detailed presentation on chronic diarrhoea

1. Approach to Chronic Diarrhea
PRESENTER:DR.ABHINAV KUMAR

2. CHRONIC DIARRHOEA
• AS A SYMPTOM
– Frequency of bowel action
– Looseness of stools
– Increase in stool volume
– AS A SIGN Stools weight more than 250 gm/24 hours

3. – Stools weight more than 250 gm/24 hours
• Patients conception as regards symptoms is variable
• Stools weighting is tedious.
• A consensus statement by the AGA
• Chronic Diarrhea = Decrease in fecal consistency for 4 or more
weeks

4. Normal stool fluids processing
• 8-9 L/d enter GI system
– Ingest 1-2 L/d
– Create approx 7 L/d
• saliva, gastric, biliary,
pancreatic secretions
• Small bowel reabsorbs 6-7 L/d
• Large bowel absorbs 1-2 L/d
• 100-200 gm/d stool created
• Reduction of water
absorption, due to decrease
in absorption or increase in
secretion, by as little as 1%
can lead to diarrhea

5. Causes of Diarrhea
In almost all cases; it is a manifestation of 1 of 4 Mechanisms:
– Osmotic diarrhea
– Secretory diarrhea
– Inflammatory and infectious diarrhea
– Diarrhea associated with deranged motility
• More than one of these mechanisms may be involved in the
pathogenesis of a given case.

6. Classification of causes
• Secretory
• Osmotic
• Steatorrheal
• Inflammatory
• Dysmotile Causes
• Factitial Causes

7. Characterstics of Factitial diarrhea
• accounts for up to 15% of unexplained diarrheas referred to tertiary care
centers.
• self-administer laxatives alone or in combination with other medications
(e.g., diuretics)
• surreptitously add water or urine to stool sent for analysis.
• typially women with histories of psychiatric illness
• disproportionately from careers in health care.
• Hypotension and hypokalemia are common co-presenting features.
• they benefit from psychiatric counseling

8. OSMOTIC GAP
• 290 mosm/kg - 2 x (Na+ K) = Osmotic Gap
• 125 mosm/kg = Osmotic diarrhea
• 50 mosm/kg = Secretory diarrhea

9. Osmotic Diarrhea
IN THE SMALL INTESTINE
Ingestion of non-absorbable solutes
Fluid entry into the small bowel
Intraluminal solutions become iso-osmotic with the plasma
Intraluminal Na+ concentration drop below 80 ml osmol
Steep lumen to plasma gradient

10. Osmotic Diarrhea
IN THE COLON
Carbohydrate
Metabolized by Bacteria
Non metabolizable substrates
Na+ and H2O
may be absorbed by colon
Short Chain fatty acids
(Organic anions)
A linear relation between ingested
osmotic load & stool water output
Quadrupling the Osmolality

11. Osmotic Diarrhea
Short-Chain Fatty Acids
(Organic Anions)
Promote more fluid in the colon
Obligate retention of inorganic cations
Further increasing the osmotic load
More fluid in the colon

12. Causes of Osmotic Diarrhea
Exogenous
• Osmotic Laxatives
• Antacids containing MgO or Mg(OH)2
• Dietetic foods, candies and elixirs
• Drugs e.g.:
– Colchicine
– Cholestyramine

13. Drugs Causing Diarrhea
• Antibiotics
– Clindamycin
– Ampicillin
– Cephalosporins
• Antacids + Mg++
• Anti-HTN Agents
– Propranolol
– Methyldopa
– Hydralazine
• Antimetabolites
• CV Agents
– Digitalis
• Alcohol
• Nutritional Supplements
• Potent Diuretics
– Furosemide
– Bumetanide

14. Causes of Osmotic Diarrhea
Endogenous
• Congenital
– Specific Malabsorptive Disorders e.g Disaccharidase deficiencies
– Generalized Malabsorptive Diseases e.g Abetalipoproteinemia
– Pancreatic insufficiency e.g cystic fibrosis
• Acquired
– Specific Malabsorptive Diseases
– Generalized Malabsorptive Diseases
– Pancreatic insufficiency
– Celiac disease
– Infections

15. Osmotic Diarrhea

16. Osmotic Diarrhea
• Mg can be measured directly in stool water
by spectrophotometry.
Excretion >30 mEq of Mg daily or concentrations in stool
water > 90 mEq/L strongly suggests Mg-induced diarrhea
• Ingestion of poorly absorbed carbohydrates
( fecal pH < 6 is highly suggestive, which is confirmed by Breath H2 test):
• Lactose
• Sorbitol or manitol
• fructose
• Acarbose (may lead to carbohydrate malabsorption)

