Diarrhea Pathophysiology: Causes, Mechanisms, and Treatment PDF

Section 12: Pathophysiology of Diarrhea I. Causes and consequences of hypovolemia (low ECFV) low ECF volume Causes: Consequences: less blood perfussion Diarrhea and luminal fluid sequestration in bowel Tissue ischemia → producin...

Section 12: Pathophysiology of Diarrhea I. Causes and consequences of hypovolemia (low ECFV) low ECF volume Causes: Consequences: less blood perfussion Diarrhea and luminal fluid sequestration in bowel Tissue ischemia → producing lactaid Hemorrhage lots of anarobic glycolysis Metabolic acidosis → acid Vomiting Circulatory collapse Salt and water deprivation hypotension, peripheral vasoconstriction, Excessive sweating and loss of consciousness Renal disease II. Mechanisms of Diarrhea 5 mechanisms! A. Filtration Secretion #1 1. Pathophysiology: Abnormal Starling forces at submucosal capillaries a) Normal Starling forces near equilibrium in submucosa Hydrostatic pressure (HP) > colloid osmotic pressure (COP) = net fluid out of capillary -Arterial end of capillary: -Venous end of capillary: COP > HP = net fluid into capillary Fig. 50 govern the passive exchange of H2O between capillary microciculation and ine interstitial fluid "+" pushing force "-" pullng force Colloid Osmotic Pressure (COP): pressure exerted by large molecules that holds H2O within the vascular space; created by plamsa proteins (e.g., albumin( that dont reasily cross the capillary membrane Hydrostatic pressure (HP): pushing force of fluid on a surface (i.e.m vascular wall) 80a  b) Pathology: Net interstitial Starling forces at submucosa exceed +15 mm Hg - Disrupts epithelial tight jcts (particularly at villus tips) due to increased submucosal fluid pressure dissects between epithelial cells. c) Filtration secretion of fluid and interstitial fluid protein Fig. 50a PLE = protein losing entropathy low level fluid loss from intersitial fluid > PLE high level fluid loss > diarrhea, fluid sequestration, sepsis 2. Conditions resulting in filtration secretion a) Occulsion of venous return from intestine ↑ HP with venous occlusion e.g., volvulus/torsion - thin walled veins collapse, thick-walled arteries stay open b) Portal hypertension Heart failure - ↓ venous flow from liver > back pressure on portal vein c) Excessive volume expansion with IV fluids ↑ Blood volume > ↑ capillary HP d) Lymphatic obstruction -lymphatic disease, inflammation, cancer Increase HP due to blocked lymphatic drainage from lacteal > physically occldes villus venules E.g., lymphangectasia: congestially malformed lymph vessels 80a Causes of Filtration Secretion – Upper, volvulus; Lower, lymphangectasia 80a  Osmotically active molecules: sugars, VFAs, ions (Ca2, Mg2, SO4), B. Osmotic diarrhea #2 polyethylene gylcol (PEG) [lacative] Pathophysiology: Extracellular fluid moves passively (not active transport) into the intestine in response to an intraluminal load of osmotically active molecules (like sugars, amino acids, etc.) paracelular movement of ECF Fig. 51. Osmotic diarrhea Common causes: Increase CHO to large intestine 1. Carbohydrate overload > increase VFA production > osmotic diarrhea -Grain overload -Lactose intolerance Fig. 51a Lactase breaks down lactose into glucose and galactose lactose intolerance = too little / no lactase no lactase = lactose reaches LI > increase VFAs > osmotic diarrhea 2. Villous atrophy - Many infectious agents (particularly viral) cause osmotic diarrhea by destruction of the villous epithelium resulting in: - maldigestion decrease BB enzymes - malabsorption decrease surface area Diarrhea results from nutrients + water bypassing the small intestine and exceeding the absorptive capacity of the large intestine (osmotic diarrhea) and often accompanied by excessive fermentation product formation. VFAs Fig. 51b. Consequences of villous atrophy 80a  no villi - no digestion and fluid absorption elongated crypts - increased fluid secretion no villi - no digestion and fluid absorption elongated cryptes - increased fluid secretion 80a C. Secretory diarrhea #3 Pathophysiology: Bacterial enterotoxins activate intracellular cyclic nucleotides (cAMP, cGMP) in the epithelium resulting in: 1. Inhibition of electroneutral NaCl absorption at the villi add glucose to oral rehydration solutions > NaCl + H2O absorption Note: Na+-coupled substrate absorption is unimpaired. Brush border enzyme intact. 