
141
What 3 regions of the abdomen does the stomach lie in?
- Epigastric
- Umbilical
- Left hypogastric
142
What are the 4 parts of the stomach?
1. Cardia
2. Fundus (full of gas)
3. Body
4. Pyloric (antrum & canal)
143
What happens to the circular muscle coat at the pyloric region of the stomach?
Thickened to form pyloric sphincter that controls outflow of gastric contacts into duodenum
144
What are the mucosal fold of the stomach also called?
Rugae / "Magenstrasse"
145
Describe the left gastric artery and what it supplies?
- Arises from coeliac artery
- Passes upward & left to reach oesophagus
- Descends along lesser curvature
- Supplies lower 1/3 of oesophagus & proximal part of lesser curve & adjacent body of stomach
146
Describe the right gastric artery and what it supplies?
- Arises from hepatic artery at upper pylorus
- Runs left along lesser curvature
- Supplies distal part of lesser curve & adjacent body of stomach
147
Where does the short gastric arteries arise from?
| What does it supply?
- Splenic artery at hilum of the spleen
| - Fundus
148
Where does the left gastro-epiploic (omental) artery arise from?
What does it supply?
- Splenic artery at hilum of spleen
| - Stomach
149
Where does the right gastro-epiploic artery arise from?
| What does it supply?
- Gastroduodenal branch of hepatic artery
| - Stomach
150
Where does the gastroduodenal artery lie?
Posterior to 1st part of the duodenum
151
What does the left & right gastric veins of the stomach drain into?
Portal veins
152
What does the right gastroepiploic vein of the stomach drain into?
Superior mesenteric vein
153
What does the short gastric veins & left gastroepiploic veins drain into?
Splenic vein
154
What does all the lymph of the stomach eventually pass to?
Coeliac nodes
155
What is the nerve supply of the stomach?
- Sympathetic fibres (pain & vasomotor) T5-9 via greater splanchnic nerves & coeliac plexus
- Parasympathetic fibres from right & left vagus nerves (secretion & motility)
156
Where is referred pain of the stomach to?
Lower chest & epigastrium
157
What is Vagotomy?
- Surgical operation where 1/+ branches of vagus nerve are cut to reduce rate of gastric secretion (in treating peptic ulcers)
- Motility is affected so cut after those going to pyloric sphincter
158
What is Bariatric surgery for?
Obese patients
159
What are the boundaries of the stomach bed?
POSTERIOR- lesser sac, retroperitoneal structures, post. ado wall
SUPERIOR- left crus of diaphragm, spleen, left suprarenal gland, upper pole of left kidney
INFERIORLY- body & tail of pancreas, transverse mesocolon, left colic flexure & splenic artery
160
How long is the small intestine?
6-7m
161
Where does the duodenum receive bile and pancreatic ducts?
Major papilla/ Ampulla of Vater
162
Describe the 1st / superior part of the duodenum?
- Begins at pylorus
| - Runs up, backwards & right starting on transpyloric plane at level of L1
163
Describe the 2nd / descending part of the duodenum?
Runs vertically down in front of hilum of right kidney on right side of L2 & L3
164
Describe the 3rd / horizontal part of the duodenum?
- Runs horizontally to left on subcostal plane
| - Pass infant of L3 & following lower margin of head of pancreas
165
Describe the 4th / ascending part of the duodenum?
Runs up & left to duodenojejunal flexure at L2
166
What are the boundaries/relations of the 1st / superior part of the duodenum?
ANTERIOR- quadrate lobe of liver & gallbladder
POSTERIOR- lesser sac, gastroduodenal artery, bile duct & portal vein, IVC
SUPERIOR- entrance of lesser sac
INFERIOR- head of pancreas
167
What are the boundaries/relations of the 2nd / descending part of the duodenum?
