GI Flashcards
1
Q
What does GORD stand for?
A
Gastro-oesophageal reflux disease
2
Q
When does GORD occur?
A
- prolonged gastric reflux
- causes oesophageal stricture / Barrett’s oesophagus
3
Q
What can cause GORD?
A
- lower oesophageal sphincter hypotension
- hiatus hernia
- loss of oesophageal peristaltic function
- abdominal obesity
- gastric acid hyper secretion
- slow gastric emptying
- overeating / fat / chocolate / coffee
- smoking / alcohol
- pregnancy (inc. abdominal pressure)
- drugs
- systemic sclerosis
4
Q
Pathophysiology of GORD
A
- MUCH MORE transient lower oesophageal sphincter relaxations
- allows gastric acid to flow back into oesophagus
5
Q
Why are there more transient LOS relaxations in GORD?
A
LOS has reduced tone
6
Q
When do clinical features of GORD present?
A
When anti-reflux mechanisms fail
- causes prolonged acid contact with lower oesophageal mucosa
7
Q
What might contribute to transient LOS relaxation?
A
- increased mucosal sensitivity to gastric acid
- reduced oesophageal acid clearance
- delayed gastric emptying after eating
- delayed nocturnal reflex
- hiatus hernia
8
Q
List the oesophageal clinical presentations of GORD
A
- heartburn
- belching
- food/acid/bile regurgitation
- water brash - increased salivation
- sinusitis
9
Q
List the extra-oesophageal clinical presentations of GORD
A
- nocturnal asthma
- chronic cough
- laryngitis
- sinusitis
10
Q
What actions can aggravate heartburn?
A
- bending
- stooping
- lying down
(promote aid exposure)
11
Q
List the differential diagnoses of GORD
A
- CHD
- biliary colic
- peptic ulcer disease
- malignancy
12
Q
What are the alarm bell signs of GORD?
A
- weight loss
- haematemesis
- dysphagia (swallowing difficulties)
13
Q
What investigations should you conduct to diagnose GORD if there are alarm bell sings?
A
- endoscopy
- barium swallow
- use LA classification of GORD/ Oesophagitis
14
Q
When would you conduct an endoscopy?
A
- alarm bell signs
- symptoms for more than 4 weeks
- persistent vomiting
- GI bleeding
- palpable mass
- over 55
- symptoms despite treatment
15
Q
What might a barium swallow show?
A
Hiatus hernia
16
Q
What are the types of hiatus hernia?
A
- Sliding hiatus hernia (80%)
2. Rolling / para-oesophageal hiatus (20%)
17
Q
Describe sliding hiatus hernia
A
- G-O junction / part of stomach slides up into stomach
- lies slightly above diaphragm
- LOS = less competent = acid reflux
18
Q
Describe rolling / para-oesophageal hiatus
A
- G-O junction remains in abdo
- fundus prolapses through hiatus
- reflux is uncommon because junction is intact
19
Q
What are the aims of investigating for GORD?
A
- assess oesophagitis
- document reflux by intraluminal monitoring - 24 hr pH
20
Q
What does oesophagitis/Barrett’s confirm?
A
Reflux
21
Q
What lifestyle changes can treat GORD?
A
- weight loss
- smoking cessation
- small, regular meals
- avoid hot drinks, alcohol, citrus fruits
- don’t eat <3 hours before bed
22
Q
What pharmacological treatments are used for GORD?
A
- antacids
- alginates
- PPI
- H2 receptor antagonists
23
Q
Example of antacid
A
Magnesium trisilicate mixture
24
Q
How does antacid treat GORD?
A
- forms gel / foam raft with gastric contents
- reduces reflux
- relieves symptoms
25
What is a side effect of magnesium contains antacids?
Diarrhoea
26
Example of alginates
Gaviscon - relieves symptoms
27
Example of PPI
Lansaprazole - reduces gastric acid production
28
Example of H2 receptor antagonist
Cimetidine
29
How do H2 receptor antagonists treat GORD?
- blocks histamine receptors on parietal cells
| - reduces acid release
30
What are the complications of GORD?
1. Peptic stricture
| 2. Barrett's oesophagus
31
What is peptic stricture?
- inflammation of oesophagus
- results from gastric acid exposure
- causes narrowing of oesophagus
32
How does peptic stricture present?
Gradually worsening dysphagia
33
How do you treat peptic stricture?
- endoscopic dilatation
| - long term PPI
34
What is Barrett's oesophagus?
Distal oesophageal epithelium undergoes metaplasia from squamous to columnar
35
What is always present in Barrett's oesophagus?
Hiatus hernia
36
What is the risk of Barrett's?
- can progress into cancer
| - premalignant for adenocarcinoma of oesophagus
37
What is a Mallory-Weiss tear?
- linear mucosal tear at the oesophagogastric junction
38
What produces a Mallory-Weiss tear?
By a sudden increase in intra-abdominal pressure
39
Epidemiology of Mallory-Weiss tear
- more common in males
| - mainly in ages 20-50
40
Risk factors of Mallory-Weiss tear
- alcoholism
- forceful vomiting
- eating disorders
- male
- NSAID abuse
41
What are the clinical features of Mallory-Weiss tear?
- vomiting
- haematemesis after vomiting
- retching
- postural hypotension
- dizziness
42
What are the differential diagnoses of Mallory-Weiss?
