GI Diseases Clinical Flashcards
Explain why upper GI conditions occur?
Due to acid:
-wrong location eg through oesophagus reflux/ overflow into duodenum
-overproduction
-faults with protective mechanisms- Lower Oesophageal Sphincter (LOS) and pyloric sphincter- if not working acid can pass through, protective lining (gastric cytoprotection is faulty)
What is dyspepsia?
A broad term for a range of symptoms in upper GI tract:
upper abdominal pain, gastric reflux, heart burn, nausea and vomiting, wind
What is the epidemiology of upper GI conditions?
Prevalence varies from 20-40%
Quarter of which will have peptic ulcer disease
90% of patients self medicate, this can make potentially serious problems
What is the epidemiology of gastric cancer?
UK incidence-10/10000
4400 deaths from stomach cancer
17th most common cancer cause death
54% are preventable
Describe the aetiology of gastric cancer:
More common in smokers and drinkers (decrease in protective mechanisms)
Salt intake
Related to H Pylori infection
Less common in vegetarians
More common in 45 years + and x2 prevalence in men
Name common upper GI conditions:
Gastro-oesophageal reflux disease (GORD) 10-20%
Duodenal stomach ulcer disease (PUD) 10-25%
Gastritis 30%
Functional dyspepsia 30%
Oesophageal and gastric cancer 2%
What is the function of HCl and parietal cells?
Parietal cells secrete HCl and intrinsic factor- secreted from fundus
They activate pepsinogen and kills bacteria
Intrinsic factor aids absorption of vitamin B12
Name the 4 phases of controlling acid secretion via parietal cells:
Cephalic phase
Gastric phase
Intestinal phase
Basal state
What occurs in the cephalic phase?
Nervous control, parasympathetic
Thought, smell, taste or sight of food
What occurs in the gastric phase?
Local control, parasympathetic
Distention of stomach and chemical makeup
What occurs in the intestinal phase?
Hormonal control
Food in the duodenum (chyme) causes secretion of somatostatin which inhibits acid production (-ve feedback, enterogastric reflex)
What occurs in the basal state?
Occurs in time between meals, level of acid secretion during these times are regulated by body weight, nº parietal cells and time of day
What is gastrin and how is it produced?
Produced in response to vagal stimuli, a rise in pH (decrease in acidic conditions) and ingested protein and calcium
Stimulates growth of gastric mucosa- protective function
Describe how Ach has an affect on H2:
Vagal stimulation causes Ach to have a direct effect on parietal cell (minor)
Major effect is Ach release onto enterochromaffin like cells
Gastrin has same effect
Describe how somatostatin has an affect on acid production:
PGE2 receptor on parietal cells, somatostatin binds here as its a PG, it stops acid production, negative feedback due to contents of duodenum
Describe what gastric cytoprotection is:
Auto digestion of the stomach is prevented by a thin layer (500microns) above the mucosa surface (neutral)
Complex matrix of bicarbonate and mucus- unstirred layer
How can a stress ulcer be formed in shocked/ critically ill patients?
H+ is normally taken away by submucosal blood flow
In shocked pts, there is a decrease in blood flow, so necrosis in mucosa by increase in H+ conc and decrease in O2
How does somatostatin offer gastric cytoprotection?
Increase mucus secretion
Increase bicarbonate
Increase blood flow
Decrease in acid
How does the Lower Oesophageal Spincter (LOS) have a role in oesophageal protection?
Permanent state of contraction, relaxes to allow food
Reflux can be caused this way
What is gastritis?
Inflammation of the gastric mucosa
What is the pathophysiology of gastritis?
It is a precursor for ulceration
80% of cases due to H pylori-> chronic gastritis-> PUD-> gastric cancer
What are the symptoms of gastritis?
For many they can be asymptomatic
Symptoms include indigestion, sickness, burning
What other health issues can gastritis cause?
40x increased risk of PUD
6x increased risk of gastric cancer
How does Helicopactor Pylori survive in the stomach?
Adapted to survive in acidic conditions
They protect themselves by hydrolysing urea to produce ammonia, which causes a buffer H+ions
Have flagella to burrow into mucosa in the antrum
How does H.Pylori cause a duodenal ulcer?
Chronic inflammation, decrease somatostatin, increase in gastrin production, increase stomach acid production, chronic inflammation in duodenum, where H.Pylori moves into the duodenum and reduces local protection-> duodenal ulcer
What are the 2 different types of H Pylori infection and why?
Depending on the natural acidity status of the body
HP prefers decreased acidity, it won’t affect a healthy duodenum but will affect it if the stomach has passed through and damaged it
For many it leaves the acid unchanged so asymptomatic so no ulcers
How does HP cause gastritis?
Damaged cells and decrease acid production, decrease in mucosa, which long term leads to gastric ulcer and gastric cancer
Who does HP normally infect?
50% of population over 60 infected, almost all over 80
Can get it through childhood/kissing/contaminated vomit
Some strains are more pathogenic than others
How can the HP bacteria be tested for and identified?
Breath test or stool antigen test
Give radio labelled urea and CO2 (radiolabelled) will be produced in breath
Stool needs to be stored at -20ºC before testing (most common)
For both tests pts need to avoid antibiotics for 4 weeks before to avoid a false negative
How would you improve an ulcer if someone has the HP infection?
Eradication, it is the cure
How many people who have duodenal and stomach ulcers also have the HP infection?
Duodenal, more than 90%
Stomach ulcer, 70-80%
What is the epidemiology of PUD?
10-15% of population will suffer from it
GU rare in under 40
DU predominately in males between 20-50
What are the factors causing PUD?
Gastric hyper secretion (DU)
Reduced mucosal resistance (GU) e.g smoker
What is the prognosis of PUD?
Bleeding (perforation, lining splits open) in 10-15% of pts
5-10% with DU will perforate, 1 in 7 will die
5-15% of GU eventually found malignant
60% of pts with DU will relapse after a 1 year
50% of pts with GU will relapse after 2 years
What are the risk factors in PUD?
HP is the major cause
NSAIDs are common cause
More common in smoker- increase number increases prevalence
Salt- can change acid secretion as suppressive effect on parietal cells
Genetic link- people with parents with PUD are 3x more likely
No evidence for stress vs PUD
Which drugs can induce dyspepsia?
Cause peptic ulcers:
NSAIDs
Sulfasalaizine
Iron preparations
Corticosteroids
K (particularly in mr forms)
Bisphosphonates
May reduce LOS pressure:
Theophylline
Ca agonists
Nitrates
How many patients with RA suffer from PUD and what is the safest NSAID to use?
1/3
Ibuprofen is the safest
What are the gastric symptoms of PUD?
Pain on eating
Epigastric area (below sternum but above naval)
What are the duodenal symptoms of PUD?
Pain occurring between meals and at night
Localised dull pain
What are other symptoms for both gastric and duodenal PUD?
Bloatedness
Nausea
Anorexia
Belching
Haematemesis (blood in vomit)
Melaena (dark sticky faeces)
What is GORD?
5-10% of adults have symptomatic reflux
Caused by gastric juice and occasionally duodenal contents in the oesophagus
Defective LOS may be the most important abnormality
Name factors which can contribute to lowering the pressure of the LOS:
Dietary factors (fat, chocolate, caffeine, alcohol, large meals)
Cigarette smoking
Endocrine factors (high levels of oestrogen and progesterone e.g pregnancy, HRT, Oral contraception)
Drugs
What is Hiatus Hernia?
Part of stomach is pushed up through diaphragm
Prevents LOS from closing
Allowing stomach contents to escape
Affects 30-50% of population
Majority of pts are asymptomatic
May present as GORD
Which drugs can contribute to GORD?
Anticholinergics
B2 agonists
Diazepam
CCBs
Nitrates
Alcohol
Progesterones
COC
Theophylline
Which drugs can cause oesophageal ulceration?
NSAIDs
Bisphosphonates
Clindamycin
Clotrimazole
Doxycyline
Potassium
Tertacycline
Theophylline
Antibiotics responsible for 50% of drug induced oesophagitis, especially clindamycin capsule
What are the symptoms in GORD?
Motility of oesophagus may be abnormal
Gastric emptying is delayed in 40% of pts
Main symptom is heart burn
May also suffer dysphagia or odynophagia (pain on swallowing)
What are complications of GORD?
Barrett’s oesophagus (RF for cancer cell lining of oesophagus changes)
Haemorrhage
Stricutre
What is the diagnosis for GORD?
Endoscopy is the only diagnosis
What is functional dyspepsia?
Not associated with risk of cancer
Half of patients with chronic dyspepsia with no evidence of organic disease with investigations done
Could be hypersensitivity to gastric acid
What are the 4 groups of symptoms for functional dyspepsia?
These all can overlap
Ulcer like
Dysmotility like
Reflux like- ongoing heart burn/ reflux but no GORD with investigation
Non-specific
What is the treatment for functional dyspepsia?
Eradicate HP if present
Neutralise acid or prevent production (symptomatic relief)
Periodic monitoring (safety netting)
What should be the management of stomach and duodenum ulcers?
Identify and eradicate HP
Stop inappropriate therapy
Reduce production of acid to reduce gastritis and enable mucosa to repair- block H2 or PPI
Once ulcer is healed (8weeks) then test for HP
Describe the eradication therapy for HP?
