Week 2: GI Fluids and Electrolytes Flashcards
1
Q
How do small changes in fluid absorbed or secreted impact the amount of fluid excreted in the stool?
A
- in the normal setting, only excrete about 100mL of fluid in stool
- but with modest increase in secretion ~10%, there is 9x increase in excretion
- fluid balance between absorption and ingestion+secretion
2
Q
How do leaky tight junctions of the small intestine affect absorption?
A
- small intestines is leaky to NaCl
- there is only small difference between IF and lumen. Able to maintain a large membrane potential on the apical side
- leakiness allows Na+ to flow back from IF to lumen, keeps voltage change to -3mV across epithelium
- want the voltage drop across the apical membrane as large (negative) as possible, gives most electrochemical energy driven by Na
3
Q
How does the small intestine absorb water when the osmolarity of the chyme is equal or greater (up to 20mM) than that of plasma?
A
- NaCl in lumen about equal to plasma
- accomplished by local osmosis
- there’s a large basolateral intercellular space. Most solutes are transported into lateral intercellular space
- sigma (reflection coefficient) is large on apical membrane (impermeable to solutes). Solutes of intercellular space draw water into the space.
- sigma of basement membrane is smaller (more permeable to solutes). Salt and nutrients diffuse through basement membrane to reach plasma membrane. Greater hydrostatic pressure in intercellular space compared to plasma allows movement of water into plasma
4
Q
Impact of non absorbed solutes on small intestines due to leaky epithelium. (osmotic diarrhea)
A
- amount of diarrhea is actually out or proportion of what is actually ingested (e.g. lactose)
- start with NaCl in equal concentrations in lumen and IF
- lactose would initially trap a little water
- NaCl would diffuse from intercellular spaces into lumen to dissipate concentration difference
- Enough NaCl to dissipate the electrochemical difference, would double the osmolarity, which brings more water into the lumen, followed again by NaCl
- until the fluid transits the small intestines. Distention activates peristalsis.
- faster transit time means less time for absorption->diarrhea spiral
5
Q
How does the small intestine absorb NaCl independently of glucose or amino acids?
A
- via NHE and AE: Na goes into the cell, H goes out. Bicarb goes out and interacts with H+. Cl- goes into the cell.
- KCC channels on basal membrane allows Cl- to flow from cell to IF
6
Q
How does the colon absorb NaCl and water?
A
- colonic epithelium is tight to NaCl, doesn’t leak through paracellular pathway
- NHE and AE on apical membrane. NKATPase and KCC on basal membrane.
- Lumen is more negative, smaller (less negative) voltage drop across apical membrane.
- Allows ion selective channels such as CFTR and ENac to absorb NaCl. Cl- only has to go against a 30mV gradient instead of a 57mV.
- colonic epithelium is leaky to water.
7
Q
How does the large intestine secrete K+ and HCO3-? Why does the volume of stool excreted impact their balance in the body?
A
- more AE channels than NHE channels, leading to HCO3 secretion into lumen
- apical K+ channels allow K+ to flow from cytosol to chyme
- stool K+ and HCO3 concentrations are constant, proportional to volume of stool
- in cases of diarrhea, excessive excretion of K+ and HCO3 can lead to hypokalemia and metabolic acidosis
8
Q
How does cholera influence intestinal secretion in intestinal crypts?
A
- cholera toxin uses NAD as substrate and catalyzes ADP-ribosylation of G(alpha)s. Locked in active state with activation of adenyl cyclase, producing cAMP, which activates PKA, which activates CFTR, driving Cl efflux from cell to lumen.
- Na moves paracellular and water follows.
9
Q
How does cholera influence intestinal villi?
A
- inhibits absorption in villi, by inhibiting NHE. less ability to absorb Na
- but it was discovered that SGLT was not impaired (Na/glucose cotransporter)
- high glucose in electrolyte solution can be given to drive Na Cl absorption.
