Diarrhoea and Malabsorption Flashcards
How much fluid enters the GIT each day?
9L
How much fluid is absorbed in the small intestine?
7L
How much fluid is absorbed in the colon?
1.8L
How much water can be absorbed in the colon?
4.5L
How much water leaves the GIT each day?
200mL
What enzymes are responsible for CHO breakdown?
Salivary amylases
Pancreatic amylases
Brush border enzymes
What factors/enzymes are responsible for protein breakdown?
HCl
Gastric pepsin
Pancreatic proteases (peptidases)
What factors are responsible for fat breakdown?
Bile
Pancreatic lipase
Define diarrhoea
Abnormal frequency and liquidity of stool >200g stool/day and >3 movements/day
When is diarrhoea considered chronic?
When it lasts >4 weeks
What location and pathological mechanisms does large volume diarrhoea suggest?
Small bowel disease
Secretory diarrhoea
What is small volume diarrhoea suggestive of?
Colonic diseases and IBS
List 4 tests routinely performed on faeces which could help diagnose the cause of diarrhoea
MCS
Faecal elastase
Faecal fat and microglobules
Calprotectin, lactoferrin (for IBD)
List 4 other tests less commonly used to help diagnose diarrhoea
Faecal electrolytes and osmolarity (look for stool osmotic gap)
C. difficile toxin
Faecal laxative screen
Faecal a1-antitrypsin
What is faecal elastase a marker of?
Exocrine pancreatic sufficiency
What laxatives are usually screened for?
Anthroquinones
Bisacodyl
Phenolphthalein
What is faecal a1-antitrypsin a marker of?
Protein-losing enteropathy
What other tests (non-faecal) may be indicated in the case of diarrhoea?
FBE
BGL
B12 and folate levels
Iron studies
What is the pathological mechanism of osmotic diarrhoea?
Presence of excess unabsorbed substrates in gut lumen
What is the most common cause of osmotic diarrhoea?
Fermentable CHO malabsorption (FODMAPs)
What is the typical stool volume in osmotic diarrhoea?
<1L
Describe the stool osmotic gap in osmotic diarrhoea
Increased (>100)
What findings would be expected on a H2/methane breath test in the case of osmotic diarrhoea?
Increased breath H with malabsorption
What is the pathological mechanism of secretory diarrhoea?
Active anion secretion from enterocytes
What are the most common causes of secretory diarrhoea?
Bacterial toxins (e.g. cholera, toxigenic E.coli)
Hormone-secreting tumours
Laxative abuse
Hyperthyroidism
Give 2 examples of hormone-secreting tumours which may cause secretory diarrhoea
Carcinoid tumours
Gastrinomas
What is the typical stool volume in secretory diarrhoea?
>1L/d, watery
Describe the stool osmotic gap in secretory diarrhoea
Normal osmolality (<100)
What is the effect of fasting on secretory diarrhoea?
Diarrhoea persists
Are stool leukocytes detected in secretory diarrhoea?
No
What is the pathological mechanism of inflammatory diarrhoea?
Altered membrane permeability leading to exudation of protein, blood and mucus
What are the 4 most common causes of inflammatory diarrhoea?
Invasive bacteria
Entamoeba histolytica
CMV colitis
IBD
Give 4 examples of bacteria which can cause inflammatory diarrhoea
Shigella
Salmonella
Campylobacter
C. difficile
Describe the stool volume in inflammatory diarrhoea
Usually small
Are stool leukocytes and RBCs detectable in inflammatory diarrhoea? What clinical features might accompany these findings?
Yes (may even be frank blood)
Associated with urgency, tenesmus and constitutional upset (including fever)
List 3 conditions which may cause rapid transit of GI contents
IBS
Thyrotoxicosis
Diabetic neuropathy
What is the mechanism of diarrhoea caused by slow transit of GI contents?
Bacterial overgrowth results in bacteria consuming nutrients in GIT and inactivation of bile salts NB Slow transit diarrhoea may be associated with malabsorption
What pathologies may cause slow transit of GI contents?
Intestinal stasis due to strictures, blind loops, surgical procedures, etc
What is the difference between maldigestion and malabsorption?
Maldigestion: intraluminal
Malabsorption: intramural and disorders of transport
List 4 causes of maldigestion, giving specific examples of disease processes
Mechanical (mixing) disorders: post-gastrectomy (mixing disorder)
Reduced nutrient availability: co-factor deficiency (e.g. pernicious anaemia), bacterial overgrowth (nutrient consumption)
Defective nutrient hydrolysis (digestion): pancreatic insufficiency (e.g. in chronic pancreatitis)
Reduced fat solubilisation (reduced bile salt concentration): cholestasis, bacterial overgrowth
Where is the most fluid from the GIT absorbed?
Small intestine
Where is iron absorbed?