2 antibiotics and a PPI
Normally amoxicillin and clarithromycin
85% effective
What should be the management of stomach and duodenum ulcers if there are no causes?
PPI can be prescribed for 4-8 weeks
If still unhealed look for adherence, stopping NSAIDS e.g OTC, or other diseases present e.g Crohns
What should be prescribed if the symptoms of ulcers heals but then the symptoms come back again
Low dose PPI
Give diet advice for the management of GORD:
Eat small meals
Avoid foods which lower LOS pressure (alcohol, caffeine etc)
Avoid fatty foods which slow gastric motility
Avoid eating within 4 hrs and drinking 2 hrs before going to bed
Reduce alcohol intake
Give other lifestyle advice for the management of GORD:
Avoid drugs which lower LOS pressure
Avoid tight fitting clothes
Attention to posture (bend form knees)
For nocturnal heart burn, raise top head of bed by 15-23cm
Stop smoking
What are antacids made up of and how do they work?
Al, Mg, Na and Ca salts
Neutralise acid, releasing CO2 (eructation aka burp)
Increase in LOS pressure by gastric alkalinisation
Mucosal protection, stimulate PG synthesis
Which formulation of antacids work quicker but what negative aspect does it come with?
Liquids work quicker but have a shorter DoA
Why should antacids only be taken for short term use?
As they only releive symptoms in the short term, can cause an acid rebound
When are antacids best taken?
An hour after a meal, when gastric emptying is slow, so they remain in the stomach for longer, DoA = 3hrs
What are common side effects with antacids and how are these resolved?
Constipation with Al based salts
Diarrhoea with Mg based salts
Can be used in combo to counteract each other
What medical conditions can antacids interact with and why?
Al binds to phosphate in gut- osteoporosis
Al can be absorbed- neurotoxicity
Rebound GA secretion with prolonged use
Na- avoid in patients with cardiac problems and hypertension
Are antacids safe to take during pregnancy?
Generally safe but got to look at sodium content
How do alginates work?
Formulated with antacids
Form a high pH viscid mass (raft), trapping air bubbles and CO2 from the reaction of antacid with the stomach contents
So can float to the top of stomach and protects oesophageal mucosa from stomach contents
How does dimeticone work?
Anti foaming agent
Reduces surface tension
Allows bubbles to escape- reduces feeling of bloating
Name examples of H2 receptor antagonists:
Cimetidine, Ranitidine, Famotidine, Nizatidine
How do H2 receptor antagonists work?
Compete for H2 receptor on parietal cells, overidden by powerful stimulus e.g large meal (competition)
Has a longer duration than antacids
What are the healing rates of H2 antagonists used in PUD?
High healing rates, no reduction in relapse
What are the healing rates of H2 antagonists used in GORD?
After 12 weeks, 80-90% of pts with mild oesophagitis improved
Not effective in moderate to severe GORD
Only use if an inadequate response to PPI (NICE)
What are the side effects of different H2 antagonists?
Generally safe 1-7% of pts experience ADRs
Headache/ dizziness
Cimetidine- Gynaecomastia, breast tissue in men (0.2%), impaired libido
Nizatidine- sweating/ abnormal dreams
Confusional states in elderly
Name interactions of Cimetidine?
Binds to P450
Phenytoin, theophylline, warfarin
Enhances their effects
Name a H2 antagonist sold OTC and its dosage:
Ranitidine- Zantac 75
Symptomatic relief of HB, dyspepsia, hyperacidity
6 days continuous treatment, maximum 2 days daily
Name some examples of PPI and their structure:
Omeprazole, Lansoprazole, Esomeprazole, Pantoprazole
Enteric coated preparations, due to being destroyed by stomach acid (acid labile)
Absorbed in SI
Take 1-2 days to reach full effect
Describe the MoA of PPIs:
Blocks H-K ATPase enzyme
Prolongued suppression acid secretion
-20mg omeprazole causes 80% decrease acid secretion for a day
-40mg 100% decrease
Heals ulcers more rapidly than H2, but healing rate is same at 8 weeks
PPIs superior in treatment of reflux/GORD
Lisenced to treat acid aspiration if going under general anaesthetics
What are short term side effects of PPIs?
Nausea, diarrhoea, flatulence, epigastric pain, dry mouth, headache
Arthralgia and myalgia
What can be the concerns of taking PPIs long term?
Bacterial overgrowth as may increase risk of salmonella/ HP
When is the best time of day to take a PPI?
Before food as food can decrease bioavailability
What PPIs are available OTC and at what dose and indication?
Omeprazole 10+20mg +esomeprazole
Reflux symptoms in over 18s
Swallowed whole with plenty of liquid
20mg daily until symptoms have improved then 10mg
When should you refer to the GP for pts wanting to take PPIs OTC?
If after taking them for 2 weeks still no relief
If treatment required continuously for 4 weeks then refer
Pt is over 45 and present with new or changes symptoms (or child)
Continuous dyspepsia (5 days)
Weight loss, appetite, signs of anaemia
Pain on exercise, cardiac origin, pain radiating to arms (heart attack?)
Blood in vomit/ stools
Name other drugs which can be prescribed for upper GI conditions:
Metoclopramide+ domperidone
Sucralfate
Bismuth
Misoprostol
Describe metoclopramide+ domperidone as a treatment for GI conditions:
Increase gastric emptying and LOS tone
Describe sucralfate as a treatment for GI conditions:
Not very common
Polymerizes below pH 4 to form a sticky gel
Adheres to ulcer- physical protection
Describe bismuth as a treatment for GI conditions:
Not very common
May act similar to sucralfate
Strong affinity for mucosa- especially ulcers
May blacken teeth and stools
Describe misoprostol as a treatment for GI conditions:
Promotes ulcer healing by stimulating protective mechanisms- sometimes used with NSAIDs
What is the main treatment used for FD, gastritis and PUD?
H2 antagonists or PPI
What is the main treatment used for GORD?
PPIs or alginates (not H2)
What is the function of bacteria in the LI?
Ferment non digestible polysaccharides, some metabolites absorbed
Produce vitK and biotin (vitB7), which can be absorbed
Produce gases from undigested polysaccharides
Essential for development of caecum and lymphatics
What is constipation?
A symptom, not a disease
Difficulty opening the bowels:
-less than 3 times a week
-straining to open bowels for more than 25% of occasions
-hard or pellet like stool for more than 25% off occasions
What is chronic constipation?
More than 4 weeks
Generally more than 12 weeks in the last 6 months
What is the epidemiology of constipation?
1 in 7 adults
1 in 5 older people
1 in 3 children
More common in women than men
What is imaginary constipation?
Elderly patient may not go as frequently when younger due to not eating as much but this is expected
Describe the types of food that increase chances of having constipation:
Low fibre
High animal fat
Inadequate fluid intake
Caffeine/ alcohol (both diuretics)
Name some medications which can cause constipation:
Antacids (Ca and Al)
Antispasmodics
Antidepressents
Anticolinergics^
Iron tablets e.g ferrous sulfate
Diuretics (encouraging patient to urinate so decreased fluid)
Painkillers (codeine)
CCBs
ACEi
Ulcer healing (PPI)
Antipsychotics
Describe the aetiology of constipation:
Intestinal obstruction:
-scarring from IBD, diverticulitis or post surgery
-adhesions
-intestinal cancers
-abdominal hernia
-gall stones wedged in intestine
-volvous
-foreign bodies
-haemarroids
What are diseases that can cause constipation?
Diabetic autonomic neuropathy (damage to nerve production in bowel area so decrease movement)
Spinal cord injury or tumours
Cerebrovascular accident
Multiple sclerosis
Parkinsons
Connective tissue disorders
Hirschsprung’s disease
What mechanical problems of the anus/rectum can cause constipation?
Rectal prolapse
Poor thyroid function
Lead poisoning
Pregnancy
Travel
Immobility
What factors would you need to gather to get a wider diagnosis for constipation?
Medical history
History of symptoms:
-normal pattern
-other symptoms
-freq and consistency, faecal impaction, incontinence
-how long/ intense are the symptoms
-impact on daily life
Medications
Changes in diet/lifestyle :
-change in jobs
-holiday
-diet
What is the aetiology of constipation in children?
Prevalent in 5-30% of children
Aetiology often unknown, may be due to weening off breast milk
What are the symptoms of constipation in children?
Infrequent bowel activity
Foul smelling wind/stools
Excessive flatulence
Irregular stool texture
Abdominal pain, distension, discomfort
Soiling/over flow
What are the causes of constipation in older people?
Age related decline in GI motility, decrease in elasticity
Decreased mobility
Poor diet- low solid and liquid intake
Wasting of pelvic floor muscles
SEs of medication
Describe the Bristol stool chart:
Type 1/2 = constipation
separate hard lumps
Type 6/7 = diarrhoea
watery, no solid pieces
Aim for Type 4
Name examples of bulking agents:
Ispagula husk
Methylcellulose
Name examples of stimulant laxatives:
Bisacodyl (oral/rectal)
Senna
Dantron (co-danthrusate/ co-danthramer)
Sodium picosulfate
Name examples of faecal softeners:
Docusate (oral/rectal)
Glycerol (suppository)
Arachis oil (enema)
Name examples of osmotic laxatives:
Lactulose, macrogols (inert polymers of ethylene glycol)
MgOH and MgSulfate, phosphate (enema/suppository)
Sodium citrate (microenema)
How long does acute constipation last for?