ANTERIOR- gallbladder, right lobe of liver, transverse colon, coils of small intestine
POSTERIOR- hilum of right kidney & right ureter
LATERALLY- ascending colon, right colic flexure, right lobe of liver
MEDIALLY- head of pancreas, bile duct, main pancreatic duct
168
What are the boundaries/relations of the 3rd / horizontal part of the duodenum?
ANTERIOR- root of mesentery of small intestine, superior mesenteric vessels, coils of jejunum
POSTERIOR- right ureter, right psoas muscle, IVC, aorta
SUPERIOR- head of pancreas
INFERIOR- coils of jejunum
169
What are the boundaries/relations of 4th / ascending part of the duodenum?
ANTERIOR- root of the mesentery, coils of jejunum
| POSTERIOR- left margin of aorta, medial border of left psoas muscle
170
What can be the rare problem of the duodenojejunal gaining a mesentery?
There may be small paraduodenal recesses into which bowel may herniate
171
What is the upper 1/2 of the duodenum blood supply?
Gastroduodenal branches of common hepatic artery (Coeliac trunk, foregut)
172
What is the lower 1/2 of the duodenum blood supply?
Superior mesenteric artery (midgut)
173
What artery is at risk with posterior ulcers of the 1st part of the duodenum?
Gastroduodenal artery
174
What veins drain the duodenum?
- Superior pancreaticoduodenal vein drains into portal vein
| - Inferior vein joins superior mesenteric vein
175
What is the lymph drainage of the duodenum?
Coeliac & Superior mesenteric (SM) nodes
176
What is the nerve supply of the duodenum?
- Sympathetic greater (T5-9) & lesser splanchnic (T10-11)
- Parasympathetic (vagus) via coeliac & superior mesenteric plexuses
177
List the 3 different layers/types of muscle in the stomach?
1. Outer- longitudinal
2. Middle- circular
3. Inner- oblique
178
How does the muscle wall thickness change throughout the stomach?
Increases proximal to distal
179
What is the extrinsic nerves supplying the stomach?
| What do the different nerves do?
1. Parasympathetic- stimulate gastric smooth muscle motility & secretions
2. Sympathetic- inhibit motility & secretions
180
What is the enteric nervous system supplying the stomach?
Myenteric plexus:
- parasympathetic via vagus
- sympathetic via coeliac ganglion
181
What is the sensory afferent fibres supplying the stomach?
Between sensory receptors & the ENS (pressure, distention, pH, pain) & centrally via the vagal & splanchnic nerves
182
What is the orad region?
Proximal part of the stomach
183
What happens at the orad region of the stomach?
- Distention of lower oesophagus induces relaxation of lower oesophageal spinchter
- Reduces pressure & increases volume of stomach (1.5litres)
184
In the vagovagal reflex what is the afferent information?
Mechanoreceptors associated with chewing, oesophageal & stomach distension relay information to CNS via sensory neurons
185
In the vagovagal reflex what is the efferent information?
Neurotransmitter, VIP, released from postganglionic peptidergic vagal neurons is responsible for orad relaxation
186
What is the purpose of thin muscle fibres in the fundus & body?
Weak contractions, contents settle into layers based on density
187
What is the purpose of thick muscle fibres in caudad region?
- For mixing
| - Contraction waves begin in middle of body. move distally with increasing strength towards pylorus
188
What are the 3 movement patterns in the stomach?
1. Propulsion- bolus pushed toward the closed pylorus
2. Grinding- antrum churns the trapped material
3. Retropulsion- bolus pushed back into proximal stomach
189
What increase action potential frequency of the muscle in stomach?
Parasympathetic stimulation, gastrin & motilin
190
What decrease action potential frequency of the muscle in stomach?
Sympathetic stimulation & secretin
191
What are Migrating myoelectic complexes (MMCs)?
- Mediated by motilin, released from endocrine cells in the upper GI tract
- 90min intervals to clear residual chyme
192
What are the 3 steps to gastric emptying?