Mostly duodenum
Where is vitamin B12 absorbed?
Terminal ileum (after binding to intrinsic factor)
List 4 mechanisms causing diarrhoea
Osmotic
Secretory
Inflammatory
Altered intestinal motility
What can be identified with an MCS?
Gram stain for bacteria
Examination for ova, cysts, parasites
Culture for pathogens WBCs (suggestive of colitis) and/or RBCs
What is faecal calprotectin and lactoferrin indicative of?
GIT inflammation
What is the effect of fasting on osmotic diarrhoea?
Stops
Are stool leukocytes detectable in osmotic diarrhoea?
No
Are there changes in the level of faecal calprotectin in osmotic diarrhoea?
No
Are there changes in the level of faecal calprotectin in secretory diarrhoea?
No
Are there changes in the level of faecal calprotectin in inflammatory diarrhoea?
Yes (elevated)
List 3 causes of mucosal phase (malabsorption) and defective transport, giving examples of specific disease processes
Inadequate absorptive surface: intestinal resection or bypass due to disease (short gut syndrome)
Diffuse mucosal disease: Coeliac disease, Crohn’s disease, Giardia infection, brush border enzyme deficiency (e.g. lactase)
Mucosal absorptive defects: lymphoma, lymphatic obstruction, radiation damage, vascular problems
Brian, 42, presents with 3/12 of feeling unwell with loose stools 6-8 times/day (normally once every 1-2 days), often bloody with mucous mixed in, crampy abdominal pain prior to defecation, urgency and tenesmus, and occasional nocturnal diarrhoea
O/E: afebrile, looks tired and pale, abdominal examination unremarkable
What other Hx should you ask about?
Constitutional Sx
Recent travel or other context (e.g. exposure to “off” food)
SHx
PMHx
Rx
FHx of bowel pathology
Brian, 42, presents with 3/12 of feeling unwell with loose stools 6-8 times/day (normally once every 1-2 days), often bloody with mucous mixed in, crampy abdominal pain prior to defecation, urgency and tenesmus, and occasional nocturnal diarrhoea
O/E: afebrile, looks tired and pale, abdominal examination unremarkable
Occasionally feverish, sleeping poorly, weight loss 2-3 kg in past 3/12
Recent travel: 6/12 ago holiday in Thailand but was not unwell there
SHx: lawyer, lives with partner Paul
PMHx: nil significant, non-smoker
No regular Rx (including OTC)
No significant FHx
DDx?
Clinical presentation is of bloody, mucousy diarrhoea with tenesmus, which usually has an inflammatory mechanism and of which common causes include:
Infection (dysentery; e.g. Salmonella, Shigella, Yersinia, Entamoeba histolytica - amoebiasis, CMV)
IBD
Ischaemic colitis
Radiation colitis
Other causes of bleeding per rectum include:
Haemorrhoids (“piles”)
Colorectal cancer
Brian, 42, presents with 3/12 of feeling unwell with loose stools 6-8 times/day (normally once every 1-2 days), often bloody with mucous mixed in, crampy abdominal pain prior to defecation, urgency and tenesmus, and occasional nocturnal diarrhoea
O/E: afebrile, looks tired and pale, abdominal examination unremarkable
Occasionally feverish, sleeping poorly, weight loss 2-3 kg in past 3/12
Recent travel: 6/12 ago holiday in Thailand but was not unwell there
SHx: lawyer, lives with partner Paul
PMHx: nil significant, non-smoker
No regular Rx (including OTC)
No significant FHx
Initial Ix? Definitive Ix?
Faecal MCS
Faecal calprotectin
FBE
ESR, CRP
Nutritional studies (iron, B12/folate, vit D)
Definitive Ix: colonoscopy and colonic biopsy
Brian, 42, presents with 3/12 of feeling unwell with loose stools 6-8 times/day (normally once every 1-2 days), often bloody with mucous mixed in, crampy abdominal pain prior to defecation, urgency and tenesmus, and occasional nocturnal diarrhoea
O/E: afebrile, looks tired and pale, abdominal examination unremarkable
Occasionally feverish, sleeping poorly, weight loss 2-3 kg in past 3/12
Faecal sample: unformed, mucoid and bloody, leucocytes and erythrocytes on direct examination (no Giardia cysts), C. dif toxin/rotavirus Ag/adenovirus Ag/norovirus by RTPCR all not detected, no Salmonella/Shigella/Campylobacter on culture
Faecal calprotectin >300 mcg/g (N 19.5-50) FBE: low Hb ESR 25, CRP 80 (both elevated)
Nutritional studies normal
Colonoscopy performed and colonic biopsies taken; interpret the results
Superficial ulceration with distorsion of crypts
Acute and chronic diffuse inflammatory infiltrate
Goblet cell depletion
Crypt abscesses
Lymphoid aggregates but no granulomas
What is IBD?