Less than 4 weeks
What is the treatment plan for acute constipation?
Lifestyle advice and managing underlying causes
Bulk forming (1-3 days if insufficient response)
+/OR osmotic e.g macrogol (on its own if bulk isn’t working)
Stimulant
Gradually reduce and stop after producing soft, formed still without straining at least 3x a week
What is the treatment plan for chronic constipation?
Same as acute, but after everything else can try Prucalopride
Describe when prucalopride is used:
Used when 2 other laxatives have been used for max dose for at least 6 months
Prokinetic serotonin agonist which stimulates GI motility
What is faecal loading?
Build up of faecal matter within the colon
What is impaction?
Dry, hard stools as has been in the colon for a long while
What would be the first line treatment for impaction (hard stools) and how quick do they work?
High dose oral macrogol (48hrs max)
Stimulant (12hrs)
What would be the second line treatment for impaction if there was no initial response or slow?
Glycerol alone or glycerol +bisacodyl suppository (30 mins)
What would be the third line treatment for impaction if there was still an inadequate response?
Sodium phosphate (most powerful osmotic laxative) or arachis oil retention enema
What would be the first line treatment for faecal loading (soft stools) and how quickly do they work?
Stimulant (12hrs)
What would be the second line treatment for faecal loading if there was no initial response or slow?
Docusate or sodium citrate mini enema
What laxative would you not give in opioid induced constipation and why not?
Bulk forming laxative (antagonists)
MoA is to increase faecal mass causing colon to become distended leading to peristalsis, opioids decrease peristalsis
What would be the first line treatment for opioid induced constipation?
Osmotic laxative (or docusate) and a stimulant laxative
What would be the second line treatment for opioid induced constipation if first line unsuccessful and how does it work?
Naloxegol (oral)
Peripherally acting mu-opioid receptor antagonist (PAMORA)
They don’t antagonise the important central opioid receptors
What would be the third line treatment for opioid induced constipation if all unsuccessful?
Methylnaltrexone (sc)- PAMORA
Naldemedine (oral)
What would be some lifestyle advice to give to a patient if they have constipation?
High fibre diet
30g fibre a day with sufficient fluid
Caution in obstructive symptoms or fecal impaction
Ineffective in slow transit constipation or defecatory disorders
Switch from white to wholemeal
Increase physical activity
2L water per day (8 glasses)
What would be the guidelines for suggesting a laxative for a person who is pregnant and experiencing constipation?
Offer a bulk forming
Add or switch to an osmotic
Can consider a short course of stimulant such as Senna (NEVER close to term as can stimulate contractions and prescribed only)
Glycerol suppository
What would be the guidelines for suggesting a laxative for a person who is breastfeeding and experiencing constipation?
The same as pregnancy but can use bisacodyl or Senna and doesn’t need to be prescribed only
What would be the treatment steps for children with constipation?
1st- macrogols and negotiated and non punitive behaviour
2nd- add stimulant laxative
3rd- add lactulose (or other softening) if macrogol not tolerated
What are the considerations when looking at laxatives for children?
Some paediatric aren’t licensed for children under 2 so verbal onset documented needed
Suppositories and enemas not reccomened in primary care
What are the counselling points for ispagula husk?
1 sachet BD (12 years and over)
Sachets poor in a full glass of water and drink straight away
Take after meals, and not before bed as it encourages peristalsis and no peristalsis in sleep
Take 1/2 to 1 hr before/after other meds
Remains effective despite long term use
What is the strength and brand of Ispagula husk?
Fybogel 3.5g sahcets
High fibre is same as original
What are the counselling points for methylcellulose?
3-6 tabs BD with atleast 300ml of liquid
Break tabs in mouth before swallowing
Do not take just before bed
Ensure good fluid intake
2-3 days for effect
What is the strength and brand of methyl cellulose?
Celevac 500mg tabs
What are the counselling points for macrogol?
1-3 sachets daily, in divided doses
Sachets dissolve in 125ml of water
High in Na so CI in hypertension, heart disease and renal impairment
Don’t take other medicines an hour before or after
1-3 days for effect
What are the counselling points for lactulose?
15-45ml daily in single or divided doses
Very sweet tasting liquid
Can cause bloating or colic- caution if intolerant to lactose
No issue for diabetic patients as not absorbed through gut wall so no impact on sugar levels
Up to 2 days for effect
What are the counselling points for MgOH, Milk of Magnesia?
Mainly seen as liquid 30-45ml PRN
Take at bedtime
Can be abused (strong effect)
Old fashioned- caution in elderly
Commonly seen OTC, max 3 days
Around 3-6 hrs for effect
What are the counselling points for Docusate?
Up to 500mg daily in divided doses
12-72 hrs for effect of tabs, 15 mins for suppositories
Softening agent and stimulant
May be useful alternative for people who find it hard to increase fluid intake
Generally well tolerated
What are the brand names for docusate?
DulcoEase
Dioctyl
What are the counselling points for suppositories and enems?
Quick action, making it better, less likely for hospitalisation
Arachis oil enema contains peanut
Describe how you would insert a suppository:
Lay on left side- use a water soluble lubricant
Hold it between thumb and finger and put blunt edge into anus
Go to the depth of your finger
Lie still and hold for 10-15 mins
Describe how you would insert an enema:
Warm enema in bowl of warm water
Lay on left side and keep knees up to chest
Push nozzle in 3 inches
Squeeze contents in and hold for 5 mins, go to the toilet when needed
Stay near the toilet for the next hour
Some people have stomach cramps for a while and occasionally people feel faint and dizzy, lay down if this occurs
Why are stimulant laxatives for short term use only?
Work directly on SM of bowel promoting peristalsis and can cause lazy bowel
What are the counselling points for senna?
Senokot
Tabs and syrups 7.5-15mg daily (max 30mg)
Onset of action is 8-12 hours, take in evening for morning movement
Syrup is unpalatable
What are the counselling points of dantron?
Co-danthramer includes PEG
Co-danthrusate includes docusate
Colours urine red
Avoid prolonged contact with skin
Only in terminally ill patients (potential carcinogen)
Oral solution
Onset of action 6-12 hrs
What are the counselling points for sodium picosulphate and name the brand:
Dulcolax (liquid)
5-10mg OD
Tabs and syrup
Syrup is palatable
Onset of action 10-14 hrs
What are the counselling points for bisacodyl and name the brand:
Duclolax (tabs and suppositories)
Acts on SI
5-10mg OD, increase to 20mg OD if necessary
Tabs act in 10-12 hrs
Suppositories act in 20-60 mins
Suppositories can cause local inflammation
How does prucalopride work and when should it be prescribed?
A SS5HT4 receptor agonist with pro kinetic properties (promotes gut motility)
Should only be prescribed by clinicians experienced in treating constipation after careful review
What is the dosing of prucalopride and how long does it take to work?
2mg tabs OD, review treatment if no response after 4 weeks (reduce dose in elderly 1mg)
1-2 weeks for effect, increasing dose will not improve response
What are the side effects of prucalopride?
Headache
GI disturbances
What are bulk forming laxatives made of?
Mostly of plant origin, including non digestible polysaccharides including cellulose
What are the red flags of constipation?
Pain on defecation- causing suppression of reflex
Pt over 40 years with sudden change in bowel habits and no obvious cause
Greater than 14 days duration and no obvious cause
Associated fatigue
Presence of blood
Repeated failure of laxatives
Suspected laxative abuse
What is acute diarrhoea?
Abrupt onset of 3 or more loose stools a day and lasts no longer than 14 days
How does acute diarrhoea normally resolve?
Majority resolves in 2-3 days without specific treatment, just oral rehydration sachets
What is chronic diarrhoea?
Pathological cause which lasts more than 14 days, possible flare up of previously diagnosed condition
What is the pathophysiology of diarrhoea?
Change in the balance between absorption and secretion of water and electrolytes
What can be one reason to why the pathophysiology of diarrhoea occurs?
Osmotic force that drives water into the gut lumen e.g after ingestion of non absorbable sugars e.g xylitol, sorbitol, pancreatic insufficiency, cystic fibrosis
Proportional to the intake and responsive to fasting e.g can be avoided if don’t eat
What is another reason to why the pathophysiology of diarrhoea occurs?
Enterocytes actively secreting fluid e.g enterotoxin-induced diarrhoea
Not responsive to fasting
Ion transporters activated by e.g bacteria resulting in pathogens:
-invading enterocytes or
-producing enterotoxins (toxic to mucosal lining of GIT)
-induce cytokine secretion to produce PG which stimulates secretion of fluid and electrolytes
Describe the mechanism of invasive bacteria induced diarrhoea:
Directly attack mucosal cells with causes diarrhoea
Stools may contain blood/pus
Fever
e.g shingella, salmonella, Yersinia, Enterinvasive Ecoli
Describe the mechanism of non-invasive bacteria induced diarrhoea:
Doesn’t directly damage the gut
Bacteria produce enterotoxins that disrupt secretion
Watery diarrhoea
e.g saureus, C perfingens, E coli
Describe the mechanism of virus induced diarrhoea:
Mechanism not fully understood
Enterocytes become secretory, results in watery diarrhoea
What are faecal studies that can occur for someone who has diarrhoea?
