tbl 3 clinical: irritable bowel syndrome Flashcards
Irritable bowel syndrome – functional disorder of the gastrointestinal tract
- Characterised by chronic abdominal pain and altered bowel habits in the absence of an ____________
o One of the most common diagnosis in the outpatient clinic (30% of referrals), a chronic and often disabling functional disorder
- Subtypes of IBS - 4 subtypes of IBS – Constipation (IBS-C), Diarrhoea (IBS-D), Mixed type, _________
o Mixed type IBS – Patient reports that abnormal bowel movements are usually both constipation and diarrhoea (more than one-fourth of all the abnormal bowel movements were constipation and more than one-fourth were diarrhoea)
o Unspecified – Patients who meet diagnostic criteria for IBS but cannot be accurately categorized into one of the other three subtypes
- IBS is classified based on the percentage of the type of stool that a patient passes during bowel movement – ____ is the threshold for classification
organic cause; Unspecified; 25%
Features of IBS – patients often complain of abdominal pain (often colicky), bloating and alternating bowel habits
o More occurrence in females, duration of symptoms may be long (years), induced by ______
o Often happens only during waking hours and frequently after _______
- If patients have ______________, there should be investigations first
–> Abdominal pain is associated with at least 2 of the following 3 symptoms: ____________, change in the frequency of stool, change in form of stool
stress; meals; warning signs (Rome IV); pain related to defectation
[Factors in pathophysiology of IBS]
- GI motility and IBS – no predominant pattern of motor activity has emerged as marker of IBS
- Motor abnormalities observed in IBS –
o Increased frequency and irregularity of luminal contraction
o Prolonged transit time in ________ patients
o Exaggerated motor response to cholecystokinin and meal ingestion in ______ patients
- Although the relevance of these motor function alterations has yet to be established, pharmacologic stimulation of gut motility tends to reduce gas retention and improve symptoms – suggests motility disturbance may underlie complaints in certain patients
IBS-C; IBS-D
[Factors in pathophysiology of IBS]
2) Visceral hypersensitivity – increased sensation in response to stimuli, a frequent finding in patients with IBS
- Perception in the GI tract results from stimulation of various receptors in the gut walls – these receptors transmit signals via the afferent neural pathways of the __________ of the spinal cord and up to the brain
- Several studies have focused on selective hypersensitisation of visceral afferent nerves in the gut mainly triggered by bowel distention or bloating
o Distension – studies have shown that awareness and pain are experienced at lower balloon volumes in IBS patients compared with controls when the intestines are distended by a balloon
§ Increase in sensitivity may be specific for visceral afferents – patients with IBS have normal or even increased thresholds for _________
o Bloating – 50% of patients (especially IBS-C) have measurable increase abdominal girth associated with bloating (may not be related to the volume of intestinal gas)
§ Patients who complain of bloating in IBS exhibits _________________ rather than increase in gas volume (similar to asymptomatic individuals)
- It is still unclear if heightened sensitivity is mediated by local GI nervous system, central modulation from the brain or combination of both
dorsal horn;
somatic pain;
impaired transit of intestinal gas loads
[Factors in pathophysiology of IBS]
- Intestinal inflammation – immunohistological investigations can reveal mucosal immune system activation
- Characterised by alterations in particular immune cells – can be seen in some patients, particularly in IBS-D and _____________
o Lymphocytes may infiltrate ___________ – release of mediators such as nitric oxide, histamine, proteases which can stimulate the enteric nervous system abnormal motor and visceral response within intestine
o Stool examinations from IBS-D patients have revealed a high level of __________ activity
§ When these faecal samples were injected intracolonically in mice, there was increased cellular permeability and visceral pain – these effects were prevented by serine protease inhibitors
o Mast cell – increase numbers seen in _______, jejunum and colon of IBS patients
§ Studies have demonstrated correlation between abdominal pain and activated mast cells in proximity to colonic nerves
o Proinflammatory cytokines – elevated plasma levels (pro-inflammatory interleukins) are seen in IBS patients
§ Peripheral blood mononuclear cells produce higher levels of ____ than healthy controls
post-infectious IBS; myenteric plexus; serine protease; terminal ileum; TNF
[Factors in pathophysiology of IBS]
- Alteration of intestinal microbiota (IM)
- Speculation that changes in IM composition is associated with IBS – emerging data suggests IM of IBS patients differ from healthy controls and vary with predominant symptoms
o Colonic hypersensitivity can be transferred from IBS patients to germ-free animals by inoculation with faecal microbiota from IBS patients (but not healthy people)
- Potential microflora alteration – it is possible that IBD-D patients would benefit from probiotics which influence the metabolism and composition of the microflora
o A placebo RCT showed that administration of probiotic _________ did not alter IM, but it did improve symptoms and decrease ________
- Some studies also point towards presence of small bowel bacterial overgrowth as a potential trigger of IBS symptoms, and there was improvement in symptoms with antibiotics
Lactobacillus plantarum; flatulence
[Pathophysiology of IBS]
- Food sensitivity – precise role of food in pathophysiology of IBS is unclear
- Some patients with IBS report worsening of symptoms after eating – perceived food intolerance to certain foods
- Multiple factors in IBS have been considered as due to food sensitivity – food related antibodies, carbohydrate malabsorption and gluten sensitivity
Food allergy: IBS patients have greater number of positive skin prick tests than normal controls – however, they did not exacerbate their symptoms when challenged with allergens
Carbohydrate malabsorption:
- FODMAP – _________________________ enter the distal small bowel and colon where they are fermented. Leads to symptoms, increased intestinal permeability and possibly inflammation
- _____________ has been suggested as a form of carbohydrate malabsorption – contributing to GI symptoms such as flatulence, pain, bloating, belching and altered bowel habits
- An exclusion diet such as a low carbohydrate diet or exclusion of fructose and fructans may lead to improvement in symptoms
Gluten sensitivity
- Several studies suggest some overlap between IBS and coeliac disease
- A study suggested that absence of villous atrophy but presence of ____________ and HLA-DQ2 may predict response to gluten free diet in IBS-D patients
- In IBD-D patients without celiac disease, dietary gluten alters small intestine permeability and had a greater effect on bowel movement frequency in patients who were HLA-DQ2 or 8-positive compared to HLA DQ negative patients.
