GIS27 Diarrhoea - Nutritional, Fluid And Electolyte Consequences Flashcards
Fluid movement in the GI tract
Daily intake: 1-2 L fluid
Daily secretion (from salivary glands, stomach, bile, pancreas, small intestine) into lumen: 7L
- 85% of water and Na absorbed by small intestine
- about 1.5L enter the colon; 95% absorbed by large intestine
- overall 99% of fluid absorbed, 1% excreted in faeces
Intestinal fluid absorption and secretion
- absorption and secretion go simultaneously
Absorption:
- predominates in ***Enterocytes
- most fluid absorption at ***jejunum
- water absorption is a passive process due to active electrolyte transport, esp Na
Secretion:
- secretion predominates in ***Crypt cells of small intestine and colon
—> normally absorption > secretion, resulting in net absorption
—> secretion > absorption —> diarrhoea
Route of absorption
- Paracellular:
Transmucosal movement of **H2O and **ions through:
- Tight junctions:
—> impermeable to macromolecules
—> permeability (leakiness of epithelium) to H2O and ions varies —> ***higher in duodenum, lower in colon - Lateral intercellular spaces
Difference in ionic composition and osmolality between lumen and plasma depends on leakiness (higher difference for less leaky epithelium):
—> small intestine: leaky —> **isosmotic
—> large intestine: less leaky —> **conc gradient exist
- Transcellular: across both apical and basolateral membranes
Intestinal transport of electrolytes
Absorption:
- Na
- Cl
- K
- H2O
Secretion:
- Na
- Cl
- K
Sodium absorption by intestine (transcellular only)
- Na salts (main driving force) account for most of the actively absorbed solutes in chyme
- 95% reabsorbed, remainder excreted
- absorbed along entire length of intestine
- mostly in **small intestine, highest rate in **jejunum
- rate ***enhanced by glucose, galactose and amino acids presence in the lumen
Mechanism in small intestine:
Apical membrane:
- ***Co-transport with organic solutes e.g. glucose, a.a (secondary active transport of glucose by low [Na] in cell created by Na/K-ATPase)
- Na/H exchanger + HCO3/Cl exchanger
Basolateral membrane:
1. ***Na/K-ATPase
Mechanism in colon:
Apical membrane:
- Diffusion through ***ENaC channel
- Na/H exchanger + HCO3/Cl exchanger
Basolateral membrane:
1. ***Na/K-ATPase
Chloride absorption + HCO3 secretion (trans + paracellular)
- Paracellular
- ***paracellular diffusion of Cl
—> Na absorption provides electrical potential difference (less +ve charge in lumen —> negativity repel Cl into blood via paracellular route) - Transcellular
- ***Cl/HCO3 exchanger (generation of HCO3 within cell by hydration of CO2 which is catalysed by carbonic anhydrase) (Cl into cell, HCO3 into lumen)
—> coupled to Na transport through the Na/H exchanger (Na into cell, H into lumen)
H2O absorption (trans + paracellular)
- almost 99% H2O and ions in ingested food and GI secretions are absorbed
- mostly in small intestine
- H2O absorption is ***secondary and dependent on solute absorption —> passive, driven by osmotic forces
- largely determined by
1. **permeability of apical and basolateral membrane
2. **paracellular pathways to H2O
Small intestine
- leaky epithelium
- ***solvent drag (bulk transport)
- isotonic absorption
Large intestine
- tight epithelium
- ***hypertonic absorption (H2O absorption slower than solute absorption)
- lumen become hypotonic (cell is more hypertonic)
Intestinal secretion of NaCl and H2O (trans + paracellular)
Secretion of NaCl and H2O by ***Crypt cells in small and large intestine
- secretion stimulated after meals, assists in digestion and absorption
- secretagogues stimulated by Ca (ACh) / cAMP (Secretin)
Basolateral membrane:
1. NaKCl2 co-transport (**NKCC1) allows neutral influx of Na, K and Cl into cell
—> energy dependent; coupled to **Na/K-ATPase
Apical membrane: 2 types of Cl channels
- **Ca activated Cl channels (stimulated by **ACh)
-
**cAMP activated Cl channels (cystic fibrosis transmembrane conductance regulator **CFTR) (stimulated by Secretin)
—> activated by phosphorylation mediated by cAMP-dependent protein kinase A
—> identical to Cl channel in apical membrane of pancreatic acinar cells
—> ***Cystic fibrosis: impaired intestinal + pulmonary + pancreatic secretion
Paracellular:
- Na into lumen via paracellular pathway (***follow Cl movement)
- H2O flows along ***osmotic gradient
Potassium absorption (paracellular) + secretion (transcellular)
K absorption (luminal K: from diet + secretory fluid): - Passive diffusion through ***paracellular pathway (caused by absorption of H2O)
K secretion (active secretion in colon):
- Basolateral membrane: ***Na/K ATPase
- Apical membrane: permeable to K, K exit at apical membrane
- ***Aldosterone stimulate colonic Na reabsorption and K secretion
Balance between absorption and secretion
Importance of Secretion:
- assists in digestion and absorption (lubrication etc.)