- gastroenteritis
- peptic ulcer
- cancer
- oesophageal varices
43
How do you diagnose Mallory-Weiss?
Endoscopy to confirm
44
How do you treat Mallory-Weiss?
- most bleeds heal within 24 hours
- haemorrhage stop spontaneously
- sometimes surgery to sow the tear
45
What is dyspepsia?
```
ONE OR MORE OF:
1. Postprandial fullness (after eating)
2. Early satiation
3. Epigastric pain or burning for >4 weeks
(essentially indigestion)
```
46
What % of the population are affected by dyspepsia?
25%
47
What are dyspeptic symptoms caused by?
- Disorders of the GI tract = most commonly is functional dyspepsia
- peptic ulcers
48
Clinical presentation of dyspepsia
- reflux when lying flat
- heartburn
- acid taste
- bloating
- indigestion
49
What are the red flag symptoms of dyspepsia for cancer?
- unexplained weight loss
- anaemia
- GI bleeding (melaena / haematemesis)
- dysphagia
- upper abdominal mass
- persistent vomiting
- over 55
50
What could gastric ulcers cause?
- postprandial pain
| - pain relieved by milk
51
What could early postprandial pain be due to?
- gastritis
- GORD
- gastric carcinoma
52
What are the differential diagnoses according to history?
- heartburn/ regurgitation / cough = GORD
- alarm symtpoms/ family history = malignancy
- onset (acute vs chronic)
53
Management of dyspepsia
- reassurance
- dietary review
- antidepressants
- test for helicobacter pylori
- endoscopy
54
Name an example of antidepressants that could be given for dyspepsia
CITALOPRAM
| - type of SSRI
55
Why would you give an antidepressant for dyspepsia?
Low doses reduce sensitivity of gullet
56
How can you look for helicobacter pylori in dyspepsia?
- faecal antigen test
| - breath test (less common)
57
How many layers does the smooth muscle wall of the stomach have?
3
58
What are the 3 layers of the stomach's smooth muscle wall?
1. Outer longitudinal
2. Inner circular
3. Innermost oblique layers
59
Name the 2 sphincters of the stomach
1. Gastro-oesophageal sphincter
| 2. Pyloric sphincter
60
What is the pyloric sphincter largely made up of?
- thickening of the circular muscle layer
61
How many layers does the duodenum have?
2 smooth muscle layers
1. Outer longitudinal
2. Inner smooth
62
What does the mucosa in the upper 2/3 of the stomach contain?
- parietal cells
- chief cells
- enterochromaffin-like cells (ECL)
63
What do parietal cells secrete?
HCl
64
What do chief cells produce?
Pepsinogen
65
What do ECL cells release?
Histamine (stimulates acid release)
66
What does the astral mucosa of the stomach contain?
- mucus secreting cells
- G cells
- D cells
67
What do mucus secreting cells secrete?
- mucin
| - bicarbonate
68
What do G cells secrete?
Gastrin (stimulates acid release)
69
What do D cells secrete?
Somatostatin (suppressant of acid secretion)
70
What is the mucosal barrier made up of?
- plasma membranes of mucosal cells & mucus layer
71
What does the mucosal barrier do?
- protects gastric epithelium from damage by acid
72
What stimulates mucus secretion?
Prostaglandins
73
What inhibits synthesis of prostaglandins?
- aspirin
- NSAIDs
(inhibit cyclo-oxygenase)
74
What does the duodenal mucosa contain?
- villi
| - Brunner's glands
75
What do Brunner's glands secrete?
Alkaline mucus
76
What neutralises acid secretion from stomach in the duodenum?
- alkaline mucus from Brunner's
| - pancreatic & biliary secretions
77
Describe peptic ulcer disease (PUD)
Consists of a break in the superficial epithelial cells penetrating down to the muscularis mucosa of stomach/duodenum
- fibrous base
- increase in inflammatory cells
78
Where does a peptic ulcer penetrate down to?
Muscularis mucosa of stomach or duodenum
79
Where are duodenal ulcers most commonly found?
In the duodenal cap
80
Where are gastric ulcers most commonly seen?
- lesser curvature of stomach
| - can be anywhere though
81
What % of the population are affected by duodenal ulcers?
10%
82
How many time more common are duodenal ulcers than gastric?
2-3 times more
83
Where are ulcers more common?
- in the elderly
| - developing countries
84
Why are ulcers more common in developing countries?
Because of helicobacter pylori
85
Describe incidence of PUD in men vs women
- declining in men
| - increasing in women
86
Why are ulcers increasing?
Due to use of NSAIDs
87
What are the main causes of PUD?
- helicobacter pylori
- drugs (NSAIDs, steroids, SSRIs)
- smoking
- increasing gastric acid secretion
- delayed gastric emptying
- blood group O
88
What do ulcers result in?
Gastritis
89
Why do NSAIDs cause ulcers?
- inhibit cyclo-oxygenase
- prostaglandin synthesis is inhibited
- reduced mucosal defence
90
Where does helicobacter pylori colonise?
- gastric epithelium
| - inhibits mucous layer / just beneath it
91
What does helicobacter pylori cause?