17. • Electrolyte transport diarrhea
• The intestine is able to
– Secrete Fluids & electrolytes
– Absorb
• Secretion originates in the crypts
• Absorption is mainly a villous function
• Intracellular cyclic-AMP & -GMP are a corner stone in initiating
Intestinal secretion

18. Mechanism of Secretory Diarrhea
Neurotransmitters
Hormones
Bacterial Enterotoxins
Cathartics
Stimulate receptors on the enterochromaffin cells
stimulate
Cyclic AMP – Cyclic GMP
Ca ions
stimulate
Cl-, H2O and CHO3
Secretion by the enterocytes

19. causes of Secretory Diarrhea
• Exogenous
• Stimulant Laxatives e.g. Anthraquinones, senna
• Medications
– Diuretics
– Asthma medication
– Eye drops
– Bladder stimulants
– Cardiac drug
– Prostaglandins
• Toxins
– Metals
– Organophosphorous
– Seafood toxins
– Bacterial toxins

20. Endogenous
• Congenital e.g. Chloridorrhea
• Bacterial enterotoxins
• Hormone-producing tumors

21. Secretory Diarrhea
peptide-secreting tumors :
• Carcinoid syndrome (5HIAA, Metanephrine)
• ZE syndrome (Gastrin)
• Mastocytosis (Histamine)
• VIPoma (VIP)

22. Secretory Diarrhea
• Common endocrinologic diseases that cause diarrhea:
• Diabetes mellitus
• Hyperthyroidism (TSH)
• Addison's disease (ACTH)
•
• Other blood tests for evaluating secretory diarrhea :
• Serum protein electrophoresis and immunoglobulin electrophoresis
(IgA deficiency recurrent intestinal infections such as
giardiasis, CVID may mimic sprue , Testing for HIV and HIV2 )
• Cholestyramine trial is recommended for bile acid diarrhea.

23. Secretory Diarrhea
small bowel
Diseases that may be detected by small intestinal biopsy :
• Crohn's disease,
• Celiac sprue,
• Intestinal lymphoma,
• Eosinophilic gastroenteritis,
• Tropical sprue,
• Whipple's disease,
• Lymphangiectasia,
• Abetalipoproteinemia,
• Amyloidosis,
• Mastocytosis,
• (Many of these disorders usually, but not always, present with
steatorrhea)

24. Colon
• Colonic causes of chronic secretory diarrhea tend to produce diffuse
changes sigmoidoscopy usually is adequate
• Colonoscopy is preferable :
• older blood in the stool the clinical suspicion of right colonic or ileal
disease is strong the patient has AIDS Diseases with colonic mucosa
appears normal endoscopically, but that can be diagnosed
histologically:
• microscopic colitis (lymphocytic and collagenous colitis) amyloidosis
• granulomatous infections schistosomiasis

25. • Cholera and enterotoxigenic E. coli
• Bile acids and long chain fatty acids (postileal resection, Crohn’s
disease, malabsorption syndromes)
• Gastrointestinal hormones (VIPoma, gastrinoma, carcinoid)
• Anthraquinone laxatives
• Mechanism: Agents ↑ intracellular cAMP→ ↑secretion (Na+K+
ATPase is also inhibited)

26. Inflammatory Diarrhea
• Luminal or invading
• Viruses
• Bacteria
• Protozoa
• Helminths
Minimal or severe inflammation
Enterocyte damage or death
Malabsorption and secretion
• Immunological mechanisms
• Complement
• T-lymphocytes
• Proteases
• Oxidants

27. Chronic Inflammatory Diarrhea
Diagnostic considerations include
• IBD,
• Infections,
• Pseudomembranous enterocolitis,
• Ischemia,
• Radiation enteritis,
• Neoplasia.

28. Chronic Inflammatory Diarrhea
• Infections:
– Bacteria
– Viruses
– Parasites
– Helminthes
• Anticancer agents
• Radiation therapy
• Hypersensitivity e.g. celiac disease
• Autoimmune
• Ulcerative colitis
• Crohn's disease
• Collagenous colitis
• Lymphocytic colitis

29. Chronic Inflammatory Diarrhea
• The pathogens most likely to cause chronic inflammatory diarrhea :
• C. difficile
• Cytomegalovirus
• Entamoeba histolytica
• Yersinia spp
• Mycobacterium tuberculosis