1. After a meal stomach contains 1.5L of solids, liquids & gastric secretions
2. Emptying of gastric contents takes approx. 3hrs
3. Rate is regulated to ensure gastric H+ is neutralised in duodenum & there is adequate time for digestion & absorption of nutrients
193
What are the 3 physical factors affecting gastric emptying?
1. Liquids empty more rapidly that solids
2. Isotonic fluids empty more rapidly than hypo- or hypertonic
3. Solids must be reduced to particles <1mm3, retropulsion continues until this is achieved
194
What 2 chemical factors inhibit gastric emptying when in duodenum?
1. Fat
| 2. H+ ions
195
What is the effect of fat on gastric emptying?
Mediated by cholecystokinin (secreted when fat reaches duodenum)
196
What is the effect of H+ on gastric emptying?
- Mediated by reflexes in enteric nervous system.
- H+ receptors in duodenum detect low pH & relay information to gastric smooth muscle via interneurons in myenteric plexus
197
What are the 3 purposes for motility in the small intestine?
1. Mixes chyme with digestive enzymes & pancreatic secretions
2. Exposes nutrients to intestinal mucosa for absorption
3. Propels unabsorbed chyme into large intestine
198
How frequent are the slow waves in the duodenum & ileum?
- Duodenum 12 per min
| - Ileum 9 per min
199
What are segmental contractions for?
Mixing
200
What 2 things stimulate orad contraction (peristalsis)?
ACh & Substance P
201
What 2 things stimulate caudad relaxation (peristalsis)?
VIP & nitric oxide
202
What is Taeniae (tenia) coli?
3 separate longitudinal bands of smooth muscle on the outside of the colon
203
What is the parasympathetic innervation of the colon?
- VAGUS: caecum, ascending colon, transverse colon
| - PELVIC NERVES: descending & sigmoid colon, rectum & anal canal
204
What does sympathetic innervation of the colon do?
Stops colonic movements
205
Where can reverse peristalsis occur in the colon and why?
- Towards the caecum
| - Retention favours Na+ & water absorption
206
What happens after the contents of the small intestine enters the caecum & proximal colon?
Ileocaecal sphincter contracts
207
How much chyme does the colon receive per day?
500-1500ml
208
What are haustra/haustrations?
Small pouches caused by sacculation which give the colon its segmented appearance
209
What is the faeces like in the distal colon?
Semi-solid due to water being absorbed
210
What 2 reflexes is the mass movements in the colon caused by?
1. Gastrocolic reflex
| 2. Duodenocolic reflex
211
What is the gastrocolic reflex?
Distension of stomach by food increases motility of colon & frequency of mass movements
212
What is the afferent limb in the stomach mediated by?
Parasympathetic nervous system
213
What is the efferent limb of the reflex increasing colon motility mediated by?
CCK & gastrin
214
What happens to the rectosphincter reflex during defecation?
Smooth muscle of rectum contracts & internal anal sphincter relaxes
215
What does the external anal sphincter do (striated muscle & voluntary control)?
Remains tonically contracted
216
Where is the vomiting centre?
In medulla
217
During vomiting what is the afferent information?
- Vestibular system
- Back of throat
- GI tract
- Chemoreceptor trigger zone in the 4th ventricle
218
During vomiting what is the efferent response?
- Reverse peristalsis in small intestine
- Relaxation of the stomach and pylorus
- Forces inspiration to increase abdominal pressure
- Relaxation of lower oesophageal sphincter
- Forceful expulsion of gastric & duodenal contents
219
What are the host defences in the mouth (4)?
- Flow of liquids
- Saliva
- Antimicrobials
- Normal Microbiota
220
What are the host defences in the oesophagus (2)?
- Flow of liquids
| - Peristalsis
221
What are the host defences in the stomach (3)?
- Acid pH
- Antimicrobials
- Mucus
222
What are the host defences in the small intestine (7)?
- Flow of gut contents
- Peristalsis
- Mucus
- Bile
- Secretory IgA
- Antimicrobial peptides
- Normal bacterial microbiota
223
What are the host defences in the large intestine (4)?