Chronic inflammatory disorders of uncertain aetiology (genetics, environment, immune response are contribute)
Comprises of Crohn’s disease and ulcerative colitis (in some patients it is difficult to decide between the two diagnoses and so they are given the Dx of “indeterminate colitis”)
Epidemiology of IBD
Compare the features of UC and Crohn’s disease
UC: affects large bowel starting at rectum and proceeding proximally (i.e. no skip lesions), increased risk of colonic malignancy in longstanding UC
Crohn’s disease: focal transmural inflammation with fissures, ulcers and granulomas, and with healthy intestine between the lesions (skip lesions), can affect any part the gut from mouth (aphthous ulcers) to anus (most commonly terminal ileum and colon, extra-intestinal features include arthritis, uveitis and rashes
Compare Sx of UC and Crohn’s disease
UC: frequent episodes of rectal bleeding, urgency and tenesmus often a feature of distal disease, other Sx include abdominal cramps, weight loss and fever in severe cases
Crohn’s: abdominal pain, diarrhoea, weight loss, fever, failure to thrive, disease progresses with relapses and remissions
Compare the Mx of UC and Crohn’s disease
UC: 5-ASA compounds (sulphasalazine) and steroids, topical therapy (suppositories/enemas) used for distal disease, immunosuppressants used in severe or recurrent disease, surgery for severe or refractory cases (this is curative)
Crohn’s: steroids, 5-ASA compounds, immunosuppressants (e.g. azathioprine, methotrexate), biologicals (monoclonal Ab e.g. adalimumab), surgery (not curative - repeated surgeries can cause short gut syndrome)
Mandy, 26, presents with ~10 year Hx of intermittent diarrhoea with bloating and flatulence, passing up to 2-5 bowel motions per day (erratic) but no blood and no weight loss
Stress, dairy products and some fruits make her Sx worse
Tried a gluten free diet on advice from friend and felt better
SHx: office manager, lives with partner
FHx: sister is “gluten intolerant”
PHx: depression
Rx: nil, non-smoker
O/E: anxious, afebrile, abdo examination normal
DDx?
IBS
Coeliac disease
Infection e.g. Giardia
IBD
How is IBS diagnosed?
1) Typical clinical Hx: “Rome III” criteria
- Sx for at least 3/12
- Recurrent abdominal discomfort or pain associated with 2 or more of:
- Improvement of Sx with defecation
- Change in stool appearance (form)
- Change in stool frequency
2) Exclude other Dx
* Presence of “red-flag” Sx or signs such as weight loss, PR bleeding, nocturnal Sx, age >45 should prompt further Ix before Dx of IBS is made
How is coeliac disease Dx?
Screen for coeliac disease:
- Blood test measuring tTG-IgA and DGP-IgA/-IgG (Abs to deamidated gliadin peptides)
- DGP assay replaces older and less accurate anti-gliadin Abs (AGA-IgA/-IgG) test
If Abs are abnormally elevated, small bowel biopsy showing villous atrophy is required to confirm Dx
Current Dx criteria requires:
- Demonstration of small bowel damage (villous atrophy, crypt hyperplasia, raised IELs) whilst a person is consuming gluten, and
- Improvement in histology, serology and clinical picture following a gluten free diet
How accurate is coeliac serology? What are the clinical implications?
tTG-IgA and DGP Ab assays have a sensitivity of ~90% (i.e. 10% of true coeliac Dx will not be detected using serology alone)
FPs can occur, so a Dx of coeliac disease is never made on the blood test alone (biopsy is required)
Accuracy of a Dx test is affected by pre-test probability
What might cause false negative serology results?
Gluten free diet (esp if >6/52)
IgA deficiency (seen in ~3% of coeliac disease, which is why the total IgA level is measured or the IgG isotype of DGP assessed)
Immunosuppression e.g. prednisolone
How can you test for coeliac disease if a person is already following a gluten free diet?
HLA-DQ2/8 gene test; seen in most (99.6%) patients with coeliac disease, so can be used to EXCLUDE coeliac
6 week gluten challenge (~4 serve gluten/day) followed by small bowel biopsy
How can infection and IBD be excluded from a DDx?
Faecal assessment
Inflammatory markers
Gastroscopy and colonoscopy with biopsies may be required in some instances
Mandy, 26, presents with ~10 year Hx of intermittent diarrhoea with bloating and flatulence, passing up to 2-5 bowel motions per day (erratic) but no blood and no weight loss
Stress, dairy products and some fruits make her Sx worse
Tried a gluten free diet on advice from friend and felt better
Ix?
