What is the real value of a kidney? part 1
According to textbooks, renal function is no mystery (https://en.wikipedia.org/wiki/Kidney).
It is simply the homeostatic regulation (https://en.wikipedia.org/wiki/Homeostasis) of body fluids, the main mechanism of which is urination of excess water, salts, acids, and nitrogen (https://www.niddk.nih.gov/health-information/kidney-disease/kidneys-how-they-work).
Other organs such as the skin (https://pubmed.ncbi.nlm.nih.gov/24577280/#:~:text=The%20skin%20excretes%20substances%20primarily,metabolism%20and%20excretion%20of%20sweat.) and intestines (https://humanbiology.pressbooks.tru.ca/chapter/18-2-organs-of-excretion/) also contribute to the elimination of potentially toxic wastes from the blood. However, the kidney - according to textbooks - is the only organ, shared by all vertebrates, that is dedicated to excretion.
However, this conventional view is unsatisfactory.
The true electrochemical function of the kidney is deceptive and subtle:
- 'homeostatic regulation', although valid, is too vague to give an understanding of renal physiology, and
- 'urination' also falls short, because it is a secondary, rather than primary, function of the kidney.
Clues to the real specialisation of the kidney - which I hypothesise to be the balancing and reformulating of pro-oxidants and anti-oxidants throughout the body - lie in four observations.
Firstly, the intricacy (https://en.wikipedia.org/wiki/Nephron) and energetic cost of the kidney suggest that its true function is more fundamental than any aspect of excretion.
(Please see the four comments below, with the headings 'energy-exorbitance of kidney', parts 1-4.)
The pair of kidneys accounts for only about 0.5% of the mass (https://byjus.com/question-answer/average-weight-of-adult-human-kidney-is-about/), yet uses about 10% of the energy (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232006/), of the human body. This is disproportionate by a factor of 20.
For comparison, the human brain - although renowned for being energy-expensive - is disproportionate by a factor of only 10.
Indeed, the paired kidneys are so powerful that they reformulate, molecule by molecule, all the blood plasma (https://en.wikipedia.org/wiki/Blood_plasma) of the whole human body every 22 minutes (https://www.ncbi.nlm.nih.gov/books/NBK500032/ and https://www.sciencedirect.com/topics/medicine-and-dentistry/kidney-blood-flow and https://courses.lumenlearning.com/suny-ap2/chapter/physiology-of-urine-formation/).
Secondly, the kidney provides a uniquely neutral environment. This is because
- oxygen is excluded, and
- the active transport of ions across renal cell membranes does not generate action potentials (https://en.wikipedia.org/wiki/Action_potential).
Thirdly, nearly all substances filtered from the blood into the renal tubules (https://en.wikipedia.org/wiki/Glomerular_filtration_rate) are reabsorbed into the blood, with only a small fraction being excreted.
This is partly because urea (https://en.wikipedia.org/wiki/Urea) and uric acid (https://en.wikipedia.org/wiki/Uric_acid), although often assumed to be mere wastes, are
- costly to synthesise, and
- useful as anti-oxidants (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895915/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571786/#:~:text=Urea%20not%20only%20protects%20the,present%20study%2C%20against%20oxidative%20stress.).
And lastly, most of the true excreta subsequently pass directly from the blood into the urinary tract (https://mcb.berkeley.edu/courses/mcb135e/kidneyprocess.html).
Based on these observations, renal physiology transcends the mere maintenance of ionic balance in the blood via excretion and acid/alkaline buffering.
Instead, diverse molecules can routinely be quarantined - separate from blood and lymph - in a body compartment where electrons can be traded among the intercepted pro-oxidants (https://en.wikipedia.org/wiki/Pro-oxidant), anti-oxidants (https://en.wikipedia.org/wiki/Antioxidant), and ions (https://en.wikipedia.org/wiki/Ion).
In the resulting reformulation, radicals can be processed to optimise the overall effects of redox reactions throughout the body. In this process, the various pro-oxidant and anti-oxidant substances are mixed and matched appropriately.
In this way, homeostasis can be achieved in the precise sense of controlling 'free radicals' (https://en.wikipedia.org/wiki/Radical_(chemistry)), yet retaining enough pro-oxidants of appropriate types to kill cancerous cells and current pathogens.
In summary, the anatomy and function of the kidney are consistent with a dedication as an 'oxido-transformer' for the whole body, balancing the overall costs and benefits of respiration in all organs.