- Normal microbiota
- Peristalsis
- Mucus
- Shedding & replication of epithelium
224
What is the commensal bacteria and host's relationship?
One population is benefited (bacteria) and the other is neither benefited / harmed (host)
225
What is the symbiotic bacteria and host's relationship?
Both host and bacteria have a cooperative / mutually dependent relationship
226
What is a parasitic bacteria and host's relationship?
Host is being killed off as bacteria is draining it and using up all its nutrients
227
What are the 3 examples of probiotics?
1. Lactobacillus spp.
2. Bifidobacterium spp.
3. Bacteroides spp.
228
What is a Probiotic?
- "Friendly" bacteria
| - Live bacteria & yeasts that are good for digestive system
229
What are Prebiotics?
- Non-digestible food ingredients
| - Stimulate growth/activity of gut microbiota
230
What 6 things can Probiotics & Prebiotics do?
1. Development of mucosal barrier
2. Synthesis of vitamins
3. Metabolism of bile acids
4. Production of short-chain fatty acids
5. Reduction in pH in large bowel
6. Immune system activation
231
Where is Lactobacillus spp. usually found in the GI tract?
- Oesophagus
- Stomach
- Duodenum
UPPER GI TRACT
232
Where is Bacteroides spp. usually found in the GI tract?
- Large bowel
- Faecal material
LOWER GI TRACT
233
What are the 5 different roles of the gut microbiota?
1. Prevent colonisation by pathogens
2. Excrete useful metabolites
3. Ferment unused energy substrates
4. Synthesise & excrete vitamins
5. Produce hormones
234
What is Bacteriotherapy?
- Also known as Fecal Transplantation
- Transfer of stool from healthy donor into the GI tract of someone with devastated microbiota for the purpose of treating recurrent C. difficile colitis
235
What are the different factors controlling gut microflora?
- Physiological status
- Underlying disease
- Intestinal secretions
- Intestinal motility
- Immune mechanisms
- Environmental factors
- Use of antibiotics
236
How many lymphocytes are there in the GI tract?
>10 million per gram tissue
237
What are the different pathogen recognition receptors in the GI tract?
- PAMPs/MAMPs: pathogen/microbe associated molecular patterns
- TLRs: toll-like receptors
- NODs: nucleotide-binding oligomerization domain-containing proteins
- NLRs: NOD-like receptors
238
How are most GI infections acquired?
Via the faecal-oral route
239
Why is infection not the same as colonisation?
Infection only occurs when micro-organism causes ill-health
240
Commensals may become ______ if the circumstances are right?
Pathogenic
241
What are the 3 different ways you can develop intestinal infection?
1. Ingestion of infected food & water
2. Ingestion of bacterial toxins
3. Oral antibiotics
242
Describe Gastroenteritis?
- Inflammation of stomach & intestines
- Resulting from bacterial toxins / viral infection
- Causing vomiting & diarrhoea
243
What is Enterocolitis?
Inflammation of mucosa of both small & large intestine
244
What does diarrhoea cause?
Increased fluid and electrolyte loss
245
Describe Dysentery?
- Inflammation of GI tract
- Large intestine usually
- Blood & pus in faeces
- Pain, fever, abdominal cramps
246
What are the 7 possible clinical effects of pathogenic invasion of GI tract?
1. Diarrhoea/dysentery
2. Malaena (black stools)
3. Blood in faeces
4. Pus in faeces
5. Abdominal cramps
6. Fever
7. Sepsis
247
What are the 4 different secretory fluids, enzymes & mucous which go into the lumen of the GI tract?
1. Salivary glands (saliva)
2. Gastric mucosa (gastric secretion)
3. Exocrine cells of pancreas (pancreatic secretion)
4. Liver (bile)
248
What are the characteristics of Saliva?
