GI salt and water transport Flashcards
How much net fluid enters the bowel every day?
8.5L
How much net fluid is reabsorbed by the bowel a day?
8.4L
How much net fluid is excreted by the bowel a day?
100ml
What does the jejunum reabsorb?
Na+, K+, Cl- and H2O.
What does the ileum secrete and reabsorb?
Secretes HCO3- and absorbs H2O.
What does the colon reabsorb and secrete?
reabsorbs Na+, Cl- and H2O and it secretes K+ and HCO3-
Where are most ions actively absorbed?
Along the length of the small intestine
describe the movement of Na+ and K+ in the small intestine
Na+ is coupled with absorption of glucose and amino acids
Anions passively follow the electrical potential established by Na+
K+ diffuses across the intestinal mucosa in response to osmotic gradients
Describe the absorption of water along the intestinal membrane
Water transported through the intestinal membrane entirely by diffusion
Diffusion follows the laws of osmosis:
Define chyme hyperosmotic
Chyme hyperosmotic –
water transferred by osmosis to make chyme isoosmotic with the plasma
Describe chyme hypoosmotic
Chyme hypoosmotic (diluted)- water is absorbed through intestinal mucosa into the blood of the villi
Describe the structure of enterocytes
Polarised cells:
Apical - faces lumen has microfolds
Basal - communicates with bloodstream and lymphatic lacteals
Lateral - in contact with neighbouring cells
Apical and basolateral are kept seperate by tight junctions
What are tight junctions used for?
Intracellular TIGHT JUNCTIONS restrict passive flow of solutes after secretion or absorption
(i.e. serve as stopgaps preventing water and solute transport across the membrane)
What are the two types of epithelial transport occur?
Paracellular
Transcellular
Describe the transcellular transepithelial transport
Employs membrane transporters to move molecules and water through cells (think motor of the intestinal luminal activity)
Their activity drives ion flux and establishes concentration gradients, which dictates passive transport of water and solutes.
May work against electrochemical gradient
Requires energy/ATP
Describe the paracellular transepithelial transport
Movement of solutes and water through tight junctions (as opposed to transcellular transport)
Dictated primarily by electrochemical gradient
What is transepithelial transport determined by?
Determined by a type of transport proteins:
1) channels
2) carriers
3) pumps
Describe how different areas of the small intestine differ in their transport
The transport properties of apical and basolateral membranes differ.
Enterocytes in crypts and villi express different combination of transport
Proteins
Enterocytes in different regions of the intestine express different combination of transport proteins
Describe why GI fluid and electrolyte balance is crucial
- Regulation of fluid transport in the gut is critical for normal intestinal function
- Large amounts of fluid are secreted into and absorbed from the gut daily
- Because water follows an osmotic gradient, the understanding of electrolyte transit is key to understanding intestinal fluid balance in health and disease
- Under normal conditions, losses via the gastrointestinal tract are small but can greatly increase in pathologic states such as diarrheal disease (excretion controlled by the kidney.)
Describe the overall process of fluid movement in the GI tract
Put simply, water (fluid) transport must follow solute transport.
Transcellular Solute transport establishes concentration gradients.
Water follows via paracellular movement through tight junctions.
Describe the K+ ATPase
This critically important transport is found on the basolateral aspect of the enterocyte. It actively drives sodium out of the cell.
Na, K ATPase creates a Na electrochemical gradient between enterocyte and lumen
Describe Na+ coupled transport
The Na gradient created by Na, K ATPase allows Na-coupled transport from lumen into cell
Secondary active transport (couples the uphill movement of the glucose/aa to downhill movement of Na, which is itself set up Na/K ATPase (primary active transport)
The process is electrogenic(lumen becomes more negative and drives the parallel absorption of Cl)
Describe how oral rehydration occurs
Utilizing the mechanism of glucose-coupled sodium absorption, oral rehydration solutions
promote fluid absorption by coupling sodium with glucose in solution.
In other words, the carrier-specific for Na-glucose cotransport, SGLT-1, is preserved in most diarrheal diseases and forms the basis for oral rehydration therapy.
SGLT-1 binds two Na molecules to one glucose molecule, transporting them into the cell.
Describe NaCl cotransport
Sodium chloride is absorbed in conjunction with export of Hydrogen and bicarbonate. Again, this relies on the Na, K ATPase to establish the electrochemical gradient.
Na/H (cation) exchanger works in conjunction with HCO3/Cl (anion) exchanger, allowing NaCl absorption
Describe chloride secretion
Primarily at the level of the crypt, involves coupled import of Na, K, and Chloride.