2. Stimulation of electrogenic Cl- and HCO3- secretion at the crypts Fig. 52 a,b Small intestine Colon mucosa undamaged if not an invasive bacteria (enterotoxigenic E.coli, Bibrio cholerae) Mucosa may be reddish inhibit fluid absorption due to increased blood flow stimulate fuid secretion D. Inflammatory Diarrhea #4 - Most Common! typically, a mix of 3 mechanisms Pathophysiology: Inflammation due to the immune response to attaching/invasive infectious agents or allergenic/autoimmune diseases produce diarrhea by: Fig. 53 T cells, B cells, neutrophils, macrophages, mast cells (allergenic) Increased inflammatory mediators, prostagladins (PG), serotonin (ST), bradykinin (BK) 80a 1. Osmotic diarrhea due to villous damage maldigestion and malabsorption > osmotic diarrhea 2. Filtration secretion due to obstructed flow (vasoactive cytokines, edema, inflammatory infiltrate and antibody production) alter Starling forces increase WBCs and antibodies in submucosa > altered starling forces > filtration secretion diarrhea 3. Secretory diarrhea due to enterotoxins and inflammatory mediators stimulating intracellular second messengers E. Abnormal motility: Mechanisms of Diarrhea #5 Pathophysiology: Hypermotility increases digesta transit. I However, a flaccid, hypomotile intestine is typical of most common diarrheas. i.e., muscarinic agonist Causes: Drugs – Laxatives, Parasympathomimetics Irritable Bowel Syndrome (Humans) infection and/or inflammation in the gut > muscle spasms, cramping > pain and increase borborygmi (gut sounds) III. Diarrhea Caused by Enteric Pathogens Fig. 54 A. Certain pathogens have well-defined diarrheogenic mechanisms. Examples: - Enterotoxigenic E. coli (ETEC) secretory diarrhea - Rotavirus, coronavirus osmotic diarrhea B. Agents that produce significant inflammation cause diarrhea several ways. Examples: -Salmonella enterotoxigenic, inflammatory (invasive infection) - Cryptosporidia (protozoan) villous atrophy, inflammatory 80a Celiac disease: illness caused by an immune reaction to gluten, a protein found in wheat, barley or rye Colonoscopy of inflammed colon 80a IV. Retrieval of fluid from the gastrointestinal tract during hypovolemia 1. Sympathetic nervous system a. Inhibits enteric effector neurons and preganglionic PS neurons. Increase NaCl absorption, Decrease Cl and H2O secretion 2. Enkephalinergic interneurons 3. Renin-angiotensin-aldosterone system a. Angiotensin II promotes sympathetic transmission to the intestine b. Aldosterone increases electrogenic Na+ absorption at large intestine Fig. 55 V. Colonic Salvage reserve capacity of large intestine for fluid absorption Colonic disease typically results in diarrhea, but small intestinal disease may not necessarily produce diarrhea because of colonic salvage: 1. Colon has large reserve capacity for electrolyte and fluid absorption 3x normal volume One component of reserve capacity is microbial digestion of nutrients that bypass the small intestine and increase NaVFA + water absorption (must have colonic flora to generate VFA). VFA and Na/H exchanger > Na* VFA + H2O absorption not available to neonates - no gut microbes lacking robust gut flora sustable to diarrhea 80a Objectives: 1. Describe the physiological systems that act at the intestine to recover fluid during hypovolemic states. 2. How does aldosterone recover fluid from the colon? 3. Describe the pathophysiology of filtration secretion. 4. Know the five main mechanisms of diarrhea. 5. Describe how villous atrophy leads to osmotic diarrhea. 6. Why is diarrhea not always present in an animal with villous atrophy? 7. Know how enterotoxic bacteria cause secretory diarrhea. 8. Know the different ways that inflammatory bowel disease causes diarrhea. 9. Know how colonic salvage occurs. Related Questions: 1. Explain why villous atrophy causes more severe diarrhea in a 3 day old pig as compared to a 3 week old pig. 2. What is colibacillosis? 80a