- High HCO-3
- High K+
- Hypotonic
- α-amylase & lingual lipase
249
What are the factors which increase secretion of Saliva?
- Parasympathetic (primarily)
| - Sympathetic
250
What are the facts which decrease secretion of Saliva?
- Sleep
- Dehydration
- Atropine
251
How much saliva is secreted per day?
1 litre per day
252
What are the functions of Salivary secretion?
- Initial digestion of starches and lipids
- Dilution & buffering of ingested foods
- Lubricaton of ingested foods with mucous (mucin)
253
What is the structure of Parotid salivary gland?
Serous cells secreting an aqueous fluid composed of water, ions and enzymes
254
What is the structure of Sublingual salivary gland?
Mostly mucous cells
255
What is the structure of Submandibular salivary gland?
Mixed glands containing serous & mucous cells (mucin glycoprotein for lubrication)
256
Describe Acinar cells?
Produce initial isotonic saliva composed of water, ions, enzymes and mucus
257
Describe Myoepithelial cells?
In acini are stimulated by neural input to eject saliva
258
Describe Ductal cells?
Modify initial saliva by altering electrolyte concentrations
259
What is the combined action (4) for modification of salivary secretion?
- Absorption of Na+ and Cl-
- Secretion of K+ and HCO-3
- Because more NaCl is absorbed than KHCO3 secreted there is net absorption of solute
- Low water permeability of ductal cells means that the final saliva is hypotonic
260
What are the 4 acinar cell secretions?
1. α-amylase
2. Lingual lipase
3. Mucus
4. Kallikrein
261
What does Kallikrein do?
Enzymatic cleavage of kininogen to bradykinin (potent vasodilator)
262
What does neural stimulation of salivary glands result in?
- Increased saliva production
- HCO-3 production
- Enzyme secretion
- Myoepithelial cell contraction
263
What are the 4 different gastric secretions and what do they do?
1. HCl: protein digestion
2. Pepsinogen: Protein digestion
3. Intrinsic factor: Vitamin B12 absorption (in ileum)
4. Mucus: protects gastric mucosa & lubricates food
264
What are the factors that increase gastric secretions?
- Gastrin
- Acetylcholine
- Histamine
- Parasympathetic
265
What are the factors that decrease gastric secretion?
- H+ in stomach
- Chyme in duodenum
- Somatostatin
- Atropine
- Cimetidine
- Omeprazole
266
Where are the Parietal/Oxyntic & Chief/Peptic cells located in the stomach?
Body
267
Where are the G cells located in the stomach?
Antrum
268
What do Parietal cells secrete?
HCl which acidifies gastric contents to pH 1-2
269
What does low gastric pH do to inactive pepsinogen?
Inactive pepsinogen --> pepsin (active form)
270
What secretion happens at the apical membrane of a gastric parietal cell?
- H+ secreted into lumen via H+-K+ ATPase
| - Cl- follows by diffusion through apical channel
271
What secretion happens at the basolateral surface/membrane of a gastric parietal cell?
- HCO-3 exchanged for Cl- via chloride-bicarbonate exchanger (alkaline tide)
- Eventually HCO-3 secreted back into GI tract in pancreatic secretions
272
What happens at the Celphalic phase of gastric HCl release?
- 30% of HCl secretion
- Direct stimulation of parietal cells by vagus
- Indirect stimulation of parietal cells by gastrin
273
What does GRP stand for?
| What does it do?
- Vagal Gastrin Releasing Peptide
| - Stimulates gastrin release from G cells, gastrin hormone stimulates parietal cells to release HCl
274
What happens at the Gastric phase of HCl release?
- 60% of HCl secretion
| - Distension of stomach & presence of breakdown products of proteins, amino acids and small peptides of stomach
275
In the gastric phase what does Distention cause?
- Direct vagal stimulation of parietal cells
- Indirect stimulation via gastrin
- Local reflexes in antrum that stimulate gastrin release
276
What happens at the Intestinal phase of gastric HCl release?
