Thursday, October 22, 2009

Liver, Brain and Kidney

In my last posting but one I described the clinical features of liver failure. It is interesting that many problems in the management of liver failure are caused by the secondary failure of other organs, especially the brain and kidney. The direct consequences of liver failure - jaundice, blood clotting defects, low blood glucose and low body temperature - are less threatening or are easily treated.

Secondary brain and kidney failure occur together, though one may more severe. If the liver goes down it takes brain and kidney down with it.

Perhaps brain and kidney functions are impaired by the same abnormality, caused by loss of liver function.

If liver function recovers, naturally or after transplant, brain and kidney recover too. The problems are functional, not structural.

I have seen a woman in liver coma for five days recover consciousness in less than twelve hours after a successful liver transplant.

What do brain and kidney have in common? How might liver, brain and kidney interact?

Liver function is central to these questions: kidney failure from other causes does not affect liver or brain function; similarly, coma from other causes does not affect liver or kidney.

High blood flow is a common feature of these three organs. Each takes about a quarter of cardiac output at rest - over a litre per minute in each case. Reduced blood flow may be a factor in the secondary failure of the kidney, but not for the brain.

Brain and kidney also share a dependency on the sodium-potassium pumps in their cell membranes. These produce the chemical and osmotic gradients fundamental to kidney function, and the electrical potentials on which the brain depends.

The conventional wisdom is that liver failure is an intoxication, Substances accumulate in the blood which poison brain and kidney.

Ammonia is the traditional culprit. The problem is that clinical severity does not correlate with blood ammonium values, and washing out ammonium by dialysis does not improve the patient.

The ammonium ion is physically similar to the potassium ion: it is conceivable that ammonium could interfere with sodium-potassium pumps.

There is a long list of other candidate toxins, including methionine and tyrosine or derivatives, diazepam-like substances, and bacterial endotoxins. The same problems apply: poor correlation of biochemical values and clinical state, and failure to improve on dialysis.

These objections weaken if the toxin binds to plasma proteins, or is itself a protein or other macromolecule. But exchange transfusion is no benefit either.

The intoxication hypothesis is strengthened by the undoubted improvement after emptying the colon: patients in stupor or early coma may be aroused by purging or enema. 'Bowel sterilisation' using antibiotics may also be beneficial. Unfortunately these manoeuvres fail if the liver failure is severe.

[A doctor prescribing an enema for a patient in liver coma should do it himself.]

Deficiency is the alternative to intoxication. The liver produces substances essential for brain and kidney function: loss of these essentials causes the secondary organ failures.

Glucose is an obvious example. Reduced blood glucose content will certainly impair and eventually damage the brain, but most patients in liver coma have adequate blood glucose, naturally or by infusion.

The rapid start-up of brain and kidney after transplant does suggest the restoration of something vital for brain and kidney cell function, either a substrate or an activator of a metabolic process.

Poor activity of membrane sodium-potassium pumps can be demonstrated in white blood cells from patients in liver failure. Incubating the cells in normal plasma rapidly restores full activity.

Such depressed pump activity resembles the effect of digoxin on normal cells. Patients in liver failure do not show the ECG changes familiar after digoxin dosage.

But, it is legitimate to ask, why do membrane sodium-potassium pumps have a receptor for digoxin? The same question asked of the brain and morphine led to the discovery of endorphins.

Digoxin and bile acids share the unusual 5-beta steroid nucleus. So far as I know, this type of steroid is produced only by the liver in humans. Bile acids accumulate in the blood if the bile duct is obstructed. They cause intense itching, and may affect the ECG, but brain and kidney functions are maintained.

So this is my hypothesis. The liver produces a regulating activator of the sodium-potassium pumping enzymes in cell membranes, especially in brain and kidney. Perhaps other ion transporting enzymes are similarly regulated. Function of these enzymes is impaired if supply of the liver activator fails, with consequent encephalopathy and nephropathy.

The activator may be a 5-beta steroid molecule, similar to a bile acid. It may be short lived in the body, so constant synthesis is necessary. The activator binds to the digoxin receptor on the enzyme, and increases its activity. Digoxin binds but does not activate, and blocks access of the activator.

Cerebral oedema is a lethal complication of liver coma. It must happen because the pumping of salt and water out of brain cells has collapsed. This is a hint that membrane pumps are failing, but of course other causes must be considered.

And. of course, the putative activator might not be a 5-beta steroid, but some other substance produced by the liver, maybe a peptide, maybe an active vitamin such as adenosyl-cobalamin, or something else entirely.