To see if any protein loss- indicates damage in GIT:
-Serum albumin
-Fecal alpha 1 antitrypsin
Intestinal biopsy- very severe cases
What are the common causes of diarrhoea in infants?
Infectious gastroenteritis
Toddlers diarrhoea (pick up and licks things)
Food intolerances
Coeliac diease
What are the common causes of diarrhoea in school children?
Infectious gastroenteritis
Drugs (antibiotics)
Name the most common organism that causes diarrhoea in children older than 5 years old:
Rotavirus- onset 12-48 hr
Name the most common organism that causes diarrhoea in adults:
Campylobacter- onset 2-5 days followed by rotavirus
Name other organisms that can cause diarrhoea and their onset of symptoms:
Ecoli (1-6 days)
Salmonella (12-24 hrs)
Shingella (1-7 days)
C difficile (usually starts during Ab therapy)
Name examples of drugs that cause diarrhoea:
Antibiotics- most common are broad spectrum
Laxatives
Metformin
Ferrous sulfate
NSAIDs
Colestryamine
Antacids (Mg salts)
B blockers
Digoxin
Misoprostol
What is the prescribed dose for loperamide?
Opioid agonist
More than 12 years old:
Initially 4mg, followed by 2mg after each loose stool (for up to 5 days max), usual dose 6-8mg daily, max 16mg per day (8 tabs)
What is the GSL/P dose for loperamide?
More than 12 years old:
Initially 4mg, followed by 2mg after each lose stool (for up to 48 hrs max), usual dose 6-8mg, max 12mg per day (6 tabs)
What is the purpose of ORT and give an example:
Dioralyte (if under 2 years only under medical supervision)
To prevent or correct dehydration
Maintain appropriate fluid intake once rehydration established
Mix sachet with 200ml of water
What is dioralyte relief and how does it work?
Contains rice starch (bulks)
The rice swells with water, so retains water in colon and bulks up stools so increases water retention
If under 1 year old, under doctor supervision
Severe cases require hospitalisation for IV fluid
What are the history taking points for patients presenting with chronic diarrhoea?
Determine underlying cause:
-foreign travel
-laxative abuse
-medications (PPI/Abs)
-immunocompromised
-FH of IBS/coeliac disease
-lactose intolerance, excess caffeine/ sorbitol
-refer for specialist investigations
Should loperamide be used in pregnancy/ breastfeeding, why/ why not?
Pregnancy:
Manufacturers advise avoid, weigh up risks
Breastfeeding:
Amount PROBABLY too small to be in breastmilk- avoid
Should ORT be used in pregnancy/ breastfeeding, why/ why not?
It is essential
If symptoms warrant loperamide, refer in both instances
What would be the advise and medications used in children with diarrhoea?
Feeding babies: encourage to still feed with normal breast milk as the milk has the right antibodies to fight off diarrhoea
Children: encourage plenty of fluids/ ORT
Loperamide is not recommended by NICE but BNF does state dose for children via prescription
What measures should be taken to prevent the spread of diarrhoea?
Careful washing and drying of hands after using toilet, nappy changes, before meals
Don’t share towels
48hr exclusion from school following cessation of symptoms
Avoid swimming for 2 weeks following last episode of diarrhoea
Describe co-phenotrope as a treatment for diarrhoea:
Atropine and diphenoxylate (anticholingeric and opioid)
100 parts diphenoxylate HCl to 1 part atropine sulphate
Licensed as adjunct to rehydration in acute diarrhoea
Initially 4 tabs followed by 2 tabs every 6 hours until diarrhoea controlled
Describe bismuth subsalicylate as a treatment for diarrhoea:
Pepto-bismol (never in under 16s due to Reye’s syndrome)
Limited evidence, not recommend by NICE or BNF
Inhibits intestinal fluid secretion
Suppress intestinal inflammation
Bactericidal action
What are red flag symptoms in diarrhoea?
Recent travel abroad
Blood or mucus in stools
Severe vomiting or fever
Severe or persistant abdominal pain
Pregnancy/ breastfeeding
Signs of dehydration
How long should an age group have diarrhoea before being referred to GP?
> 1 day= infants and children under 1
2 days= children under 3 and frail/older people
3 days= children over 3 and healthy adults
What is travellers diarrhoea?
3 or more loose stools in 24 hours with or without at least one symptom of cramps, nausea, fever or vomiting
What are the causes of travellers diarrhoea?
Bacteria (Ecoli)- most common
Viruses, protozoan parasites
Lower food hygiene and sanitation facilities in destination
What is the advice for prevention of travellers diarrhoea?
Food, water and personal hygiene
-drink bottled water, avoid ice, ice creams, salads, uncooked veg, fish, meat, unpasteurised milk, street vendors
-vaccines (hep A, typhoid and cholera)
What are examples of intermediate and high risk countries for travellers diarrhoea?
Intermediate- Israel, south Africa, carribean
High- Asia, Africa, Latin America
What are signs of dehydration?
Unwell/ deteriorating
Altered responsiveness
Tachycardia
Decrease skin turgor
When should you follow the sick day rules?
When unwell with any of the following:
-vomiting or diarrhoea, unless minor
-fevers, sweats, shaking
What medications should be stopped when following the sick day rules and when can they be started again?
ACEi
NSAID
ARBs
Diuretics
Metformin- increase risk of causing lactic acidosis
Restart when well again 1-2 says after eating/ drinking normally
Why should you follow the sick day rules?
They can be problematic if becoming dehydrated, can leads to acute kidney injury leading to kidney failure
Describe how a C Diff infection can occur:
It is a bacterium usually present in the gut
Broad spectrum Abs upset microbiome, allowing C Diff to flourish (enterotoxin produced)
Toxins can damage lining of colon and cause diarrhoea which is highly contagious and be fatal
What are the risk factors for a C Diff infection?
Broad spectrum Ab use
Over 65 year olds
Prolongued stay in hospital care
Immunocompromised
What is the treatment for a C Diff infection?
Vancomycin 125-500mg every 6 hours for 10 days (orally)
Describe the epidemiology for IBS:
Onset most common at ages 20-30
x2 more common in females than males
Estimated to affect 10-20% of population
x2 risk among 1st degree relatives
Describe the aetiology of IBS:
Exact cause not understood
Food intolerances are precursors
No lesions are present (i.e gut isn’t damages/diseased)
Post infective bowel dysfunction (gastroenteritis once cleared up), gut hypersensitivity, altered colonic motility and heightened pain sensation all implicated
Stress
Describe the pathophysiology of IBS:
Structurally the gut is normal
No detectable pathology using standard tests
Blood tests/stool samples/ colonoscopy may be used to rule out other tests
Functional conditions such as IBS requires symptom management
What are the main GI symptoms of IBS?
Abdominal cramping
Diarrhoea/ constipation/alternating
Flatulence
Bloating
Urgency to defecate
What are the other non GI symptoms of IBS?
Acid indigestion
Nausea
Lethargy
Eating may worsen symptoms
Passing mucus in stools
What would be the criteria for diagnosis in IBS?
Abdominal pain present for at least 6 months
Relieved by defecation or
Increased/decreased bowel freq or stool formation
Plus at least 2 of the following:
-abdominal bloating/distension
-altered stool passage (straining, urgency, incomplete evacuation)
-worsened by eating
-passing mucus
What is the Rome IV criteria?
In secondary care
Abdominal pain 1 day per week in last 3 months
Symptoms began at least 6 months prior
Along side more than 2 of the following:
-related to defecation
-change in stool freq
Name and describe the classifications of IBS using the Rome IV criteria:
IBS-C, predominant constipation symptoms
>25% of stools are type 1/2 and <25% are types 6/7
IBS-D, predominant diarrhoea symptoms
>25% are type 6/7 and <25% are types 1/2
IBS-M, mixed
>25% are type 1/2 AND >25% are type 6/7
IBS-U, unclassified
Person has IBS, but bowel habits can’t be categorised as above
What are the main drug class treatments for IBS?
Antispasmodic drugs
Antidepressants
Laxatives
Loperamide
Linaclotide
Name some antispasmodic drugs used for IBS and their dose:
Alverine citrate 60-120mg up to TDS
Mebervine 135mg TDS (20 mins before food) or 200mg BD for MR prep
Peppermint oil caps, 1 or 2 caps up to TDS
Hyoscine butylbromide and dicycloverine can also be used but tend to have more antimuscarinic effects
What are the CI for antispasmodic drugs in IBS?
In intestinal obstruction or paralytic ileus- as slowing down motility can be a problem when motility is already an issue
Describe the use of antidepressants for IBS:
Use is unlicensed, for people with IBS pain
People usually not respond to typical treatments
Doses given lower than you would see for mental health uses
Name some antidepressants used for IBS and their doses:
1st line= TCA e.g amitriptyline 10-30mg at night
2nd line= SSRI e.g sertraline, citalopram, fluoxetine- not a specific one
What should you specifically counsel a patient on if they are taking antidepressants for IBS?
