Frequently Asked Questions.... and other help notes

Well, at the very least, occasionally asked questions.....

See the glossary for one-word vocabulary definitions or the feedback page if what you are looking for isn't here.

Countercurrent multiplication....

You know that countercurrent thingie, what happens when it has established an osmotic gradient? Do the pumps stop working? Does it stay there forever?

The osmotic gradient in the renal medulla is a dynamic, unstable sort of thing. If the medulla was completely isolated from the rest of the body then yes, once formed, the osmotic gradient should not dissipate and the pumps could switch off. In reality it isn't. For one thing, the purpose of the gradient is to draw water out of the collecting duct, a process that will dilute the salts in the medulla. Also, the countercurrent exchange in the vasa recta is not 100% effective, deliberately so. If it was 100% effective then NO O2 would reach the medulla and there would be NO removal of CO2. A compromise is that the blood supply removes some of the gradient but, by the same token, is able to supply some O2 etc.

Ammonia production....

Ammonia is produced by proximal tubule cell metabolism in order to manufacture HCO3-. How do the proximal tubule cells know how to increase NH3 production?

The short answer is metabolic acidosis. Metabolic acidosis results from overproduction or underexcretion of acid (see also respiratory acidosis). So far as I can tell, the key step in stimulating renal NH3 production is excess acid in the urine. See the paper by Garibotto et al in Metabolic Brain Disorders for more detail. The bad news is that chronic acidosis is not good for the kidney.....

Membrane Potential....

You talked about the equilibrium potential for K+ being about -90mV, from the Nernst Eq. - That's fine I got that Also that at rest, a cell is at about -70mV, due to the ElectroChemical gradient for 140mM & 5mM K+ etc etc - I got that too. But, I didn't quite get that if there is no stimulus to generate an action potential and thus only K+ channel(s) open, what stops the resting potential from reaching the -90mV, why is it at -70mV? Why doesn't the chemical gradient 'pull' the K+ out of the cell down to the equlibrium potential?

You are nearly correct in everything you say. So long as the membrane potential (-70 mV) is less than the Nernst potential for K+ (-90 mV) then K+ will leave the cell. I always have to leave something out! This time it was Cl- channels. At "rest" Cl- conductance is a significant component of the total conductance and (as demonstrated by the Goldman equation) sufficient to keep the membrane potential below the Nernst potential for K+. Because Cl- conductance doesn't change during the action potential I ignore it unless anyone asks me... Try playing with the Goldman Software if you are having difficulty visualising how the Goldman equation works. Don't worry about the "leak" of K+, that is what the sodium pump is for...

Attraction....

How are ions and molecules attracted to their specific/target sites? Like, what drives them ultimately? Yes there are receptors for molecules etc and ions have specific charges, but these charges aren't exclusive to the one molecule.

By and large the whole thing is random. Agonists are NOT attracted to their receptors, they whiz around in all directions completely at random. If they happen, by chance, to hit a receptor then there is a probability that they will stick to the receptor long enough to activate it. The higher the afinity of the receptor for the agonist the more likely it is to bind long enough to cause activation.

Agonist / receptor binding is governed by the "Law of Mass Action" which is one of those things that only really makes sense mathematically. The maths start simple...

Water, water everywhere....

.....when the body takes in too much water, the kidney has basically stabilised the blood osmolarity before the water is absorbed from the GI tract. Basically I was jut wondering, do the osmoreceptors detect this increase in water comsumption? I was always under the impression that it was in the blood that these receptors recepted, as it were?

The water is absorbed through the gut and into the blood, a process which obviously takes a little time...The point I was trying to make is that the kidney starts to respond as soon as ANY water is absorbed.... so by the time the gut has finished absorbing the water (which it will) the kidney has already dealt with the surplus....

Chloride channels

.... you said only in abnormal function does the apical membrane open chlorine channels (which makes perfect sense to me!). But in my text book, 'human physiology' (published by mcgraw hill) it says that this is always occuring, causing secretion of NaCl into the lumen of the large intestine via the apical membrane, and in abnormal function, ie with e coli or cholera, an enterotoxin causes this secretion to be increased by activating an enzyme. Which is correct?!

I try to keep things simple.... but I didn't actually say that the Cl- channel ONLY opens in abnormal function...

Yes there is a Cl- channel in the apical membrane of (probably) all intestinal epithelial cells... After all, cholera doesn't create the channel, it just jams it open... So it follows that it must be there for a physiological, not a pathophysiological purpose.

Water & ions normally move both ways (absorption & secretion) across the intestine.... perhaps even simultaneously in the same cells. In other words, there is a circulation. The apical membrane Cl- channel is what allows for secretion. The important thing is that, under normal conditions, absorption is much greater than secretion... so there is NET absorption. In pathological conditions the net absorption is reduced because the secretory component has got bigger. So, your textbook is correct, but not necessarily clear.

Strictly Speaking....

....in your notes on 'Why do we need Kidneys' - you state that the hypothalmus produces vasopressin, when in fact the posterior pituitary does!

Strictly speaking, it IS the hypothalamus which produces ADH (in the supraoptic & paraventricular nuclei). ADH flows down the axons in the hypothalamohypophyseal tract into the posterior pituitary from where it is released....

anti-ADH...

I was just curious what advantage would an ADH confer compared to a diuretic hormone, if the water channels in the collecting tubule were active all the time? I mean wouldnt producing a diuretic hormone be more efficient than ADH in terms of reduced metabolism?

If collecting duct cells "naturally" had a high water permeability then this would have to be reduced by the action of "Diuretic Hormone"... e.g. by stimulating endocytosis and channel removal, as opposed to ADH, which stimulates exocytosis and channel insertion. There may be a good reason why one is more efficient than the other, but I can't think of it right now. Anyway, ADH is what we've got.

Irrational ATPase

It seems logical that in a Na/k pump that equal numbers of each ion should be pumped accross the pump rather than the 3:2 ratio, i don't understand why that ratio occurs,

The 3:2 ratio makes the sodium pump electrogenic. In fact it allows the sodium pump to contribute to membrane potential. Only slightly in most cells, but there are data to suggest that this may be important in some electrically excitable cell types. There are some wonderfully complex mathematical molecular models for how the sodium pump works, The bottom line in one that I (tried to) read is (I think) that:"It has to be 3:2 or else the pump doesn't", or in the phrasing of the authors, "Some of the vectorial properties of an electrogenic sodium pump appear to be inescapable consequences of the nonvectorial properties of the isolated enzyme".

pH....

...what is pH exactly?

The negative log10 of the hydrogen ion concentration. This one gets asked so often it has its own help note.

Statistics...

...how much of this !@%$#%@ stats rubbish do we really need to know?

More than you think. This one also has its own help note.

Nano to Yotta...

...what is the difference between a milligram and a microgram?

1000. The answer is nearly always 1000. See the units & prefixes help note.

OzMole...

...I nearly understand moles... What is an osmole again?

A mole who used to be lead singer in Black Sabbath. See the osmolarity help note for a more sensible answer.