May be it is another metabolic pathway which is activated, such as ATP production. Ion pumps need ATP.

I have studied liver failure for many years. I have seen theories and treatments come and go. I perceive that there is a fatigue in liver research at present, especially in the mechanisms and management of liver failure. I suspect the subject needs a breakthrough in understanding of liver function, especially its interactions with other organs.

If I had a research facility, my priority would be liver-kidney interactions - much easier to study than the liver-brain axis. Membrane ion pumps would be my first focus.


Anonymous said...

This article regarding Liver, Brain and Kidney is very interesting and useful, the liver failure issue can affect your sexual activity, and this not only happen to older people as I used to believed, young people can also be affected so you may need to buy generic viagra to help yourself on those situations. Thanks for sharing and have a nice day.

Anonymous said...

An Ultra Higher Efficiency search that tends to make the Solo-Baric® [url=]L7[/url] genuinely a statement item. The cone offers you deeper and stronger bass at greater listening levels with less distortion due to a smaller amount tendency to flex. Simply because, when a woofer cone flexes, there is a reduction of output. This decline of output translates into much less bass.

Anonymous said...


This is a question for the webmaster/admin here at

May I use part of the information from your post right above if I give a link back to your site?


Anonymous said...

Hi guys,

Do you want to buy kinect? It is not released yet but you can pre-order the kinect for the xbox 360 already!

Click here to [url=]buy xbox kinect[/url]

Anonymous said...

howdy all,

To peeps of, I hope posting here is okay this ( Mod please move my post if in the wrong category) just stopping by to say hi. I'm a student at UCLA obtaining a degree in physical education 1 more semester to go, at this time I want to lose pounds fast. How can I teach people when I'm not even in shape

Anonymous said...

When some one searches for his essential thing, therefore he/she wants to
be available that in detail, thus that thing is maintained over here.
Review my web site backup camera

Anonymous said...

It's impressive that you are getting thoughts from this piece of writing as well as from our dialogue made at this time.
Here is my homepage - web design miami beach

Anonymous said...

Hello there! I just want to give you a big thumbs up for your excellent info you have here on this post.
I'll be coming back to your website for more soon.
Feel free to surf my page ... write eBooks fast

Anonymous said...

I don't even know the way I finished up right here, however I believed this submit was great. I don't recognise
who you are however definitely you're going to a famous blogger if you aren't already.

Look at my web page : sci-fi book blog

Anonymous said...

Hello. Facebook takes a [url=]free casino bonus[/url] speculation on 888 casino see trade: Facebook is expanding its efforts to push aside forward real-money gaming to millions of British users after announcing a sell with the online gambling retinue 888 Holdings.And Bye.

Anonymous said...

Hi there are using Wordpress for your site platform?
I'm new to the blog world but I'm trying to get started and set
up my own. Do you need any coding knowledge to make your own blog?
Any help would be greatly appreciated!

Visit my homepage - safco tables

Anonymous said...

If you are going for most excellent contents like I do, just visit this website all the time as it provides quality contents, thanks

Look into my web-site inexhaustible

Anonymous said...

Highly energetic post, I liked that a lot. Will there be a part 2?

Feel free to visit my weblog: iklan poskota

Anonymous said...

Whether you are searching for specialty styling products or
specific Loreal hair products, you are sure
to find what you need. As natural products don't have any side-effects, you can rest assured for healthy hair. It has been proved that products which contain vitamins will strengthen your hair.

Anonymous said...

thnx for sharing this well put together site. i SUCK i KNOW

Anonymous said...

My partner and I stumbled over here by a different web page and thought
I should check things out. I like what I see
so now i'm following you. Look forward to looking over your web page repeatedly.

My website;

Anonymous said...

Whats up this is kind of of off topic but I was wondering if blogs use
WYSIWYG editors or if you have to manually code with HTML.
I'm starting a blog soon but have no coding experience so I wanted to get guidance from someone with experience. Any help would be greatly appreciated!

my web page; how to lose weight fast for women

Anonymous said...

The hosts file is a popular, cross-platform way of blocking access to certain domains, such as ad-serving websites.
Apparently, it actually lifts up build up from the root and therefore stimulates hair growth.

Deemark herbal hair care oil have been traditionally used to
treat irritated stressed scalp, reduce effect of aging on hair shape and growth, combat seborrhea and alopecia.

All-natural oils such as olive, coconut, and avocado oil can be used as wonderful hot oil
treatments for hair. * Apply oil unto your hair
- Run your fingertips through your hair and rub it
in an even way.

