GI - Diarrhoea & malabsorption

Question 1

Define diarrhoea

• volume

- frequency

Answer 1

Stool > 200 g/day and number of movements > 3/day

Question 2

What are the mechanisms that cause diarrhoea?

Answer 2

osmotic, secretory, inflammatory & altered intestinal motility (can occur in combination)

Question 3

What (2) are small volume stools typical of?

Answer 3

colonic diseases and IBS

Question 4

What (2) are large volume (>750ml/d) stools typical of?

Answer 4

small bowel disease and secretory diarrhoea

Question 5

What tests on faeces could help establish the mechanism or diagnosis for diarrhoea?

Answer 5

• MCS of stool
• Faecal electrolytes & osmolarity
• faecal fat
• faecal elastase
• C. difficile toxin
• faecal calprotectin
• faecal laxative screen
• faecal alpha-1 antitrypsin

Question 6

What does Faecal elastase indicate?

Answer 6

Presence of faecal elastase = marker of exocrine pancreatic sufficiency

Hence lack of = insufficiency

Question 7

What does Faecal calprotectin indicate?

Answer 7

marker of gastrointestinal inflammation

Question 8

What does Faecal laxative screen indicate?

Answer 8

anthroquinones, bisacodyl, phenolphthalein

Question 9

What does Faecal alpha-1 antitrypsin screen indicate?

Answer 9

marker of protein losing enteropathy

Question 10

Describe osmotic diarrhoea

• cause
• stool volume
• stool osmotic gap
• effect of fasting
• stool leukocytes
• H2/methane breath test

Answer 10

• Presence of excess unabsorbed substrates in gut lumen
• Common cause: Fermentable carbohydrate malabsorption (FODMAPs)
• Stool volume typically 100)
• Stops with fasting
• Not present (normal faecal calprotectin)
• Increased breath hydrogen with malabsorption

Question 11

Describe secretory diarrhoea

• cause
• stool volume
• stool osmotic gap
• effect of fasting
• stool leukocytes

Answer 11

• Due to active anion secretion from enterocytes
• Bacterial toxins (cholera, toxigenic E.coli), hormone secreting tumours (e.g. carcinoid, gastrinomas), laxative abuse, hyperthyroidism
• Stool volume > 1 litre/d, watery
• Normal osmolality (osmolar gap

Question 12

Describe inflammatory diarrhoea

• cause
• stool volume
• stool leukocytes

Answer 12

• Altered membrane permeability →exudation of protein, blood, mucus
• Invasive bacteria (Shigella, Salmonella, Campylobacter, Clostridium difficile), Entamoeba histolytica, cytomegalovirus colitis, inflammatory bowel disease (IBD)
• Volume of faeces usually small
• Increased red blood cells and leukocytes (elevated faecal calprotectin). Stools may contain visible (‘frank’) blood and be associated with urgency, tenesmus and constitutional upset e.g. fever

Question 13

Describe rapid transit as a cause of diarrhoea

• mechanism
• causes

Answer 13

Inadequate time for absorption of fluid (& nutrients)

Irritable bowel syndrome (IBS), thyrotoxicosis, diabetic neuropathy

Question 14

Describe slow transit as a cause of diarrhoea

• mechanism
• causes

Answer 14

Bacterial overgrowth -> nutrient consumption -> bile salt inactivation (unable to solubilise micelles

Intestinal stasis due to anatomical defects (strictures, blind loops, surgical procedures)

Question 15

List (4) classes of causes of luminal phase maldigestion

Answer 15

1. Mechanical - Mixing disorders
   - Post-gastrectomy
2. Reduced nutrient availability
   - Co-factor deficiency e.g. pernicious anaemia
   - Bacterial overgrowth (nutrient consumption)
3. Defective nutrient hydrolysis (digestion)
   - Pancreatic insufficiency e.g. chronic pancreatitis
4. Reduced fat solubilisation (reduced bile salt concentration)
   - Cholestasis, bacterial overgrowth

