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18 Cards in this Set
- Front
- Back
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Absorption Definition
Osmolality Definition |
The transfer of substances from the lumen of the gastrointestinal tract into the circulation (net absorption)
Osmoles of solute per kg of solvent (depends on the number of particles in solution) -Luminal contents of the intestine are isosmotic with plasma (~290 mOsmols/kg) |
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Efficient Absorption of any Substance Depends on:
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Adequate form (digestion products)
Adequate surface area for absorption Adequate rate of transit through the intestine Specific cofactors and/or carriers |
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Structural Configuration of the Small Intestine
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1) Small intestinal surface area
is amplified by the circular folds (3 fold), villi (10 fold), & microvilli (20 fold). 2) Absorption is also facilitated by movement of the villi. This stirs the chyme immediately adjacent to the mucosa and presents new surfaces for absorption. Movement of the villi is regulated by local nervous reflexes and hormonal mechanisms. 3) Extension of the microvilli is regulated to facilitate absorption by increasing surface area. |
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Functional organization of the villus
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Crypt
-Proliferative stem cells -Paneth cells at base of crypts -Mucous secreting goblet cells -Enteroendocrine -Enterocytes --Don't secrete brush border hydrolases --Low nutrient transport --Secretion --High permeability Villi -Mucous cells -Enteroendocrine -Enterocytes (3-5 day life cycle) --Abundant brush border hydrolases --High nutrient transport --Absorptive --Low permeability |
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Water absorption volumes throughout GI tract
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GI tract reclaims 98% of fluid presented to it
Only about 200mL ends up in stool Jejunum abosorbs most water -5.5L of 9L (~60% of water present, 60% of total) Ileum -2L of 3.5L (~57% of water present, 22% of total) Colon -1.3L of 1.5L (86% of water present, 14% of total) |
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Cellular mechanisms of water absorption
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Water absorption is passive and dependent on absorption of ions (principally Na+ & Cl-) and solutes (sugars, amino acids)
Water movement may be transcellular (through the cell) or paracellular (through the tight junctions between cells) Water moves bidirectionally to keep the luminal contents isosmotic with plasma Ions (& solutes) are transported via transcellular and paracellular pathways into the lateral spaces, where a “standing osmotic gradient” is established for the passive movement of water. |
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Solute permeability and water absorption
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Passive solute permeability and water absorption decreases caudally.
(Highest permeability in duodenum/jejunum) Leaky tight junction in small intestine Very tight junctions in colon |
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Ion transport in small and large intestines
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Sodium
-Absorbed in duodenum/jejunum through Na/H transporters and Na/solute coupling -Absorbed in ileum and colon through coupled Na/Cl transporters -Absorbed in rectum through Na channels Chloride -Absorbed in duodenum/jejunum, ileum, colon and rectum through PD-dependent Cl absorption -Absorbed in ileum, colon, and rectum through coupled Na/Cl absorption and HCO3 dependent absorption K+ -Absorbed in duodenum/jejunum and ileum through passive K absorption -Absorbed in rectum through active K absorption -Secreted in colon through passive and active secretion -Most K+ absorption in the small intestine is driven by water absorption (passive), that increases the lumenal K+ concentration. Hence, significant K+ loss may occur in diarrhea, leading to decreased extracellular levels and life-threatening consequences such as cardiac arrhythmias. Infants with prolonged diarrhea are particularly susceptible to hypokalemia. HCO3 -Absorbed in duodenum/jejunum -Secreted in ileum, colon, and rectum |
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Osmotic gradient and water absorption
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Transport of Na+ (and other solutes) across the cell into the lateral space establishes
a hyperosmotic gradient between the lateral space and the lumen, encouraging passive movement of water into the lateral space. This increases the hydrostatic pressure in the lateral space so that fluid moves in the direction of least resistance, into the capillary. |
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Endogenous Regulators of Intestinal Absorption of Electrolytes and Water
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Released by enteric neurons:
Stimulate secretion -Acetylcholine -Nitric oxide -Serotonin -VIP -Substance P Stimulate absorption -Norepinephrine -Neuropeptide Y -Opioids Released by enteroendocrine cells or other cells in mucosa or submucosa: Stimulate secretion -Histamine -Calcitonin -Guanylin -Bradykinin -Platelet-activating factor -Prostaglandins -Leukotrienes -Arachidonic acid -Adenosine -Inflammatory cytokines Stimulate absorption -Somatostatin Hormones: Stimulate secretion -Prostaglandins -Atrial natriuretic peptide -Gastrin -Motilin -Bombesin -GIP Stimulate absorption -Epinephrine -Enkephalins -Aldosterone -Glucocorticoids -Angiotensin II -Peptide YY -Prolactin -Growth hormone Lumenal factors: Stimulate secretion -Bile salts -Long-chain fatty acids Stimulate absorption -Short chain fatty acids |
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Diarrhea: secretory, osmotic, exudative, motility definitions
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Secretory Diarrhea: Excess water secretion into the intestine (e.g., infection, cholera,
bacterial enterotoxins, endocrine tumors, drugs) Osmotic Diarrhea: Presence of osmotically active nonabsorbable luminal contents (e.g., magnesium salts, lactose, lactulose, sorbitol, etc.) Exudative Diarrhea: Loss of epithelial cells or disruption of tight junctions allows water and electrolytes to accumulate in the lumen (e.g. ulcerative colitis, shigellosis, drugs, radiation, immune destruction – e.g. celiac disease) Diarrhea associated with Motility Disturbances: Both increases and decreases in gut motility can lead to diarrhea. (Intestinal “hurry”) - Increased motility: e.g. thyrotoxicosis, opiate withdrawal, diabetes. - Decreased motility: e.g. large diverticula, smooth muscle damage associated with scleroderma, dematomyositis, amyloidosis, & muscular dystrophy; autonomic neuropathy associated with diabetes. This diarrhea is secondary to bacterial overgrowth (bacteria disrupt electrolyte absorption and secrete osmotically active substances). |
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Mechanism of secretory and osmotic diarrhea
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Secretory Diarrhea
- Caused by overstimulation of the intestinal tract’s secretory capacity. - Driving force is always either net secretion of Cl- or HCO3-, or inhibition of net Na+ absorption. - Shows a normal Osmotic Gap. -Examples: Enterotoxins (cholera), neuroendocrine tumors (carcinoid), absence of ion transporter, loss of surface area Osmotic Diarrhea - Poorly absorbed, low molecular weight aqueous solutes create an osmotic force that quickly pulls water (and ions) into the intestinal lumen (in order to maintain an intra-luminal osmolality equal to that of body fluids). - Shows an abnormal Osmotic Gap (disappears with fasting) -Examples: magnesium ingestion, lactase deficiency |
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Stool electrolytes: secretory vs osmotic
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Osmotic Gap (mOsm) is defined as: 290 mOsm - 2{[Na+] + [K+]}
(where 290 is the assumed osmolarity of blood plasma) An Osmotic Gap < 50 mOsm is considered normal. The “Gap” is normally made up of Mg2+, Ca2+, NH4+, and organic ions Secretory Diarrhea: no excess osmotic gap in stool electrolytes, but the pattern of stool electrolytes may be altered (more common). -Osmotic Gap < 50 mOsm Osmotic diarrhea: non-absorbable organic solutes or ions constitute a greater proportion of ions & solutes. -Osmotic Gap > 50 mOsm - ~ 3.5 ml of water is retained for every - 1 mOsm of retained ion or solute |
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Principle driving forces for intestinal water absorption and secretion
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Na+ flux is the principle driving force for intestinal water absorption
Cl- flux is the principle driving force for intestinal water secretion Epithelial cells near the villus tip are active in net absorption Crypt epithelium usually functions as net secretors of ions and water |
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Example of secretory diarrhea: cholera
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Cholera toxin A chain
- irreversibly activates adenylate cyclase, increases cAMP, and activates Cl- secretion via CFTR Na+ passively follows Cl- Water passively follows the Cl- and Na+ flux Cholera toxin also inhibits non-nutrient Na+ and Cl- absorption by villus tip cells Cholera patients may produce up to 20 L/day of watery stool |
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Cholera treatment
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Treated with oral rehydration therapy: Administration of a solution of glucose & salt increases driving force for water absorption by increasing Na/glucose uptake.
Newer formulas are hypo-osmolar and include amylase-resistant starch (rice starch) to enhance colonic short chain fatty acid and water absorption. |
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Treatment of diarrhea
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Opioids
-Bind mu receptor -Decrease peristalsis -Increase contact time Bile salt sequestrants Antibiotics -Travelers diarrhea -Use with caution Probiotics -? efficacy Bismuth salts -Antimicrobial, antitoxin, anti-inflammatory |
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Treatment of constipation
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Bulk laxatives
-Pysllium, insoluble fiber Oxmotic laxative -Polyethylene glycol -Lactulose -Sorbitol -Mg salts Chloride channel activators -Lubiprostone |
