diarrhea
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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.
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