They may be shocked when they read the PIL as it says it is for depression
Describe the use of laxatives in IBS:
For IBS-C
Ispagula husk can be used for IBS-D
Can use any laxative apart from lactulose as can increase gas production and worsen symptoms
Dose should be titrated according to symptoms
Describe the use of loperamide for IBS OTC:
Only for pts over 18
Must have been diagnosed with IBS
Only for attacks lasting up to 48 hrs- refer if longer
Can be used for a max of 2 weeks as long as individual bouts are less than 48 hrs
Describe the use of linaclotide for IBS:
For moderate to severe IBS-C in adults
Person must have had IBS-C for at least 12 months
Should only be used if max tolerated doses of laxatives haven’t helped
What is the dosing for linaclotide for IBS?
290mcg OD 30 mins before food
What is the CI for linaclotide?
Avoid in GI obstruction/ IBD
What are the red flag symptoms of someone presented with suspected IBS:
Unintentional weight loss
Unexplained rectal bleeding
FH of bowel/ ovarian cancer
Loose stools for more than 6 weeks in pts over 60 years old
Anaemia
Elevated inflammatory markers
Abdominal/ rectal masses
What is diverticular disease?
Symptomatic
Presence of diverticula
-pouches protruding outwards from the LI wall
-small mucosal herniations protuding through intestinal layers and sm
What is diverticulosis?
Condition where uninflammed diverticula, usually asymptomatic
What is diverticulitis?
One or more inflamed/ infected diverticula
Describe the epidemiology of diverticular disease:
Very common, particularly in industrialised countries:
-westernisation increase in incidence
-lack of fibre
Describe the prevalence of diverticular disease:
Similar in males/females
Increase with age
Rare in people below 40
1/3>65 years, 65% of people >85 yrs
80-85% will remain asymptomatic
Describe the epidemiology of diverticulitis:
Approx 5% of pts with diverticulosis develop diverticulitis
15-25% of pts with diverticulitis develop complications requiring surgery, mortality associated with these
More common in patients who are immunocompromised , on anti-inflammatories or have severe co-morbitidies
What are the mortalities associated with diverticulitis?
Abscess formation
Intestinal rupture
Fistulas (inflammation/ abscess causing pathway)
Peritonitis (lining of abdominal wall and organs in abdomen, inflammation and infection of this)
Massive bleed (will need a blood transfusion)
Describe the aetiology of diverticular disease?
Causative agents unknown
Increase in intraluminal pressure (opening of LI) and weakening of muscle wall thought to be a 1º cause
Abnormal colonic activity e.g due to IBS/opioids
Defective muscular structure
Changes in collagen structure in ageing
What are environmental and genetic factors thought to be involved in diverticular disease?
Genetic:
-left sided diverticular predominant in the west (sigmoid colon)
-right sided predominant in Asians
Dietary factors:
-associated with a low fibre diet and constipation
-Associated with obesity
What is the pathogenesis of diverticular disease?
Colonic muscular hypertrophy results in narrowing of lumen and formation of small chamber with high pressure and subsequent diverticula- takes place in an area of weakness e.g capillaries
What is the pathogenesis of diverticulitis?
Fecal material or undigested food collect in diverticula and cause obstruction
Mucus secretion and normal bacterial overgrowth leads to distension of diverticula
Results in vascular compromise and perforations
Increase in intraluminal pressure and stuck food particles may also damage diverticular wall, resulting in inflammation and necrosis and perforation
Recurrent attack leads to scar tissue formation and lumen narrowing
What is the advice and management of diverticulosis?
Asymptomatic so no need for routine follow ups
Maintain healthy balanced diet, high in fibre (30g)
Maintain adequate fluid intake
If overweight, advise about benefit of weight loss, exercise and also smoking cessation to prevent progression
If constipated, offer bulk forming laxative
What are symptoms of diverticular disease?
Intermittent pain in lower left quadrant (with constipation, diarrhoea, rectal bleeds)
Abdominal pain worsened by eating, relieved by passing stool or wind, flatulence
Lower left quadrant tenderness on palpitation
Asian populations symptoms may present on right quadrant
No systemic symptoms
What would be the management of diverticular disease?
High fibre diet
Bran supplements/ bulk forming laxatives
Lifestyle advice as per diverticulosis
Anti-spasmodics when colic/cramping
What should you avoid in diverticular disease?
Avoid NSAIDs
Avoid anti-motility drugs which slow transit time e.g codeine and loperamide should NOT be used
Risk of diverticular perforation
What are the symptoms of diverticulitis?
Constant lower left abdominal pain with:
-fever
-sudden bowel change
-blood/mucus in stools
-lower left quadrant tender (right if asian)
-palpable abdominal mass/distension
-malaise
-N&V
-tachycarida
-increase in WBC, platelets, anaemia, CRP
Under what conditions should you refer someone to hospital with suspected diverticulitis?
These can cause increased risk of complicated acute diverticulitis:
Patient over 65
Co-morbidities/ immunocompromised
If patient can’t take oral Abs at home
Dehydrated/ at risk
Uncontrollable abdominal pain plus any signs of complicated acute diverticulitis
What are the signs of complicated acute diverticulitis?
Intra-abdominal abscess
Diverticular haemorrhage- blood in stools
Peritonitis
Stricture (decrease in GI motility, constipation, cramping)
Fistula
Intestinal obstruction
Sepsis
What are some common fistulas?
Faecaluria - faecal matter in urine
Pneumaturia- bubbles in urine
Perianal- anal canal to skin surface- most common
Entero-vesical/ colo-vesical (bowel to bladder)
Entero-vagina (bowel to vagina)
What are the signs of sepsis?
Increase respiration
Increase heart rate
Decrease systolic BP
No urine output
Skin discolouration
Cognitive impairment
What is the treatment for diverticulitis who is systemically unwell?
Co-amoxiclav 500/125 TDS x 5 days
(Cefalexin if penicillin allergy) PLUS metronidazole 400mg TDS for 5 days
OR
Trimethoprim 200mg BD for 5 days PLUS metronidazole 400mg TDS for 5 days
What would be the treatment for diverticulitis who is systemically well?
Consider no Ab strategy- stewardship
Analgesia e.g paracetamol
Re-present if symptoms worsen
What is a stoma?
An opening in front of abdomen
Surgically created:
-bowel or bladder
-enables elimination of contents
Why would somebody need a stoma?
Some disease predispose patients:
-IBD
-Diverticular disease
-Cancer of LI
Volvulus (twisted bowel)
Perforation of colon
Toxic megacolon
Colonic polyps
Name and describe the different types of stoma:
Colostomy- stoma surgically inserted within colon or LI
Ileostomy- stoma at ileum- final portion of the SI, right hand side
Urostomy- stoma at ileum where urine being expelled
Describe where a colostomy can occur:
End colostomy
Descending- firmer stool due to increased contact time in colon so increased absorption of water
Ascending/ transverse- more fluid stool
Can be permanent/ temporary
Describe the details of a urostomy:
Following bladder removal
Ileal conduit urinary diversion:
-small piece of bowel connected to the uterus to ileum
Not reversible
Describe colostomy bags:
Generally closed bag, disposable
Change once or twice a day
Opaque/ beige more discreet
Normally use one or two piece system
What is a one piece system colostomy bag?
The bag is already attached to the base plate, which is the contact point for the bag to the skin
This is a disadvantage as can irritate the skin as have to remove everything
What is a two piece system colostomy bag?
Base plate is separated from bag
Can change base plate every 3-7 days
Describe ileostomy bags:
Generally drainable bags, reusable
-change ever 3-5 days
Also one or two piece systems
Integrated clip, or no closure system
With clip, patient has the ability to close off system- preffered
Describe urostomy bags:
Many different types available
Also one or two piece systems
Tap outlet bag needs changing even 1-3 days
Empty when half full
Night drainage bag used as can’t keep emptying at night- a connected tube to tap of day bag with tap open so drains into night bag
What are other items that can come with stoma bags and why?
Adhesives
Adhesive removers- can irritate skin/ difficult to remove
Deodorants- can be inserted into bag to decrease odour
Skin fillers and protectives- if area of skin uneven to attach to base plates
Stoma caps- smaller volume when want to do something for a short period of time e.g swimming
What are the common food problems associated with stomas?
Gas producing- alcohol, asparagus, bananas
Odour producing- some cheeses, cauliflower
Loosen stool- figs, apples
Cause blockage- beef, broccoli, grapes, lamb
Red stools- beetroot, strawberries, tomato
What are the common drug problems associated with stomas?
Diarrhoea- Abs, furosemide, iron, fluoxetine
Constipation- anticholinergics, opioids, verapamil
Intestinal disability- TCAs, CCBs
GI SEs
What is the lifestyle advice for someone with constipation and who has a stoma?
Diet and med review
Increase fluid and fibre
Consider use of ispagula husk- not in ileostomy patients
Increase water and salts
What is the lifestyle advice for someone with diarrhoea and who has a stoma?
Diet and med review
ORT use
Loperamide (liquid and dispersible tabs)
-caps may pass too quickly to be absorbed
What are the causes of pancreatic exocrine insufficiency?
Lack of pancreatic digestive enzymes being secreted into duodenum
Specifically lack of amylase, lipase and protease
What are the underlying causes of a lack of digestive enzymes?
