What is the real value of a kidney? part 2

...continued from https://www.inaturalist.org/journal/milewski/81803-what-is-the-real-value-of-a-kidney-part-1#

The following is an explanation of how Dipodomys (https://www.inaturalist.org/observations?place_id=any&taxon_id=44098&view=species), a genus of rodents extremely adapted to arid conditions, manages to produce extremely concentrated urine, without particular metabolic cost.

One needs to understand this energetically cheap mechanism, in order fully to see through the view (stated or implied in all textbooks) that the kidney is mainly an organ of excretion.

For context, I remind readers that Dipodomys is so well-adapted to deserts that it need never drink; it obtains water from its diet of dry seeds, by virtue of the fact that the oxidation of the carbohydrate in the seeds produces carbon dioxide and 'metabolic water'/'oxidation water' (https://www.biologyonline.com/dictionary/metabolic-water#:~:text=Metabolic%20Water-,Definition,as%20carbohydrates%2C%20fats%20and%20proteins.).

My source is pages 168-170 in Schmidt-Nielsen (1964) Desert animals: physiological problems of neat and water. Clarendon Press, Oxford (https://www.amazon.com/Desert-Animals-Physiological-Problems-Water/dp/0486238504 and https://books.google.com.au/books/about/Desert_Animals.html?id=u9k9AAAAIAAJ&redir_esc=y and https://www.abebooks.com/first-edition/Desert-Animals-Physiological-Problems-Heat-Water/30970210856/bd)

"...the structure of the kangaroo rat kidney...is similar to the kidney of other rodents; its size is not unusual, and the number of glomeruli and their size are normal for this size animal".

My commentary:

This establishes that the renal cortex is normal in Dipodomys, and presumably as energetically exorbitant as in other mammals.

Schmidt-Nielsen (1964) goes on to explain that the water-conserving part of the kidney lies in the renal medulla, and that the mechanism of retrieval of water, from the renal tubule back into the bloodstream, depends not on metabolic activity but instead on a counter-current system (https://journals.physiology.org/doi/full/10.1152/ajpregu.00657.2002#:~:text=It%20is%20generally%20accepted%20that,Henle%20and%20collecting%20ducts%2C%20respectively. and https://www.khanacademy.org/test-prep/mcat/organ-systems/the-renal-system/a/renal-physiology-counter-current-multiplication).

Please also see Schmidt-Nielsen, 1981 (https://www.jstor.org/stable/24964421).

This energetically cheap counter-current system consists of a loop in the renal tubule, in which the urine flows in opposite directions, setting up an osmotic gradient. The more arid-adapted the mammal, the longer this loop, and the better-developed the renal medulla.

"Desert rodents, antelope, camel, giraffe...have the greatest relative development of the renal medulla (which contains the loop structure), and animals that have an aquatic habitat such as beavers, water rats, and platypus have a thin medulla and very short loops".

My commentary:

The economical mechanism of conservation of water in the kidney is structural rather than metabolic; the process of reabsorption is thus 'passive' in terms of energy-use, because it uses osmosis instead of 'pumping'. This is in contrast to the mitochondrial activity in the walls of the renal tubules in processing the filtrate within the renal cortex.

DISCUSSION

Where does this leave us, w.r.t. the conventional view?

If we take the account in Wikipedia (https://en.wikipedia.org/wiki/Kidney) as typical, it is remarkable that the thermodynamic exorbitance of the kidney - which is perhaps its most significant aspect - is not even mentioned.

The conventional view has been perpetuated, from one generation of students to the next, by a combination of

  • ignoring a thermodynamic 'elephant in the room',
  • remaining caught up in detail (the 'reductionist' trap, so familiar in Science),
  • failing to bring together the recent proliferation of research on antioxidant biochemistry and the older research on renology, and
  • continuing to refer in the vaguest way to 'homeostasis'.

It is only when one stands back far enough to see matters in perspective that one realises that, to this day, the main function of one of the most important organs has never been explained in any conventional publication.

More sobering: a suitable resolution seems to be nowhere on the horizon, in the peer-reviewed literature.

Posted on July 07, 2023 10:54 PM by milewski milewski

Comments

@tonyrebelo @matthewinabinett

There is a simplistic notion, as follows, about the function of urea (https://en.wikipedia.org/wiki/Urea) in physiology:

Proteins in food are broken down in the body, and the excess nitrogen is excreted in the form of an essentially toxic substance, namely urea.

This notion has a germ of truth, but is misleading overall.

