PATHOPHYSIOLOGY OF DIARRHEA Diarrhea info: Normal stool volume = 100 g (people with high fiber intake 500 g) Clinical

cal definition of diarrhea = Daily stool volume of >250 g Does NOT depend on stool consistency or # bowel movements/day. Multiple loose stools a day with volume <250 g Hyperdefecation or pseudodiarrhea. Hyperdefecation often seen in pts with irritable bowel syndrome or proctitis. Water usually = 60-85% stool weight This is higher in diarrhea. About 7-15% of dry weight is bacteria. Two types (but most diarrhea is a combo of these): Secretory diarrhea = Excess water & electrolytes actively transported into the lumen. Most often due to stimulation of salt secretion. Example: Cholera Osmotic diarrhea = Water retained in the lumen by osmotically active agents. Due to ingestion of nonabsorbable substances or by malabsorption/maldigestion of nutrients that are normally absorbed. Example: Milk of magnesia GI motility also contributes to diarrhea influences # water getting to rectum. Rate of transit thru gut determines time available for intestinal absorption of H2O. Most anti-diarrheals slow gut transit water absorption stool volume. Pathophysiology: Fluid & Electrolyte Transport Fluid volumes: Average oral water intake = 2 L/day Fluid passing thru duodenum/day = 8-10 L/day Small intestine: Majority of water absorbed by gut = recycling of salivary, gastric, pancreatic, biliary, & intestinal secretions for digestion. Most fluid absorbed by SI ~ 1 L reaches colon. Large surface area (folds, villi, microvilli) help SI absorb WAY more water than colon. Colon: Stool is formed & retained in colon. It continues to absorb water fecal water volume. Max absorptive capacity of colon = 4 L/day. If more than this enters the small intestine, diarrhea results (even with normal colonic fxn). Water movement: Passive H2O follows osmotic gradients created by electrolyte movement. Electrolytes move via active processes. Meal enters duodenum fluids shift from plasma across mucosa make luminal contents isotonic
ELECTROLYTE Na SMALL BOWEL: DUODENUM SMALL BOWEL: ILEUM 130 COLON 30 Due to active Na uptake & mucosal permeability, preventing diffusion of Na & H2O back into colon. 80 Rises b/c active secretion of K & negative electric potential in colonic lumen favors passive K secretion. K loss & arrhythmias can be BIG problem if secretory diarrhea. 20 Active chloride absorption 25 Exchanged for Cl- in the lumen, but molecules from bacterial metabolism become main anions. Breakdown of fiber to FAs concentrations of organic anions as high as 180 mmol/L

Same as amounts in serum Cl HCO3 70 Principal anion in the small intestine 80

Cellular Basis for Intestinal Fluid & Solute Transport Cells in villus tip promote fluid & solute absorption; cells in crypt promote fluid & solute secretion Water Transport is Passive Water follows solute Overall osmotic effect of solute is greater if solute is restricted to compartment of interest. In lactose intolerance, unabsorbed glucose cannot leave the luminal compartment & exerts osmotic effect water into lumen osmotic diarrhea. Intestine is Highly Permeable to Water Water moves across cell plasma membranes or in-between cells via paracellular pathway (tight jxns & lateral intercellular spaces btw adjoining epithelial cells).

Isotonic Water Transport Driven by Salt Transport Normal absorption of water and salt occurs in a way that makes intestinal contents isotonic with plasma (even though electrolytes and water move from lumen to blood). Water absorption driven by osmotic forces generated by salt absorption. There are probably intraepithelial compartments (i.e. lateral intercellular space) in which salt accumulation can produce local gradients ( flow). Fluid secretion driven by salt secretion by cells at crypts of Lieberkuhn. Surface Cells & Crypt Cells are Specialized for Absorption & Secretion Absorption @ villus driven by active Na transport. Secretion @ crypt driven by active Cl transport. Na-driven absorption requires Cl-absorptive path, and vice versa. Essential element in absorptive & secretory cells = Na/K ATPase Exclusively in basolateral membranes Maintains low intracellular Na & high intracellular K energy from ATP hydrolysis Oral Rehydration Therapy Oral rehydration solutions made of mixture of salt & glucose designed to maximally stimulate salt & water absorption in villus cells. Based on idea that secretory diarrhea (i.e. induced by cholera toxin) reflects net in salt & water secretion (probably based on inhibition of coupled entry of Na and Cl in apical membrane). Na-glucose transporter is NOT affected. So, if person infected with cholera is exposed to glucose, salt absorption is stimulated by apical Na entry. Glucose in lumen will induce compensatory absorption of Na & reduce/reverse fluid loss. CLASSIFICATION OF DIARRHEA Acute vs. chronic Osmotic vs. secretory Infectious vs. noninfectious Inflammatory vs. noninflammatory
Acute Less than 2-3 weeks in duration Majority due to infx Not usually investigated unless pt is toxic or immunosuppressed, AIDS Often self-limited Ex: E. coli, Salmonella, Shigella, Vibrio, Clostridium, Giardia, Cryptosporidium, Entamoeba histolytica, Campylobacter, Gonococcus, Syphilis Chronic At least 4-6 weeks Blood in stool = marker of ischemia or inflamm; suggests colonic dz (b/c blood from SI not passed as RED) Tenesmus suggests rectosigmoidal dz Frequent small bowel movments suggests colonic dz Less frequent large volume bowel movements SI dz If subsides w/fasting think osmotic diarrhea Consider family hx: 10% of 1st degree relatives with IBD Ex: Giardia, Entamoeba histolytica, Strongyloides, Yersinia, Aeromonas hydrophila, Small bowel bacterial overgrowth, Tropical sprue

IRRITABLE BOWEL SYNDROME Emotional factors strongly influence large intestinal motility via the extrinsic ANS. IBS may occur during periods of stress and may result in constipation or diarrhea. Characterized by gastrointestinal signs and symptoms including constipation, diarrhea, gas and bloating, all in the absence of organic pathology. Associated with uncoordinated and inefficient contractions of the large intestine. MEDICATION Loperamide: Loperamide HCl is indicated for the control and symptomatic relief of acute nonspecific diarrhea and of chronic diarrhea associated with inflammatory bowel disease. Loperamide HCl is also indicated for reducing the volume of discharge from ileostomies In vitro and animal studies show that loperamide HCl acts by slowing intestinal motility and by affecting water and electrolyte movement through the bowel. Loperamide HCl inhibits peristaltic activity by a direct effect on the circular and longitudinal muscles of the intestinal wall.

In man, loperamide HCl prolongs the transit time of the intestinal contents. It reduces the daily fecal volume, increases the viscosity and bulk density, and diminishes the loss of fluid and electrolytes. Tolerance to the antidiarrheal effect has not been observed.