Diarrhea

DIARRHEA - Dr Go Major cause of worldwide morbidity & mortality  3-5 Billion Episodes per Year  5 million Deaths per year, 80% under 1 yr of age  A major cause of work absenteeism  A major economic burden, particularly in developing nations As a symptom

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↑ Frequency ↑ Volume

↓ Consistency As a sign  Stool Weight >150 to 200 g per 24 hr  Stool water > 150 to 200 mL per 24 hr Daily intake & endogenous secretions are efficiently absorbed by the gastrointestinal tract  Oral intake = 2000  Endogenous secretions: 7000  Salivary glands = 1500  Stomach = 2500  Bile = 500  Pancreas = 1500  Intestine = 1000  Total presented to intestines = 9000  Absorbed = 8800 (%absorbed = 98%)  Net Balance (2000 - 200 = 1800)  Stool 200 Intestinal Epithelial layer has many functions:  Barrier and Immune defense  Fluid & electrolyte absorption  Protein synthesis & secretion  Nutrient digestion & absorption  Fluid & electrolyte secretion & IgA secretion  Mediator production The intestine has a very large absorption Type of surface Amplification Factor Mucosal cylinder 1 Fold of Kerkring 3 Villi 10 Microvilli 20

surface area for Surface (cm2) 3,300 10,000 100,000 2,000,00

Area

Total surface area = 200 m2 Double Tennis Court = 175 m2 Intestinal epithelial cells are continually renewed:  Turnover time ~ 48 – 72 hrs  Normally: # Cells entering villus = # of Cells dying  Villus Region = Cell death & sloughing  Crypt Region = Dividing cells & Paneth Cells Digestive & Transport properties of villus & crypt regions differ Brush Nutrient Net Permeability border transport water/ ion hydrolases transport Villus ↑ Absorption ↓ ↑ Crypt ↓ Secretion ↓ ↑ Many factors regulate or modulate intestinal water & electrolyte transport  Luminal stimuli  Mucosal endocrine cells

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 Enterocytes Myofibroblasts Blood hormones Capillary blood flow Lymphatics Immune cells Enteric neurons Smooth muscle

Mucosal endocrine cells regulate intestinal ion transport by paracrine action Prosecretory Proabsorptive Neurotensin Somatostatin Serotonin (5HT) Substance P Secretin

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Luminal stimuli   5 HT   Net secretion

The intestinal mucosa changes with nutrient availability & disease Normal mucosa Villus atrophy Villus Hypertrophy Starvation Diabetes, short bowel syndrome Nutrient & ↓ ↑ electrolyte absroptive capacity per unit area There are two major pathophysiological mechanisms for diarrhea  Decreased absorption of fluid & electrolytes  Inhibited or defective absorption of fluid & electrolytes  Luminal presence of osmotically active agents  Increased propulsive activity causing decreased contact time  Increased secretion of fluid & electrolytes  Stimulated anion secretion  Secretion from crypts Some diarrheal pathogens are not invasive, but may cause alterations in microvillus function & structure  Examples:  Enteroadherent E Coli  Giardia lamblia  Cryptosporidia  Possible actions  Increased mucosal permeability  Inhibition of nutrient & electrolyte absorption  Stimulation of anion secretion Some secretory diarrheas are caused by hormone producing tumors Hormone producing tumor Putative secretagogue Carcinoid Serotonin, PG, bradykinin, tachykinin VIPoma VIP & others Gastrinoma Gastrin Medullary Carcinoma of the Calcitonin, PG thyroid Ganglioneuroma Probably VIP Inflammation-induced diarrhea results from several mechanisms

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⊕ secretion &  absorption

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⊕ of enteric nerves causing contractions & ⊕ secretions

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mucosal destruction & ↑ permeability nutrient maldigestion & malabsorption

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propulsive

Bile induced diarrhea results from ileal dysfunction  The ileum is the only site of active bile absorption Diarrhea is a common manifestation of celiac sprue & is caused by several different mechanisms (GLUTEN causing…)