Pancreatic resection (surgical removal of pancreas)
Pancreatitis
Diabetes
Coeliac disease (pancreatic fibrosis)
Pancreatic tumours
CF (pancreatic duct becomes blocked with mucus)
What are the internal symptoms of pancreatic exocrine insufficiency?
Macronutrients are maldigested
Malnutrition, lack of energy, low blood levels of fat soluble vits (A,D,E,K)
Low blood levels of Zn, Se so poor thyroid function, poor wound healing, immune response
What are the physical symptoms of pancreatic exocrine insufficiency?
Malnutrition:-
Lethargy, depression, poor conc, muscle loss, dry skin, brittle nails
Diarrhoea*
Cramping/ bloating/ flatulence
Steatorrhoea/ fatty/foul smelling stools, usually light in colour
What are the aims of pancreatic exocrine insufficiency treatment?
Pancreatic enzyme replacement (amylase, lipase, protease)
What are the drugs used to treat pancreatic exocrine insufficiency?
Pancrex V
Creon
Nutrizym 22
What are the counselling points for treatment of pancreatic exocrine insufficiency?
Dose will be tailored according to treatment
Higher doses for main meals
Smaller doses for snacks
Physical symptoms should ease
Clinal manifestations should also improve due to vitamins being digested and absorbed properly
Name the two types of IBD:
Crohn’s disease
Ulcerative colitis
What are the main features of CD?
Affects any part of the GI, from mouth to rectum
Inflammation extends through all 4 layers of gut wall-fistula
Inflammation is patchy in distribution
What are the main features of UC?
Affects the colon and rectum only, not the anus
Only affects the mucosa (sometimes the submucosa)
Inflammation is diffuse (constant) in distribution
What is the epidemiology of IBD?
World wide
More common in industrialised counties
Affects all races and sexes
Peak incidence occurs between 10-40 years of age but can occur at any age, 15% over 60
What is the incidence of CD?
5-10/ 100000 population per year
Prevalence of 50-100 cases/ 100000
What is the incidence of UC?
10-20/100000 population per year
Prevalence of 100-200 cases per 100000
What is the epidemiology of CD?
Slightly more common in females
M:F 1:1.2
Occurs at a younger ages
Mean age at onset around 26
What is the epidemiology of UC?
Slightly more common in males
M:F 1.2:1
Occurs at an older age
Mean age at onset around 34
What is the aetiology of IBD?
Causative agents unknown
Numerous factors thought to have a role:
Environmental, maybe cause of exacerbation:
-diet, smoking, infection, drugs
Genetic
Describe how diet can influence IBD:
E.G fat intake, fast food ingestion, milk and fibre consumption, refined carbs
Evidence is inconclusive
Many patients are able to identify foods that aggravate symptoms e.g cows milk, spicy foods
Describe how smoking can influence IBD:
Worsens the clinical course of the disease
Increase risk of relapse and need for surgery
40% of CD patients are smokers (10% UC)- more likely to be an ex smoker (quit within first 2-5 years) or non smoker
Shows smoking may help prevent onset of UC
-chemicals affect colon sm, nicotene incline NO which alters gut motility and transit time
Describe how infection can influence IBD:
Some evidence that exposure to mycobacterium paratuberculosis (TB-found in unpasteurised milk) can cause CD
UC can occur after episode of infective diarrhoea, no definite association with infective agent
Association with measles and mumps infection
Describe how drugs can influence IBD:
NSAIDs can exacerbate IBD as inhibits synthesis of cytoprotecotive PGs
Abs can change enteric microflora
Oral contraceptive, can increase risk of developing CD, possible caused by vascular changes in gut or oestrogen enhancing inflammatory response
Isoterinoin for acne
How can an appendectomy influence IBD?
Has a protective effect on both UC and CD
How can stress influence IBD:
Can trigger relapse
Activates inflammatory mediators at enteric nerve endings in gut wall
How can genetic factors influence the risk of IBD?
Disruption of epithelial barrier integrity (leakage, immune cells through)
Deficits in autophagy (cell death)
Deficiencies innate pattern recognition receptors
Problems with lymphocyte differentiation, especially in CD
Inappropriate response to IS in the mucosa of GIT to normal enteric flora
What mutated genes can influence IBD risk?
Mutations of the gene CARD15/NOD2 (inflammatory receptor) located on chromosome 16, associated with small intestine in CD in white population
The genes OCTN1 (solute carrier) on chromosome 5 and DLG5 on chromosome 10 (structural protein in gut) have been linked to CD
Does IBD have an autoimmune component?
70% of UC pts have anti-neutrophil cytoplasmic antibodies (p-ANCA)
What are ethical factors relating to IBD?
Jews are more prone than non-jews
IBD incidence is lower in non-white races
What are familial factors relating to IBD?
1st degree relatives of those with IBD have up to a 20 fold increase in developing IBD
15 fold greater concordance for IBD in identical twins than non identical twins
What is the pathophysiology of IBD due to?
Increased activity to effector lymphocytes and pro-inflammatory cytokines that override normal control mechanisms
1º failure of regulatory lymphocytes and cytokines
In CD T cells are resistant to apoptosis after inactivation
What is the pathophysiology of CD?
Involving one or multiple areas
Usually the terminal ileum and ascending colon
Discontinuous (skip lesions)
Affected areas are thickened, oedematous and narrow
Deep ulcers can appear
Mucous membrane between fissures has a cobblestone appearance, strictures
Also can lead to bowel obstructions, abscesses and gut perforations
What would CD look like microscopically?
Non specific granulomatous inflammation (macrophages which can’t get rid of the inflammation)
Inflammation extends throughout all layers of bowel (transmural)
Inflammatory cells are seen throughout
Th1 associated - IFN-g
Chronic inflammation leads to risk of cancer
What are the different types of UC?
Starts in rectum- proctitis
SI+rectum- left sided colitis
LI+SI+rectum- universal= dancolitis
Not patchy, works its way up
What is the pathophysiology of UC?
40% proctitis
40% left sided
20% whole colon
Formation of crypt abscesses and mucosal ulceration
Mucosa looks red, inflamed and bleeds easily
-purulent and granular with superficial ulceration
-pseudopolyps in severe infection
What would UC look like microscopically?
Inflammatory cells infiltrate the lamina proprietary and crypts
Th2 associated
Dysplasia (pre cancerous) can be seen from biopsies, can progress into carcinomas
What are the symptoms of IBD?
Depends on site, severity and extent:
-diarrhoea
-abdominal pain
-fever
-malaise
-lethargy
-N&V, more common in CD as related to upper GI
-weight loss, more common in CD as more severe and small bowel affected so decreased absorption
-malabsorption
-growth retardation in children
What are the clinical features of CD?
Tends to be more disabling than UC
Pain (particularly in lower right quadrant)
Palpable masses- can feel a lump
Anaemia
Small bowel obstructions
Abscesses
Fistulas
Gut perforation
What are the clinical features in UC?
Diarrhoea- possible with blood/ mucus
-up to 20 liquid stools a day
Abdominal cramp with fever
Constipation- due to narrowing
50% of UC pts have a relapse each year
-severe attacks can be life threatening
What parts of the body can experience complications of IBD?
Joints and bones
Skin
Eyes
Liver
Why do complications occur in patients with IBD?
50% of patients with IBD will get at least 1
Inflammation will spill over into other tissues, immune cells in gut can go to different areas
Describe the joint and bone complications in IBD:
Arthropathies (arthritis) and osteopenia (weakness bone matrix- cytokines activates OCs)
Describe the skin complications in IBD:
Erythema nodosum- tender hot red nodules, subside over a few days to leave brown skin discolouration
Pyoderma gangrenosum- pustule, develops into an ulcer
Describe the eye complications in IBD:
Episcleritis- intense burning and itching of BVs involved
Uveitis- headache, burning red eye, blurred vision
Describe the liver compilcations in IBD:
Sclerosing cholangitis
-chronic inflammation of the biliary tree
-leads to progressive fibrosis and biliary structures
What is the morbidity like in IBD?
QoL generally lower in CD than UC, especially because of recurrences after surgery
Increase risk of peritonitis (abdominal cavity) and malignancy
Malnutrition and chronic anaemia common in long standing CD
What would be the full history gathering to test for IBD?
Recent travelling
Medication
Smoking
FH
What questions would be asked to determine a patients symptoms for suspected IBD?
Stool frequency and consistency
Urgency
Rectal bleeding
Abdominal pain
What physical signs and examinations could be used to help diagnose IBD?
General well being
Pulse
BP
Temperature
Weight loss
Abdomen tenderness or distension- right iliac foss a mass
Anus- oedematous anal tags, fissures or perianal abscesses
What are the investigative tests carried out to help diagnose IBD?
Blood tests
Microbiology testing for infectious diarrhoea
Serological tests
Abdominal radiography
Sigmoidoscopy
Rectal biopsy
Colonoscopy
Double contrast barium enema
Small bowel radiography
Ultrasound
Computer tomography and magnetic resonance imagine
Describe blood tests for diagnosis of IBD:
Anaemia is common (iron and/or folate)
Raised ESR and CRP and a raised WCC
Hypoalbuminemia- some protein loss in gut
LFTs may be abnormal
Describe serological tests for diagnosis of IBD?