This may be described as the maintenance of homeostasis, but is different from - and incomparably more expensive than - the kind of homeostasis invoked in textbooks.
Does this new interpretation - which I first worked out in 2010 - not better explain the complexity and power of the kidney, based on the realisation that management of the chain reactions of oxidation is the ultimate challenge for aerobic metabolism?
After all, metabolism is identical to combustion, in that both processes take fuels and oxidise them, converting compounds of CHO to carbon dioxide and water. The difference is one of control: metabolism (enzymatic oxidation) promotes cellular function, whereas combustion (non-catalytic oxidation) destroys it.
This difference is so basic to life that nobody should be surprised that an organ is devoted to it. And that organ, I suggest, is the kidney.
to be continued in https://www.inaturalist.org/journal/milewski/81889-what-is-the-real-value-of-a-kidney-part-2#...
Comentarios
Surely not: too much water and you explode. Too much Ca or K and muscles and nerves misbehave. Too much urea and you die. Even if the kidneys did nothing more than secreting water, urea and excess salts, they are essential. True, 90% of the time you only need a fraction of one kidney, but there will be times when a rapid response is needed and one kidney will reduce performance for a time.
But hopefully you will get to 3 more points soon ...
@tonyrebelo
ENERGY-EXORBITANCE OF KIDNEY, part 1:
Excretion is important, but should in itself be inexpensive.
Water, salts, acids, and nitrogen can be 'skimmed' out of the blood without intense metabolic cost, and indeed this happens in the skin.
The cheapest excretum for nitrogen would be ammonia (https://en.wikipedia.org/wiki/Ammonia), yet for some reason the body goes to the trouble and expense of synthesising urea and uric acid - and then, instead if excreting these 'wastes', repeatedly conserving and recycling them via the kidney.
The skin is a particularly large organ, and its full potential in waste-disposal is easily overlooked. However, with slight modifications, the skin - together with the intestines and salivary glands - could perform much of the excretory function of the body, with minimal additional cost in energetic terms.
Instead, the kidney exceeds the brain, in the intensity of its metabolism (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980962/) - indicating some function more profound and difficult than mere excretion.
In humans, the kidneys receive 20-25% of cardiac output. This is at least an order of magnitude greater than what would be needed for the purpose of excretion.
From an energetic viewpoint, the excretory function of the body could potentially be achieved by small additions to the metabolic costs of skin and intestines. Instead, the kidney is anomalously costly in metabolic terms (as measured by rates of conversion of sugar and oxygen to carbon dioxide and water, rate of production of heat, density of mitochondria in the cells, rate of flow of blood, and rate of generation if ATP), suggesting that whatever it is that is the main function of the kidney is extremely costly, with excretion being 'thrown in' as a 'bonus' function.
@tonyrebelo
ENERGY-EXORBITANCE OF KIDNEY, part 2:
Please see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980962/.
The relative values for resting metabolic rate are, in decreasing order:
kidney 426
heart 426
brain 233
liver 194
(Please bear in mind that the 'resting' heart is still beating, which in the human species is at a rate of about 72 beats per minute, more frequently than once every second.)
The liver is acknowledged as a metabolically intense organ, a kind of 'chemical factory' in the body; yet each cell of the liver has, on average, a resting metabolic rate less than half that of each cell of the kidney - which is supposed to perform mere waste-disposal.
The heart is the most dynamic part of the body; yet its resting metabolic rate is no greater than that of the static-seeming kidney, which is passive in the sense that it does not even 'squirt' urine into the ureters.
The brain is renowned for intense metabolism (https://www.urmc.rochester.edu/news/story/study-sheds-new-light-on-brains-source-of-power#:~:text=The%20brain%20requires%20a%20tremendous,percent%20of%20body%27s%20energy%20supply.), such that it accounts for 20% of whole-body energy-expenditure despite contributing only 2% of body mass; yet the kidney has a resting metabolic rate nearly double that of the brain.
@tonyrebelo
ENERGY-EXORBITANCE OF KIDNEY, part 3:
The liver uses much energy, to perform many and varied chemical reactions.
The heart uses much energy, to perform kinetically.
The brain uses much energy, to maintain the electrical charges essential to the function of neurons.
So, in crude terms, we can envisage the liver as a factory, the heart as a pump, and the brain as a computer.
It makes sense that these functions are energy-consuming, and demand complex and specialised infrastructure.
But, if we apply the same logic to the kidney, this organ is a ?, and its energy-consumptiveness is analogous to that of a ?