- major destruction to mucin layer that protects mucosa
- decreases duodenal HCO3-
- therefore, increases stomach acidity
(less alkali to buffer acid)
92
What does helicobacter pylori secret and why is this bad?
1. Urease
- splits urea into CO2 & ammonia
2. Proteases
3. Phospholipase
4. Vacuolating cytotoxin A
93
Why is urea being split into ammonia bad?
- NH3 + H+ = ammonium
- ammonium is toxic to gastric mucosa
= means less mucous produced
94
What does secretion of proteases/phospholipase/ cytotoxin A result in?
- gastric epithelium is attacked
- reduces mucous production
= inflammatory response
= less mucosal defence
95
What does helicobacter pylori increase?
- gastrin
- parietal cell mass
(MEANS more acid production)
96
What does helicobacter pylori decrease?
- somatostatin
| can't inhibit acid secretion - so acid increases
97
Overall effects of helicobacter pylori
- inflammation (antral gastritis)
- gastric cancer
- peptic ulcers
98
What is gastric cell ischaemia caused by?
- low BP
| - atherosclerosis
99
Why is gastric cell ischaemia bad?
- less mucin produced
- less protection from acid
- damages mucosa
= ulcers
100
What can cause increased acid production?
Stress
101
What is used to treat increased acid production?
- PPI
| - H2 receptor antagonists
102
Clinical presentations for PUD
- recurrent burning epigastric pain
- nausea accompanying pain
- anorexia / weight loss
103
When is duodenal ulcer pain typically worse?
- at night
| - when patient is hungry
104
Red flag symptoms of PUD for cancer
- unexplained weight loss
- anaemia
- GI bleeding (melaena / haematemesis)
- dysphagia
- upper abdominal mass
- persistent vomiting
105
Suggest complications of ulcers
- duodenal ulcers can go v deep = hit an artery
- peritonitis
- acute pancreatitis
106
Which artery would be most commonly hit if duodenal ulcers go too deep? Why is this bad?
Gastroduodenal artery
| - causes MASSIVE haemorrhage = EMERGENCY
107
How can ulcers cause peritonitis?
- acid can leak into peritoneum if ulcers are too deep
108
How would you diagnose peritonitis in PUD?
Air can be seen under the diaphragm in an erect X-ray
109
What diagnostic tests would you carry out on under 55s for PUD (H. pylori)?
NON-INVASIVE TESTING
- serology
- C-urea breath test
- stool antigen testing
110
What would you do if tests for PUD came back positive?
Start eradication immediately
| - lansoprazole
111
What do you do if a gastric ulcer is found in an endoscopy?
Re-scope 6-8 weeks later
| - ensures no malignancy
112
When is an endoscopy essential?
- in all alarm patients
| - patients over 55
113
What does a serology test for PUD detect?
IgG antibodies
114
Why does serology testing not confirm current PUD?
Because IgG takes 1 year to fall by 50%
115
How does the C-urea breath test work?
- measures CO2 in breath after ingestion of C-urea
| - monitors infection after eradication
116
Advantages of C-Urea breath test
- quick
- reliable test for H. pylori
- highly sensitive / specific
- no antibiotics / PPI before test
117
Describe the stool antigen test
Immunoassay using monoclonal antibodies
- detects H.pylori
- monitors efficacy of eradication
118
How long should patients be off PPIs for before stool antigen test?
2 weeks
119
What is an endoscopy useful to look at?
- histology
| - biopsy urease test
120
What will histology show in an endoscopy?
- direct visualisation of H.pylori
| - reduced if on PPIs
121
How will a biopsy urease test show?
- solution will rapidly change from yellow to red
| - because of release of ammonia
122
Why shouldn't a patient be on PPIs/antibiotics before biopsy urease test?
Will give false negatives
123
Treatment for PUD/ H. pylori
- lifestyle adjustments
- stop NSAIDs
- H. pylori eradication (triple therapy)
- H2 antagonists
- surgery
124
What lifestyle adjustments would you suggest to reduce PUD?
- reduce stress
- avoid irritating foods
- reduce smoking
125
How long will H. pylori eradication take?
7-14 days
126
What is the triple therapy for H. pylori?
1. PPI
| 2 & 3 (any 2 of these): Metronidazole / Clarithromycin / Amoxicillin / Tetracycline / bismuth
127
Which drugs are high resistance?
1. Metronidazole
| 2. Clarithromycin
128
Which drugs are low resistance?
1. Amoxicillin
| 2. Tetracycline
129
When are quinolones used to treat PUD?
When standard regimens have failed
| - as 'rescue therapy'
130
Examples of quinolones
- ciprofloxacin
- furozolidone
- rifabutin
131
Example of H2 antagonists to treat PUD
- ranitidine
| - cimetidine
132
When would you conduct surgery for PUD?
In case of complications:
| - haemorrhage
133
What are varices?
Dilated veins that are at risk of rupture
| In GI system = lead to GI bleeds / haemorrhage
134
What is the normal pressure in the hepatic portal vein?
5-8mmHg
135
What are the classifications of portal hypertension?
1. Pre-hepatic
2. Intra-hepatic
3. Post-hepatic
136
What is pre-hepatic obstruction?
Blockage of hepatic portal vein BEFORE liver
137
What is intra-hepatic obstruction?
Distortion of liver architecture (pre or post sinusoidal)
138
What is post-hepatic obstruction?