SC antibody usually present in CD
pANCA antibody, -ve in CD, +ve in UC
Describe abdominal radiography for diagnosis of IBD:
Essential in the initial assessment of suspected severe IBD
Excludes colonic dilation
Helps assess disease extent in UC
Identifies proximal constipation
Givens an impression of right iliac fossa mass in CD
Can show evidence of small bowel dilation- only in CD
Describe sigmoidoscopy for diagnosis of IBD:
Internal examination of colon (lower third) using a sigmoidoscope
Used for all patients presenting with diarrhoea
Used to confirm diagnosis in UC
Describe rectal biopsy for diagnosis of IBD:
Detects non specific histological changes in mucosa
Describe colonoscopy for diagnosis of IBD:
Internal examination of colon (entire length) using a colonoscope
Used for mild to moderate disease to assess extent
Biopsy can be performed aswell
Describe double contrast barium enema for diagnosis of IBD:
Inferior to colonoscopy
Can detect early mucosal changes
Describe small bowel radiology for diagnosis of IBD:
Current standard for assessing SI in CD
Describe an ultrasound for diagnosis of IBD:
Sensitive and non invasive
Identifies thickened small bowel loops in CD
Describe computer tomography and magnetic resonance imaging for diagnosis of IBD:
Evaluates activity and complications of disease
What is the correlation between breastfeeding and IBD?
Breastfeeding in infancy can help protect from IBD
What is the correlation between vitamin D and IBD?
A deficiency is common
What does the bacteria C difficule cause and how does it come about and diagnosed?
Causes pseudomembranous colitis
Usually after prologued use/ multiple course of antibiotics
The use of PPIs predispose patients to the CDiff infection
Diagnosis by sigmoidoscopy and detection in stool
Describe the correlation of cancer with IBD:
Increased risk of colorectal cancer in patients with colonic disease (apart from isolated proctitis)
Increased risk of leukaemia in UC and lymphoma in CD, unless return of baseline inflammation
What is the Crohn’s disease activity index (CDAI) score?
<150 or Harvey Bradshaw Index 4 or below = patient in remission
≥300 or HBI more than 8= severe active disease
Define what acute severe UC is:
Medical emergency
More than 6 bloody stools a day + 1 more:
-pulse >90bpm
-temp>37.5ºC
-Hb<10.5g/dL
-ESR>30mm/h
When and why would patients with UC need surgery?
15-20% may need it after 10 years due to:
-poor response to treatment
-emergency problems- complications
What are the surgical interventions in UC?
Subtotal colectomy- to remove colon but leave rectum
Proctocolectomy- removal of colon, rectum and anal canal
What are the aims of therapy in UC?
Reduce symptoms- improve QoL
Induce remission
Maintain remission
Minimise toxicity related to drugs
What is acute treatment?
Often termed induction treatment to induce remission
What is maintenance treatment?
To maintain remission, preventing relapse
Describe the Montreal classification in UC:
E= extent
E1= proctitis E2= left sided E3= extensive
S=severe
S0=clinical remission S1=mild S2= moderate
S3= severe
Explain the severe section meanings in the Montreal classification:
S0= asymptomatic
S1= 4 or less stools, +/- blood, no systemic illness, normal inflammatory markers
S2= more than 4 stools, minimal toxicity
S3= more than 6 stools a day and rest
What is the advantage and disadvantage of using the Montreal classification to classify UC?
+Doesn’t require invasive procedures
-Asymptomatic but can still be showing inflammation
What affects the choice of therapy in UC?
*Disease severity
*Disease extent/ location
Previous response to therapy
Disease pattern
Presence of complications
What is the first line treatment for inducing remission for mild to moderate UC- proctitis?
Topical aminosalicylate
Suppositories preferred over enemas due to delivering drug to rectum than further up
Suppositories increase mucosal conc and work better than oral
If patient decline topical consider oral aminosalicylate
What is the second line treatment for inducing remission for mild to moderate UC-proctitis?
If remission not achieved by 4 weeks, consider adding oral aminosalicylate (higher response with both together)
What is the third line treatment for inducing remission for mild to moderate UC- proctitis?
Consider adding topical or oral corticosteroid- time limited
Oral prednisolone- 40mg OD for 6-8 weeks
or prednisolone 5mg suppositories OD
What is the first line treatment for inducing remission for mild to moderate UC- proctosigmoiditis and left sided?
Topical aminosalicylate
Enemas preferred as go up further
1g day
What is the second line treatment for inducing remission for mild to moderate UC- proctosigmviditis and left sided?
If remission not achieved by 4 weeks,
add a high dose oral aminosalicylate or
switch to a high dose oral aminosalicylate and time limited topical corticosteroid
What is the third line treatment for inducing remission for mild to moderate UC- proctosigmviditis and left sided?
Stop topical treatment and offer oral aminosalicylate and time limited oral corticosteroid
What is the dosing for high dose oral aminosalicylates?
OD dosing is as effective as divided dosing
Greater than 2g a day were more effective at inducing remission, most pts respond to 2-3g day, higher doses are reserved for non-responders/severe
What is the first line treatment for inducing remission for mild to moderate UC-extensive?
Topical aminosalicylate AND high dose oral aminosalicylate
What is the second line treatment for inducing remission for mild to moderate UC-extensive?
If remission not achieved in 4 weeks,
stop topical treatment and offer a time limited course of oral corticosteroids
What is the treatment for inducing remission for moderate to severe UC?
Oral corticosteroid
Prednisolone 40mg-60mg OD (OD as causes less adrenal suppression)
Greater than 40mg doses lead to increased SEs
50% experience short term corticosteroid events
Improvements may be seen within 2 weeks of treatment
What are short term corticosteroid events?
Glucose intolerance
Oedema
Acne
Sleep disorders
What would be the weening off dosing for patients on long term, high dose corticosteroids?
2.5-10mg every week over 6-8 weeks
What are the biological treatments for inducing remission for moderate severe active disease in UC?
Biologics and JAKi
Infliximab, adalimumab, golimumab
Vedolzumab- inadequate response to above
Tofacitinib
What is the first line therapy for inducing remission in acute severe UC (all areas)?
IV corticosteroids and assess likelihood of needing surgery
Methylprednisolone 60mg daily
Hydrocortisone 100mg QDS
Consider IV ciclosporin in these intolerant/decline/CI to corticosteroids
Symptoms should improve by day 3
What is the second line therapy for inducing remission in acute severe UC (all areas)?
If symptoms worsen or little improvement within 72 hours, consider adding IV ciclosporin to the corticosteroid
If ciclosporin CI, infliximab is an option
Also increase in VTE so need thromoboprophylaxis
What is the treatment for maintaining remission for mild to moderate proctitis and protosigmoiditis in UC?
Topical aminosalicylate alone (daily, at night or intermittent, every third night)
Oral aminosalicylate+ topical aminosalicylate (daily or intermittent)
Oral aminosalicylate alone- explain this isn’t as effective as combined
What is the treatment for maintaining remission for left sided and extensive UC?
Offer low maintenance dose oral amino salicylate
What is the treatment for maintaining remission in UC in all areas after aminosalicylates fail/other reasons?
Consider mercaptopurine or azathioprine
-after 2 or more inflammatory exacerbations in 12 months that require systemic corticosteroids or if remission is not maintained by aminosalicylates
What is the treatment for inducing remission in CD?
Monotherapy with traditional glucocorticoid steroid (at first presentation or single inflammatory exacerbation in 12 months)
Prednisolone- PO 40mg OD
Methylprednisolone
Hydrocortisone IV
What is the second line treatment for inducing remission in CD and why?
Budesonide may also be considered
CI/ refusal to conventional corticosteroids
Not for severe presentations as not effective
Less effective than conventional but has fewer SEs
What is the third line treatment for inducing remission in CD?
Aminosalicylates if patient CI/decline corticosteroids- less effective than above but has fewer SEs
What would be the add on therapy for CD if 2 or more exacerbations in 12 months or if glucocorticoid dose cant be tapered?
Consider adding azathioprine (2.5mg/kg/day) or mercaptopurine (1-1.5mg/kg/day) to glucocorticoid or budesonide to induce remission
Slow onset of action 8-12 weeks
Consider MTX to GC or budesonide in those who can’t tolerate aza/mer or low TPMT levels
Name and describe the biological agents used to treat CD:
Infliximab and adalimumab
For adults with moderately/ severe (fistulating) active disease, who hasn’t responded to conventional therapy
Should be given as a planned course until treatment failure or 12 months after initiation
Continue if there is clear evidence or ongoing active disease
May also see therapy given with immunosuppressant
What are the symptoms of severe CD?
Very poor general health and/ more of the following:
-weight loss
-fever
-severe abdominal pain
-usually frequent 3-4 stools a day
Describe the usage of Ustekinumab for CD:
Moderate/ severe active CD, adults who have had inadequate response or loss of response to all previous therapies
Describe the usage of vedolizumab for CD:
Moderate/ severe active CD if TNFai has failed or can’t be tolerated or is CI
What is the treatment for CD for maintaining remission?
Offer azathioprine or mercaptorupine when previously used in induction or if not previously received with adverse onset
MTX (15mg OD) only in those who needed it in induction, tried and did not tolerate/ CI azathioprine/ mercaptopurine
DON’T offer conventional glucocorticoid/ ASA/ budesonide
What is the follow up for maintaining remission in CD with no treatment?
