okay well welcome to another MedCram
lecture we're going to talk about
diabetic ketoacidosis
DKA now DKA is a pretty significant
illness that accounts for about a
hundred and thirty-five thousand
hospital admissions every year in the
United States and it has an estimated
cost of about 2.4 billion u.s. dollars
every year so pretty sizable chunk of
cash is used to treat these patients so
it behooves us to understand a little
bit more about what is DKA how does
present and how to treat it the first I
want to do is take you to the cellular
level so over here I will show you our
cell wall and on it it's got a insulin
receptor also inside the cell you'll
recall that we have mitochondria and
you'll recall that there is a inner
membrane space along with the matrix the
matrix is that inner part now remember
where things are you've got glucose
outside the cell that wants to move
inside and you've got fatty acids as
well I'll draw a fatty acid here you'll
recall this is where Krebs cycle occurs
I'll abbreviate that as KC and this is
where you have beta oxidation remember
these a fatty acids move inside the cell
you'll also recall that glucose once it
gets inside the cell is going to undergo
glycolysis and that it will also go
inside the cell in the form of pyruvate
which will eventually get broken down to
the same product and enter Krebs cycle
as acetyl co a so we'll just do it acid
Co Co a massive teal a ok so in the
normal situation you've got insulin
insulin binds to its receptor and
insulin also
prevents for the most part fatty acids
from moving on into the cell for a
process of beta oxidation so in the
normal situation what you have is you've
got insulin hitting receptor causing
glucose to go into the cell glycolysis
is occurring which the end result is
pyruvate pyruvate then moves into the
mitochondria Krebs cycle occurs and you
get boom ATP great in the situation with
diabetes mellitus type 1 where you have
no insulin being secreted or in the case
of diabetes type 2 where you have a very
strenuous state high glucagon levels
high epinephrine low insulin levels what
you have then is in either of these
cases no insulin secretion or insulin
resistance in which case and here's the
key point here glucose can no longer
come into the cell there is no
glycolysis
there is no pyruvate this mode of energy
source is cut off similarly insulin is
no longer available to prevent beta
oxidation and so what you get at that
point is you get quite a lot of Paul
Mathilde Co a tomatillo Co a through the
enzyme palmitoyl Co a transfer ace now
no longer being inhibited or being
disinhibited and allowing quite a lot of
these Paul Mathilde Koei's to go inside
the cell and of course what happens
there is that they are chopped up into
two carbon units so that's called beta
oxidation so chop chop chop chop chop
chop and so you're getting quite a bit
of two carbon units in here and these
high two carbon units can be used as you
know a steel Kawai in Krebs cycle to
make energy it's not the best way of
making energy but they can make energy
and those ketone bodies are acetone
which looks like this as you might
recall
acetoacetate which looks like this and
something called beta-hydroxybutyrate
which looks like this as you can see it
these are a result of these two carbon
units coming together and the breaking
up of ketone bodies and so all of these
actually are ketone bodies acetone is
very volatile and so it can turn into a
gas and this is what you smell on the
breath of somebody who is in
ketoacidosis you get this acetone smell
but particularly the thing I want you to
pay attention to here is this carboxylic
acid chain and this is the whole
carboxylic acid group right here but
particularly this OAH group because this
proton comes off very nicely and when it
does what you have left behind is the
conjugate base which is negatively
charged which is what's going to account
for your anion gap and if you want more
information on the anion gap please see
our lectures on ABG interpretations and
Medical acid-base so I think I want to
review that and tell you exactly what
I'm thinking there number one in DKA we
have a lack of insulin and as a result
of that we see blood sugars go up yes
but I think the biggest thing that you
ought to pick up from that is number two
is that there is no in abyssion of fatty
acid transport into matrix of Myto
Condrey a-- that's important because
this means that fatty acids are pouring
into the matrix of the mitochondria as
we showed you on the last slide that
means beta oxidation is occurring which
as you as you recall beta oxidation is
simply when you have these long chain
fatty acids getting chopped up into two
carbon units these
two carbon yards are then being fed into
the krebs cycle but because there's so
many of them they start combining and
forming these ketone bodies and these
ketone bodies are acidic so where's the
acid coming from the acid is coming from
the ketone bodies which are coming from
the acid coa which are coming from the
fatty acids which are coming from the
outside which are being transported
because there is no insulin that's very
important
okay so let's review that number one
what we're going to see here is low
insulin and as a result of that this is
what we're going to see low insulin
leads to ketone bodies which is going to
lead to acidosis specifically and an ion
gap acidosis which is going to lead to
increased potassium now why does that
potassium go up in this case it goes up
in this case because there is a proton
potassium exchange mechanism between the
cells and so as protons are being
increased in the serum and they go into
the cells
potassium have to leave the cells and go
into the serum to replace them so you'll
see an increased potassium level at
least initially now decreased insulin
also leads to high glucose high glucose
is going to lead to dehydration and why
is it going to do that well because the
glucose levels become so high that they
exceed the reabsorption threshold in the
kidneys and so what you get then is a
osmotic diuresis that simply means that
there's too many particles in the urine
because of the excess glucose that the
kidney can't reabsorb at all and that
excess osmotic pressure causes fluid to
go with it and that causes dehydration
that dehydration is going to do a couple
of things
it's going to make all your potassium
shift out of your cells and get dumped
and so this kind of then leads back into
this but then as well you get a total
body potassium depletion even though
your potassium level and your serum is
high you're being depleted of your total
body potassium so what have we seen here
we've seen ketone bodies we've seen
hyperglycemia we've seen acidosis we've
seen dehydration we've seen osmotic d hi
guya rhesus and we've seen total body
potassium depletion and along that you
can also put total body phosphate
depletion as well
now the dehydration can lead to
increased creatinine because of renal
failure and so this is what you
typically see in a patient who comes in
with DKA they are at risk because they
have low insulin you can test their
blood by checking for ketone bodies and
because of this you'll see an anion gap
metabolic acidosis again look at our
lecture on acid-base but what ketone
bodies show us is the anion gap
metabolic acidosis what that means is
the anion gap which is if you look at
the chem 7 sodium subtracted the
chloride and the bicarb won't be greater
than 12 and that's usually the first
sign you'll have so you'll have an anion
gap metabolic acidosis and that anti get
metabolic acidosis is kind of a
surrogate for how big the ketone bodies
are but you can actually measure ketone
bodies some hospitals measure serum
ketones okay and some also measure
something called beta hydroxy butyrate
you look at the acidosis as mentioned
sometimes you'll see a high potassium
usually you'll see a high potassium but
again the total body potassium is
depleted because a lot of those
a lot of the bodies potassium has been
depleted outside of the cells and into
the serum you see these patients very
dehydrated with maybe sometimes
hypotension and tachycardia because the
osmotic diuresis you'll see an increased
creatinine because of dehydration and of
course you'll see a high glucose which
is one of the things that we all look
for but may not be there you'll also see
sometimes a low phosphorous sometimes a
normal phosphorous so this is the
hallmarks of somebody presenting with
DKA let's talk about how we treat that
coming up here next
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