This document defines and classifies chronic diarrhea and outlines its various causes. It discusses secretory, osmotic, steatorrheal, inflammatory, dysmotile, factitial, and iatrogenic causes. A thorough history and physical exam are important to determine the etiology and guide appropriate testing. Common investigations include complete blood count, electrolytes, thyroid function tests, and serologic markers for celiac disease and inflammatory bowel disease. Chronic diarrhea has many potential organic and functional causes and careful evaluation is needed.

1. DEFINITION
• Abnormally liquid or unformed stools
,>2-3 times/day.
• Stools weighing >200 gm/day

2. CLASSIFICATION
• Acute - <2 wks
• Persistent - 2-4 wks, and
• Chronic - >4 wks

3. Causes of Chronic Diarrhoea
➢ Secretory causes
• Exogenous stimulant laxatives
• Chronic ethanol ingestion
• Drugs and toxins
• Endogenous laxatives (dihydroxy bile
acids)

4. • Idiopathic secretory diarrhea
• Certain bacterial infections
• Bowel resection
• Partial bowel obstruction or fecal
impaction

5. • Hormone-producing tumors
(carcinoid, VIPoma, medullary
cancer of thyroid, mastocytosis,
gastrinoma, colorectal villous
adenoma)
• Addison's disease
• Congenital electrolyte absorption
defects

6. ➢ Osmotic causes
• Osmotic laxatives
(Mg2+ , PO4–3, SO4–2)
• Lactase and di-saccharidase def.
• Non-absorbable carbohydrates
(sorbitol, lactulose, PEG)

7. ➢ Steatorrheal causes
• Intraluminal maldigestion
(pancreatic exocrine insufficiency,
bacterial overgrowth, bariatric surgery,
liver disease)
• Mucosal malabsorption
(celiac sprue, Whipple's disease,
infections, abetalipoproteinemia,
ischemia)

8. • Postmucosal obstruction
(1° or 2° lymphatic obstruction)

9. ➢ Inflammatory causes
• IBD
• Lymphocytic and collagenous colitis
• Immune-related mucosal disease (1°
or 2° immunodeficiencies, food
allergy, eosinophilic gastroenteritis,
graft-vs-host disease)

10. • Infections (invasive bacteria,
viruses, and parasites)
• Radiation injury
• Gastrointestinal malignancies

11. ➢ Dysmotile causes
• Irritable bowel syndrome (including
postinfectious IBS)
• Visceral neuromyopathies
• Hyperthyroidism
• Drugs (prokinetic agents) Postvagotomy
➢ Factitial causes
• Munchausen
• Eating disorders

12. ➢ Iatrogenic causes
• Cholecystectomy
• Ileal resection
• Bariatric surgery
• Vagotomy, fundoplication

14. Secretory diarrhoeas-
• derangements in fluid and
electrolyte transport .
• watery, large-volume, painless and
persist with fasting.

15. • Medications- most common secretory
causes
• stimulant laxatives [e.g., senna,
cascara, bisacodyl, ricinoleic acid
(castor oil)].
• Chronic ethanol consumption

16. Bowel Resection, Mucosal Disease, or
Entero-colic Fistula
• Inadequate surface for reabsorption
of secreted fluids and electrolyte
• Worsen with eating.

17. Idiopathic secretory diarrhea
• With disease (e.g., Crohn's ileitis) or
resection of <100 cm of terminal
ileum, di-hydroxy bile acids may
escape absorption and stimulate
colonic secretion (cholorrheic
diarrhoea).
• Bile acids are functionally
malabsorbed from a
normal-appearing terminal ileum.

18. • Reduced -ve feedback regulation of bile
acid synthesis by FGF-19 produced by
enterocytes- increase bile-acid synthesis
s- bile acid diarrhoea.
• 40% of unexplained chronic diarrhea.

19. Hormones
• Metastatic gastrointestinal carcinoid
tumors or, rarely, primary bronchial
carcinoids
• carcinoid syndrome -episodic flushing,
wheezing, dyspnea, and right-sided
valvular heart disease, Pellagra like skin
lesions.
• serotonin, histamine, prostaglandins, and
various kinins.

20. • Gastrinoma- most typically presents
with refractory peptic ulcers,
diarrhea (1/3rd
) ,only clinical
manifestation in 10%.
• VIPoma- watery diarrhea,
hypokalemia, achlorhydria syndrome
(pancreatic cholera)
• VIP, PP, secretin, gastrin, GIP ,
neurotensin, calcitonin, and PG.

