Flashcards in Transport energetics and organic solute transport Deck (47)
What are the 2 types of mediated transport?
Passive and active
What is passive transport?
1. facilitated diffusion through pores and channels
2. fluxes are always passive and usually uncoupled
3. Substrates move down their chemical (if uncharged), or net electrochemical gradient (if charged) --> Dissipates gradients (equilibrates)
4. Can saturate
What is active transport?
• Transport of a particular solute is active when net flux occurs against an opposing gradient of electrochemical potential (Δμ)
What is the electrochemical potential?
If there is a solute in solution which is more concentrated on inside vs. outside membrane, there is a chemical potential.
The (passive) net flux of a solute between two compartments is driven by the difference in chemical potential on each side of the membrane.
How can we calculate the chemical potential?
μ~i = μ~' + RTlnCi + zFi + RT lnfi
RTlnCi = chemical work
zFi = electrical work
RT lnfi = work of interractions between solute molecules
How can we change the formula so that all of the parameters can be measured?
Although the chemical work and work of interactions cannot be determined experimentally, these terms can be combined by replacing solute concentrations (Co) with activities (Ao), which are measurable using selective electrodes. They will measure the activity of the solute (sum of concentration and interaction terms).
What happens to the formula when an ion with z = 1 is at equilibrium?
then eqn. (6) is easily rearranged to the familiar Nernst equation.
Nernst equation: relationship between the ion concentration gradient across the membrane and the voltage.
At equilibrium, the above equation becomes the Nernst equation
Vm = (- RT / zF) ln (Ai/Ao)
Name the 2 types of active transport
What is primary active transport? Give examples
• The energy for "uphill" transport is provided directly by ATP hydrolysis (energy input).
• Ion transporters (“pumps”) use ATP
• Examples: 3Na/2K ATPase exchange pump, H+-ATPase pump, H+/K+ ATPase pump
What is the Na/K ATPase? Where is it located?
uses 1 ATP; found in virtually all cells of the body; on basolateral membrane of kidney
What is the H+ ATPase? Where is it located?
vacuolar proton pump; generally on apical membrane or intracellular vesicles; important for proton secretion in collecting duct and proximal tubule (to a lesser extent)
What is the H+/K+ ATPase? Where is it located?
exchanger; also important in extruding protons and bringing potassium in cells; important in the gut, stomach; take inhibitors of that in case of gastric ulcers) in the outer medullary collecting duct
What is secondary active transport? Give examples
"Uphill" flux of one solute driven by the "downhill" flux of another solute.
E.g. Na+/H+ exchanger, Na-Glucose cotransport
What is the Na+/H+ exchanger? Where is it located?
secretes protons into the lumen of the proximal tubule. The large inward concentration gradient favoring Na+ influx into the cell through the apical membrane provides the driving force for proton secretion from the cell to the lumen. Occurs by transporters that couple solute movements. Energy from the downhill flux of one molecule or ion drives the uphill transport of another
In which part of the kidney are most solutes reabsorbed?
The proximal tubules
What are gap junctions? What is their function? where are they located in the kidneys?
Gap junctions are between epithelial cells of the tubules.
Gap junctions between the cells allow large solutes or signalling molecules to pass from one cell to the next within the tube. All cells around are connected. If ATP is used in one cell then it can pass through and be used in another cell.
Where is the basement membrane of the tubules and what is its main function?
Basement membrane on the outside of the renal tubule is continuous with the renal capsule. (forms “sheet” over bowman’s capsule and around tubule). High pressure in tubules; is a supporting structure. Keeps epithelium intact despite high pressure.
What is present in the apical membrane of the proximal tubule but not other parts of the tubules?
The apical membrane of the proximal tubule (ONLY PROXIMAL TUBULE) forms tightly packed microvilli, the brush border --> increased surface area for absorption, covered with transporters
Where is the dividing line between apical and basolateral membrane?
At the tight junctions
How are the tight junctions in the proximal tubules vs. the more distal segments?
The tight junctions are leaky to ions and water in the proximal tubule but are tight in more distal segments.
This trend is reflected in the transepithelial electrical resistance, which is 6 ohms •cm2 in the proximal tubule and 200 ohms•cm2 in the collecting duct.
Makes sense: in proximal tubule, absorbing liquid around that is practically isotonic. Small gradient, so need a lot of active transport. As we move further, gradient develops; thus, need to close gaps to maintain gradient.
--> tightness of epithelium varies tremendously.
Name an example of heterogenous cell types in the collecting duct
the collecting duct consists of potassium-secreting "principal" cells interspersed with acid- or bicarbonate secreting "intercalated" cells.
How does inulin concentration vary in the tubule as you go through the proximal tubule
It increases almost linearly because it is not secreted nor reabsorbed, but water is reabsorbed. So there is half the amount of water there was at the beginning after filtration.
How does concentration if Na and Cl ions vary in the tubule as you go through the proximal tubule
Ions (Na, Cl): Very little change in Na concentration despite water reabsorption, meaning the sodium was also reabsorbed.
Chloride increases then reaches a plateau; because Na starts to be reabsorbed with other solutes so the Cl is left behind in the lumen, then concentration builds up as fluid is reabsorbed.
The leaky pathway between epithelial cells is selective to which ion?
Chloride: gradient of chloride from lumen to interstitium, an electrical potential is developed. This is why the polarity in the lumen switches and lumen becomes positive. Cl concentration has become bigger in the lumen, Cl wants to diffuse out.
How does concentration bicarbonate vary in the tubule as you go through the proximal tubule
Bicarb: starts normal at glomerulus but then decrease in concentration, meaning it is reabsorbed faster than water is.
How does the net osmotic pressure change along the proximal tubule?
Net effect --> only slight change in osmotic pressure along tubule (water is absorbed but along with many other solutes, leaving a relatively constant pressure).
What is splay of the glucose titration curve?
The Tm of glucose is not reached abruptly but is reached gradually, causing splay of the titration curve
What is the glucose threshold?
The level of plasma glucose at which glucose begins to "spill" into the urine is called the glucose "threshold".
In normal man, the threshold is at a plasma glucose concentration of 180-200 mg% (about 10 mM).
In what cases might splai be exaggerated?
splay has clinical importance because it may be exaggerated in some hereditary tubular diseases. Such patients excrete glucose at lower than normal plasma glucose levels but have a normal Tm at high glucose loads.