Dear Dr. Topf,
I hope you are doing well! My name is XXXXXX and I am a second year medical student at OUWB. Thank you for your excellent lectures [ed: I added the bold because I love flattery] that you gave yesterday on sodium and water metabolism. During the second lecture, I did get a little confused on some of the core concepts regarding hyponatremia. I am trying to conceptually understand why your urine volume decreases when you have low solute and high amounts of water intake.
I can see why you are confused, let me try to reteach this.
This slide is supposed to demonstrate how the kidney handles water and solute.
In the absence of kidney failure, solute absorption = solute kidney excretion. Often this will be abbreviated solute in = solute out since our indescrimnate GI tracts pretty much absorb all the minerals and protein they are exposed to and, besides the kidney, no other organ system does meaningful solute excretion. In fact, a failure of solute in = solute out to hold true is a pretty good functional definition of kidney failure.
For people on a western diet (i.e. omnivorous) solute intake can be estimated at 10 mOsm per Kg body weight. So for the 70 kg adult, estimate solute load at 700 mOsm per day.
The kidney can get rid of that solute load in a variable amount of urine. If the person is drinking a lot of water, lowering body osmolality, the hypothalamus will detect this and decrease ADH resulting in dilute urine as indicated on the left side of the slide (absence of ADH, urine osm of 50) and get rid of that solute load with 14 liters of water. The loss of 14 lite3rs of water will increase the serum osmolality back toward normal.
If the patient has a low water intake (which will push the serum osm up) or high serum osmolality, the hypothalamus will release ADH and the urine osm will increase so the body will excrete that same osmolar load of 700 mOsm in only 0.6 liters, retaining any water intake in excess of this 0.6 liters. This retained water will dilute the serum osmolality back toward normal.
This is supposed to demonstrate that the kidney can get rid of the daily osmolar load in a wide range of urine volume to balance water intake and excretion in order to maintain homeostasis.
The next slide shows what happens when the patient is not on a normal western diet. In this case instead of eating 700 mOsm a day the patient is only taking in 100 mOsm a day
Now with ADH turned down to zero, and the urine osmolality bottoming out at 50 mOsm/Kg H2O the maximum amount of urine the body can produce is only 2 liters, an amount that people may exceed with normal, habitual fluid intake. The serum osmolality is low and the body wants to get rid of excess water, but turning down urine osmolality does not produce the expected copious amount of dilute urine needed to correct this situation, because the urine volume is limited by a lack of ingested solute. To increase the urine output to 3 liters would require 150 mOsm of solute (3 L x 50 mOsm/g H2O) but they are only eating 100 mOsm! So while in most cases urine volume is determined by ADH, with increasing urine volume with decreasing urine Osm, once the daily osmolar load is excreted no more urine can be produced.
If the patient has hyponatremia, wouldn’t the interstitial medullary gradient not form due to little sodium being filtered in the tubules at all and thus leading to low amounts of sodium leaving the NKCC2 proteins, thus leading to lower amounts of water being reabsorbed (this is how I’m currently thinking and why I am getting so confused)?
This is not proper thinking. An example of severe case of hyponatremia would be a sodium of 110 mEq/L. Given a GFR of 100 ml/min (0.1 L/min), this is still:
110 x 0.1 L/min x 1440 min/day = 15,840 mEq of Na filtered.
Plenty of Na to keep the medullary interstitium fully concentrated. Also remember half of the osmoles in the medullary interstitium are urea which is not really affected by the hyponatremia (not entirely true, but true enough for MS2s)
I am also aware that ADH is still going to be low here because you wouldn’t want to continue reabsorbing water with hyponatremia,
True
so this is also why I got confused and thought you’d be producing a higher volume of urine rather than a lower one. With the patient drinking lots of water AND having low sodium (hyponatremia), can you reiterate what happens?
When the osmolality is low the body will suppress ADH, unless there is some other stimuli of ADH: volume depletion (hypovolemic hyponatremia) decreased perfusion (hypervolemic hyponatremia from cirrhosis or heart failure) or SIADH. THe lack of ADH increases urine production until all of the daily solute is excreted. With a normal diet, the 700 mOsm will allow the production of 14 liters of dilute urine, enough to correct just about any hyponatremia. But if the patient is drinking 15 liters of water, even with maximally dilute urine there will be progressive hyponatremia, must have fluid intake below excretion to normalize serum Na.
Hope this helps
Link to PDF of the above GiF
Link to Keynote of the above GIF
Link to PowerPoint of the above GIF