21. • Often massive,volumes >3 L/d; (20
L/d)
• Dehydration; neuromuscular
dysfunction from associated
hypokalemia, hypomagnesemia, or
hypercalcemia; flushing; and
hyperglycemia
• Medullary carcinoma of the
thyroid-calcitonin, other secretory
peptides, or PGs.

22. Congenital Defects in Ion Absorption
• Defective Cl–/HCO3– exchange (congenital
chloridorrhea) with alkalosis (mutated DRA
[down-regulated in adenoma] gene)
• Defective Na+/H+ exchange (congential
sodium diarrhea)with acidosis ( mutation in
the NHE3 [sodium-hydrogen exchanger]
gene)
• Adrenocortical insufficiency-diarrhoea
accompanied by skin hyperpigmentation.

24. Osmotic Causes
• Poorly absorbable, osmotically active
solutes
• draw enough fluid into the lumen to
exceed the reabsorptive capacity of the
colon- increase fecal water output.
• ceases with fasting or with
discontinuation of the causative agent.

25. Osmotic Laxatives
• Mg-containing antacids, health
supplements, or laxatives
• stool osmotic gap (>50 mosmol/L):
serum osmolarity (typically 290
mosmol/kg)-[2 x (fecal sodium +
potassium concentration)].

26. Carbohydrate Malabsorption
• Acquired or congenital defects in
brush-border disaccharidases and
other enzymes
• Osmotic diarrhea with a low pH.
• Lactase deficiency -One of the most
common causes of chronic diarrhea in
adults

28. Steatorrheal Causes
• stool fat - > 7 g/d
• Fat malabsorption -greasy,
foul-smelling, difficult-to-flush, wt
loss and nutritional def.
• rapid-transit diarrhea -up to 14 g/d
• small intestinal ds - 15–25 g/d and
• pancreatic exocrine insufficiency -
>32g/d

29. Intraluminal Maldigestion
• Pancreatic exocrine insufficiency, Chronic
pancreatitis, cystic fibrosis; pancreatic
duct obstruction; and, somatostatinoma.
• Bacterial overgrowth -deconjugate bile
acids and alter micelle formation,
impairing fat digestion.
• Cirrhosis or biliary obstruction - deficient
intraluminal bile acid conc.

30. Mucosal Malabsorption
• Celiac disease(enteropathies)-villous
atrophy and crypt hyperplasia ,prox small
bowel, fatty diarrhea with multiple
nutritional deficiencies .
• Tropical sprue -similar histologic and
clinical syndrome , residents of or
travelers to tropical climates

31. • Whipple's disease-histiocytic infiltration of
the small-bowel mucosa,young or
middle-aged men.
• Abetalipoproteinemia - defect of
chylomicron formation, children,
,acanthocytic erythrocytes, ataxia, and
retinitis pigmentosa.

32. Postmucosal Lymphatic Obstruction
• Congenital intestinal lymphangiectasia
or acquired lymphatic obstruction
secondary to trauma, tumor, cardiac
disease or infection,
• Fat malabsorption with enteric losses of
protein (often causing edema) and
lymphocytopenia. Carbohydrate and
amino acid absorption are preserved.

34. Inflammatory Causes
• Pain, fever, bleeding, or other manifestations of
inflammation.
• Idiopathic Inflammatory Bowel Disease
• CD and UC- among the mc organic causes of
chronic diarrhea in adults, mild to fulminant
and life-threatening.
• Microscopic colitis(lymphocytic and
collagenous colitis), typically responds to
anti-inflammatory drugs (e.g., bismuth), to the
opioid agonist loperamide, or to budesonide.

35. Primary or Secondary Forms of
Immunodeficiency
• Prolonged infectious diarrhea (selective
IgA def. or common variable
hypogammaglobulinemia)
• Giardiasis, bacterial overgrowth, or
sprue.
Eosinophilic Gastroenteritis
• Atopic history, Charcot-Leyden crystals,
and peripheral eosinophilia in 50–75% of
patients.

36. Chronic diarrhoea in HIV
➢ Protozoa-Cryptosporidia, microsporidia, and
Isospora belli -most common .
• Cryptosporidium- self-limited or intermittent
diarrheal,life threatening. CD4+ T cell <300/L -
1% per year.
• crampy abdominal pain(75%), nausea and
vomiting(25%) .
• stool examination or biopsy of the small
intestine.
• noninflammatory, oocysts that stain with
acid-fast dyes.