Venous blockage OUTSIDE the liver (rare)
139
When do varices form?
- portal pressure >10-12mmHg
- venous system dilates
- varices formed within systemic venous system
140
Where can varices form?
- G-O junction
- rectum
- L renal vein
- diaphragm
- anterior abdominal wall via umbilical vein
141
Describe gastro-oesophageal varices
- superficial
- tend to rupture
- result in GI bleeding
- when pressure >12mmHg
142
What % of cirrhosis patients develop G-O varices?
90% - over 10 years
| only a 1/3 bleed
143
What are main causes of varices?
- alcoholism / viral cirrhosis
| - portal hypertension (pre, intra, post hepatic)
144
What can cause pre-hepatic portal hypertension?
Thrombosis in portal / splenic vein
145
What can cause intra-hepatic portal hypertension?
- cirrhosis
- schistosomiasis
- sarcoid
- congenital hepatic fibrosis
146
What can cause post-hepatic portal hypertension?
- Budd-Chiari syndrome
- RH failure
- constrictive pericarditis
147
What is Budd-Chiari syndrome caused by?
Hepatic vein obstruction by tumour / thrombosis
148
What are the risk factors for varices?
- cirrhosis
- portal HT
- schistosomiasis
- alcoholism
149
Pathophysiology cascade of varices
Liver injury / fibrogenesis > increased resistance to blood flow > portal HT > splanchnic vasodilation > drop in BP > inc. CO > inc. salt & water retention > hyper-dynamic circulation/increased portal flow > formation of collaterals between portal & systemic systems > GO varices
150
Why does liver injury / fibrogenesis result in increased resistance to blood flow?
Because of contraction of the activated myofibroblasts
151
What is contraction of activated myofibroblasts mediated by?
- endothelin
- nitric oxide
- prostaglandins
152
Why is there an increased CO in pathophysiology of varices?
To compensate for decreased BP
153
Why is there inc. salt & water retention in pathophysiology of varices?
To increase blood volume & compensate
154
Clinical presentations if varices has ruptured?
- haematemesis
- abdo pain
- shock (if major blood loss)
- fresh rectal bleeding
- hypotension / tachycardia
- pallor
155
When should you suspect varices as cause of GI bleeding?
- alcohol abuse
| - cirrhosis
156
Other clinical presentations of varices
- splenomegaly
- ascites
- hyponatraemia
157
How do you diagnose varices?
Endoscopy
158
How do you treat varices?
- resuscitate until haemodynamically stable
- blood transfusion if anaemia
- correct clotting abnormalities
- vasopressin
- prophylactic antibiotics
- varical banding
- balloon tamponade
- trans jugular intrahepatic portoclaval shunt (TIPS)
159
What level should Hb aim to be after blood transfusion?
80g/L
160
How would you correct clotting abnormalities?
- Vitamin L
| - platelet transfusion
161
Example of vasopressin
IV terlipressin
162
Why do you administer vasopressin for varices?
- cause vasoconstriction
163
What do you use if terlipressin is contraindicated? (e.g in ischaemic heart disease)
IV somatostatin
164
Why do you administer prophylactic antibiotics for varices?
- treat / prevent infection
| - reduce re-bleeding and mortality
165
What is variceal banding?
- band put around avarice
- using endoscope
- banded varix degenerates after a few days
- leaves scar
166
How does balloon tamponade work?
- reduces bleeding
| - places pressure on avarice if banding fails
167
When is TIPS used to treat varices?
- if bleeding can't be controlled
- it is a shunt between systemic & portal systems
- reduces sinusoidal & portal vein pressure
168
Prevention of varices
- non- selective B blockage
- variceal banding repeatedly
- liver transplant
169
What does non-selective B blockage achieve?
- reduces resting pulse rate
- decrease portal pressure
e. g PROPRANOLOL
170
Define gastritis
Inflammation associated with mucosal injury
171
What does gastropathy indicate?
Epithelial cell damage & regeneration without inflammation
172
What are the causes of gastritis?
1. H. pylori
2. Autoimmune gastritis
3. Virus (CMV / herpes simplex)
4. Duodenogastric reflux
5. Crohn's
6. Mucosal ischaemia
7. Increased acid
8. Aspirin / NSAIDs / alcohol
173
What parts of the stomach does autoimmune gastritis affect?
1. Fundus
| 2. Body
174
What does autoimmune gastritis lead to?
Atrophic gastritis
- loss of parietal cells
- intrinsic factor deficiency
= causes pernicious anaemia (low RBC due to low B12)
175
Clinical présentation of gastritis
- abdo bloating
- haematemesis
- epigastric pain
- nausea
- indigestion
- vomiting
176
Differential diagnoses of gastritis
- PUD
- GORD
- non-ulcer dyspepsia
- gastric lymphoma / carcinoma
177
How to diagnose gastritis?
- endoscopy
- biopsy
- H. pylori breath test
- H. pylori stool antigen test
178
Treatment for gastritis
- remove causative agents
- reduce stress
- H. pylori eradication (triple therapy)
- H2 antagonists
- PPI
- antacids
179
Prevention of gastritis
- PPIs + NSAIDs
| = prevents bleeding from acute stress ulcers / gastritis
180
Define malabsorption
Failure to absorb nutrients because of destruction to epithelium OR problem in the lumen meaning food can't be digested
181
Examples of small intestine diseases that can result in malabsorption
- Crohn's
- Topical sprue
- Coeliac disease
- parasite infection
182
What must be ruled out before diagnosing malabsorption?