31. Diarrhea Associated with
Deranged Mobility
• Adequate absorption requires
• Adequate and long enough exposure to intestinal epithelium
• Accelerated Transit time
– Decreased absorption
– Large fluid load to the colon
– Colonic irritability
– → Diarrhea
• Diminished peristalsis
– Bacterial overgrowth
• → Secretory diarrhea

32. Diarrhea Associated with
Deranged Mobility
• IBS-D
• Functional Diarrhea
• Diabetic neuropathy
• Scleroderma
• Thyrotoxicosis

33. Evaluation of Chronic Diarrhea
Systemic symptoms
– Fever
– Joint pains
– Mouth ulcers
– Eye redness
Physical examination
– Skin Rash
– Mouth ulcers.
– Eye manifestation and exophthalmos
– Physical signs of anemia
– Dehydration and cachexia
– Abdominal masses
– Anal sphincter tone
– Presence of blood on PR examination

34. Diarrhea and Abdominal Pain
• Suggests IBS if pain is in the left lower quadrant or suprapubic region
• Suggests a disease of the small bowel (e.g., Crohn’s disease) if the
pain is periumbilical or in right lower quadrant
• Gastrinoma (Zollinger-Ellison Syndrome) – peptic ulcers responsible
for upper abdominal pain

35. Evaluation of Chronic Diarrhea
• Stool characteristics
– Watery stools → osmotic & Secretory Diarrhea
– Greasy and malodorous → Fat malabsorption
– Visible blood → Inflammatory
• Stool Volume
– Large Volume → Small intestinal
– Small volume and frequent → Large intestine

36. Evaluation of Chronic Diarrhea
• Relation to food
– After meals ?? → IBS
– Stops with fasting → Osmotic diarrhea
– Occurs in spite of fasting and during sleep → Secretory
• Measure stools electrolytes
• Calculate the osmolality

37. Evaluation of Chronic Diarrhea
• Specific Testing
• A large number of tests are available
• No firm Rule as to what and to whom testing should be done
– The minimum laboratory evaluation Complete blood picture
and ESR
– Total proteins and albumin
– Serum electrolytes Thyroid functions
– Stools examination and fecal occult blood are Mandatory.
– Some patients may need endoscopic evaluation

38. Evaluation of Chronic Diarrhea
• The Osmotic Gap
• 290 mosm/kg - 2 x (Na+ K) = Osmotic Gap
• 125 mosm/kg = Osmotic diarrhea
• 50 mosm/kg = Secretory diarrhea
– Further studies Stools culture
– Selective testing for secretagogues
• Gastrin
• Vasoactive Intestinal Peptide (VIP)
• Testing for bile acid malabsorption
• Imaging the small and large intestine

39. • History
• Physical Exam
• Endoscopy
• Laboratory studies
• Radiological studies
• Other studies

42. Secretory diarrhea

43. History of Organic Disease
• Floating stools and undigested food are not helpful as they may
be seen in functional and organic diarrhea
• The association of diarrhea with milk or hyperosmolar solutions
may not be recognized by the patient
• Detailed drug history is important
• Arthritis and arthralgias may suggest inflammatory bowel
disease, Whipple’s disease, Reiter’s syndrome
• Weight loss suggests malabsorption, hyperthyroidism or a
malignant tumor

44. Physical Exam
• General: Weight loss
• Vital signs: Postural hypotension in diabetes with autonomic
dysfunction
• Neurology:
– Peripheral neuropathy due to vitamin B deficiency
– Carpopedal spasm due to hypocalcemia
• Skin:
– Erythema nodosum and pyoderma gangrenosum in inflammatory
bowel disease
– Hyperpigmentation in Whipple’s and Addison’s disease

45. • Musculoskeletal:
– Non-deforming arthritis - Whipple’s disease/IBD
• Abdominal:
– Hepatosplenomegaly and lymphadenopathy suggest
lymphoma or Whipple’s disease
– Arterial bruit or an aortic aneurysm suggests ischemic
bowel disease
• Rectal:
– Perianal disease (e.g., abscess, fistula Crohn’s disease)
– Rectal tumor
– Fecal impaction

46. Radiological Studies
• Abdominal plain film
– Pancreatic calcifications (chronic pancreatitis)
– Dilated small bowel
– Abnormal bowel contour suggesting lymphoma or inflammatory
bowel disease
• Small bowel series:
– Distinguishes mucosal disease (celiac sprue), inflammatory
conditions (Crohn’s disease) and infiltrative processes (Whipple’s
disease or amyloidosis
– Clarifies anatomy in post-surgical patients
– Detects localized areas of dilation and stasis