- Steps must be taken to confirm the absence of Coeliac disease before diagnosis of IBS in patients with symptoms suggestive of celiac disease.
fermentable oligo-, di- and monosaccharides and polyols; Fructose intolerance
serum IgG antigliadin antibodies;
Management of IBS
- IBD is a complex pathology – establishment of a clinician-patient relationship and continuity of care are critical in the management of IBS
o Reassurance – ensure adequate investigations
o A detailed lifestyle and dietary modification are adequate in patients with mild intermittent symptoms – discover trigger factors that patients can avoid
o Pharmacologic therapy can be considered if there are more symptoms are affecting quality of life
- Dietary modification in IBD – based on predominant symptoms
o Bloating and gas – exclusion of gas producing foods e.g. (beans, onions, celery, carrots, bananas)
o Low ________
o Specific food exclusions – lactose (if patient has history of lactose intolerance) and _________
§ In the case of gluten, need to differentiate between gluten intolerance and gluten allergy (as in celiac disease)
FODMAP; gluten avoidance
[Adjunctive pharmacologic therapy- Constipation]
1. Constipation – ensure adequate daily fluid intake and physical activity to encourage conic motor activity
- Soluble fibre – _____________
- ___________ – PEG improves constipation, but does not improve abdominal pain
o However, side effects of bloating and abdominal discomfort limit its use
- _________ – locally acting Cl channel activator –> enhances chloride-rich intestinal fluid secretion
o Not been directly compared with other treatment options for IBS-C, and its long-term safety remains to be established
- Guanylate cyclase agonists (________ and ________) – stimulates intestinal fluid secretion and transit
o Unknown long-term risk, limited use in refractory IBS C patients
Fybogel; Osmotic laxatives; Lubiprostone
Linaclotide; Plecanatide
[Pharomacology- diarrhoea]
2. Diarrhoea – anti-diarrhoeal drugs
- __________ – inhibits peristalsis and prolong transit time, decreasing stool frequency and consistency but not bloating, abdominal discomfort and other IBS
symptoms
- Fybogel (stool bulking agent) – reduced colonic transit time, allows for more time for body to absorb the content of stool
- Bile acid sequestrants (__________) – up to 50% IBS-D patient has degree of bile acid malabsorption
o Bile acids stimulates colonic secretion and motility, leading to diarrhoea
Loperamide; Cholestyramine
[Pharmacology- Abdominal pain and bloating]
Antispasmodic – for IBS-C, only initiate antispasmodics when abdominal pain persists despite treatment of constipation
o ________ – direct action on intestinal smooth muscle
o ________ – act by anticholinergic or antimuscarinic properties
o Should be administered on an as-needed basis and/or in anticipation of stressors with known exacerbating effects – provides short term relief for abdominal pain
o The selective inhibition of gastrointestinal smooth muscle by antispasmodics reduced ___________________ – may be beneficial in patients with postprandial abdominal pain, gas, bloating, and faecal urgency
- Antidepressants – recommend a trial of antidepressants when abdominal pain persists with antispasmodics
o Analgesic properties independent of mood improving effects
o For treatment of abdominal pain in IBS, antidepressants should be started at low doses
§ Initial dose should be adjusted based upon tolerance and response
§ Due to the delayed onset of action of antidepressants, three to four weeks of therapy should be attempted before increasing the dose
o _______ also slow intestinal transit time (anticholinergic effect) – should be used cautiously in patients with constipation
o SSRIs and SNRIs – less data compared with TCAs. - Probiotics – use has been associated with improvement in symptoms – related to the role of microbiota interaction in IBS
o Magnitude of benefit and most effective species or strains are uncertain - Antibiotics – in patients with moderate to severe IBS without constipation, particularly those with bloating, who have failed to respond to other therapies, a 2 week trial of ________ is suggested
Mebeverine; Hyoscine; stimulated colonic motor activity;
TCAs; rifaximin