Insufficient intake
183
Causes of malabsorption
1. Defective intraluminal digestion
2. Insufficient absorptive area
3. Lack of digestive enzymes
4. Defective epithelial transport
5. Lymphatic obstruction
184
Examples of defective intraluminal digestion
1. Pancreatic deficiency
2. Defective bile secretion
3. Bacterial overgrowth
185
When might there be pancreatic deficiency?
1. Pancreatitis
| 2. Cystic fibrosis
186
Why does pancreatitis lead to pancreatic deficiency?
- damages glandular pancreas
| - means less/no enzymes are released
187
Why does CF lead to pancreas deficiency?
- blocks pancreatic duct
- due to excess mucus
- enzymes fail to be released
188
Why is defective bile secretion bad?
There will be a lack of fat solubilisation
189
When might there be defective bile secretion?
1. Biliary obstruction (gall stone)
| 2. Ileal resection
190
Why does ileal resection lead to defective bile secretion?
- bile salts are reabsorbed in terminal ileum
| - if removed = bile salt reuptake is decreased
191
What might cause insufficient absorptive area?
1. Coeliac disease (gluten sensitive enteropathy)
2. Crohn's
3. Giardia lamblia
4. Surgery
192
Describe coeliac disease
- villous atrophy / short villi
- crypt hyperplasia
- lots of lymphocytes in epithelium
193
Describe Crohn's
- inflammatory damage to lining of bowel
= cobblestone mucosa
- significant reduction of absorptive SA
194
Describe how giardia lamblia causes insufficient absorptive area
- extensive surface parasitisation of villi & microvilli
- parasites coat villi surface
- food can't be absorbed
195
Describe how surgery causes insufficient absorptive area
Small intestine resection/ bypass
| - in small bowel infarction
196
What causes a lack of digestive enzymes?
1. Disaccharidase deficiency (lactose intolerance)
| 2. Bacterial overgrowth
197
Why does lactose intolerance mean malabsorption?
- lactose can't be broken down into glucose
| - not absorbed
198
What happens to indigested lactose?
- passes into colon
- eaten by bacteria
- release CO2
- leads to wind & diarrhoea
199
What does bacterial overgrowth cause?
Brush border damage
200
Examples of defective epithelial transport
1. Abetalipoproteinaemia
| 2. Primary bile acid malabsorption
201
What is abetalipoproteinaemia?
Lack of transporter protein to transport lipoprotein across cell
202
What is primary bile acid malabsorption?
Mutations in bile acid transporter protein
203
What can cause lymphatic obstruction?
- lymphoma
| - tuberculosis
204
Describe coeliac disease
Inflammation of the mucosa of the upper small bowel
| - improves when gluten is withdrawn from diet
205
What is describe coeliac disease?
T cell mediated autoimmune disease of small bowel in which prolamin intolerance causes villous atrophy & malabsorption
206
What is prolamin?
Alcohol- soluble proteins in wheat, barley, rye, oats
| prolamin is a component of gluten protein
207
Examples of prolamins
1. Gliadin in wheat
2. Hordeins in barley
3. Secalins in rye
208
What % of population are affected by coeliac disease?
1%
209
At what age does coeliac disease peak?
- infancy
| - 50-60 years
210
What is the risk in relatives for coeliac disease?
- 10% in 1st degree relatives
| - 30% in siblings
211
What is gluten found in?
- wheat
- barley
- rye
212
What are the risk factors for coeliac disease?
- type 1 diabetes
- thyroid disease
- Sjorgen's
- IgA deficiency
- breast feeding
- rotavirus infection in infancy
213
Why is gluten bad?
- prolamin a-Gliadin is toxic
| - it's resistant to digestion by pepsin & chymotrypsin
214
Why is a-gliadin resistant to digestion?
Because of high glutamine & proline content
- so remain in intestinal lumen
- triggers immune response
215
What happens to the gliadin peptides?
- pass through epithelium
| - deaminated by tissue transglutaminases
216
What are gliadin peptides deaminated by?
Transglutaminases
217
What happens to gliadin peptides when they're deaminated?
Increases immunogenicity
218
What happens after deamination of gliadin peptides?
They bind to antigen presenting cells (APC)
219
What happens after gliadin peptides bind to APC?
- interact with CD4+ T cells
- in lamina propria
- via HLA class II molecules DQ2 or DQ8
220
What do DQ2/DQ8 do?
Activate gluten sensitive T cells
221
What do gluten sensitive T cells do when they're activated?
Produce pro-inflammatory cytokines
| - initiate inflammatory cascade
222
What does imitation of inflammatory cascade do?
- releases metaloproteinkinases
| - releases other mediators
223
What do metaloproteinkinases / other mediators contribute to?
- villous atrophy
- crypt hyperplasia
- intraepithelial lymphocytes (result in malabsorption)
224
What does mucosal damage mean?