37. • Microsporidia -small, unicellular,
obligate, intracellular, cytoplasm of
enteric cells(Enterocytozoon
bieneusi).
• Abdominal pain, malabsorption,
diarrhea, and cholangitis.
• Chromotrope-based stains, stool
samples by light microscopy.
• Definitive diagnosis
-electron-microscopic examination of
a stool specimen, intestinal aspirate,
or intestinal biopsy specimen.

38. • I. belli- cysts are large, acid-fast +ve
that can be differentiated from those
of cryptosporidia on the basis of size,
shape, and number of sporocysts.

39. ➢ Bacteria - Salmonella, Shigella, and
Campylobacter
• Homosexual men and are often
more severe.
• Untreated HIV -a 20-fold increased
risk of infection with S.
typhimurium.
➢ Fungal infections- Histoplasmosis,
coccidioidomycosis, and penicilliosis

40. ➢ CMV colitis- 5–10% of patients with
AIDS.
• Diarrhea(nonbloody), abdominal pain,
weight loss, and anorexia.
• Diagnosis -endoscopy and biopsy.
• Endoscopy-Multiple mucosal ulcerations
and biopsies reveal characteristic
intranuclear and cytoplasmic inclusion
bodies.

41. HIV enteropathy
• Pts with HIV infection -chronic diarrheal
syndrome for which no etiologic agent
other than HIV can be identified.
• Direct result of HIV infection in the GI
tract.
• Histologic examination of small bowel-
low-grade mucosal atrophy ,decrease in
mitotic figures, suggesting a
hyporegenerative state.

42. Other Causes
Radiation enterocolitis, chronic
graft-versus-host disease, Behçt's
syndrome, and Cronkhite-Canada
syndrome.

44. Dysmotility Causes
Diabetic diarrhea- peripheral and generalized
autonomic neuropathies.
IBS (10% point prevalence, 1–2% -incidence)
• disturbed intestinal and colonic motor and
sensory responses to various stimuli.
• Stool frequency typically cease at night,
alternate with constipation, accompanied
by abdominal pain relieved with
defecation, and rarely weight loss.

46. Factitial Causes
• Munchausen syndrome (deception or
self-injury for secondary gain) or Eating
disorders
• Covertly self-administer laxatives alone or
in combination with other medications
(e.g., diuretics) or surreptitiously add
water or urine to stool.
• Women, h/o of psychiatric illness.

48. HISTORY

49. AGE
➢ Young patients
• Inflammatory Bowel Disease
• Tuberculosis
• Functional bowel disorder (Irritable bowel)
➢ Older patients
• Colon Cancer
• Diverticulitis

50. DIARRHEA PATTERN
➢ Diarrhea alternates with Constipation
• Colon Cancer
• Laxative abuse
• Diverticulitis
• Functional bowel disorder (Irritable
bowel)

51. ➢ Intermittent Diarrhea
• Diverticulitis
• Functional bowel disorder (Irritable
bowel)
• Malabsorption

52. SMALL BOWEL/LARGE BOWEL
➢ Small intestine or proximal colon involved
• Large stool Diarrhea
• Abdominal cramping persists after
Defecation
➢ Distal colon involved
• Small stool Diarrhea
• Abdominal cramping relieved by
Defecation

53. DIURNAL VARIATION
➢ No relationship to time of day: Infectious
Diarrhea
➢ Morning Diarrhea and after meals
• Gastric cause
• Functional bowel disorder (e.g. irritable
bowel)
• Inflammatory Bowel Disease
➢ Nocturnal Diarrhea (always organic)
• Diabetic Neuropathy
• Inflammatory Bowel Disease

54. WEIGHT LOSS
➢ Despite normal appetite
• Hyperthyroidism
• Malabsorption
• Associated with fever
• Inflammatory Bowel Disease

55. ➢ Weight loss prior to Diarrhea onset
• Pancreatic Cancer
• Tuberculosis
• Diabetes Mellitus
• Hyperthyroidism
• Malabsorption

56. STOOL CHARACTERISTICS
➢ Water: Chronic Watery Diarrhea
➢ Blood, pus or mucus: Chronic
Inflammatory Diarrhea
➢ Foul, bulky, greasy stools: Chronic Fatty
Diarrhea

57. MEDICATION AND DIETARY INTAKE
➢ Drug induced diarrhea
➢ Food borne illness
➢ Waterborne illness
➢ High fructose corn syrup
➢ Excessive sorbitol or mannitol
➢ Excessive coffee or other caffeine

