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Investigation of chronic diarrhoeaBritish Society of Gastroenterology
Guidelines 2nd Edition 2003
Investigation of chronic diarrhoeaBritish Society of Gastroenterology
Guidelines 2nd Edition 2003
Dr. P.D. Thomas
Consultant GastroenterologistTaunton and Somerset Hospital
OutlineOutline Definitions Initial assessment Factitious diarrhoea Functional bowel problems Colonic investigations Small bowel investigations
Investigation of fat and carbohydrate malabsorption Investigation of malabsorption due to pancreatic
insufficiency Specific conditions
small bowel bacterial overgrowth, bile salt malabsorption, hormone secreting tumours
Mechanisms
• Intestinal secretions and food- 7l per day• 5L absorbed in small intestine• 1.5-2L absorbed by colon• Stool 100-200mL water• 10% decrease in fluid absorbed by colon will
double stool volume• Considerable reserve capacity of colon to absorb
increased ileal effluent
Approaches to the classification of diarrhoea
• MechanisticOsmotic - eg carbohydrate/ fat
malabsorption Secretory- mucosal disease, defects of ion absorption, stimulant laxatives Gut hormone Deranged motility
- post vagtomy, IBS carcinoid
• Distinguishing osmotic from secretorydiarrhoea
- fasting - osmotic diarrhoea should stop
- osmotic gaplow stool osmolality <290 mosmol/kg suggests contamination with hypotonic fluid290-2x (Na and K conc)Osmotic gap >125mosmol/kg osmotic diarrhoea
<50 in secretory diarrhoea
Causes of diarrhoeaColonic
Colonic neoplasia EndocrineUlcerative and Crohn's colitis HyperthyroidismMicroscopic colitis Diabetes
Small bowel HypoparathyroidismCoeliac disease Addison's diseaseCrohn's disease Hormone secreting tumours
(VIPoma, Other small bowel enteropathies, gastrinoma, carcinoid)(e.g. Whipples disease, tropical sprue, amyloid, intestinal lymphangiectasia )
Bile Acid malabsorptionDisaccharidase deficiency
Small bowel bacterial overgrowthMesenteric ischaemiaRadiation enteritis OtherLymphoma Factitious diarrhoeaGiardiasis Surgical' causes (e.g. small bowel
Pancreatic resections)Chronic pancreatitis Autonomic neuropathy Pancreatic carcinoma DrugsCystic fibrosis Alcohol
DefinitionsDefinitions
>200g stool/24 hours
More than three loose stools/day
Chronic > 4 weeks
Layman’s definition
Initial assessment
• Organic vs functional<3 months, continuous, nocturnal, alarm
symptoms
• Malabsorptive or colonic/inflammatory
• SpecificDrugs, family history, surgery, systemic
disease, alcohol, infective
Initial investigations
• Blood testsFBC, UE, LFT, B12, folate, fe studies, ESR, CRP, TFT
• Serological tests for coeliac diseasePrevalence of 1:200 in asymptomatic western pops. IgA anti-endomysium antibodiesanti-tissue transglutaminase antibodies
Stool tests
• Stool microscopy cultureProtozoal eg Giardia, amobae,
cryptosporidia• Non specific
Stool osmolalitystool fat
• Specificstool elastase
other..
• Stool markers of intestinal inflammatione.g. lactoferrin
• Stool calprotectincytosolic protein in monocytes, neutrophils
stable for 1 week at RT
• Use of surrogate markers of inflammtion and Rome criteria to distinguish organic from non-organic disease Tibble et al Gastroenetrology 2002
• N=602 all patients underwent invasive imaging Ix
Rome criteria, Intestinal permeability• Results
263 organic disease, 339 IBS Sensitivity
specificity stool calprotectin 8979 intestinal permeability 6387 Rome criteria 8571
Factitious diarrhoeaFactitious diarrhoea
4% of patients attending district gastroenterology clinic
20-33% attending tertiary referral centres Association with medical training/eating disorder In patient assessment/monitoring
- stool collections- 24-48 hour fast
‘Laxative screen’ - anthraquinones, biascodyl,phenolphthaleins, oils, Mg, PO4.
Case 1
• 50 year old female• 6 months watery diarrhoea up 6 x day• Normal baseline investigations including TFT,
coeliac serology• Normal flexible sigmoidoscopy with bx 2 years
ago
Next investigation?
Microscopic colitis
• Lymphocytic or collagenous colitis
• Rectosigmoid biopsies alone may miss up to 40% of cases (Offner1999)
Overlap between functional and organic disease
• Irritable Bowel syndromeRome criteria (II) > 3 months
abdominal pain or discomfort with 2 or more - altered stool frequency
- altered stool consistency - relieved by defecation bloating or distention or mucous supportive
Discriminant factors
• >45• Family history
• <45• Female sex• Other ‘functional’ Sx
Irritable bowel Colonic pathology
Chronic diarrhoea in patients <45yrs
• Flexible sigmoidoscopy Fine et al 2000
800 patients studied Microscopic colitis
10% >Crohn’s >UC 99.7% of pathology accessible with FS
Chronic diarrhoea in patients >45yrsRationale for total colonic examination
• Neoplasia 37% asymptomatic
individuals have adenomas 8% adenomas>1cm (Lieberman 2000) Prevalence in symptomatic?