- 10% of HCl secretion
| - Presence of breakdown products of proteins in the duodenum
277
What is the origin, action and second messenger of neurocrine Acetylcholine?
ORIGIN: Vagus nerve
ACTION: binds to muscarinic (M3) receptors on parietal cells
SECOND MESSENGER: IP3/Ca2+
278
What is the origin, action and second messenger of paracrine Histamine?
ORIGIN: vagus nerve
ACTION: diffuses to & binds to H2 receptors on parietal cells
SECOND MESSENGER: cAMP
279
What is the origin, action and second messenger of hormone Gastrin?
ORIGIN: G cells in stomach antrum
ACTION: binds to CCKB receptors on parietal cells
SECOND MESSENGER: IP3/Ca2+
280
When is HCl secretion inhibited?
After Chyme moves into small intestine and H+ buffering capacity of food is no longer a factor
281
What is the direct and indirect pathway of Somatostatin produced from the small intestine?
DIRECT: binds to receptors on parietal cells & inhibits adenylate cyclase via Gi protein
INDIRECT: inhibits histamine release from ECL cells and gastrin release from G cells
282
What are the 2 ways inactive pepsinogen is secreted?
- Secreted by chief & mucous cells in oxyntic glands in response to vagal stimulation
- H+ triggers local reflexes which stimulate chief cells to secrete pepsinogen
283
What is required for Vitamin B12 absorption in the ileum?
Mucoprotein released from parietal cells
284
What does a lack of intrinsic factor cause?
Pernicious anaemia
285
What is given to patients following a gastrectomy?
Injections of Vitamine B12 to bypass the absorption defect and stop pernicious anaemia from occuring
286
What is Zollinger-Ellison syndrome?
- Rare condition in which tumours (Gastrinoma) form in small intestine or non-β cell of the pancreas
- Secrete large amounts of hormone gastrin, which causes stomach to produce too much acid
287
What does the high circulating levels of gastrin in Zollinger-Ellison syndrome cause?
- Increased H+ secretion by parietal cells
- Hypertrophy of the gastric mucosa
- Duodenal ulcers (constant secretion of gastric H+)
- Acidification of intestinal lumen (inactivation of pancreatic lipases)
288
Where in the abdomen does the jejunum lie?
Upper left abdomen
289
Where in the abdomen does the ileum lie?
Lower right abdomen
290
What is the physical difference between jejunum and ileum?
- Jejunum is wider, thicker walled and redder than ileum
291
Why does the jejunum's walls feel thicker than the ileum's?
Permanent infolding of submucosa, the plicae circulares, are larger, more numerous and more closely set in the jejunum
292
Describe the mesentery suspending the jejunum?
- Attached to post. abdominal wall above & left of aorta at L2
- Vessels form only 1/2 arcades, with long & infrequent branches
- Fat deposited near root
293
Describe the mesentery suspending the ileum?
- Attached below & right of aorta at SI joint
- Numerous short terminal vessels arising from 3/4+ arcades
- Fat deposited throughout
294
What is the ileocaecal valve?
- 2 horizontal folds of mucous membrane that project around orifice of ileum
- At junction of small & large intestine
295
Where do the jejunal and ill arteries arise from?
Superior Mesenteric Artery (SMA) & its ileocolic branch
296
Where do the veins corresponding to branches of SMA drain?
Superior Mesenteric vein, which forms portal vein
297
What is the lymph drainage of jejunum and ileum?
Superior Mesenteric nodes
298
What is the nerve supply of the jejunum & ileum?
- Sympathetic, lesser splanchnic nerve T10 & 11
| - Parasympathetic (vagus) nerves via superior mesenteric plexus
299
Where does the referred pain of jejunum & ileum go to?
Peri-umbilical (T10)
300
Where does the Superior mesenteric artery (SMA) arise from and what does it supply?