Textbooks skirt the question, but imply that the answers are 'filter' (https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/kidneys), and 'cleaner/garbage-disposer' (https://www.thesaurus.com/browse/cleaning%20person).
Does that make sense, given how simple and cheap filters are, and how little of an industrial budget is spent on cleaning services/garbage-disposal?
My whole life, I have thought of 'janitor' as meaning essentially 'cleaner'.
I now see my error:
https://www.merriam-webster.com/words-at-play/janitor-word-history-job-custodian#:~:text=Appropriately%2C%20janitor%20derives%20from%20the,out%20with%20his%20gate%2Dkeys.
So, 'janitor' is not appropriate as an analogy for the (unsatisfactory) main function of the kidney, as stated/implied in textbooks.
What would be a more appropriate word (remaining within the unsatisfactory interpretation seen in textbooks)?
https://www.youtube.com/watch?v=SVqSqPOcahY
https://www.kidney.org/atoz/content/gfr
An unresolved puzzle in human physiology is that there is no mechanism for the excretion of excess iron (Fe, https://en.wikipedia.org/wiki/Iron) - via either the kidney or any other organ.
@tonyrebelo
ENERGY-EXORBITANCE OF KIDNEY, part 4:
'Everyone knows' that the human brain - even in sleep - is energetically expensive (10-fold more than predicted for its mass).
However, how many realise that, in the case of the pair of kidneys, this disproportionality is twice as much, viz. 20-fold more than predicted for the mass?
And how many have pondered what it could possibly be, going on inside the kidneys, that demands so much energy and so much blood, and generates so much heat?
The answer cannot possibly be 'urination', which is ultimately merely a process of 'controlled leakage'.
Yes, but in the kidneys excretions is merely a pressure issue. Resorption of the component leaks out and that dare not be lost is active. Can that resorption not account for the energetic costs? It has to be fast and active. Unlike the liver and gut and other organs that can run at a passive pace, the kidney works at a high pace. The alternative is an organ 20 times bigger than works at 1x the expected rate, but then the initial pressure filtration wont work
Given that you seem to think that urea/uric acid is not so important. Why not compare relative sizes of kidneys in mammals that secrete concetrated pee (say a Gemsbok), and then mammals versus birds that secrete uric caid. What are the sizes and metabolic rates of their kidneys?
@tonyrebelo
How does the kidney of camels (Camelus) differ from that of bosts (Bos)?
On page 48 in https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC1233081&blobtype=pdf, it is stated that Bos (which produces dilute urine) and Camelus (which produces concentrated urine) hardly differ in the number of glomeruli (https://en.wikipedia.org/wiki/Glomerulus_(kidney)).
It is the glomerulus, with the associated Bowman's capsule, in which the energy-consuming work of the kidney is done. These form the cortex of the kidney (https://en.wikipedia.org/wiki/Renal_cortex).
Where the kidneys of Camelus and Bos differ is in the thickness of the medulla (https://en.wikipedia.org/wiki/Renal_medulla).
However, the supply of blood to the medulla is far smaller than that to the cortex (https://en.wikipedia.org/wiki/Renal_medulla#/media/File:Kidney_PioM.png and https://www.alamy.com/anatomy-of-the-kidneys-and-renal-blood-vessels-image7710319.html).
Therefore, I suspect that this water-retrieving part of the kidney is relatively cheap, energetically.
I infer that the kidney of camels, although far more efficient at retrieving the water from the filtrate, may have similar energetic cost to that of bosts.
Another way of saying this is that, in both camel and bost, there is an energetically intense renal cortex, where the 'mysterious' functions of the kidney are performed. In the camel, the renal medulla is additionally developed, which saves water, and is crucial for xeric adaptation. However, this requires limited additional expenditure of metabolic energy.
Also see:
https://www.jstor.org/stable/30156120
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948238/
https://www.sciencedirect.com/science/article/pii/S2405844019367982
@tonyrebelo
Excretion, whether in the kidney, the skin, or the intestines, is not performed by vascular 'pressure'. Instead, it is performed by a process similar to secretion (https://en.wikipedia.org/wiki/Secretion).
For example, when one sweats, the water is actually secreted (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508982/#:~:text=Eccrine%20glands%20form%20a%20thermoregulatory,down%20body%20temperature%20as%20necessary.).
Glands, which are organs of secretion, do not seem to be particularly costly in terms of metabolic energy, as indicated by the supply of blood, or the density of mitochondria.