Question 16

List (3) classes of causes of mucosal phase maldigestion & defective transport

Answer 16

1. Inadequate absorptive surface
   - Intestinal resection or bypass due to disease
2. Diffuse mucosal disease
   - Coeliac disease, Crohn’s disease, Giardia infection
   - Brush border enzyme deficiency e.g. lactase
3. Mucosal absorptive defects
   - lymphoma, lymphatic obstruction, radiation damage
   - vascular problems

Question 17

42yo male
Three months of feeling unwell
Loose-stools, 6-8 times a day (normally once every 1-2 days)
Often bloody with mucous mixed in
Crampy abdominal pain prior to defecation
Urgency and tenesmus
Occasional nocturnal diarrhoea

Afebrile. Looks tired. Pale.
Abdominal examination: unremarkable

Constitutional symptoms: Feeling lethargic & sleeping poorly, occasionally “feverish”; weight loss 2-3 kg in past 3 months
Recent travel: 6 months ago holiday in Thailand. Was not unwell there.
Social History: Lawyer, lives with partner Paul

Mechanism of diarrhoea? DDx?

Answer 17

The clinical presentation is of bloody, mucousy diarrhoea with tenesmus This is usually due to an INFLAMMATORY mechanism

Common causes are:

1. Infection (“dysentery”) e.g. Salmonella, Shigella, Yersinia, Entamoeba histolytica (amebiasis) and cytomegaloviral colitis
2. Inflammatory bowel disease
3. Ischaemic colitis
4. Radiation colitis

Question 18

How do you confirm the diagnosis of IBD?

Answer 18

colonoscopy and colonic biopsies

Question 19

Describe what you’d see on colonoscopy & colonic biopsy of UC

Answer 19

• superficial ulceration with distortion of crypts
• acute and chronic diffuse inflammatory infiltrate
• goblet cell depletion
• crypt abscesses
• lymphoid aggregates but no granulomas

Question 20

Rx of ulcerative colitis

Answer 20

–5-ASA compounds (sulphasalazine) and steroids.
–Topical therapy (suppositories/enemas) used for distal disease.
–Immunosupressants used in severe or recurrent disease
–Surgery for severe or refractory cases (this is curative)

Question 21

Rx of Crohn’s disease

Answer 21

Steroids, 5-ASA compounds, immunosupressants (e.g. azathioprine, methotrexate), biologicals (monoclonal Ab), surgery

Question 22

26yo female
~ 10 year history of intermittent diarrhoea with bloating & flatulence
Up to 2-5 bowel motions per day (erratic), no blood
No weight loss
Stress, dairy products and some fruits make her symptoms worse
She tried a gluten free diet on advice of a friend and felt better.
SHx: Office manager, lives with partner
FHx: Sister is “gluten intolerant”
PHx: Depression
Meds: Nil. Non-smoker.

DDx?

Answer 22

1. Irritable bowel syndrome
2. Coeliac disease
3. Infection such as Giardia
4. Inflammatory bowel disease

Question 23

How do you diagnose irritable bowel syndrome?

Answer 23

1. Typical clinical Hx
“Rome III” criteria
•Symptoms for at least 3 months
•Recurrent abdominal discomfort or pain associated with (2 or more of):
–Improvement of symptoms with defecation
–Change in stool appearance (form)
–Change in stool frequency

2. Exclude other Dx
   Presence of “red-flag” symptoms or signs such as weight loss, rectal (PR) bleeding, nocturnal symptoms, and age >45 should prompt further investigation before a diagnosis of IBS is made

Question 24

How do you diagnose coeliac disease? (c.f. screen)

Answer 24

1. demonstration of small bowel damage (villous atrophy, crypt hyperplasia and raised intra-epithelial lymphocytosis) whilst a person is consuming gluten, and
2. improvement in histology, serology and clinical picture following a gluten free diet

Question 25

How do you screen for coeliac disease?