- Aorta at L1
- Carries sympathetic nerves from T10 & 11
- Supplies Midgut
301
What is the purpose of a lacteal in the centre of each villus on the mucous membrane of small intestine?
Absorption of digested fats & lipids (chyle)
302
What is the route of passage of Chyle in the small intestine?
From lacteals into mesenteric lymph channels (NOT through lymph nodes), converge on the cistern chyli
303
Where is the Peyer's patches located?
Ileum
304
What is the route of passage of Lymph in the small intestine?
Into mesenteric lymph channels, filter through mesenteric nodes, afferents from nodes converge on nodes at root of SMA then pass to cisterna chyli
305
What/How is a Meckel's Diverticulum formed?
- Remnant of vitello-intestinal duct
- End of ileum
- 2% of people
306
What parts of the colon are retroperitoneal?
Ascending & Descending
307
What parts of the colon are intraperitoneal?
Transverse & Sigmoid
308
What are omental appendices/appendices epiploicae?
Little sacs of fat projecting along serous coat of colon
309
What are the 3 taeniae coli?
Condensations of the longitudinal muscle layer outside the colon
310
What are the 3 internal differences that the large intestine lacks compared to the small intestine?
- Lacks plicae circularis
- Lacks villi
- Lacks peyers patches
311
Describe the caecum?
- Covered by peritoneum
- Not on a mesentery
- In right iliac fossa
312
Where is the root of the appendix at?
McBurney's point
313
Describe the appendix?
- Narrow blind ended tube hanging from caecum
- Submucosa packed of lymphoid tissue
- Suspended on meso-appendix that transmits appendicular vessels
314
What are the 5 different positions of the appendix?
| from common to least common
1. Retrocaecal
2. Pelvic
3. Subcaecal
4. Pre-ileal
5. Retro-ileal
315
Due to the appendicular artery being close to appendix, what can happen during an inflamed appendix?
Artery can become obstructed causing gangrene and rupture of appendix
316
Describe the appendicular artery?
From ileocolic branch of superior mesenteric, from aorta at L1
317
What is the nerve supply of the appendix?
Derived from T10/11
318
What is the referred pain of the appendix?
Early appendicitis refers pain to peri-umbilical region, then pain moves to right inguinal region
319
What is the lymph drainage of the caecum and appendix?
Nodes on the SMA
320
Where does the sigmoid colon lie in the abdomen?
In front of the pelvic brim, becomes continuous with rectum at S3
321
What is Sigmoid volvulus?
When the sigmoid colon rotates upon itself
322
What can a colonic diverticulae mimic when obstructed?
Left sided "appendicitis"
323
What are the Superior Mesenteric Artery (SMA) branches?
| What do they supply?
- Ileocolic, right colic & middle colic branches
| - Caecum, ascending colon, hepatic flexure & 2/3 transverse colon
324
What are the Inferior Mesenteric Artery (IMA) branches?
| What do they supply?
- Left colic & sigmoid branches
| - 1/3 of transverse colon, splenic flexure, descending colon & sigmoid colon
325
What nerve supply does the Inferior Mesenteric Artery carry?
Sympathetic nerves derived from T12 (least splanchnic nerves) and parasympathetic from S2,3,4 (not vagus)
326
What does the Inferior Mesenteric artery continue as?
Superior Rectal Artery supplying rectum & anal canal
327
Is the rectum intra- or retroperitoneal?
Retroperitoneal
328
What are the characteristics of pancreatic secretions?
- High HCO-3 (isotonic)
| - Pancreatic lipase, amylase & proteases
329
What are the factors that increase pancreatic secretion?
- Secretin
- Cholecystokinin (CCK)
- Parasympathetic supply
330
How much fluid per day does the exocrine pancreas secrete?
1L
331
What is the innervation of the pancreas?
- Parasympathetic from vagus stimulates secretion
| - Sympathetic inhibits secretion
332
Where are the pancreatic enzymes stored?