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↓ brush border hydrolases  unabsorbed osmols Villus atrophy (Fluid, nutrient & electrolyte malabsorption) Crypt hyperplasia (↑ endogenous secretion) Inflammatory-induced secretion

Duration of diarrhea helps guide evaluation Acute Chronic Duration <2-3 weeks >3 weeks Etiology Usually Multiple infections Course Usually self Variable limited The management & treatment of acute diarrhea depends on the patient’s hx & condition Course Benign Dehydration & prior episode Aproach Observe Evaluate Recovery Spontaneous After appropriate treatment History is helpful in evaluating px w/ diarrhea  Hx: duration, travel, Rx, age, diet  Character: freq, vol, blood, consistency  Other: fever, wt loss, anorexia, n/v, dehydration Site of involvement: Small bowel & colonic Rectosigmoid Large volume, Small amount of stool Frequency Moderate ↑ in # Urgency Minimal urgency Tenesmus No tenesmus Mucus Little mucus blood Chronic & recurrent diarrhea should always be investigated.  Hx PE  Stool Exam  Cultures, ova & parasites  Blood, leukocytes, microscopic fat  Quantitative volumes & fat studies as indicated  Other studies:  Endoscopic examinations with biopsy  Absorption studies  Special studies: imagins (CAT scan, ultrasound, etc.) Barium studies Stool & urine analyses for laxative & diuretics. Fecal leukocytes from patients with bacterial colitis

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Salmonella colitis --> ??? Ulcerative colitis --> ???

Sudan Fat stain

Stool analyses may be helpful osmotic & secretory diarrhea Stool Osmotic Diarrhea measurement Volume <200 mL/day Osmolality > [Na + K] x 2 Sodium < 70 mEq/liter pH * <5 Reducing (+) substances * * applies to children under the age of 5

in distinguishing Secretory Diarrhea > 200 mL/day 70 mEq/liter >6 (-)

Several approaches can be taken in the treatment of diarrhea  Specific (e.g. lactase deficiency)  Cure underlying disease  Correct Pathophysiology  Non-specific (e.g. chronic idiopathic)

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↓ net fluid secretion

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↓ secretion, ↑ absorption modify motility ↓ propulsive contractions, ↑ mixing contractions

Guideline for treatment of chronic diarrhea

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Specific diagnosis established--> eliminate cause --> if cause cannot be eliminated, treat specfic pathophysiological mechanism --> if specific treatment no available or successful -->institute therapies to ↓ net secretion & propulsive contractions

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Specific diagnosis NOT established --> institute therapies to ↓ net secretion & propulsive contractions

Disorder (examples) Antibiotic associated diarrhea (C. difficile) Giardiasis VIP-secreting tumor

Treatment Stop antibiotic or Vancomycin Metronidazole Resection of Islet adenoma

use Cell

Disorder Lactase deficiency Ileal dysfunction Pancreatic insufficience

Causative factor Lactose

Treatment Lactose-free diet

Bile Acids Fatty acids

Watery Diarrhea syndrome Ulcerative colitis

VIP

Cholestyramine Low Fat Diet and/or Pancreatic Enzymes Somatostatin analog Steroids, aminosalicylates

Inflammation

Nani? Oral rehydration solutions can correct metabolic abnormalities: Plasma Values Untreated Treated Na (mEq/L) 141 142 Cl 107 106 K 4.5 3.6 HCO3 9 21 Arterial pH 7.21 7.43 Plasma specific 1.05 1.026 gravity Stool output 7.5 8.0 (liters/day

Somatostatin has several sites of antidiarrheal action

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 of endocrine cell secretion (by hormone producing tumor cells)

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↓ propulsive & ↑ segmental contractions ↑ mucosal absorpton & ↓ secretion of water & electrolytes

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 of secreto-motor neurons  modulation of immune cells  modulation of blood flow Diarrhea caused by arachidonic acid metabolites can be treated with antinflammatory agents

Opiates prolong transit time & ↑ efficiency of absorption

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