DIARRHEA

A pathophysiological Approach to Diagnosis and

Treatment

Prof. J. ZimmermanGastroenterology

Hadassah-Hebrew University Medical Center

Diarrhea = Increased loss of water from the GI tract

• Diarrhea is a common complaint. • In the USA, >3.5 million outpatient

visits for diarrhea occur each year.

About 10 liters of fluid pass daily through the GI Tract

0 500 1000 1500 2000

small intestine

pancreas

bile

gastric

saliva

diet

Volume, ml/day

10 L

6 L absorbed

2.5 L absorbed

JEJUNUM ILEUM COLON

4 L

1.5 L

1.4 L absorbed

0.1 L

Water Absorption in the GI Tract

• Water movement in the GI tract is passive and follows osmotic gradients.

• The efficiency of water absorption is highest in the colon.

• The normal colon can absorb as much as 4-5 L of water daily.

Motility of the Intestine and Colon

• Normal motor functions are essential for absorption.

• Regulated gastric and ileal emptying facilitate reabsorption of electrolytes and fluid.

• Normally, the transit time through the small bowel is about 3 hours.

DEFINITIONS OF DIARRHEA

• As a symptom: Abnormal frequency:

> 3 bowel movements/day;

Abnormal consistency: increased stool fluidity;

• As a sign: Stool weight >200 g/day;

“Diarrhea” must be distinguished from:

• Hyper defecation: Passage of stool of a normal consistency ≥3 times/day; AND FROM

• Incontinence

CLINICAL CLASSIFICATION OF DIARRHEA

• BY TIME COURSE (ACUTE vs. CHRONIC);• BY VOLUME (LARGE vs. SMALL);• BY PATHOPHYSIOLOGY (OSMOTIC vs.

SECRETORY);• BY STOOL CHARACTERISTICS (WATERY,

FATTY or INFLAMMATORY);• BY EPIDEMIOLOGY AND CLINICAL

BACKGROUND (TRAVEL, ANTIBIOTICS, etc.) ;

ACUTE DIARRHEA (< 4 week duration): Most Likely Causes

• Infection;• Food poisoning;• Medications;• Initial presentation of chronic

diarrhea;

INFECTIONS THAT CAUSE DIARRHEA

• Bacteria• Shigella, salmonella, campylobacter

jejuni, C. difficile; E. coli, vibrio, aeromonas, yersinia

• Viruses• Rotavirus, adenovirus, norovirus

• Parasites/protozoa• Giardia, E. histolytica, cryptosporidium,

microsporidia, cyclospora.

MEDICATIONS THAT CAUSE DIARRHEA (1)

• Acid reducing agents (PPI, H2 blockers)

• Antacids• Antiarrhythmic (quinidine)• Antibiotics• Anti-inflammatory (NSAIDs)• Antihypertensives ( -blockers)

MEDICATIONS THAT CAUSE DIARRHEA (2)

• Antineoplastic agents• Antiretroviral agents• Colchicine• Heavy metals• Prostaglanding analogs

(misoprostol)

Workup of Diarrhea:Obey Sutton’s Law

Willie Sutton 1901-1980

Stool Examination in Diarrhea

• Microscopy (WBC, RBC, parasites);• Cultures;• C. difficile toxin (when appropriate);• Giardia antigen (if appropriate);

• IN CHRONIC DIARRHEA:

• Occult blood;• Fecal fat; • Stool [Na+] and [K+];• pH (if < 6 indicates CHO malabsorption) ;• Laxative screen;

Diagnostic Importance of Fecal WBC

Abundant WBC No or few WBC

Infections: dysentery viralC. difficile, ameba food

poisoningIBD medicationsIschemia laxative

abuseIrradiation steatorrhea

CHRONIC DIARRHEA

WATERY FATTY INFLAMMATORY

CHRONIC WATERY DIARRHEA

• Osmotic• Secretory

Water Transport in the GI Tract

• The intestinal epithelium cannot maintain an osmotic gradient.

• The luminal content from the duodenum to the rectum is iso-osmotic (about 290 mOsmol/kg) .

OSMOTIC DIARRHEA

Caused by the presence of unusual amount of poorly

absorbable, osmotically active solute in the lumen

Causes of Osmotic Diarrhea

• Disaccharidase deficiency;• Monosaccharide malabsorption

(fructose-corn syrup in soft drinks);• Ingestion of nonabsorbable

materialsCHO: sorbitol, lactulose, mannitolMinerals: MgSO4, Na2SO4, Na citrate, antacids

• Generalized malabsorption

SECRETORY DIARRHEA

Intestinal ion secretion or inhibition of normal active ion absorption

Causes of Secretory Diarrhea

• Enterotoxins (cholera, E. coli);• Secretagogues elaborated by

tumors(VIP, calcitonin);

• Laxatives (ricinoleic acid, phenol-phthalein, oxyphenisatin, aloe, senna);

• Bile acids/ FFA (in the colon);• Congenital defects;

Differentiation between Osmotic and Secretory Diarrhea

• Effect of fasting;• Volume;• Stool electrolytes and osmotic

gap;

CHARACTERISTICS OF OSMOTIC AND SECRETORY DIARRHEA

OSMOTIC SECRETORY

• Volume, L/day: <1 >1

• Fasting (48 hrs): stopscontinues

Calculation of Stool Osmotic Gap

• The osmolarity of fecal fluid as it exits the rectum is close to that of plasma, i.e. 290 mOsmol/Kg.