In condensed zymogen granules until release
333
Where is the aqueous component of pancreatic secretion released from?
Centroacinar cells & ductal cells
334
What does modification of the pancreatic secretion by ductal cells result in?
Fluid secretion rich in HCO-3
335
where is the enzymatic component of pancreatic secretion released from?
Acinar cells
336
Where are pancreatic (inactive) proteases activated?
In duodenum (enterokinase)
337
What are the 3 phases of regulation of pancreatic secretion?
1. CEPHALIC phase initiated by taste, smell & conditioning mediated by vagus (mainly enzymatic)
2. GASTRIC phase initiated by distension of stomach & mediated by vagus (mainly enzymatic)
3. INTESTINAL phase (80%) both enzymatic & aqueous secretions
338
What do duodenal I cells secrete?
CCK in response to presence of amino acids, small peptides & fatty acids in lumen
339
What do vagal release?
ACh potentiates CCK action
340
What do S cells of the duodenum release?
Secretin which is the major stimulus for aqueous rich HCO-3 secretion
341
How is secretin release triggered?
Arrival of acidic chyme in duodenum
342
What is ACh & CCK's effect on secretin?
Increase action
343
What is bile secretion a mixture of?
- Bile salts (50%)
- Bile pigments (2%)
- Cholesterol (4%)
- Phospholipids (40%)
344
What is the purpose of bile salts?
Emulsify lipids to prepare them for digestion & solubilise products of digestion into "packets" called micelles
345
What are the 3 functions of the gallbladder?
1. Reservoir for bile
2. Concentration of bile
3. Ejection of bile
346
How is bile ejected from the gall bladder?
- Begins 30mins after a meal
| - Stimulus is release of Cholecystokinin from I cells in duodenum & jejunum
347
What is Cholecystokinin?
33 amino acid peptide hormone related to gastrin
348
When is Cholecystokinin released from I cells of duodenal & jejunal mucosa?
In response to presence of monoglycerides, fatty acids, small peptides & amino acids
349
What are the 5 hormonal actions of Cholecystokinin
1. Contraction of gall bladder & relaxation of sphincter of Oddi to eject bile (emulsification & solubilisation of dietary fat)
2. Secretion of pancreatic enzymes (lipase & proteases)
3. Secretion of pancreatic HCO3
4. Growth of exocrine pancreas & gallbladder
5. Inhibition of gastric emptying
350
What is the role of Hepatocytes?
Liver cells which synthesise & secrete constituents of bile
351
What happens to bile salts when lipid absorption is complete?
They are recirculated to the liver by enterohepatic portal circulation
352
What is the structure of a mixed micelles (core and surface)?
- Core contains products of lipid digestion
| - Surface coating of bile salts which are amphipathic
353
What is the definition of absorption?
Movement of nutrients, water and electrolytes from lumen of intestine to blood
354
What is the arrangement of the surface of small intestine?
Circular folds of Keckring
355
What are the only carbohydrates that can be absorbed?
Monosaccharides
356
What is the different mechanisms for carbohydrate digesting in the small intestine?
- Na+ dependant cotransport
| - Facilitated diffusion
357
In Secondary Active Transport, what does SGLT1 stand for?
| What does it do?
- Sodium dependent glucose transporter 1
| - Transports glucose & galactose across apical membrane
358
In Facilitated Diffusion, what does GLUT 5 stand for?
| What does it do?
- Glucose Transporter 5
| - Transports fructose across the apical membrane
359
What is the difference between Endopeptidases & Exopeptidases?
- Endopeptidase break peptide bonds of nonterminal amino acids (within the molecule)
- Exopeptidases break peptide bonds from end-pieces of terminal amino acids
360
What is the 3-step protein digestion in the small intestine?
1. Pancreatic proteases secreted as inactive precursors
2. Activation of trypsinogen to active form, trypsin, by brush-border enzyme enterokinase
3. Trypsin catalyses conversion of other inactive precursors to active enzymes
MD3002
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