In the kidney, an excretory function, similar to secretion but depositing materials in urine, occurs in the medulla, as opposed to the cortex. This is not energy-expensive, judging from the relatively small supply of blood to the medulla.
One way to think of the kidney is as a 'duplex' organ, in which a relatively easy function is hitched to a difficult function. The easy function is excretion (performed not via pressure, but via a process similar to secretion), and the difficult process is the 'oxido-transformation' that I have invoked.
The easy function occurs in the medulla, whereas the difficult function occurs in the cortex (https://www.researchgate.net/figure/The-human-kidney-with-anatomical-compartments-cortex-medulla-and-pelvis-The-filtration_fig4_261444832).
In the cortex, blood pressure is involved in the conversion of plasma (in blood) to filtrate (in the renal tubule).
However, the main reason for the metabolic expense in the cortex is that the entire chemical content of this liquid is a) reformulated rapidly within the renal tubule, and then b) reabsorbed into the blood, in an underestimated process for which we have yet to invent a satisfactory term.
This thorough processing of the filtrate, which is enzymatic, is so rapid that the whole volume of the plasma in the human body - totalling up to about 3 litres - is reformulated in the kidneys every 22 minutes.
So, the duplex nature of the kidney is that it is an expensive organ of reformulation, with an inexpensive organ of excretion seamlessly 'tacked on' to it, by virtue of the convenience in the 'plumbing'.
'Pressure' is an unimportant part of the functioning, in both cases, in the sense that it does not explain the astonishing metabolic costliness of the kidney.
What the conventional (textbook) interpretation has erroneously done is to subsume the non-excretory function into the excretory function, instead of vice versa.
This misleading approach (an 'inverted reality') has been perpetuated by ignoring the extreme metabolic costliness of the kidney. This cost cannot be accounted for - even to the nearest order of magnitude - by the excretory function.
Another way of putting this is that the excretory cost of the kidney is a 'rounding error' in the overall cost. This means that the kidney, overall, cannot logically be described as an excretory organ - any more than the heart can be described as a glandular organ, even though it does have a (subsidiary) endocrine function (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832599/#:~:text=The%20heart%20has%20an%20endocrine,pressure%20over%20the%20long%20term.).
@tonyrebelo
Please note that hormones promoting excretion of sodium, via the kidney, are produced not by any renal tissue, but instead by tissues in the main chambers (atria and ventricles) of the heart. The hormones in question are natriuretic peptides.
Various organs in the body have subsidiary functions, and in various organs a subsidiary function is hormonal. However, it strikes me as particularly noteworthy - bearing in mind that one of the main excreta of the kidney is sodium - that, in one excretory function, the heart is more kidney-like than the kidney itself.
https://en.wikipedia.org/wiki/Natriuresis#:~:text=Natriuresis%20is%20the%20process%20of,by%20chemicals%20such%20as%20aldosterone.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855512/#:~:text=Natriuretic%20peptides%20are%20a%20family,cardiac%20atria%20and%20ventricles%2C%20respectively.
The kidney 'wrangles electrons', particularly to the effect of repairing enzymes.
@tonyrebelo @jeremygilmore @ludwig_muller @zarek @botswanabugs @muir @matthewinabinett @paradoxornithidae @alexanderr @dejong @yvettevanwijk1941 @simontonge @davidbygott
Please listen to https://www.youtube.com/watch?v=Kb2qO_ncy-w.
Thank you so much, @milewski for the discussion and the interesting youtube. So if people have a kidney removed they require 5% less energy and the heart doesnt have to pump so much blood so much, so quickly. Does this mean people with a kidney removed put on weight and have to start going on a diet .
Do enzymes get repaired or just replaced ?
I am an ignoramus when it comes to Biology so please forgive my silly questions.
Do other non-human primates suffer from gout as they become utic acid excreters ?
Which mammals don't sweat and which do ? How does the presence or absence of sweating in a mammal effect the kidney size and its energy usage and blood flow through it ?
@botswanabugs
The following is a worthwhile general introduction to enzymes, for which there are about 5,000 functions in the human body:
https://digital.library.unt.edu/ark:/67531/metadc798116/.