FBE
Iron studies
ESR, CRP
TFTs
HLA-DQ2/8 genotyping
Faecal MCS and calprotectin
Mandy, 26, presents with ~10 year Hx of intermittent diarrhoea with bloating and flatulence, passing up to 2-5 bowel motions per day (erratic) but no blood and no weight loss
FBE normal
Iron studies: low normal ferritin,
ESR normal, CRP normal
TFTs normal
HLA-DQ2/8 genotyping shows no genetic susceptibility for coeliac disease
Faeces: unformed, no leucocytes/erythrocytes/Giardia cysts, no C. diff toxin or growth, no rotavirus Ag/adenovirus Ag/norovirus by RTPCR, no Salmonella/Shigella/Campylobacter isolated
Faecal calprotectin: low
Dx?
IBS
Describe the epidemiology of IBS
Common, affecting 15-20% of general population of Western countries
F>M
Clinical presentation of IBS
Constipation-predominant, diarrhoea-predominant, pain-predominant or mixed pattern
Describe the pathogenesis of IBS
- 5HT is a key mediator
- Disordered intestinal motility
- Altered perception of nociceptive stimuli (visceral hypersensitivity)
- Psychogenic factors
- Post-infectious component in some people
- “Stress” and small bowel bacterial overgrowth can be a trigger
- Role of genetics unclear
Why might foods like dairy, wheat and fruit trigger Sx in an IBS patient?
FODMAP (poorly absorbed fermentable CHOs) malabsorption is a common trigger for IBS
Malabsorption of these sugars leads to fermentation by bacteria in the colon, and hydrogen/methane gas production (causing distension), osmotic diarrhoea and triggering of other IBS Sx
Hydrogen/methane breath testing is available to test for lactose and fructose malabsorption
Mx for IBS
Primarily aimed at alleviating Sx
Dietary modification: avoiding common food triggers (low FODMAP diet), avoiding caffeine, alcohol and smoking
Pharmacological therapies: probiotics, antispasmodics, antidiarrhoeals, laxatives, Abx (rifaximin) to treat bacterial overgrowth, ?increase or decrease fibre
Psychological therapies: relaxation, CBT, hypnotherapy
In the future, targeted treatments will become available that address the underlying ENS dysfunction (e.g. modify 5HT signalling)
List the poorly absorbed fermentable CHOs, and their significant food sources
Peter, 62, presents with 6/12 Hx of pale, smelly greasy stools which are difficult to flush, frequently feels bloated and nauseated after meals, more lethargic and has lost weight in past 6/12, denies drinking alcohol for past 2 years
PHx: HTN, ex-smoker, previous EtOH abuse, alcoholic pancreatitis 10 years ago and subsequent 2 episodes
O/E: bruises on arm, evidence of subcutaneous fat loss, several spider naevi on chest, abdominal examination normal, no hepatic flap or fetor
What features suggest malabsorption might be present and how can we confirm it?
Hx of steatorrhoea, lethargy, weight loss, examination findings of bruising, muscle wasting, weight loss
Ix: nutrient levels (Iron studies, B12/folate, vitamins), faecal assessment: increased faecal fat
Peter, 62, presents with 6/12 Hx of pale, smelly greasy stools which are difficult to flush, frequently feels bloated and nauseated after meals, more lethargic and has lost weight in past 6/12, denies drinking alcohol for past 2 years
PHx: HTN, ex-smoker, previous EtOH abuse, alcoholic pancreatitis 10 years ago and subsequent 2 episodes
O/E: bruises on arm, evidence of subcutaneous fat loss, several spider naevi on chest, abdominal examination normal, no hepatic flap or fetor
What are potential causes for Peter’s malabsorption and how might they cause it?
- Defective nutrient hydrolysis (digestion): pancreatic insufficiency due to chronic pancreatitis or pancreatic cancer
- Reduced nutrient availability: poor oral intake (especially if still an alcoholic); bacterial overgrowth
- Reduced fat solubilisation (reduced bile salt concentration): cholestasis (failure of bile flow) due to underlying liver disease; bacterial overgrowth will inactivate bile salts
- Diffuse mucosal disease: e.g. coeliac disease, Giardia infection, brush border enzyme deficiency
- Mucosal absorptive defects: e.g. lymphoma, lymphatic obstruction
Ix for pancreatic insufficiency
Imaging with CT scan (?chronic pancreatitis, ?cancer)
Faecal elastase level as marker of exocrine sufficiency
Empiric trial of pancreatic enzyme supplementation
Secretin stimulation test (rarely done)
Ix for bacterial overgrowth
Hydrogen/methane breath test (assess for “early rise” in breath hydrogen due tofermentation in the small bowel)
Empiric trial of broad-spectrum antibiotics
Ix for cholestasis/liver disease
Assess for underlying liver disease and alcoholic cirrhosis
LFTs, liver imaging (ultrasound), possibly biopsy
History of jaundice, dark urine and pale stools suggest extrahepatic cholestasis
Corroborate history of alcohol intake with family
Describe the clinical approach to diarrhoea
