Diarrhoea

Introduction

• Acute diarrhoea
  • Sudden onset of increased water content of stool
  • 3 or more times daily in 24 hour period
• Pathophysiology
  • 4 mechanisms
    • Increased intestinal secretions
    • Decreased intestinal absorption
    • Increased osmotic load
    • Abnormal intestinal motility
  • Healthy small intestine absorbs 75% of normal fluid load
  • Large bowel absorbs 90% of it’s usual fluid load (around 2L/day)

Pathophysiology

• Intestinal villi absorb and crypts secrete
• Fluids absorbed by 2 mechanisms:
  • Passively with sodium
  • Actively with glucose
  • Glucose-dependent mechanisms are often unaffected by enterotoxins and can therefore be exploited with glucose-containing ORS
• Inflammatory conditions selectively affect villi with less crypt involvement with subsequent reduced absorption and unopposed crypt secretion
• If faecal evidence of inflammation and Shigella, Salmonella, Campylobacter, C. difficile and E. histolytica have all be excluded – suspect IBD

History

• Resolve with fasting – osmotic
• Persist with fasting – secretory
• Small volume stools– large bowel
• Large volume stools – small bowel
• Fever or abdominal pain – Diverticulitis, infectious gastro, IBD
• Seizures – Shigellosis, theophylline, hyponatraemia
• Paraesthesia and reverse temperature sensation – ciguetera
• Heat intolerance and anxiety – thyrotoxicosis
• Travel, medications, sick contacts, food poisoning

Examination

• Thyroid enlargement
• Oral ulcers, erythema nodosum, episcleritis, anal fissure – IBD
• Reiter’s syndrome should raise concern of Salmonella, Shigella, Campylobacter and Yersinia
• Faecal impaction – Overflow
• Check stool for blood – infection, inflammation, ischaemia
• Elderly patient with bloody diarrhoea and pain out of proportion = mesenteric ischaemia

Diagnostic stool evaluation

• If present within 24 hours – no further testing unless septic or suspicious for dysentery
  • Acute abdominal pain, fever, diarrhoea that is voluminous, purulent, bloody
• Wright’s stain
  • Historically differentiated invasive from non-invasive infectious diarrhoea
  • Used to identify faecal leukocytes
• Bacterial stool culture
  • Expensive and labor intensive. 
  • Diagnostic yield <5% unless careful patient selection
  • Recommended if:
    • Unwell child
    • Toxic, dehydrated or febrile patients
    • Diarrhoeal illness >3 days
    • Blood or pus in stools
    • Immunocompromised

Diagnostic stool evaluation

• Ova and parasites
  • Evaluate in travelers exposed to untreated water and those with diarrhoea >7 days
  • Lack sensitivity as many parasites are fastidious and shed organisms intermittently
  • Multiple samples may be required
  • Direct immunofluorescence staining improves sensitivity for Giardia and Cryptosporidium
• C. diff toxin assay
  • Most common antibiotic- and healthcare-associated diarrhoea
  • 10% false-negative rate and turnaround time of near 24 hours

Treatment

• Mild dehydration – Gatorade
• Mild-moderate – 30-50mL/kg ORS over 4 hours
• Moderate dehydration – 100mL/kg ORS over 4 hours
• Severe dehydration – IV therapy
• Encourage avoidance of caffeine, chewing gum and lactose initially
• Early food (other than above) expedites recovery

Acute infectious diarrhoea

• Norovirus causes 50-80% of all infectious diarrhoea
• 40% of travellers to developing countries have diarrhoea within first 2 weeks
• History of foreign travel = 80% probability of bacterial diarrhoea
• Other risk factors include level of food contamination, season of travel (wet season higher risk), use of PPI, previous traveller’s diarrhoea (suggesting genetic predisposition) and type of travel (adventure travel, camping, backpacking and living with native inhabitants)

Acute infectious diarrhoea

• Clinical features
  • Severe abdominal pain, fever or bloody/purulent stool warrants MCS
  • If >7 days, OCP testing
• Treatment
  • Antibiotics shorten illness by 24 hours and do NOT increase carrier state of Salmonella as previously thought
  • Cipro recommended (Tint) for all patients believed to have an infectious diarrhoea who do not have a contraindication to the drug (children, allergy, pregnancy or drug interaction)
    • There are reports of increasing fluoroquinolone resistant strains
  • Bactrim also effective but slightly higher resistance rates
• Loperamide
  • Shortens duration of symptoms when combined with antibiotic regime
  • Do not use in bloody diarrhoea or suspected inflammatory diarrhoea due to possibility of prolonged fever, toxic megacolon in C. diff and HUS in Shiga-toxin producing E. coli

