Basic Science applied to medicine

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