enzymes again
Thanks to Arnold (and Walter) for your comments on my post, which was
trying to summarise my understanding on this iniquitous disease. It
is very kind of you to comment like this. I have read and re-read
what you have written and taken it all in, but may I make some
comments of my own.
The interesting thing, it seems to me, is this "gout attack waiting
to happen" issue.
I understand your point that we have crystals in the synovial fluid
caused by excess uric acid in the synovial fluid, which is related
somehow to excess uric acid in the blood. Reduce uric acid at source
(i.e. in the blood) cures the crystal problem in the synovial fluid.
Lots of articles that I have read refer to a BUILD-UP of uric acid
(for which I THINK that the correct term is serum urate) in the
blood. They also refer to DEPOSITS of crystals.
So we seem to have a time delay on the fuse with things building up.
Presumably this might be what causes the gaps between attacks.
Logically a build-up of serum urate should lead (in the case of
susceptible people) to a build up in the synovial fluid and therefore
a build-up of the deposits of crystals.
But can that be true ? My uric acid has been down at 464 then 362
(reported as 3.62 which I assume is simply a decimal point issue)
then 548. This doesn't seem to be a build-up as such. It seems to
me that it fluctuates during the phase of a gout attack and then
returns to a sort of standard high level during the intervening phase.
Maybe they mean a build up in the synovial fluid. That would make
more sense, and suggests a delayed transfer from the stable high
level in the blood.
Then there is the comment that "uric acid levels drop [during a gout
attack] because so much of it has left the bloodstream and is now
crystallised in the joint fluid". I have read this several times in
other articles as well.
But can that be true? How much mass of crystals would need to be
formed to remove all that uric acid out of the blood and why doesn't
the kidneys simply top up the reduced uric acid in the blood again.
And if the drop off of uric acid in the blood can happen so fast
(i.e. during the phase of a gout attack) it seems to suggest that the
idea of a slow delay in build up can't be right.
And if crystals build up, and if it is the physical shape of the
crystals (your nasty jagged particles of glass like substance) that
causes the pain, then why doesn't the pain build up slowly as the
deposits of crystals build up ?
As an engineer (so you can see why I am like a blind person stumbling
along in this field) it seems to me more logical that some other
control mechanism must be at work, which I have attributed (in my
ignorance) to other enzymes.
Nevertheless I take your point entirely that the formation of
xanthine is an intermediate stage in the production of uric acid and
that the enzyme xanthine oxidase (XO)[which presumably initiates this
formation] is inhibited by Allopurinol. I understand that reducing
serum urate levels solves the problem of crystals in the synovial
fluid anyway, so I appreciate that I am being pedantic and everything
else is just academic. Just take the pill and get your life back
seems good enough advice to me.
But it is interesting to realise just how little we know about all
this other than that crystals precipitate out of solution past a
certain ph level. If it were down to me I would give the medics all
the research money they want to get a bit further on this one. But
then I am biased.
"Getting attacks in places I never got them before" after taking allopurinol. That statement worries me, as my gout travels around anyway. I no longer have "single joint" attacks, in fact there is not a joint in my body that is unaffected (including where my collarbones connect to my ribcage).
I havfe pretty much decided that I am going to burn my vacation time this year from work "weaning myself" onto allopurinol. I truly envision being crippled for a few days. I'll stock up on painkillers, steroids if I can, and plan on being bedridden for a few days.
I have bigger fish to fry before I tackle that beast though- I go in for a sleep study next week to diagnose what I already know to be severe sleep apnea. The comments I have seen in a few posts relating to sleep and gout naturally interest me because of this- perhaps the conditions are linked somehow? We'll see what happens when I get on the CPAP machine. It should be interesting, as I doubt I have ever really had a good night's sleep. I have noticed, and been confirmed by research and posts here, that gout is like a ninja and prowls the night. Attacks seldom "come on" during the day, they are always there to greet me in the morning.
I have learned more about the mechanisms of gout from reading the posts here in the last month than I have found in the years I have suffered from it, and from what (now appears) to be superficial research that I have done.
Any thoughts on what role sleep plays as a catalyst to gout attacks?
arnoldtheskier <arnoldtheskier@...