Acute infectious diarrhoea

• Probiotics
  • Safe and effective when used with rehydration therapy
• PPI’s are not effective
• Disposition
  • Counsel families about frequent handwashing and proper selection and preparation of food while travelling
  • Peel it, boil it, cook it, or forget it
  • Rotavirus and Cholera vaccines are available for travellers
  • Provide work excuses +- public health notification for food preparation, daycare and healthcare workers

Empiric treatment for travellers diarrhoea

• Ciprofloxacin 500mg stat or BD for 3/7
• Azithromycin 1000mg stat (safe for kids and pregnancy)
• Bactrim 160/800 stat or BD for 3/7
• Rifaximin 200mg PO TDS for 3 days

Empiric treatment for infectious pathogens

• Empiric (not for bloody diarrhoea or Shiga toxin E. coli 0157:H7)
  • Ciprofloxacin 500mg BD for 5/7 or Bactrim DS 1 tab BD 5/7
• C. difficile
  • Metronidazole 500mg TDS PO for 14 days or Vanc 125mg PO QID for 14/7
• E. coli 0157:H7 – No antibiotics
• Listeria monocytogenes – No antibiotics
• Yersinia – No antibiotics
• Salmonella (non-typhi) – Cipro 750mg PO BD 5/7 or Azithromycin
• Shigella – As above
• Vibrio cholerae – Doxycycline 500mg PO stat or azithromycin 1g PO stat
• Entamoeba histolytica – Metronidazole 750mg PO TDS for 10 days and paromomycin 10mg/kg TDS for 7 days
• Giardia – Tinidazole 2g PO stat OR metronidazole 500mg PO BD for 3/7

Clostridium difficile

• Spore-forming obligate anaerobic bacillus causing mild diarrhoea through to pseudomembranous colitis
• Most common cause of bacterial diarrhoea in hospitalised patients
• Causes 10-20% of antibiotic-associated diarrhoea but majority of colitis cases
• Incidence and severity increasing 25% annually
• Toxins A and B both cause secretory diarrhoea
• Three severe syndromes
  • Neonatal pseudomembranous colitis
  • Post-operative pseudomembranous enterocolitis
  • Antibiotic-associated pseudomembranous colitis
• Risk factors
  • Recent antibiotic use (PO or IV equally), chemotherapy, GI surgery, severe underlying medical illness and advancing age
  • Transmission is by direct human contact and commodes, telephones, rectal thermometers

C. diff

• Pathophysiology
  • 10-25% of hospitalised patients are colonised
  • Linear relationship with length of stay, colonisation and development of diarrhoea
  • Broad-spec Ab’s (clindamycin, cephalosporins, ampicillin, fluoroquinolones) reduce faecal anaerobes, which are needed for carbohydrate metabolism and bile acid breakdown 
  • Diarrhoea can then result from carbohydrate accumulation (osmotic), bile acid (secretory) and C. diff toxin
  • Any antibiotic (incl. vanc and metronidazole) can lead to pseudomembranous colitis + chemotherapeutic agents, PPI’s and antivirals
  • Other risk factors include bowel ischaemia, IBD, recent bowel surgery, uraemia, malnutrition, shock, advanced age, peripartum and Hirschprung’s disease

C. diff

• Toxin A – Enterotoxin
• Toxin B – Cytotoxin
• Clinical features
  • Typically 7-10 days after initiation of antibiotic therapy (but can be up to 60 days from cessation)
  • Frequent, mucoid, watery stools through to profuse diarrhoea, cramping abdo pain, leukocytosis
  • Can present with paralytic ileus
  • Faecal leukocytes increase likelihood of C. diff vs. other causes of antibiotic-associated diarrhoea
  • 1-3% of patients suffer toxic megacolon or colonic perforation

C. diff

• Diagnosis
  • Suggested by diarrhoea during or within 2 weeks of antibiotic discontinuation
  • Stool assays
    • Stool culture has sensitivity approaching 100% but lacks specificity (as may be present but not causing disease)
  • Toxins
    • Sensitivity 63-94% and specificity 75-100%
    • 5-20% of patients require >1 stool specimen to detect toxin
  • Colonoscopy
    • Yellowish pseudomembranous plaques (typically right colon)