- stimulated after meals
Normally:
—> Absorption rate > Secretion rate (net absorption)
—> Volume of fluid entering colon well below maximum absorptive capacity of colon
If secretion rate > absorption rate:
—> volume of fluid exceed absorptive capacity —> diarrhoea / loss of fluid
Diarrhoea
- Increase daily stool weight >200g in adults, abnormal increase in stool liquidity and frequency
- secretion > absorption
- Acute: **<2 weeks, Chronic: **>1 month
Causes of diarrhoea
- Impaired absorption by small / large intestine
—> inflammatory disease (Crohn’s)
—> mucosal disease (Coeliac disease) - Secretory diarrhoea
—> inflammation of small and large intestine from infection by virus / bacteria (enteritis)
—> Enterotoxins from vibrio cholerae / E. coli
—> Increased secretion of Cl ions by activation of CFTR - Osmotic diarrhoea
—> presence of un-reabsorbable, osmotic solutes in gut lumen (lactase deficiency / lactose intolerance) - Increased intestinal motility
—> accelerates transit through intestine —> limiting time available for absorption (IBS)
Consequences of diarrhoea
- Dehydration
- Electrolyte + acid-base disturbances
- ***Hypokalaemia
—> secretion of K in secretory diarrhoea - ***Hyperchloraemic acidosis (少左Cl, 多左HCO3)
—> increased secretion of HCO3 (metabolic acidosis)
—> increased secretion of Cl stimulates Cl/HCO3 exchanger —> secretion of HCO3 couple to absorption of Cl —> hyperchloremia - Hyper/Hyponatremia/no change in Na (depend on relative loss of Na and fluid replacement)
3. Malnutrition - bidirectional (acute diarrhoea make malnutrition worse)
—> direct loss of protein + other nutrients
—> poor appetite, vomiting, deliberate withholding of food resulting in poor intake
—> malabsorption of macro and micronutrients, ↓ intestinal transit time during diarrhoea - poor nutrition
—> poor absorption of glucose and a.a
—> less Na absorbed
—> more serious and prolonged diarrhoea
Oral rehydration therapy
- WHO reduced osmolarity of ORS formula
—> ↓ need for unscheduled IV infusion, ↓ stool volume, ↓ vomiting, avoid osmotic diarrhoea
—> concern: potential risk of Hyponatremia - Glucose essential: ***promote absorption of Na and H2O in the intestine
- K: replaces ***large K loss associated with acute diarrhoea, preventing serious hypokalaemia
- Citrate: prevent correct ***base deficit acidosis
***Summary
Na:
- **Absorption (transcellular):
1. Co-transport with organic solutes (by Na/K ATPase)
2. Na/H exchanger + Cl/HCO3 exchanger
3. ENaC
4. Na/K-ATPase
Secretion (trans + paracellular):
- NKCC coupled to Na/K-ATPase
- Na into lumen via paracellular pathway (follow Cl movement)
K:
Absorption (paracellular):
1. Passive diffusion (caused by absorption of H2O)
Secretion (colon; transcellular):
- Na/K-ATPase
- Apical membrane permeable to K
Cl:
Absorption (trans+paracellular):
1. Paracellular diffusion of Cl
2. Cl/HCO3 exchanger + Na/H exchanger (transcellular)
- **Secretion (transcellular):
1. NKCC coupled to Na/K-ATPase
2. Ca activated Cl channels (stimulated by ACh)
3. cAMP activated Cl channels (cystic fibrosis transmembrane conductance regulator CFTR) (stimulated by secretin)
H2O: Absorption (trans+paracellular): 1. Small intestine (leaky epithelium) - solvent drag (bulk transport) - isotonic absorption 2. Large intestine (tight epithelium) - hypertonic absorption (H2O absorption slower than solute absorption) - lumen become hypotonic
Secretion (paracellular):
1. Paracellular (H2O flows along osmotic gradient)
HCO3:
Secretion (transcellular):
***1. Cl/HCO3 exchanger + Na/H exchanger