• The osmolarity of fecal fluid can be estimated from the ion concentrations:

([Na+] + [K+]) x 2• An osmotic gap is the difference between

this value and 290. A gap of up to 50 is normal.

OSMOTIC AND SECRETORY DIARRHEA:

FECAL FLUID ANALYSIS

OSMOTIC SECRETORY• [Na+], meq/L 30 100• [K+], meq/L 30 40• [Na+]+[K+] 60 140• 2x([Na+]+[K+]) 120 280• Solute gap 170 10

0

50

100

150

200

250

300

OsmoticSecretory

X

Anions

K

Na

OSMOLALITY,

mOsmol/Kg

Osmotic and Secretory Diarrhea

• In secretory diarrhea, calculated stool osmolarity is close to 290. The osmotic gap is <50.

• In osmotic diarrhea, the stool osmolarity, as estimated from the fecal ion concentrations, is lower by more than 50 from a value of 290.

ABNORMAL MOTILITY AND DIARRHEA

• BOTH A RAPID AND A SLOW TRANSIT TIME MAY CAUSE DIARRHEA.

• A RAPID TRANSIT TIME PREVENTS ADEQUATE TIME FOR ABSORPTION (INTESTINAL HURRY).

• THE MECHANISM INVOLVES DYSFUNCTION OF THE ENTERIC NERVOUS SYSTEM.

• EXAMPLES: DIABETES, POST- VAGOTOMY, AMYLOIDOSIS, IBS.

ABNORMAL MOTILITY AND DIARRHEA (2)

• SLOW TRANSIT TIME PROMOTES BACTERIAL OVERGROWTH AND MAY CAUSE MALABSORPTION AND DIARRHEA.

COMPLEX DIARRHEA

• Many of the clinically significant diarrheas are complex and have both osmotic and secretory components.

Chronic Diarrhea ( >4 weeks’ duration): Most Likely Causes

• Lactase deficiency;• IBS;• IBD;• Infections, mainly parasitic;• Medications and food supplements;• Previous surgery;• Endocrine: DM, hyperthyroidism,

Addison’s disease;

Diarrhea Evaluation (1)

• Dietary history: Intake of lactose, sorbitol, fructose, caffeine;

• Medications: antacids, antibiotics, quinidine, colchicine, Fe, etc.

• Abdominal pain;• Tenesmus, rectal bleeding, mucus;• Intermittent diarrhea and constipation;• Nocturnal diarrhea;• Exposure to infectious agents (travel,

sexual preferences);

Diarrhea Evaluation (2)

• Past surgical procedures (vagotomy, gastrectomy, cholecystectomy, others);

• Desire to reduce weight;• Family history (cancer, IBD, celiac);

Clues to diagnosis-Additional Symptoms

Sx Dx

• Fever infection, IBD, TB, Ly• Weight loss malabsorption,

cancer, thyrotoxicosis

• Flushing Carcinoid

Clues to diagnosis-Associated Diseases

DISEASE Dx

• Liver disease IBD, cancer• Chr. Lung disease CF• Peptic ulcer ZE

syndrome• Frequent infections Ig deficiency

Clues to diagnosis-Physical Findings

Finding Suggested Dx• Arthritis IBD, infection,

Whipple’s disease

• Lymphadenopathy Ly, AIDS, Whipple

• Neuropathy DM, amyloid• Postural hypotension DM, Addison

Diarrhea Evaluation Physical Examination

SEVERITY CAUSE

HYPOVOLEMIA?FEVER?ABDOMINAL FINDINGS?

Diarrhea Evaluation Physical Examination

SEVERITY CAUSE

• Clubbing; • Abdominal mass or tenderness;• Perianal disease; • Rectal examination

Chronic Diarrhea

Exclude medications and surgery

Blood Features Pain No blood;p.r. Suggest relieved features of

malabsorption with BM malabsorption

Colonoscopy small bowel Bx ?IBS ?CHO malabsor+ Bx etc. Screen lactose BT

REFERENCE

• Sleisenger and Fordtran’s Gastrointestinal and liver disease. Chapter on diarrhea contains many useful tables of DD’s of diarrhea in different clinical settings.