58. TRAVEL
➢Traveler’s diarrhea
➢Infectious diarrhea

59. ASSOCIATED SYMPTOMS
➢ Abdominal pain
➢ Alternating constipation
➢ Tenesmus
➢ Unintentional wt. loss
➢ Fever

60. PAST MEDICAL HISTORY
➢ Childhood
diarrhea-resolves-re-emergence in
adulthood– celiac disease
➢ Uncontrolled diabetes
➢ Pelvic radiotherapy

61. PAST SURGICAL HISTORY
➢ Jejunoileal bypass
➢ Gastrectomy with vagotomy
➢ Bowel resection
➢ Cholecystectomy

62. RED FLAGS-suggestive of organic
causes
Painless diarrhea
Recent onset in an older patient
Nocturnal diarrhea (especially if wakes
patient)
Weight loss
Blood in stool
Large stool volumes: >400 grams stool per day
Anemia
Hypoalbuminemia
Increased ESR

63. PHYSICAL EXAMINATION

64. GPE
➢ General appearance and mental status
➢ Vital signs
➢ Body weight
➢ Orthostasis- volume depletion,autonomic
dysfunction

65. ➢ Exophthalmos (hyperthyroidism)
➢ Aphthous ulcers (IBD and celiac disease)
➢ Lymphadenopathy (malignancy,
infection or Whipple's disease)
➢ Enlarged or tender thyroid (thyroiditis,
medullary carcinoma of the thyroid)
➢ Clubbing (liver disease, IBD, laxative
abuse, malignancy)

66. SKIN LESIONS
➢ dermatitis herpetiformis (celiac disease)
➢ erythema nodosum and pyoderma
gangrenosum (IBD)
➢ hyperpigmentation (Addison's disease)
➢ flushing (carcinoid syndrome)
➢ migratory necrotizing erythema
(glucagonoma)

67. SYSTEMIC EXAMINATION
➢ Wheezing and right-sided heart
murmurs (carcinoid syndrome)
➢ Arthritis
• IBD,
• Whipple's disease

68. ABDOMINAL EXAMINATION
➢ Surgical scars
➢ Abdominal tenderness
➢ Masses
➢ Hepatosplenomegaly
➢ Borborgymus on auscultation
• Malabsorption
• Bacterial overgrowth,
• Obstruction, or rapid intestinal transit.

69. PERINEAL AND RECTAL
EXAMINATION
➢ Signs of incontinence –
• skin changes from chronic irritation,
• gaping anus,
• weak sphincter tone.

70. ➢ Crohn's disease
• perianal skin tags
• Ulcers
• Fissures
• Abscesses
• Fistulas
• Stenoses.
➢ Fecal impaction or masses might be
noted.

71. INVESTIGATIONS

72. BLOOD TESTS
• CBC
• TSH ,T3,T4
• Serum electrolytes
• Serum albumin
• ELISA for HIV
• Antiendomysial antibodies,
Anti-tTG-Celiac ds
• pANCA, ASCA - IBD

73. STOOL EVALUATION
• Stool pH (<6 in carbohydrate
malabsorption )
• Fecal electrolytes (Fecal sodium and
osmolar gap)
• Differentiates chronic watery diarrhea
category
• Fecal occult blood test
• Fecal leukocytes

74. •Fecal fat (abnormal if >7 grams/24 hours)
•Stool ova and parasites (2-3 samples)
•Giardia lamblia antigen
• Indicated for diarrhea >7 days and >10
stools/day
•Clostridium difficle toxin
• Indicated if recent antibiotics or
hospitalization
•Consider testing stools for laxative abuse

75. ENDOSCOPY
•PROCTOSIGMOIDOSCOPY

78. TREATMENT

79. NON-SPECIFIC THERAPIES
➢Dietary modifications
• Smaller, more frequent meals
• Dec. carbohydrates
• Dec. fat intake
• Avoidance of milk
• Avoid sorbitol and mannitol

80. ➢No good evidence to support use of bulking
agents
➢Bismuth subsalicylate (i.e., Pepto-Bismol )
➢opioids and opioid agonists
• Loperamide- first line therapy
• diphenoxylate-atropine (Lomotil )
• Codeine and other narcotics – for
refractory cases

81. SPECIFIC THERAPIES
➢Clonidine-
• Diabetic diarrhea
• moderate and severe diarrhea-
predominant IBS

82. ➢Somatostatin
• Refractory diarrhea
• AIDS,
• post chemotherapy,
• GVHD,
• and hormone secreting tumors

83. ➢Bile acid binders (ie, cholestyramine)
➢Pancreatic enzyme supplementation
➢Antimicrobials –empiric fluoroquinolones
therapy