47. Radiological Studies
• Barium enema or Colonoscopy:
– Patient >40 years with recurrent/chronic diarrhea
– Not as helpful in the younger patient
– If IBD is suspected, contrast material should be refluxed into
the terminal ileum to rule out Crohn’s disease of the
terminal ileum
– A barium enema will interfere with the collection of stool for
measurement of volume and fat and with the detection of
parasites

48. Evaluation of Malabsorption
When Steatorrhea is Present
• <7% of fat is secreted into the stool per day (4-7g on average diet
containing 60-100g fat)
• Causes of steatorrhea:
– Small intestinal disease
– Pancreatic disease
– Hepatobiliary disease
– Gastric disease

49. Evaluation of Malabsorption
D-Xylose Test
• Measures absorptive capacity of proximal small bowel
• Distinguishes malabsorption from maldigestion
• Does not require pancreatic enzymes to be absorbed by an intact
small bowel mucosa
• Enters the blood and is excreted in urine
• Give 25g D-Xylose; collect urine for 5 hours
• Collect blood one hour after ingestion

50. D-Xylose Test
• If test abnormal – small bowel biopsy
• Celiac or Whipple’s disease – xylose is poorly absorbed with low
levels in blood and urine
• Massive bacterial overgrowth – abnormal xylose test may revert to
normal after antibiotics
• Dehydration, renal insufficiency, third spacing of fluid, vomiting,
hypothyroidism all ↓urine but not serum levels of D-xylose

51. • If xylose test normal, maldigestion likely due to pancreatic
insufficiency
• Pancreatic insufficiency can be confirmed by intubation of the
duodenum and collection of intraluminal contents by
gastroenterology laboratory
• Bentiramide test – utilizes a non-absorbable synthetic
peptide, cleaved by pancreatic enzymes and measured in the
urine

52. Postsurgical Diarrhea
• Short bowel syndrome – diarrhea after extensive small bowel
resections
• Limited ileal resection (<100cm)
– Sufficient bile acid pool - no steatorrhea
– Diarrhea from bile acids delivered to the colon
– Bind bile acids with Cholestyramine 4g QID
• Extensive ileal resection (>100cm)
– Steatorrhea
– Do not use cholestyamine – depletes bile acids
– Treat: medium chain triglycerides (Portagen)

53. • Gastric surgery with vagotomy
– Altered intestinal motility
– Increases concentration of fecal bile acids
– May unmask latent lactase deficiency
– May unmask celiac disease (rare)
– Blind loop syndrome with bacterial overgrowth
– Gastrocolic fistula

54. • Cholecystectomy
– Increased fecal bile acids
– Cholestyramine effective
• Subtotal colectomy with ileal-rectal anastomosis (for multiple
polyposis)
– Diminishes with time
– Treated with antidiarrheal medications

55. Osmotic diarrhea
• For practical purposes osmotic diarrhea is caused by one of
three conditions:
• Ingestion of exogenous magnesium
• Consumption of poorly absorbable carbohydrates
• Carbohydrate malabsorption

56. Chronic Inflammatory Diarrhea

58. Chronic Fatty Diarrhea
• Major causes of maldigestion :
• pancreatic exocrine insufficiency (e.g.,
chronic pancreatitis) lack of bile (e.g.,
advanced PBC)
• Common causes of malabsorption :
• Mucosal diseases (e.g., celiac sprue)

59. • The first step is to look for structural problems involving the small
bowel.
• This evaluation may include small bowel radiography, CT scan of the
abdomen, and small bowel biopsy.
• If no structural problems are discovered pancreatic exocrine function
is evaluated by stool chymotrypsin activity or Secretin test.

60. EMPIRICAL THERAPY OF CHRONIC
DIARRHEA
• Empirical therapy is used in patients with chronic diarrhea in three
situations:
• as temporizing or initial treatment before diagnostic testing
• after diagnostic testing has failed to confirm a specific diagnosis
• when a diagnosis has been made but no specific treatment is
available or specific treatment has failed to produce a cure.

61. • Therapeutic trials of pancreatic enzyme replacement and conjugated
bile acid supplementation in patients with unexplained steatorrhea
may be both diagnostic and therapeutic.
• Symptomatic treatment with opiates often is necessary in patients
with chronic diarrhea because specific treatment may not be
available.

62. Other agents that sometimes are used to treat non-specific
diarrhea :
• Octreotide : (carcinoid syndrome and other endocrinopathies,
dumping syndrome, and AIDS)
• Clonidine (special role in diabetic diarrhea)