C. diff

• Treatment
  • Mild cases – Cease antibiotic (20% effective) +- metronidaozle 500mg PO TDS for 14 days
  • Moderate (WCC >15) – Vancomycin 125mg PO QID for 14 days
  • First relapse – Metronidazole 500mg PO TDS for 14 days
  • Second relapse – Vancomycin 125mg PO QID for 14 days then taper over 2 weeks
  • Severe disease with toxic megacolon – Metronidazole 500mg IV q6h + Vancomycin 500mg PO QID (or IV if unable)
  • Emergency colectomy
    • Indicates for leukocytosis >20, lactate >5, age >75, immunosuppression, shock, toxic megacolon, colonic perforation or MODS
• Relapses occur in 20-30% of cases
  • Increased risk in prolonged antibiotic use, prolonged hospitalisation, advanced age, diverticulosis, multiple comorbidities
• Probiotics are not helpful
• Antidiarrhoeals are controversial
• Steroids rarely indicated
• Need isolation, PPE, good hand washing with soap and water (alcohol-based rubs are not effective at eliminating spores)
• IV Vancomycin not effective as does not reach therapeutic concentrations within bowel
• PO Vanc preferred if pregnant, lactating, intolerant of metronidazole or failure of metronidazole therapy

IBD

• Systemic symptoms more common in Crohn’s disease
• Extraintestinal manifestations more common in CD
• Equivalent risk of colonic carcinoma

Crohn’s disease

• Chronic granulomatous inflammatory disease of any part of GI tract
• Ileum involved in majority and in 20% isolated to colon (making Dx difficult)
• Peak incidence 15-22yo with second peak at 55-60yo
• More common in women and incidence is increasing in children
• 4x more common among Jewish people
• FHx of IBD in 10-15%
  Smoking, OCP and use of NSAID’s worsen the course of disease

Crohn’s

• Pathophysiology
  • Involves all layers of bowel wall and extends into mesenteric nodes
  • Discontinuous disease with skip lesions
  • Longitudinal, deep ulcerations are characteristic
  • Fissures, fistulae and abscesses are common
  • Cobble-stone appearance of mucosa due to criss-crossing ulcers is a late sign
• Clinical features
  • Abdo pain, anorexia, diarrhoea and weight loss evident in most
  • Chronic abdo pain, fever and diarrhoea may exist for years before diagnosis is made
  • 10-20% of cases present with extraintestinal manifestations – arthritis, uveitis or liver disease
  • PUO
  • 30% only small bowel; 20% only large bowel; 50% both
  • Extraintestinal manifestations are seen in 40% of patients

Crohn’s

• Diagnosis
  • Detailed history of long-standing abdominal symptoms may provide clue to true diagnosis
  • Must identify severity of attack, complications (obstruction, intra-abdominal abscess, life-threatening haemorrhage or toxic megacolon) and eliminate other possible causes of symptoms
  • Faecal calprotectin and lactoferrin are markers of disease activity
  • Imaging
    • CT may identify abscesses, fistulae, bowel wall thickening, segmental narrowing, obstruction or extraintestinal manifestations such as gallstones, renal calculi, sacroiliitis and osteomyelitis
  • Colonoscopy confirms diagnosis

Crohn’s

• DDx
  • Lymphoma
  • Ileocecal amoebiasis
  • Sarcoidosis
  • Deep chronic mycotic infections
  • GI tuberculosis
  • Kaposi’s sarcoma
  • Campylobacter enteritis
  • Yersinia ileocolitis
  • If isolated to large bowel, must consider ulcerative colitis and pseudomembranous colitis

Crohn’s

• Treatment goals
  • Relief of symptoms
  • Induction of remission
  • Maintenance of remission
  • Prevention of complications
  • Optimising timing of surgery
  • Maintenance of nutrition

Crohn’s

• Initial therapy
  • Rehydration, analgesia, electrolytes, NG
  • Broad-spec Ab’s for fulminant colitis or peritonitis – PIpTaz or Amp + Gent + Metronidazoe
  • IV steroids hydrocortisone 300mg daily or equivalent for severe disease
• Salicylates
  • Sulfasalazine 3-5g/day for mild-moderate disease
  • Sulfapyridine is a toxic byproduct of sulfasalazine which can cause nausea, anorexia, diarrhoea, headache, epigastric pain and vomiting
  • Mesalamine is the active moiety and newer agents have just this without sulapyridine compound (more effective in colonic disease and mild disease)
• Corticosteroids
  • Oral prednisone 50mg daily for induction therapy and severe flares
  • Ileal-released budesonide may be helpful for ileal/right colon disease
  • Not ideal for maintenance therapy