Proteins, including enzymes, are prone to molecular deterioration from oxidation, racemisation, etc. This deterioration is cumulative, and can affect various parts of the molecule. The general phenomenon has been called 'protein fatigue' (https://www.google.com.au/search?q=Why+do+enzynes+wear+out%3F&sca_esv=592420132&sxsrf=AM9HkKkfyBAYsjSY85ZiX5IAefrQasZKEQ%3A1703049738928&source=hp&ei=CnqCZe-ENpWH4-EPkLCd-AQ&iflsig=AO6bgOgAAAAAZYKIGoQ7VTAwF4yMt68Hq6YjyGciKsSr&ved=0ahUKEwjvseLVop2DAxWVwzgGHRBYB08Q4dUDCAw&uact=5&oq=Why+do+enzynes+wear+out%3F&gs_lp=Egdnd3Mtd2l6IhhXaHkgZG8gZW56eW5lcyB3ZWFyIG91dD8yBxAhGKABGAoyBxAhGKABGAoyBxAhGKABGApI_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&sclient=gws-wiz).
Please read under the heading 'significance' in https://www.pnas.org/doi/10.1073/pnas.2023348118#:~:text=Like%20all%20proteins%2C%20enzymes%20are,function%20(9%E2%80%9311). In microbes and plants, which spend little energy on bodily movement, the metabolic cost of replacing proteins (including enzymes) can amount to as much as half of total metabolic cost.
Also see https://digital.library.unt.edu/ark:/67531/metadc798116/.
Certain enzymes are devoted to repairing genetic molecules such as deoxyribonucleic acid (DNA). However, I infer that enzymes themselves are not repaired by other enzymes, at least outside of the kidneys.
A simple way to think of the problem is that proteins, including enzymes, are 'molecular machines' or 'machine-molecules'. Like all machines, they are prone to wearing out. The idea is that the fluid spaces in the cortex of the kidneys are a kind of 'workshop' in which maintenance and repair of enzymes can be performed, temporarily free of the constant burdens/drags of a) redox reactions/free radical actions and b) the ionic electrical charges of action potentials (https://en.wikipedia.org/wiki/Action_potential) associated with membranes elsewhere in the body.
Yes, but most enzymes do not move in an out of cells, so the kidneys function would be solely on free enzymes in the blood, a function shared with the spleen, bone marrow, liver (red blood cell removal) and other organs. Replacing and repairing enzymes would be done within cells, with just waste products (urea, amino acids) excreted into the blood stream.
Might the costs not be associated with resorbing blood chemicals from the urea after filtration, or the possibility that some of these resorption enzymes like running hot?
My question is really about whether or not enzymes are ever repaired at all or just ' digested' into amino acids and co-factors and get completely reassembled. If enzymes are repaired, rather than destroyed and replaced , I need to find out more about that. Im asking as a Chemist !
@botswanabugs
The answer seems to be yes, according to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132211/.
Each type of enzyme has a certain optimum temperature and pH for its catalytic action. This implies that an enzyme is not an absolute agent; instead, it operates more or less efficiently, depending on various conditions affecting electronic action.
Another way of viewing this is that an enzyme molecule at suboptimal temperature and/or pH is effectively not as 'intact' as the same molecule at optimal temperature and/or pH.
Does this not raise the possibility that, even at optimum temperature and/or pH, an enzyme molecule can be compromised (= 'damaged' and in need of repair), by the wear-and-tear called 'protein fatigue'?
@tonyrebelo
Good thinking, thank you...
@botswanabugs
Thanks for asking about perspiration (https://en.wikipedia.org/wiki/Perspiration and https://www.houstonmethodist.org/blog/articles/2020/aug/how-sweat-works-why-we-sweat-when-we-are-hot-as-well-as-when-we-are-not/).
Please see under the heading 'physiological adjustments' in https://climatechangeresponses.biomedcentral.com/articles/10.1186/s40665-016-0024-1, for a useful summary of perspiration and thermoregulatory panting in mammals.
Mammals vary greatly in their ability to perspire, and their rates of perspiration, with humans and equids among the sweatiest of mammals.
It is a strange thought that a man riding a horse in the heat is one of the sweatiest phenomena in Nature.
However, some mammals, notably elephants, lose much water through the skin without having sweat glands.
A whole book could be written merely on the topic of how various mammals use evaporation, in different ways, for thermoregulation.
However, this would not necessarily matter much w.r.t. the point that, between the skin and the salivary glands, there is plenty of scope for excretion - whether in sweat and saliva, or in skin cells moving to the surface and being sloughed off, or in hair.
This potentiality is not exercised to the full by mammals, but this is subject to interpretation. I suggest that the main reason is that the kidneys, although designed mainly for functions other than excretion, provide an easy accessory route for excretion, i.e. adding a function with only small additional cost.
@milewski Thank you for the paper about the repair of enzymes.
@milewski Thank you for the paper about the repair of enzymes.
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