- B12 / folate / iron can't be absorbed
| - results in anaemia
225
Describe pattern of mucosal damage along length of bowel
- damage DECREASES towards ileum
| - gluten digested into non-toxic fragments
226
Clinical presentations of coeliac disease
- stinking/fatty stools
- diarrhoea
- abdo pain
- bloating
- nausea / vomiting
- angular stomatitis
- weight loss
- fatigue / anaemia
- dermatitis hepetiformis
227
What proportion of coeliac disease patients are asymptomatic?
1/3
228
What is the most important thing to remember when diagnosing coeliac disease?
Gluten in diet should be maintained for at least 6 weeks before testing to get true results
229
How would you diagnose coeliac disease?
- FBC
- duodenal biopsy (GOLD STANDARD)
- serum antibody testing
230
What will a FBC show if patient has coeliac disease?
- low Hb
- low ferritin
- low Hb
231
What will a duodenal biopsy show of coeliac disease?
- villous atrophy
- crypt hyperplasia
- increase intraepithelial white cell count
(reverse on gluten free diet)
232
What do you look at when you carry out a serum antibody test for coeliac disease?
- Endomysial antibody (EMA)
- tissue transglutaminase antibody (tTG)
(both are IgA antibodies)
233
Do EMA & tTG correlate with severity of mucosal damage?
Yes
| - used for dietary monitoring
234
How sensitive is serum antibody testing?
95% (unless patient is IgA deficient)
235
How to treat coeliac disease?
- life long gluten free diet
- correction of mineral/vitamin deficiencies
- DEXA scan
- inform 1st degree relatives of risk
236
Why are coeliac disease patients given DEXA scans?
Monitor osteoporotic risk (patients are at a higher risk of osteoporosis)
237
What are coeliac disease patients at a higher risk for?
- osteoporosis
| - lymphoma malignancy
238
Complications of coeliac disease
- non-responsive coeliac disease (if not diet compliant)
- anaemia
- secondary lactose intolerance
- T-cell lymphoma
- increased malignancy risk (due to inc. cell turnover)
- osteoporosis
239
What are the 2 major forms of inflammatory bowel disease (IBD)?
BOTH ARE CHRONIC AUTOIMMUNE:
1. Ulcerative colitis (UC)
2. Crohn's disease
240
Which part of the GI tract does ulcerative colitis affect?
Only the colon
241
Which part of the GI tract does Crohn's affect?
Any part of the GI - mouth to anus
242
Which ethnic group are more prone to IBD?
Jewish
243
When does IBD occur?
- when mucosal immune systems exert inappropriate response
- to luminal antigens (bacteria)
- may enter mucosa via leaky epithelium
244
Describe ulcerative colitis (UC)
Relapsing and remitting inflammatory disorder of the colonic mucosa
245
What is UC called when it affects just the rectum?
Proctitis (50%)
246
What is UC called when it affects rectum & L colon?
Left-sided colitis (30%)
247
What is UC called when it affects the entire colon? (up to ileocaecal valve)
Pancolitis / extensive colitis (20%)
248
Where is the highest incidence/prevalence of UC?
- Northern Europe
- UK
- North America
249
Epidemiology of UC
- males & females affected equally
- 15-30 years old
- 3 times more common in non/ex smokers
- 1 in 6 have first degree relative with UC
250
Risk factors of UC
- family history
- NSAIDs
- chronic stress
- chronic depression
251
Macroscopic pathophysiology of UC
- begins in rectum & extends
- circumferential & continuous inflammation
- no skip lesions
- reddened/inflamed mucosa that bleeds easily
- ulcers & pseudo-polyps (severe disease)
252
Microscopic pathophysiology of UC
- mucosal inflammation (doesn't go any deeper)
- no granulomata
- depleted goblet cells
- increased crypt abscesses
253
Clinical presentations of UC
- remissions & exacerbations
- restricted pain in lower L quadrant
- episodic/chronic diarrhoea with mucus/blood
- cramps
- bowel frequency linked o severity
254
What clinical presentations might there be in acute UC?
- fever
- tachycardia
- tender distended abdomen
255
What clinical presentations might there be in an acute attack of UC?
- blood diarrhoea
| - diarrhoea at night - urgency & incontinence
256
Extraintestinal signs of UC
- clubbing
- aphthous oral ulcers
- erythema nodusum (red round lumps below skins surface)
- amyloidosis
257
Which parts of the body might suffer from complications of UC?
- liver
- colon
- skin
- joints
- eyes
258
What complications might the liver have in UC?
- fatty change
- chronic pericholangitis
- sclerosing cholangitis
259
What complications might the colon have in UC?
- blood loss
- perforation
- toxic dilation
- colorectal cancer
260
What complications might the skin have in UC?
- erythema nodusum
| - pyoderma gangrenous
261
What complications might the joints have in UC?
- ankylosing spondylitis
| - arthritis
262
What complications might the eyes have in UC?
- iritis (iris inflammation)
- uveitis (inflammation of uvea - middle layer of the eye)
- episcleritis
263
Differential diagnoses of UC
- other causes of diarrhoea
| E.G salmonella spp, giardia intestinalis, rotavirus
264
How do you diagnose UC?
1. Blood test
2. Stool samples
3. Faecal calprotectin
4. Colonoscopy with mucosal biopsy (GOLD STANDARD)
5. Abdo X-ray
265
What will a blood test of UC show?