Answer 25

–blood test measuring antibodies to transglutaminase (tTG-IgA) and gliadin (“deamidated gliadin peptides”, DGP-IgA and DGP-IgG). –The DGP assay replaces the older and less accurate anti-gliadin antibodies (AGA-IgA, AGA-IgG) test. If antibodies are abnormally elevated (positive), a small bowel biopsy showing villous atrophy is required to confirm the diagnosis

Question 26

What (3) might cause false negative serology results in Coeliac disease screening?

Answer 26

–Gluten free diet (especially if > 6 weeks) –IgA deficiency (seen in 3% of coeliac disease – that is why the total IgA level is measured or the IgG isotype of DGP assessed –Immunosuppression e.g. prednisolone

Question 27

How can you test for coeliac disease if a person is already following a gluten free diet?

Answer 27

HLA-DQ2/8 gene test. This is seen in most (99.6%) patients with coeliac disease. If negative, it can be used to exclude coeliac disease. 6 week gluten challenge (~4 serves gluten/day) followed by small bowel biopsy

Question 28

How can you exclude infection and inflammatory bowel disease?

Answer 28

* Faecal assessment * Inflammatory markers * Gastroscopy and colonoscopy with biopsies may be required in some instances

Question 29

(4) pathogenesis of irritable bowel syndrome

Answer 29

Serotonin (5-HT) a key mediator in IBS 1. disordered intestinal motility 2. altered perception of nociceptive stimuli (visceral hypersensitivity) 3. psychogenic factors 4. post-infectious component in some people “Stress” and small bowel bacterial overgrowth can be a trigger Role of genetics is unclear

Question 30

Rx of IBS

Answer 30

•Dietary modification - Avoiding common food triggers – FODMAPs - Avoiding caffeine, alcohol, smoking •Pharmacological therapies - Probiotics - Antispasmodics, antidiarrhoeals, laxatives - Antibiotics (Rifaximin) to treat bacterial overgrowth - ? Increase fibre ? Decrease fibre •Psychological therapies -Relaxation, cognitive behaviour therapy, hypnotherapy

Question 31

62yo male 6 month history of pale, smelly, greasy stools, difficult to flush Frequently feels bloated and nauseated after meals. More lethargic and has lost 15 kg weight in past 6 months. Denies drinking alcohol for the past 2 years PHx: 1. Hypertension 2. Ex-smoker. 3. Heavy drinker in the past 4. Alcoholic pancreatitis 10 years ago, subsequent two recurrent episodes O/E: Bruises on arm. Evidence of subcutaneous fat loss. Several spider naevi on chest. Abdominal exam normal. No hepatic flap or fetor DDx?

Answer 31

1. Defective nutrient hydrolysis (digestion): Pancreatic insufficiency due to chronic pancreatitis or pancreatic cancer 2. Reduced nutrient availability: Poor oral intake (especially if still an alcoholic); bacterial overgrowth 3. Reduced fat solubilisation (reduced bile salt concentration): Cholestasis (failure of bile flow) due to underlying liver disease; bacterial overgrowth will inactivate bile salts 4. Diffuse mucosal disease: e.g. coeliac disease, Giardia infection, brush border enzyme deficiency 5. Mucosal absorptive defects: e.g. lymphoma, lymphatic obstruction

Question 32

What features suggest malabsorption might be present and how can we confirm it?

Answer 32

* History of steatorrhoea, lethargy, weight loss * Examination findings of bruising, muscle wasting, weight loss Confirm it by: •Nutrient levels (Iron studies, B₁₂, folate, vitamins) •Faecal assessment: Increased faecal fat

Question 33

Differing clinical picture associated with peritonitis - red - grey - white

Answer 33

–Red: vasodilated, warm peripheries, flushed (bacterial peritonitis) –Grey: shutdown, clammy, sweaty (chemical peritonitis/severe pancreatitis/MI/PE) –White – pale, shut down, cold peripheries (haemorrhagic shock)