So let's take a step back and
talk about what is gout.
We'll talk about the pathophysiology in a
moment but actually the history can help us
to remember some things
about the disease as well.
This is a picture of a classic 18th century
depiction of gout, specifically podagra.
Podagra is the term that we use to
describe gout when it afflicts the 1st MTP
and that just happens to be the most common place
that people have their first episode of gout.
The word gout comes from an old Latin
term, "gota", which simply means, drops.
The thought was that gout was essentially an accumulation
of toxic humourous inside an afflicted joint.
In fact, when you use the term "insulin
drip" in the hospital and you write "gtt"
which is sort of how we use to write
orders on paper, that "gtt" means "gota",
so it means drops when
you're ordering a drip.
Same thing with guttate psoriasis where we see guttate
being used to describe little dew drops on the skin.
So the etymology can help us here.
Podagra comes from 2 Greek words,
"pod, podus" which means foot
and "agrar" which means to seize or to bite,
which is what we're seeing in this picture.
Those who have ever had an acute flare of gout,
they know there is an intense onset of pain
can come on in span of hours with heat,
redness, tenderness, swelling, the works.
and that's exactly what's captured
in this 18th century picture.
To continue with our history lesson for just a
moment, gout used to be called the "disease of kings".
But because it was only people
who were affluent and wealthy
and had access to have seafood and
high protein, meats, alcohol,
those were the folks who
were likely to get gout.
And that tells us a little bit
about the pathophysiology.
We know that gout is associated with
purine rich foods: meat, seafood, alcohol
and also it's associated with
obesity and hypertension
which is also something you would see in
the affluent who could afford to be obese.
So let's talk now about the
pathophysiology of gout.
Specifically, when we're talking
about what causes gout,
we're talking about hyperuricemia,
how much uric acid is in the body.
To start this off, I'd like you to think of
that circle in the middle that says urate
as essentially the total body
content of urate in our body.
I'll interchangeably go between saying
urate and uric acid, just so you're aware.
So on the left of that circle,
think of that as a faucet.
Those are things that are pouring uric acid into
our body, which think of that like a bathtub.
So for stuff on the left is
your dietary purine load,
how much purine rich
substances you're consuming
and then endogenous purine synthesis.
If for some reason there's increase
cell turnover or cell death,
there's gonna be a release
of purines into the bloodstream
and that's also gonna
lead to increased urate.
On the right hand side, think of that like a
drain, draining stuff out of your bathtub.
So, renal excretion, how effectively are you getting
urate out and same thing with gut excretion as well.
Turns out there's a lot of different
factors which contribute to these things,
turning the faucet on or increasing the
activity of the drain or clogging the drain.
Ultimately, as the bathtub of uric acid
increases, we have urate supersaturation,
crystallization in joints
and boom, a gout flare.
Let's look at some of
those specific factors.
First off, I mentioned dietary purine load.
Things like meat, seafood, that's gonna
increase purines coming into your body.
Obesity, we know that that's associated
with increased endogenous purine synthesis.
Pancreatitis, this simply is meant to represent any
number of different types of chronic inflammatory states
or acute inflammatory states that
just increase protein catabolism
and they're gonna lead to
increased purine synthesis.
Likewise, a lymphoproliferative disease or
lymphoma or leukemia, those kinds of cancers,
lots of increased purine synthesis there.
And lastly, a hospitalized patient.
Someone who comes in septic shock
or has a massive surgical procedure,
there's gonna be some tissue necrosis,
tissue ischemia is gonna lead to cell death
and again, a load of purines being
released into the blood stream.
So that's the faucet, now
let's focus on the drain.
And it's important to think about
the drain because it turns out that 85%
of the contributing causes of uric acid or hyperurecemia
is really the drain problems, clogging the drain.
Chronic kidney disease, our
patient's got CKD stage III,
He's gonna have a lot of trouble getting
all that urate out of his body.
Likewise, there's certain medications which
can compromise our ability to get urate out,
Turns out that diuretics while
they may help with salt excretion,
they can also contribute to uric acid reuptake and
prevent us from getting urate out of our bodies.
Other medications to think about
are also things like cyclosporine
which can also impede the flow of
urate excretion via the kidneys.
Thirdly, the ovaries.
It turns out that having
ovaries is protective.
That's why men are more likely
to get gout than women.
But as soon as a woman
becomes as post-menopausal,
either surgically or just in
menopausal period with age,
that woman now is gonna become
susceptible to hyperuricemia.
It turns out that estrogen in ovaries
was promoting urate excretion.
Once the ovaries are not doing that
anymore then uric acid starts to build up.
And lastly, diseases like hypertension have been
associated with impaired renal excretion as well.