A good and careful, well thought out post but you have opmitted the
primary source of serum urate, that is mono sodium urate, which is
uric acid, that is th4e protonated form, which is not at all soluble
in the blood and which exists primarily in the adifose tissue, fatty
tissue, of your body. Moreover, this uris acid is thought to take
between 10 to 15 years to accumulate and in its acid form, it is not
antagonistic to you or your body.
therefore, as you have already surmised, Ph of your system must play
a very significant role in whether or not you get an attack.
I'm not going to try to say any more about this than I have in
previous posts because it would be redundant but I will take this
opportunity to make a progress report on my gout patient.
Dr. Matthews, ahemmmm. that's me, seems to be doing well now after 6
months on allopurinol. After a long period of denial and conjecture
that he was going to be able to control his monster with diet and
exercize, he finally succumed to the medication rout after 3 solid
months of not being able to walk without crutches.
You may not remember or have read my posts, but I began taking
allopurinol while in the middle of a gout attack that just was not
going to go away. Over the advise of my primary physician, but
following the advise of two different, well known and relatively
famous Rumatologists, I began allopurinol in the middle of the 3-
month attack from hell. I did follow my primary physician's
recommendation and go on Prednisone-an oral cortizone-for two weeks
while I started the allopurinol and as I came out of the cortizone
induced relief after about the third week, my faithful companion-Mr.
Gout started to creep in, late at night well after I had fallen
asleep.
My primary physician had started me on 100 mg a day, and the two
Rumatolotists recommended a minimum of 300, preferably 600 for the
first 6 months. I stayed on the 100 a day for 3 more weeks, a total
of 6 weeks on 100 mg and although I was certain the pain was a lot
less, it just hurt a lot less when I was forced to walk but not
enough less that I was able to walk without some kind of aid, cain,
crutches, etc.
I demanded 300 mg and got it and within 3 days of going on 300 a day,
my gours finally started to let up. I was hobbling without any help
after the third day and by the end of the first week I was actually
walking, albeit with a slight limp. By the second week all the pain
was gone and although I fully expected to feel Dr. Matthews's pain
every time I stepped off the bed in the middle of the night, it was
actually gone.
Is this the end of the story...Well if it were I wouldnot bother to
write this. No, not by a long shot and that is actually why I am
writing this. At that time I was careful in the extreme about what I
was eating. However, after the pain had gone for a while I started to
eat things again and by the end of the third month I was back on my
old happy go lucky diet and let the urate fall where it wanted to.
Well when you start taking your allopurinol you ain't aout of the
woods by a long site. My first problem came when I had a 3 day
business trip to Phoenix where there was lots of mexican food and
where I ate breakfast, lunch and dinner as spicy hot, cheesy, full of
beans, meat etc, food. I hobbled off the plane on that third day on
returning and had to drive home using my left foot because the right
one was so swollen and inflamed.
Fact- I had never had an attack on my right food. Always my left.
Through the last 3 months I have had numerour small attacks, always a
different joint, and never a full blown attack. The attacks are
always caused by an indescretion, either getting dehydrated or eating
too much of foods that I know are triggers for me.
the key here is this, when I get these attacks, one celebrex and one
culcchine, taken together in the evening and by morning my pain is
almost completely gone. There have been two attacks that have caused
me some discomfort the next day but not anything like a real gout
attack.
Finally, and this is important and related to, I believe, stored uric
acid in our bodies. I posted and others also said they have seen the
same thing, that my show size grew from 9 to 10.5 and it did it just
when I first got my gout attacks. That size is not down to slightly
under 10 and I can tell my ankles are a lot smaller.
I believe that my system is clearing out the uric acid and when I
take in too much of my trigger foiod, or get dehydrated, the urate
level in that area where the uric acid is stored, simply goes up too
highly.
Anyway, I plan to keep taking the allopurinol for at least two more
years and at that time I plan to reduce the allopurinol back to 100
mg and wait for an attack to come. If it does not come I will have
won a moral battle at least----
I am not sure of why, nor do I need to know. I do, however know that
the attacks are much less intense, they are never in the same place
twice and they go away within 36 hours.
In other words, when you go on allopurinol you will still get gout
attacks in the begining of your treatment but the attacks will be
minor, they will be managable and they will be in places you have not
had attacks before.
I am taking it on faith that they will eventually go away completely.