Crohn’s

• Immunosuppresants
  • 6-mercaptopuraine, azathioprine and thioguanine are useful steroid-sparing agents for maintenance, healing fistulas and contraindications for surgery
  • Associated with leukopaenia, fever, hepatitis, pancreatitis
  • Take 3-6 months to work
  • Parenteral methotrexate is third-line
• Antibiotics
  • First-line for perianal disease and help induce remission
  • Cipro induces remission in 55% (similar to mesalamine)
  • Metronidazole is also effective for perianal and fistulous complications

Crohn’s

• Biologics
  • Anti-TNFalpha for medically-resistant moderate-severe disease
  • Infliximab and adalimumab (Humira)
  • Raise risk of infection and TB, lymphoma and possibly progressive multifocal leukoencephalopathy
• Anti-diarrhoeal agents
  • Loperamide and cholestyramine are helpful

Crohn’s

• Disease complications
  • 75% require surgery within first 20 years of onset
  • Abscess and fissure formation are common
  • Fistulas most commonly form between ileum and sigmoid, cecum, another ileal segment, urinary bladder, vagina or skin
  • Obstruction due to strictures and oedema of bowel wall
    • Most commonly distal small bowel
  • Perianal complications include abscesses, fissures, fistulas, rectovaginal fistulas and prolapse
  • Major GI bleeding is rare but can occur due to erosion into bowel wall vessel
  • Toxic megacolon is uncommon but 50% of cases have massive GI haemorrhage
    • >6cm = toxic megacolon
    • >12cm = imminent perforation
  • Hypocalcaemia, malnutrition, malabsoorption and vitamin deficiency can occur
  • Complications of therapy include leukopaenia, thrombocytopaenia, fever, infection, profuse diarrhoea, pancreatitis, renal insufficiency and liver failure
  • Incidence of bowel cancer is 3x higher

Crohn’s disease

• Crohn’s disease activity index
  • Weight
  • Ideal body weight
  • Total number of soft/liquid stools in last 7 days
  • Abdominal pain
  • General well-being
  • Antidiarrhoeal use
  • Abdominal mass
  • Haematocrit
  • Extraintestinal manifestations
    • Arthritis/arthralgia
    • Iritis/uveitis
    • Erythema nodosum/pyoderma gangrenosum/aphthous stomatitis
    • Anal fissure/fistula/abscess
    • Other fistula
    • Fever >37.8

Crohn’s disease

• Crohn’s disease activity index
  • Total score <150 = Remission
  • >450 = Severe Crohn’s disease

Crohn’s

• Disposition
  • Always discuss with treating gastroenterologist prior to discharge to ensure outpatient regime is suitable

Ulcerative colitis

• Inflammation tends to progressively worsen from proximal to distal colon
• Rectum involved in almost 100%
• Bloody diarrhoea is classic presentation
• Peak incidence in 2^nd and 3^rd decades of life
• First-degree relatives of patients have 15-fold risk of developing UC and 3.5-fold risk of Crohn’s

UC

• Pathophysiology
  • Mucosa with crypt abscesses, epithelial necrosis and mucosal ulceration
  • Submucosa usually spared
  • Pseudopolyps in severe cases
• Clinical features
  • Cramping abdo pain, bloody diarrhoea and tenesmus are common
  • Mild disease (60%)- <4 bowel movements per day; no systemic symptoms; few extraintestinal manifestations
    • Progression to pancolitis occurs in 10-15% of mild cases
  • Moderate (25%) – Good response to therapy, usually extends to splenic flexure
  • Severe (15%) – Frequent bowel movements, anaemia, fever, weight loss, tachycardia, hypoalbuminaemia and more frequent extraintestinal manifestations
    • Almost always pancolitis
  • Usually intermittent attacks with complete remission in between
  • Unfavourable prognostic factors and increased mortality
    • Higher severity and extent of disease
    • Short interval between attacks
    • Systemic symptoms
    • Onset of disease after 60yo