This is mainly because a) there should be no need to synthesise urea (a process requiring five enzymes), given that ammonium is the more direct waste product, eminently suitable for excretion, and b) urea is, overall, far more important in physiology as an anti-oxidant (in all mammals), and as a way of recycling nitrogen in digestive fermentation of fibre (particularly in ruminants, https://extension.psu.edu/urea-in-beef-cattle-rations) than as an excretum.

In ruminants, much/most of the urea circulates repeatedly in the bloodstream, functioning as an anti-oxidant (in a way comparable to vitamin C), and then is secreted into the rumen, where each of the atoms of nitrogen undergoes several/many additional cycles of incorporation into gut microbes, subsequent digestion of these microbes in the abomasum (https://en.wikipedia.org/wiki/Abomasum), and subsequent synthesis in the liver.

Urea is recycled from the blood into the gut via both saliva and the epithelia of the stomach (https://biomedres.us/pdfs/BJSTR.MS.ID.003401.pdf).

This use of urea as 'food' in ruminants is so basic that these mammals not only recycle urea internally between the soma and the gut, but can be fed urea in gross amounts along with their normal foods. The latter is done routinely in the nutrition of domestic Bos.

I quote from Schmidt-Nielsen (1964), page 60:

In camels, "the amount of urea excreted relative to the glomerular filtration rate may change fifty-fold, and this is not compatible with the concept that urea is filtered and merely diffuses passively back to the blood".

When Camelus dromedarius happens to have protein-rich food, it excretes urea about as freely as any other herbivore would. However, when its food is extremely protein-poor, it virtually stops excreting urea, even if it has enough access to water to urinate freely.

Instead, the animal keeps repeatedly synthesising urea and secreting it into the forestomach, where fibre-fermenting microbes can use the nitrogen in this molecule to build the protein necessary in their unicells.

In mammals in general, urea is only excreted once the maximum use of the substance has been made. A given individual molecule of urea, after being synthesised in the liver (https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/urea-cycle#:~:text=Only%20the%20liver%20possesses%20all,%2C%20argininosuccinate%20lyase%2C%20and%20arginase.), may possibly circulate in the bloodstream and through the kidneys hundreds/thousands of times, before finally being excreted.

And even then, the reason for excretion is not that the substance is toxic, but simply that, in the flow intrinsic to living systems, everything must ultimately exit the body at some rate or at some stage.

Presumably, one of the functions of the kidney is to repair the molecules of urea repeatedly by extracting them from the plasma and then operating on them, electronically, within the neutral 'sanatorium' of the filtrate (in the renal tubules of the renal cortex).

Although metabolically expensive, this repair is presumably cheaper than synthesising a new molecule in the liver.

Another way of putting this:
In reality and in contradiction to a common notion, the excretory use of urea is the least important function of this substance.

Posted by milewski about 1 year ago

OK. So what happens then to humans who only drink enough water to counter thermoregulation? What are the consequences of a minimal water diet? How do the kidneys respond?
On scout hikes (naive, inexperienced hikers under heat duress) the first question to most complaints is almost always: what is the colour of your pee?

Posted by tonyrebelo about 1 year ago

@tonyrebelo

Schmidt-Nielsen (1964) answers this on page 11:

"In a moderate climate, the kidneys [of Homo sapiens] usually excrete from 1.0 to 1.5 litres of water each day...When water intake is restricted urine volume...may be less than 0.5 litre, but urine formation ceases entirely only in the severest dehydration when physiological processes deteriorate and kidney function fails. In a desert climate...the lowest rate observed...was 230 ml per day...As far as we know, similar volumes of urine continue to be formed as dehydration progresses, until kidney function ceases in advanced stages. When the kidney conserves water it does so by forming a urine where the excretory products are in as high concentrations as possible. When the maximum concentrating ability of the kidney is reached no further amount of water can be withheld, and the urine volume is therefore determined by the amount of excretory products...The kidney of man is not particularly powerful; rats and dogs have kidneys about twice as powerful and can therefore eliminate a given amount of excreta with only half as much water. There is no indication that man can be trained to excrete a highly concentrated urine; the maximum concentrating power of the kidney is not subject to any appreciable modification. Also, since the urine output remains about the same under increasing dehydration, no saving in water use is accomplished by permitting man to become increasingly dehydrated. The minimum urine volume is dictated by the amounts of excretory products and is modified with changes in the diet. The amount of urea depends on the protein intake, but does not decrease to zero even on a protein-free diet."

Posted by milewski about 1 year ago

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