Share plans for follow up (freq and who should it be with)
Symptoms of relapse are known and action required (unintentional weight loss, abdominal pain, diarrhoea)
Knowledge of how to access health care
Smoking cessation
What is the treatment for maintaining remission in CD after surgery?
After completing macroscopic resection
Within the last 3 months, consider azathioprine in combo with metronidazole (for up to 3 months post op)
Azathioprine alone in those who cant tolerate metronidazole, don’t offer biologics/ budesonide
What infections are associated with IBD and what should occur?
Novovirus
Camplybacter
Ecoli
C difficile - increase colectomy and mortality
If present, treatment needed
What should occur if a patient with IBD has cytomegalovirus (CMV)?
Potentially associated with refractory disease, immunomodulatory therapy and corticosteroids:
IV ganciclovir followed by oral valganciclovir treatment
What should be the infection monitoring requirements for a patient with IBD before starting immunosuppressive therapy?
Assess at diagnosis:
-infection history -HSV (oral/genital), VSV
-immunisation status
If history unclear- serology should be tested for immunity
Treat active HBV, latent/active TB, HCV or HIV prior to initiating therapy
What are the monitoring requirements before and during corticosteroid treatment for IBD?
FBC
Glucose/HbA1c
Lipids
BP
Eyes (cataracts)
Sleep/mood
What is the correlation of bone health with IBD?
35-40% of pts with IBD have osteopenia
15% have osteoporosis
What are the risk factors of a patient with IBD developing osteoporosis?
Uncontrolled inflammation
Malabsorption
Weight loss
Steroids
Lack of physical activity
Alcohol intake
Low risk- retest in 3-5 years
High risk- bisphophonate
What should all patients on corticosteroids take to help prevent osteoporosis?
800-1000mg Ca
800IU vit D
Name specific malnutrition deficiencies which are difficult to diagnose in IBD due to the disease activity and how would these be treated?
13-88% suffer with mg deficiency, due to intestinal loss
PO (can worsen diarrhoea) or IV Mg
Ca/vit D
Potassium IV or PO (sandok)
Name a specific deficiency in IBD and why:
1/3 or patients have iron deficiency anaemia
-fatigue, decreased QoL, delayed recovery
Increase inflammation due to increase excretion, increase bleeding, decrease intake of dietary iron, decrease transport of Fe to blood
Quiescence- inadequate iron depletion, poor intake of iron rich foods, foods affect absorption
What should be the non pharmacological recommendations for an IBD patient to help prevent iron deficiency?
Annual FBC, ferritin and CRP monitoring
Dietary improvements- iron fortified foods, non haem iron and haem iron promotors of Fe absorption (via C rich) avoiding inhibitors (caffeine)
What are the pharmacological treatments for an IBD patient with an iron deficiency?
1st line IV iron (iron sucrose, ferric carboxymaltose,) active IBD
PO up to 100mg (elemental iron), mild anaemia with clinically active disease
Monitor every 3 months for a year, then every 6-12 months thereafter
What is the correlation with smoking and IBD?
Always check status
UC is more common in non smokers and more likely to arise in those who quit, linked to decreased surgery rates, less extensive disease, decrease need for therapy but should be encouraged to stop
What is the correlation with NDAIDs and IBD?
Conflicting data
May lead to increase in disease activity
May predicate relapse
Short term, low dose in patients with controlled disease (remission), potentially safe but try to avoid in practice
What is the correlation with UC and colerectal cancer?
Risk factors include duration of disease, amount of bowel affected and severity of the inflammation, greater risk with total disease:
-cancer risk begins to develop 8-10yrs after start of symptoms
Extensive> distal»> proctitis (no risk)
Cumulatative incidence
What is the cumulative incidence of colorectal cancer with UC?
1% at 10 years
2-3% at 20 years
5-7% at 30 years
What is the correlation with CD and colorectal cancer?
Risk similar to UC if colon main area of disease
Small bowel, intestinal lymphomas, anal cancer increased risk
Which vaccinations should a patient with IBD receive?
Shouldn’t receive live vaccinations if on immunosuppressants
Should receive covid-19
Aminosalicylate or no treatment, the vaccine should work as well as in the general population
Those on IS are though to have a decreased antibody response
Influenza vaccination- especially if on IS
Pneumococcal- 2 weeks before immunosuppressant initiation
What are the drug considerations for patients who have a stoma?
Pain control- non opioid, liquid or non coated tablets (not EC/MR)
High dose loperamide used, up to 64mg, QT prolongation (CV effects)
Antisecretory drugs (PPI) somatostatin decreases stoma output
Restrict oral hypotonic fluid (1L), use ORT
Hypocalcaemia risk- increase risk of digoxin toxicity
Describe how sulfasalazine works:
Aminosalicylate
An inert carrier
Mesalazine (5-ASA) bound to sulfapyridine via an azo bond (prevents absorption in upper GI tract)
Colonic bacteria azo reductase breaks the bond
Sulfapyridne is absorbed by colon, metabolism by liver and excreted in the urine- mainly responsible for adverse effects
Describe how mesalazine works:
Exerts therapeutic effect through topical effects on the mucosa
-30% of free mesalazine is absorbed
-metabolised locally and in liver to inactive form and free/conjugated drug is excreted in urine or faeces
What are the CI of sulfasalazine?
Hypersensitivity to sulfapyridine/ sulphonamide or 5amino salicylate
What are the cautions of sulfasalazine?
Hx of asthma- can cause dyspnoea and cough
Risk of haematological toxicity- causes blood disorders
Renal/ hepatic impairment- metabolism/ excretion routes
G6PD deficiency
Slow acetylator status
What are the common side effects of sulfasalazine?
Headache- 1/3 patients (less likely to occur if dose is uptitrated)
Nausea
Fever
Raised temp
Reversible infertility in men
Reduced WBC
Can colour urine and stain contact lenses yellow
What are the uncommon side effects of sulfasalazine?
Pancreatitis
What are the rare side effects of sulfasalazine?
Hepatitis, pneumonitis, skin reaction, haemolysis, inflammation of kidney
What are the monitoring requirements for sulfasalazine and describe when:
FBC, LFT before and every 2nd week for first 3 months, then monthly for 3 months, then every 3 months
Creatinine, eGFR monthly for 3 months then as indicated
What are the symptoms a patient should report if on sulfasalazine and why?
Sore throat, fever, malaise, jaundice, unexpected non specific illness, may indicate myelosupression, haemolysis or hepatoxicity
Name different delivery mechanism for mesalazine release to decrease side effects:
Attachment to other carrier molecules- olsalazine
pH dependant formulations (asacol, mesren)
Time dependant formulations (pentasa)
Multi-matrix systems (mezavant)
Describe the use of enteric coated systems for mesalazine:
With a specific agent to release at pH specific- prevent early disintegration in stomach and GIT
Eudragit S pH7- ileum/ colon
Eudragit L pH6- duodenum
Potential issue, pH decreases in IBD, other factors could change pH
Describe the use of time dependent systems for mesalazine:
Microspheres of mesalazine encapsulated in ethyl cellulose
Describe the use of semi-permeable membrane systems for mesalazine:
Time and moisture dependant
Theoretically releasing through GIT to rectum
Describe the use of multimatrix systems in mesalasine:
Incorporated into lipohillic matrix and entericaly coated
pH dissolution pH 7
Matrix swells to form a gel, slowing diffusion of drug into terminal ileum and enter colon
What are the monitoring requirements prior to having mesalasine?
Renal function, U&Es, LFTs, FBC, and periodically until stabilised
Renal function- 6 monthly
Urea electrolytes, FBC, LFTS 6 monthly to annually
What are rectal enemas of aminosalicylates used for?
Foam enemas used to treat the proximal sigmoid colon
Liquid enemas can go up to the splenic flexure
Equally effective in proximal UC
Foam enemas preferred as easier to administer and retain
What are suppositories of aminosalicylates used for?
Indicated for use in disease up to rectosigmoid junction
Deliver drug more effectively to rectum than enema
What is the dosing regime for thiopurines and how long do they take to work?
Start at full dose
3-6 months to see effects
What are the monitoring requirements prior to initiation of thiopruines for IBD?
FBC, U&E, LFT
Screen for HCV, HIV, HBV/ VZV
Vaccinate
Ensure cervical screening up to date (increase cervical dysplasia with IBD)
Check TPMT and alter dose dependant on result- avoid in very low TMPT
What are the ongoing monitoring requirements for thiopurines for IBD?
FBC,U&E,LFT at least 2,4,8 and 12 weeks and then 3 monthly
What are the CI of thiopurine therapy for IBD?
Hypersensitivity, serious infections, pancreatitis, impaired bone marrow
What are the cautions of thiopurine therapy for IBD?
Decreased TPMT, renal and hepatic impairment
What are the counselling points for thiopurine therapy?
Inform about signs of myelosuppresion
Reduce exposure to sun due to increase risk of skin cancer
Take with meals to decrease risk of nausea- usually decreases within a few weeks
What is a major interaction with azathioprine and what should be the actions of this?
With allopurinol- reduce azathioprine to 1/4 of usual dose
Can switch to mercaptopurine