UC

• Extra-intestinal manifestations
  • Arthritic – Peripheral arthritis, ankylosing spondylitis, sacroiliitis
  • Ocular – Episcleritis, uveitis (perilimbic injection)
  • Dermatologic – Erythema nodosum, pyoderma gangrenosum
  • Hepatobiliary – Cholelithiasis, fatty liver, pericholangitis, chronic active hepatitis, PSC, cholangiocarcinoma, pancreatitis
  • Vascular – DVT, portal venous thrombosis, mesenteric vein thrombosis
  • Malnutrition
  • Chronic anaemia
  • Nephrolithiasis (increased dietary oxalate absorption or dehydration)

UC

• Diagnosis
  • Confirmation by colonoscopy
  • DDx – Infectious colitis, Crohn’s, ischaemic colitis, radiation colitis, toxic colitis from antineoplastic agents, pseudomembranous colitis
  • If limited to rectum, consider rectal syphilis, gonococcal proctitis, lymphogranuloma venereum, herpes simplex, Entamoeba histolytica, Shigella and Campylobacter

Ulcerative colitis – Truelove +Witts

UC

• Treatment
  • Same as Crohn’s but can add IV cyclosporine or infliximab if non-responsive to IV corticosteroids
  • If mild-moderate left-sided (<60cm active disease) topical mesalamine suppositories or enemas are effective
  • Topical steroids are also nearly as effective and better tolerated
  • Systemic glucocorticoids are useful in inducing remission if topical therapy fails
  • Combination PO + topical mesalamine is used in mild-moderate attacks but is less effective than steroids in severe cases
  • Infliximab is the only biologic for UC and should be considered in mild-moderate disease who are corticosteroid-dependent or refractory and in those with immunomodular-refractory disease
  • Psyllium husk can improve stool consistency
  • Antidiarrhoeal agents may precipitate toxic megacolon

UC

• Complications
  • Blood loss from sustained haemorrhage is the most common complication
  • Toxic megacolon must not be missed
    • Occurs when severe cases involve all layers of GI wall with loss of muscular tone, dilatation and localised peritonitis
    • Plain X-ray shows long, continuous segment of air-filled colon >6cm in diameter
    • >12cm = imminent perforation
    • Loss of colonic haustra and thumb-printing represent bowel wall oedema
    • Distended atonic colon can perforate with high mortality
    • Peritonitis and leukocytosis may be masked by chronic steroid use
    • Precipitating factors include antidiarrhoeal agents, hypokalaemia, narcotics, cathartics, pregnancy, enemas and recent colonoscopy
  • 20% of patients suffer perirectal fistulas
  • Massive GI haemorrhage
  • Obstruction secondary to strictures
  • Acute perforation
  • 10-30-fold increase in colon carcinoma (highest with extensive involvement and prolonged duration of disease, early onset of disease and FHx of colon cancer)
    • Cumulative risk of cancer is 5-10% at 20 years of disease and 12-20% after 30 years

Diarrhoea in the immunocompromised

• HIV positive or primary immunodeficiency
  • Stool PCR parasite
    • Giardia, Cryptosporidium, Cyclospora, Isospora, Dientamoeba, Entamoeba, Microsporidia, Histoplasmosis, Cryptococcus
  • Stool PCR virus
    • Norovirus, Astrovirus, Adenovirus, Rotavirus, HSV, CMV
  • Stool PCR bacterial
    • Salmonella, Shigella, Shiga toxin EHEC, Campylobacter
  • Bacterial stool culture
  • C. difficile toxin testing

Diarrhoea in the immunocompromised

• Solid or haematopoietic transplant
  • C. diff toxin testing
  • Stool PCR virus
  • Stool PCR parasites
    • Giardia, Cryptosporidium, Cyclospora, Isospora, Cryptococcus, Histoplasmosis, Dientamoeba, Entamoeba, Microsporidia

Fluid and electrolytes

• Normal stool
  • Alkaline pH  Results in NAGMA
  • Na and K rich
  • Bicarb and Cl rich
  • Osmolality remains equal to serum (~300) so increased volumes means increased electrolyte loss
• Common abnormalities
  • Hypokalaemia
  • NAGMA from loss of actual and potential bicarbonate
    • HAGMA can occur from lactic acidosis volume depletion and uraemic AKI
  • Hypovolaemia +- hyponatraemia if large volumes of free water replaces losses
  • Hypernatraemia (rarer)
  • Metabolic alkalosis (rarer)
    • Can occur if hypovolaemia and hypokalaemia arise with contraction alkalosis

Last Updated on October 28, 2020 by Andrew Crofton