As intracellular Chloride concentration increases, chloride is secreted via apical Chloride channels (CFTR). It is noted that CFTR expression is higher in the ileum and colon, although this mechanism exists throughout the small intestine.
Na-K ATPase drives Na gradient, further allowing Cl secretion through apical CFTR channel
Describe the mechanism by water being absorbed
Ultimately, transport of ions, namely NaCl, leads the direction of fluid (water) flow across tight junctions.
Water will travel through intercellular tight junctions in the setting of NaCl absorption
The small intestine must absorb massive quantities of water.
Up to 95% of water is absorbed in the small intestines by osmosis
Water moves in both directions across intestinal mucosa
Net osmosis occurs whenever a concentration gradient is established by active transport of solutes into the mucosal cells
Water uptake is coupled with solute uptake, and as water moves into mucosal cells, substances follow along their concentration gradients
The absorption of water is absolutely dependent on absorption of solutes, particularly sodium.
• Absorption:
– through tight junctions;
– through ion channels along with active solute absorption by hydrostatic pressure, secondary to solute transport (standing gradient model).
– through apical Na+/glucose contransporter
Describe how water is removed?
In small intestine Cl- secretion drags Na+and water across the tight junctions
Describe the adaptations of the small intestine to allow absorption to occur
Intestinal mucosa highly folded to generate villi. Duodenum - broad, ridge-like, tall in jejenum and shorter in ileum
Villi greatly increase surface area for absorption
SA further increased by brush border
Absorption by epithelial cells on sides and tips of villus
Describe the absorption and reabsorption of Na+
• Absorption:
– through Na+/H+ exchangers (NHE1-10):
* Ex.: NHE1 on basolateral side, NHE2 and NHE3 on apical side;
* Na+/H+ exchangers can be coupled with Cl–/HCO3– exchanger resulting in Na+Cl– absorption;
– nutrient-coupled, e.g., through Na+/glucose contransporter, small bowel;
– through electrogenic Na+ channels (EnaC), in distal colon.
• Secretion:
– in the small intestine Cl– secretion drags Na+ and water across the tight junctions (not in colon!).
Describe the absorption and secretion of K+ transport
• Absorption:
– through K+/H+ exchangers;
– through K+ channels.
• Secretion:
– in colon through K+ channels, increased in
pathophysiological conditions.
Describe the water and electrolyte absorption of the large intestine
Again driven by Na+/K+ ATPase
Sodium entry by
Na+ channels (facilitated diffusion)
Na+/H+ antiport
Diffusion under aldosterone control - increases Na channels
Cl-/HCO3- to provide buffer for acid produced by bacteria and moves Cl- ions
Tight junctions ensure no ion backflow
Na+ Cl- create osmotic gradient for transcellular water movement
What is the difference between the acquired and congenital abnormalities in ion movement?
Congenital caused by genetic defects in ion transporters;
Acquired caused by infection, inflammation, hormonal abnormalities etc.
What are bacterial enterotoxins and what do they do?
Cause secretory diarrhea by interacting with receptors and signal transduction pathways in enterocytes:
secretion exceeds absorption osmolarity of secreted liquid is similar to plasma; reduced intravascular volume and low blood pressure.
List some examples of bacterial enterotoxins
Cholera toxin Heat-liable E. coli toxin Salmonella toxin Campilobacter toxin Heat-stable E. coli toxin Yersinia toxin
Describe the pathophysiology behind cystic fibrosis
Congenital autosomal recessive disease
Deletions in the cystic fibrosis trans membrane regulator gene leading to sticky mucous and high viscosity of lumenal contents which often presents as intestinal obstruction and meconium ileus in newborns
Describe the pathophysiology of lactose intolerance
Lactase deficiency
Lactose is not digested so galactose and glucose is not absorbed. Therefore osmotic diarrhoea is caused
Describe the pathophysiology of cholera toxin
Causes a functional derangement of sodium and water transport.
After the toxin binds GM1-ganglioside receptors of the luminal membrane of enterocytes, the alpha subunit is inserted into the cell. The subunit catalyzes the ADP-ribosylation of the alpha subunit of stimulatory G protein (Gs), irreversibly activating it and adenylate cyclase activity.
Resultant increases in cAMP activate cAMP-dependent protein kinase and phosphorylation of proteins involved in mediating active anion secretion or neutral sodium chloride absorption. The effects of the toxin are only diminished after the enterocyte population turns over (several days). During this time, no mucosal lesions are seen, but patients experience profuse watery diarrhea of such severity that many die of dehydration and metabolic disturbances
