Diabetic Ketoacidosis (DKA) Explained Clearly – Diabetes Complications

Diabetic Ketoacidosis (DKA) Explained Clearly – Diabetes Complications

August 8, 2019 100 By William Morgan


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 and
so it behooves us to understand a little
bit more about what is DKA how does it
present and how to treat it
first I want to kind of 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 inter 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 will 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 coA
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 then
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 palmitoyl CoA
through the enzyme palmitoyl CoA
transferase now no longer being
inhibited or being disinhibited and
allowing quite a lot of these
palmitoyl CoAs 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 this these high two
carbon units can be used as you know
Acetyl CoA 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 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 OH 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 they’re
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 inhibition of fatty acid transport
into
matrix of mitochondria 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 units 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
an 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 and 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 in 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 diuresis 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 body show up is 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 will 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 anion gap
metabolic acidosis is kind of a
surrogate for how big the ketone bodies
are but you can actually measure ketone
body some hospitals measure serum
ketones okay and some also measure
something called beta hydroxybutyrate
you get 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 body’s 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 of 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 we also see
sometimes a low phosphorus sometimes
a normal phosphorus so this is the
hallmarks of somebody presenting with
DKA let’s talk about how we treat that
coming up here next