My web-site ... hairstyles for men

Anonymous said...

With havin so much content do you ever run into any issues of plagorism or copyright violation?
My blog has a lot of unique content I've either created myself or outsourced but it seems a lot of it is popping it up all over the internet without my authorization. Do you know any ways to help protect against content from being ripped off? I'd
certainly appreciate it.

Here is my web blog

mytapworld said...

The best simple minimalisttapworld

curtains accept to be the simple chrome ones,Taps

whether that's for the kitchen as acclimated as a kitchen bore curtains

or acclimated as a ablution curtains in the bath sinks.Kitchen taps With these avant-garde

minimalist curtains the articles consistently analysis the articles afore its alien to

the customers.Shower

You can calmly acquisition superior minimalist curtains for kitchens and bath

throughout the online market.source:

robinet sale said...

J'ai ensuite place et utiliser l'outil interactif dans leur onglet de robinetterie cuisine de vie, trouver mon rêve de diriger. robinet LED et ils ont un joli petit 5 problèmes, pour vous aider à choisir le plus adapté à votre Robinetterie Vasque .

Kate moss said...

During installation, it is important that the washbasin LED Taps are mounted. Proper plumbing is important, because the installation is not an easy task and could a mess sometimes. Whenever possible, avoid Do-It-Yourself Plumbing when remodeling a Waterfall Taps, unless you're a plumber, of course r. Plumbing is a complicated job when you do not have a clue how. Thus, it is much better if you let the experts! When shopping for Antique Taps, go to online stores can offer you not only the ease of purchase, but a lot more variety and great Taps Sale .However, make sure the online store where you plan to buy your plumbing fixtures is one of Antique Kitchen Taps.

sherry jiang said...

A man of taste quality of life is high, especially bathroom design often can reflect a person's quality of life.Waterfall taps are a stylish way to make a statement in your bathroom, and are becoming increasingly popular and very affordable. will make your life more refineddand we have created a lot of artistic products of"stylish personality and quality life".

Zhu Y said...

Our pneumatic factory was founded in 2000,CHECK HERE. In decades of serving China pneumatic industry,

we have built our reputation on product knowledge, world class suppliers, application support, and value add services. Our commitment to

our employees, customers and vendors is the core of our business beliefs. In our factory, there are more than 80 front-line workers, 3000

squares working shop.Our main products are air Pneumatic Cylinder, solenoid valve and also a lot of pneumatic fittings

like Air Gun.

dc Z said...

Imagine a beautiful room that draws gasps of appreciation when people enter the room. If you are thinking of your living room, adjust your perspective and take a mental walk to your shower.

nurul iman said...

Thank you very Steady info ... hopefully more successful.
Pengobatan Herbal Liver

Amy Carry said...

In fact, now in the US people adding a lot of innovative factors, such as USB Waterfall faucet which can save power and water, as well as colorful Faucet parts which can increase your pleasure when using and enjoying the water

Eye Care Softgel said...

Thanks For Informations :)
Cara Mengobati Sperma Kosong

Heru Hendarin said...

thnks for your good information.and i hope u will update every day. :D
Manfaat Lecithin Softgel
Gastric Health tablet Green World
Khasiat Cordyceps plus capsule
Harga Ganoderma Plus capsule
Manfaat Ovary Nutrition capsule
Manfaat triflex capsule Green World
Manfaat Eye Care softgel Green world
Cara Pemesanan Ginkgo biloba plus capsule
Agen Eye Care softgel Bandung
Khasiat Braincare capsule

Obat tradisional benjolan di leher said...

Excellent information and very useful lurr. Greetings from us.
we are waiting for further information.
Obat tradisional benjolan di leher

Eye Care Softgel said...

The information is very good and very useful. I really like it and I am also waiting for the post information. And do not forget my friends visit my website :) thank you

Cara Menyembuhkan Anyang Anyangan
Obat Kolesterol Tinggi Di Apotik
Manfaat Qnc Jelly Gamat
Cara Mengobati Ulkus Kornea
Obat Tradisional Diabetes Insipidus
Obat Tradisional Degenerasi Makula
Obat Emboli Paru Di Apotik
Cara Menyembuhkan Kista Bartholin

Heru Hendarin said...

Cara Menyembuhkan penyakit tbc
Cara Menyembuhkan penyakit tipes
Manfaat QNC Jelly Gamat
Manfaat Eye Care Softgel Green World
Agen Eye Care Softgel Bandung
Obat Herbal QNC Jelly Gamat