• Higher prevalence of proximal non-neoplastic pathology
e.g microscopic colitis, IBD7-31%
• Colonoscopy or barium enema and flexi sigmoidoscopy
Case 2
• 40 year old male
• Loose offensive stools 4x/day ? ½ stone weight loss 1 year
• FBC, LFT, CRP etc normal
• IgA Antiendomysial antibodies negative
• Flexible sigmoidoscopy normal
• Selective IgA deficiency 0.14% population2.6% coeliac disease
• IgG antiendomysium Ab or IgG anti-tTG Ab are suitable alternative serological tests
• Check IgA levels
Endoscopic distal duodenal biopsies
• Little information on diagnostic yield• Serological tests have replaced D2 biopsies as the
initial investigation for coeliac disease • Coeliac disease is (by far) the most common
small bowel enteropathy in western european populations BUT other small bowel
enteropathies should be considered.
‘D2 biopsies where small bowel malabsorption is clinically suspected’
Case 3
• 55 year old male• RIF pain and diarrhoea• Tenderness RIF• Baseline Ix NAD except CRP 32• Colonoscopy incomplete (histology normal)
Next step?
Small bowel imaging
• Barium follow through Enteroclysis
-yield low, equivalent role -small bowel malabsorption suspected (distal duodenal histology normal)
Structural abnormalities
Small bowel imaging (2)
• Tc- HMPAO labelled white cell scanning
• Enteroscopydiagnostic yield up to 31%
( 20% if gastroscopically accessible lesions excluded)
Small bowel imaging (3)
• Capsule endoscopy?Established role in the investigation of
iron deficiency anaemia? Suspected small bowel malabsorption
or diarrhoea of unknown cause
• Superior to small bowel barium XR70% vs 40% diagnostic yield
Capsule Endoscopy:Detection of inflammatory lesions
in the small intestine
Thickened infiltrated folds (Jejunum) Villous erosion
Linear ulcerationsApthous ulcerations (ileum)
INVESTIGATION OF CHRONIC DIARRHOEA
Basic investigationsFBC, LFT, Ca, B12, Folate, Fe status, TFT
Coeliac serology
History suggestive of organicdiarrhoea
Abnormal basic investigations
Symptoms suggestive of functionaldisease
Age <45,normal basic investigationsirritable bowel syndrome
History or findings c/w malabsorptionHistory or findings c/w colonic
disease or small bowel inflammatorydisease
'Difficult diarrhoea'Suspicion of laxative abuse
persistent symptoms despite negative IxHigh volume diarrhoea
Small BowelD2 biopsy
Barium follow throughPancreatic
EnteropathyReview histology
?Enteroscopy Or capsule endoscopy
Flexible sigmoidoscopy if <45Complement with barium enema if >45
Colonoscopy preferred if >45
Terminal ileal disease excluded?Barium follow through
99mTc-HMPAO75SeHCAT
‘‘Malabsorption’’‘‘Malabsorption’’
Malabsorption - mucosal disease
carbohydrate>fat
Maldigestion - pancreatic disease
fat> carbohydrate
(protein quantification difficult)
Tests related to fat malabsorption (1) Tests related to fat malabsorption (1)
Stool tests 3 day faecal fat (poorly reproducible)
patients with steatorrhoea reduce fat intake no assessment of completeness of collection no quality control
faecal fat concentration (not widely available) Stool steatocrit and Sudan III (semi-quantitative)
all are non-specific
Tests of fat malabsorption (2)
Breath tests 14C-triolein 13C-hiolein Lembke 1996
8-12 hr , 30 min breath samplessensitivity 92% in severe, 46% in mild/modpancreatic insufficiency
13C- mixed chain triglyceride Only sensitive if moderate or severe steatorrhoea
Tests related to carbohydrate malabsorptionTests related to carbohydrate malabsorption
D-xylose - used in assessment of mucosal disease for
30 years - High sensitivity (98%) and specificity (95%) reported (although controvercial) - 5 hour urine collection and/or 1 hour serum sample
D-xylose breath test
Both have been largely replaced by endoscopic distal duodenal biopsies
Chronic pancreatitis
• Usually obvious
• Previous episodes of pancreatitis
• History of XS alcohol
• Weight loss
• Steatorrhoea
• Coincident diabetes?
