Active transport in gut Flashcards
Broadly describe where key electrolytes are absorbed and secreted
- Na and Cl are net absorbed by SI and LI
- K is secreted by LI and absorbed by SI (net)
- HCO3 is net secreted by SI and LI
Describe the process of sodium absorption
- Na+/nutrient cotransport
- primary mechanism
- Na is transported by either Na/glucose or Na/AA symporters
- gradient/absorption is by 3Na-2K-ATPase
- mechanism is electrogenic
- primarily occurs in jejunum, moderate amount in ileum
- Na+/H+ exchange
- Na/H exchangers 2 and 3 on apical surface (amiloride works here in mM doses)
- another exchanger NHE1 helps to regulate pH of cell
- 3Na-2K-Atpase imports Na/helps establish gradient
- Na/H exchanger activity stimulated by luminal alkalinity
- mechanism is electroneutral
- mainly occurs in jejunum, moderate amount in duodenum
- Na+/H+ & Cl-/HCO3- exchange
- NHE and Cl/HCO3 exchanger on apical surface
- CO2 diffuses into cell, with water
- water splits into H and OH
- H is exchanged for Na
- OH combines with CO2 catalysed by CA to form HCO3, which is secreted out
- Cl leaks out via transporters
- 3 Na/2K ATPase helps establish gradient
- this is Primary mechanism of Na+ absorption between meals
- Results in electroneutral absorption of NaCl
- Diminished activity results in diarrhea
- happens in both ileum and proximal colon
- Epithelial Na+ channels
- ENaC on apical surface, 3Na-2K-ATPase on basal surface
- occurs in distal colon
- electrogenic Na absorption
- amiloride acts here in uM doses
Describe chloride absorption
- Passive
- Occurs paracellularly
- Small intestine
- jejunum and ileum
- facilitated by electrogenic Na process (nutrient co-transport)
- Large intestine
- distal colon
- facilitated by electrogenic Na process (ENaC)
- Cl-/HCO3- exchange
- same process as Na/H/Cl/HCO3 – with Na/H on basolateral membrane (transporting H from splitting water)
- NHE and Cl/HCO3 exchanger on apical surface
- CO2 diffuses into cell, with water
- water splits into H and OH
- H is exchanged for Na
- OH combines with CO2 catalysed by CA to form HCO3, which is secreted out
- Cl leaks out via transporters
- 3 Na/2K ATPase helps establish gradient
- this is Primary mechanism of Na+ absorption between meals
- Results in electroneutral absorption of NaCl
- Diminished activity results in diarrhea
- happens in both ileum and proximal colon
- mainly proximal colon, also ileum and distal colon
- Na+/H+ & Cl-/HCO3- exchange
- see above
- proximal colon and ileum
Describe the physiological basis of oral rehydration solutions e.g. hydrlyte
- Takes advantage of sodium and glucose transport in small intestine.
- Water is taken up osmotically after sodium entry.
- Potassium is then absorbed via solvent drag (paracellular).
- Sodium concentration can be varied depending on degree of dehydration.
Describe the process of chloride secretion
- Involved in the pathophysiology of many types of diarrhea (bacterial enterotoxins, certain intestinal tumors (↑ VIP production), laxatives)
- occurs all along SI and LI
- insertion of pre/made Cl channel at apical surface
- cAMP nad Ca enhance this process
- also encourages Cl channels to be more open, increases 2 types of K channels at basolateral surface, driving 3Na-2K-ATPase, making Na concentration low in the cell, driving NA/K/2CL ATPase driving Cl out to lumen
Describe passive potassium transport (both absorption and secretion)
- absorption occurs via solvent drag i.e. paracellularly
- jujunum and ileum
- secretion
- paracellular
- main pathway responsible for net K secretion in colon
- net negative charge in lumen generated by Na movement through Na channel (3Na 2K ATPase)
- distal colon mainly, also proximal colon
Describe mechanisms of active potassium transport
- absorption
- H/K exchanger, gradient driven by 3Na 2K ATPase
- leaves into blood by K channels on basolateral surface
- distal colon
- secretion
- same as Cl secretion process
- K leaves via channels on apical surface
- 3Na-2K-ATPase, making Na concentration low in the cell, driving NA/K/2CL ATPase driving Cl out to lumen
- mainly proximal colon, also distal colon
Broadly describe sites of absorption of macro and micronutrients
- Macros absorbed mainly at duodenum, also jejunum or ileum
- Ca Fe and folate mainly at duodenum, moderate Ca absorption at jejunum and ileum
- bile acids mostly absorbed through ileum, moderately in jejunum and proximal colon, very low in duodenum
- cobalamin in ileum
Describe the monosaccharide transporters
- SGLT1 AND GLUT5 for Na/glucose/galactose, fructose respectively on apical surface, GLUT2 on basolateral membrane
- gradient driven by 3Na 2K ATPase
-
Describe the basis of carbohydrate malabsorption syndomes
Most are a result of a deficiency in carbohydrate digestion
(e.g. lactose intolerance)
But not all..
Glucose-galactose malabsorption syndrome
(very rare hereditary disorder)
Missense mutation in SGLT1
Broadly describe the transport of amino acids/peptides
Proteins are generally digested into peptides
and amino acids before they are absorbed
Six major amino acid transporters in small intestine
(transport the L in preference to the D forms)
Amino acid and peptide transporters
- H/di and tripeptides, Na/AA and endocytosis
- dipeptide transport most efficient
- Na co transport most common
List some amino acid malabsorption syndromes
- i minoglycinuria
- Cystinuria
- Hartnup Disorder
- Dicarboxylic Aminoaciduria
Describe the unstirred layer
- Small fatty acids penetrate unstirred water layer and are absorbed
- Effective concentration of long chain fatty acids adjacent to brush border is increased by a factor of 0.1 - 1 million by micellar solubilisation
Describe lipid absorption
- TAGs are emulsified and form micelles
- pancreatic lipase and colipase results in monoglycerides and FFAs mainly by diffusion, some facilitated diffusion or active transport
- cholesterol is transported, but some diffused
- TAGs reconstituted in cells, fats and cholesterol and proteins to form chylomicrons which go to lymph to vena cava (Too big to enter capillaries)
- note choelsterol is ‘kicked out’ by some channels
Describe the absorption of fat soluble vitamins
- Vitamin A
- Vitamin D
- Vitamin E
- Vitamin K
all passively absorbed, but K is passively and actively absorbed