- raised WBC and platelets
- iron deficiency anaemia
- raised ESR & CRP
- abnormal liver biochem
- hypoalbuminaemia
- pANCA may be positive
266
What is pANCA?
Anti-neutrophilic cytoplasmic antibody
267
Why do you take stool samples to diagnose UC?
To exclude C. diff & campylobacter
268
What does faecal calprotectin test indicate?
IBD - but not specific
269
Why do you carry out a colonoscopy in UC diagnosis?
- assess disease activity & extent
- see inflammatory infiltrate
- goblet cell depletion
- crypt abscesses
- mucosal ulcers
270
Why do you carry out an abdominal x-ray in UC diagnosis?
- to exclude colonic dilatation (in patients suffering acute severe attacks)
271
When is abdominal x-ray useful to diagnose UC?
When UC is too severe for colonoscopy
272
How do you treat UC?
- aim to induce remission
- aminosalicylate
- maintain remission
- surgery
273
What is the active component of aminosalicylate?
5-aminosalicylic acid (5-ASA)
| - absorbed in small intestine
274
What are commonly prescribed 5-ASAs?
- sulfasalazine
- mesalazine
- olsalazine
275
How do you treat mild/moderate UC?
- oral 5-ASA (for left sided / extensive UC)
- rectal 6-ASA (proctitis)
- glucocorticoid
276
What is an example of glucocorticoid?
Oral prednisolone
277
How do you treat severe UC?
Oral prednisolone
278
How do you treat severe UC with systemic features?
- hydrocortisone
- ciclosporin
- infliximab
279
How do you maintain remission of UC?
- 5-ASA
| - azathioprine
280
When do you use azathioprine
For patients who relapse despite 5-ASA or ASA intolerant
281
When is surgery for UC indicated?
For severe colitis that fails to respond to treatment
282
What surgery is performed for severe colitis?
COLECTOMY
- whole colon removed
- with ileoanal anastomosis
- rectum is fused to ileum
- terminal ileum used to form reservoir pouch (store faeces)
283
What is the terminal ileum used to form in a colectomy?
Forms a reservoir pouch
| - means patient remains continent
284
What other surgery can be performed for severe UC?
Panproctocolectomy and ileostomy
285
What is panproctocolectomy with ileostomy?
Whole colon & rectum removed
- ileum brought out on to abdominal wall
- as the stoma
286
Define Crohn's disease? (CD)
Chronic inflammatory GI disease characterised by transmural granulomatous inflammation
287
What does transmural mean?
Goes deep into mucosa
288
Which part of the GI tract does Crohn's affect?
Any part from the mouth to anus
| especially terminal ileum & proximal colon
289
How is Crohn's unlike UC?
There are bits of unaffected bowel between areas of active disease
290
What are unaffected bits of bowel in Crohn's called?
Skip lesions
291
Epidemiology of Crohn's
- highest incidence/prevalence in N. Europe, UK, N. America
- less prevalence if Asian
- females affected more
- 1 in 5 CD patients have 1st degree relative with disease
292
By how many times does smoking increase risk of Crohn's by?
3 to 4
293
When does Crohn's usually present?
20-40 years
294
Risk factors of Crohn's
- Smoking
- Genetic association stronger than UC
- Family history
- NSAIDs may exacerbate
- Chronic stress/depression triggers flares
- good hygiene
- appendicectomy
295
What is the genetic mutation in Crohn's?
Mutations on NOD2 gene on chromosome 16 = increases risk
296
Describe macroscopic pathophysiology of Crohn's
- not continuous (skip lesions)
- affected bowel is thickened & narrowed
- cobblestone appearance
- affects any part of GI tract
297
Why does Crohn's have a cobblestone appearance?
Due to ulcers and fissures
298
Describe microscopic pathophysiology of Crohn's
- inflammation extends through all layers of bowel
- increase in chronic inflammatory cells
- lymphoid hyperplasia
- granulomas present
- goblet cells present
- less crypt abscesses than UC
299
What % of people are granulomas present in?
50-60%
| - non caseating epithelioid cell aggregates with Langhan's giant cells
300
Clinical presentation of Crohn's
- diarrhoea with urgency, bleeding & pain
- abdo pain
- weight loss
- malaise
- lethargy
- anorexia
- abdo tenderness/mass
- perianal abscess
- anal strictures
- extraintenstinal signs
301
Define the urgency for diarrhoea in Crohn's
Need to go 5-6 times in 45 mins
302
What can abdominal pain present as in Crohn's?
Emergency with acute right iliac fossa pain
| - pain mimics appendicitis
303
What are some extra-intestinal signs of Crohn's?
- aphthous oral ulcerations
- clubbing
- skin / joint / eye problems
304
Complications of Crohn's
- perforation & bleeding are MAJOR
- fistula formation
- anal: skin tags, fissure, fistula
- malabsorption
- small bowel obstruction as grossly dilated
- toxic dilatation of colon
- colorectal cancer
- venous thrombosis
- amyloidosis (rare)
305
Describe a fistula in Crohn's?
Between loops of bowel
306
Differential diagnosis of Crohn's
- alternative causes of diarrhoea should be excluded
| - chronic diarrhoea
307
How to diagnose Crohn's
- examination
- bloods
- stool sample
- faecal calprotectin
- colonoscopy
- upper GI endoscopy
308
What will examination for Crohn's show?