Investigation of pancreatic
malabsorption: Imaging
• USS 50-60% sensitive
• CT74-90% sensitive
• ERCP ‘Gold standard’
• MRI ?equivalent to ERCP
Investigation of pancreatic malabsorption Investigation of pancreatic malabsorption
Invasive Pancreatic function tests
- Secretin/cholecystokinin stimulation- ‘Lundh’ test
Sensitivity 90% ERCP
secretin-cholecystokinin ERCP26/30 abnormal 21/30
Investigation of pancreatic malabsorptionInvestigation of pancreatic malabsorption
Non-invasive (1) (all tests related to fat malabsorption) (Serum enzymes) Faecal tests
- chymotrypsin (Sens 80% Spec 84%)- lipase (sensitivity 46%)- elastase
mild moderate severe sensitivity 63 100 100% (Loser 1996) 40 33 82% (Lankisch 1998)
Investigation of pancreatic malabsorptionInvestigation of pancreatic malabsorption
Non-invasive (2)‘Tubeless’ oral pancreatic function tests NBTP/PABA
- N-benzoyl-L-tyrosyl-p-aminobenzoic acid - hydrolysed by chymotrypsin- 6 hour urine collection- Sensitivity 64-83% Specificity 89%
Fluorescein dilaurate (Pancreolauryl) test- Pancreatic esterase- 10 hour urine collection- variable sensitivities reported
Investigation of pancreatic malabsorption (summary)
• Faecal elastase is the non-invasive investigationof choice
• May complement with Urine test such as pancreolauryl or NBTP-PABA but
- specificity influenced by small bowel disease - technically more demanding
Miscellaneous causes and ‘difficult diarrhoea’
• Small bowel bacterial overgrowth
• Bile acid malabsorption
• Hormone secreting tumours
Small bowel bacterial overgrowthSmall bowel bacterial overgrowth
Underdiagnosed -few data on prevalence- Up to 50% of patients with gastrojejeunostomy- Resection of ileo-caecal valve eg pouch patients- 14% asymptomatic elderly by glucose HBT
Small bowel aspirate and culture - ‘Gold standard’ >10^6 cfu/mL- Culture of anaerobes difficult- May overestimate -contamination and ‘normal’ small bowel colonisation by bacteria.
Investigation of small bowel bacterial overgrowth
Investigation of small bowel bacterial overgrowth
Breath tests- 14C-cholylglycine - now abandoned
- Hydrogen breath tests (glucose or lactulose) Sensitivity: 17 - 68%
Specificity: 70-83% - 14C-D xylose – not
available in UK Proximally absorbed No reliance on H2 production
Bile acid malabsorption
• Causesterminal ileal disease, surgical resection primary defect, post cholecystectomy rapid transport
• 75Se homotaurocholate (75SeHCAT)synthetic analogue of taurocholic acidretained fraction assessed by gamma camera 7 days after oral administration <15% suggest BAM
• 7alphahydroxy-4-cholestone-3-one
• Therapeutic trial of cholestyramine
Hormone secreting tumours
• Rare! Incidence approx. 1 per million
• VIPoma, gastrinoma, carcinoid, somatostatinoma
• Large volumes (>1 litre) of watery diarrhoea
• VIPoma 90% are pancreatic, large tumoursDiarrhoea primary symptom (100%)Can be episodic. Secretory diarrhoeaFasting VIP level >170pg/mL
Summary IN V E S TIG A TIO N O F C H R O N IC D IA R R H O E A
E n terop a th yR eview h is to log y
? E n te roscop y
B ac te ria l overg row thG lu cose h yd rog en b rea th tes tJe jeu n a l asp ira te an d cu ltu re
S m all B owe lD 2 b iop sy
B ariu m fo llow th rou g h
F u rth er s tru c tu ra l tes tsE R C P or M R C P
P an c rea ticC T p an c reas
faeca l e las tase o r ch ym otryp s inP an c reo lau ryl tes t
H is to ry o r fin d in g s c /w m a lab sorp tion
Term in a l ilea l d isease exc lu d ed ?B ariu m fo llow th rou g h
9 9 m Tc-H M P A O7 5 S eH C A T
F lexib le s ig m oid oscop y if < 4 5C om p lem en t w ith b ariu m en em a if > 4 5
C olon oscop y p re fe rred if > 4 5
H is to ry o r fin d in g s c /w co lon icd isease
G u t h orm on esS eru m g as trin , V IP
U rin ary 5 H IA A
C on s id er in -p a tien t assessm en t2 4 -7 2 h rs s too l w e ig h ts
S too l osm ola lity/osm otic g apL axative sc reen
'D ifficu lt d ia rrh oea 'S u sp ic ion o f laxa tive ab u se
p ers is ten t sym p tom s d esp ite n eg a tive IxH ig h vo lu m e d ia rrh oea
H is to ry su g g es tive o f o rg an icd ia rrh oea
A b n orm al b as ic in ves tig a tion s
S ym p tom s su g g es tive o f fu n c tion a ld isease
A g e < 4 5 ,n orm al b as ic in ves tig a tion sirritab le b owe l syn d rom e
B as ic in ves tig a tion sF B C , L F T, C a , B 1 2 , F o la te , F e s ta tu s , TF T
C oe liac sero log y
ConclusionsConclusions Baseline investigations (primary care) lower GI endoscopy with biopsy Consider factitious diarrhoea Small bowel malabsorption -
Distal duodenal biopsies - small bowel imaging
Pancreatic insufficiency - faecal elastase, Pancreolauryl test, pancreatic imaging
Other – SB bacterial overgrowth, BAM etc In 1/3 patients no diagnosis made: ‘chronic idiopathic diarrhoea’