- tenderness of R iliac fossa
| - anal examination
309
What will blood show for Crohn's?
- anaemia (due to malabsorption)
- raised ESR & CRP
- raised white cell count & platelets
- hypoalbuminaemia
- abnormal liver biochem
- negative pANCA
310
When will hypoalbuminaemia present in Crohn's?
- severe disease
- part of acute phase response to inflammation
- associated with raised CRP
311
Why do you take a stool sample for Crohn's?
To exclude C. difficile & campylobacter
312
What does faecal calprotectin indicate?
IBD - not specific
313
Why will you conduct a colonoscopy for Crohn's?
- confirms spot lesions & granulomatous transmural inflammation
314
What will upper GI endoscopy exclude in Crohn's test?
Oesophageal & gastroduodenal disease
315
Treatment for Crohn's
- smoking cessation
- anaemia treated
- maintain remission
- surgery
316
How do you treat mild attacks of Crohn's?
Controlled release corticosteroids
| - BUDESONIDE
317
How do you treat moderate to severe attacks of Crohn's?
Glucocorticoids
| - ORAL PREDNISOLONE (reduce dose every 2-4 weeks if symptoms resolve)
318
How do you treat severe attacks of Crohn's?
- IV HYDROCORTISONE
- treat rectal disease - HYDROCORTISONE per rectum
- antibiotics - IV METRONIDAZOLE
319
What is IV metronidazole used for in Crohn's?
Perianal disease (inflammation at or near anus) & abscesses
320
What treatment would you switch to if severe attacks improve?
Oral prednisolone
321
What treatment would you switch to if severe attacks DON'T improve?
Anti-TNF antibodies
- infliximab
- adalimumab
322
How do anti-TNF antibodies work?
- reduce disease activity by countering neutrophil accumulation & granuloma formation
- cause cytotoxicity to CD4+ T cells
323
How do you maintain remission of Crohn's?
- AZATHIOPRINE
- METHOTREXATE
- Anti-TNF antibodies
324
Side effects of azathioprine
- bone marrow suppression
- acute pancreatitis
- allergic reactions
325
When would you use methotrexate for Crohn's?
If intolerant of azathioprine
326
Why are anti-TNF antibodies used?
- induce remission if resistant to corticosteroids
| - immunosuppression then maintains it (infliximab / adalimumab)
327
Define intestinal obstruction (IO)
Arrest/blockage of onward propulsion of intestinal contents
328
Classification of intestinal obstruction
1. According to site
2. Extent of luminal obstruction
3. According to mechanism
4. According to pathology
329
Classification of IO: According to site
Either:
- large bowel
- small bowel
- gastric
330
Classification of IO: Extent of luminal obstruction
Either:
- partial
- complete (volvulus = overflow/sickness)
331
Classification of IO: According to mechanism
Either:
- mechanical
- true (intraluminal/extraluminal)
- functional
332
Classification of IO: According to pathology
Either:
- simple
- closed loop
- strangulation
- intussusception
333
Describe the functional mechanism classification of IO?
Paralytic ileus
- adynamic bowel
- due to absence of normal peristaltic contractions
- caused by abdominal surgery / acute pancreatitis
334
What is intussusception?
One hollow structure into its distal hollow structure
| - usually in children (bowel is softer)
335
What might obstruction of lumen be due to in IO?
- tumour
- diaphragm disease
- meconium ileus
- gallstone ileus
336
What kind of diseases in the wall of bowel may cause obstruction?
- inflammatory
- tumour
- neural
337
Inflammatory disease causing obstruction?
- Crohn's
| - diverticulitis
338
Where does diverticulitis occur?
Usually in sigmoid colon
339
Where does diverticular form?
At gaps in wall of gut where blood vessels penetrate
340
Describe diverticulitis in low fibre diet
- colon has to push harder
- pressure increases
- pushes mucosa through gaps resulting in diverticular / out pouching
- can get inflamed / burst = results in acute peritonitis / possible death
341
Neural disease causing obstruction in bowel?
HIRSCHPRUNG'S DISEASE
| - neonates = born without complete innervation of colon/rectum
342
What does Hirschprung's disease result in?
- gut dilatation
- filling of faeces that remains
- no ganglion cells to result in peristalsis & movement of contents = obstruction
343
Outside bowel causes of obstruction
- adhesions
- volvulus
- tumour
344
What are adhesions outside of the bowel that cause obstruction?
- abdo structures stick to one another
| bowel loops, momentum, other solid organs / abdo wall by fibrous tissue
345
When do adhesions outside of the bowel usually occur?
After surgery
| - most common cause of obstruction (80%)
346
What can happen at sites of adhesions outside of the bowel?
- intestine twists on itself
| - results in obstruction of blood supply / normal movement of intestinal contents
347
What is volvulus?
A twist/rotation of bowel segment
- always occurs at part of the bowel with mesentery
- type of closed loop bowel obstruction
348
Tumour causing obstruction
Peritoneal tumour
| - seen in ovarian carcinoma
349
What are most intestinal obstructions due to?
Mechanical block
350
What is one of the most common causes of hospital admission?
Intestinal obstruction
351
What is typical of obstruction?
- tinkling bowel sounds
| - tympanic percussion
