We had looked at this earlier, but let’s
just make sure that we’re clear about the
complication of diabetic ketoacidosis.
Remember, it’s much more common or it could
be more commonly found with uncontrolled type
I diabetes and in type II diabetes, it could
be found under severe stressful situations.
For example, if you have a type II diabetic
who is then undergoing surgery, that’s quite
a bit of stress that the patient’s feeling.
So, therefore, during that time, if poorly
controlled, type II diabetic may start getting
into a state of diabetic ketoacidosis.
So, what does this mean to you?
Biochemically, it means that your breaking
down lipid, you’re forced to do so.
Would you please take a look at the picture
on your right.
I want you to take a look at the title of
In other words, you’re absent of insulin
or insufficiency of insulin.
Now, in your head, you should be thinking
about a seesaw and by seesaw I mean, the balance
between insulin and the counter-regulatory
hormones referring to your stress hormones
and specifically which one would that be here?
Glucagon and whenever you have glucagon, then
you must be thinking permissive action with
If glucagon is now winning this battle or
found to be in greater abundance, you would
expect your muscle to start breaking down
glucagon, you would expect your lipids to
start breaking down… welcome to lipolysis,
beta oxidation within the mitochondrial matrix
all because of increased glucagon.
Let’s walk down further.
What do you end up finding when you breakdown
your lipid as triglycerides?
Focus on the middle cell, please, and the
glycerol would be your backbone and the tri
referring to your three fatty acids, these
are all being broken down.
In the meantime, in the liver, what kind of
things are taking place here?
Converted to glucose amino acid is because
glucagon is then in the liver which is your
middle structure here, in the grey is undergoing
gluconeogenesis, isn’t it?
What’s my topic?
Diabetes mellitus, uncontrolled… diabetic
Your patient… how much glucose is in your
plasma in DKA?
Is it 50 with plasma and glucose or would
it be a concentration of maybe 400 or 500?
The latter, 400, 500 or 600… absolutely
uncontrolled type I or type II diabetes mellitus.
With all that said, if that’s your end objective,
take a look at the bottom right corner there
and you find the blood vessel.
You would expect there to be hyperglycemia
and with uncontrolled diabetes, you’ll also
expect your ketones or ketoacids, beta-hydroxybutyric
acid, acetoacetic acid and a little bit of
acetone to be also deposited into your plasma.
Once you have these ketoacids inside your
blood vessel, then at this point, you endogenously
We will then call this metabolic acidosis,
you would expect to find your bicarb to be
less than 22 and quite remarkably depressed.
Remember, whenever you deal with metabolic
acidosis, you are focusing upon bicarb.
Normal level bicarb is between 22 to 26, if
If you find your bicarb to be 18, 15 whatnot,
then you know that you’re in a state of
You will always confirm this by looking at
the pH which would definitely be less than
7.35… might be 7.3, 7.2, right?
Protein catabolism to glucose and can also
be seen as starvation, but think type I diabetes
more so with diabetic ketoacidosis.
Further let’s give you an overview of the
complications that you can expect with uncontrolled
What’s your insulin level in this patient,
Depressed or maybe completely absent.
You’re going to breakdown your protein,
Your second line in the liver gluconeogenesis...
in the liver glycogenolysis because we don’t
have insulin, all these results in increased
glucose into circulation.
In addition, take a look at the balance here
in the box in the grey, you have decreased
insulin and the counter-regulatory hormones
These include your glucagon and epinephrine.
All of these is then going to contribute to
hyperglycemia and DKA, as I told you, could
be ridiculously high.
Now, just to make sure we’re clear, your
next step of management, management becomes
big time important, doesn’t it?
So, your next step of management here with
such massive or exaggerated hyperglycemia,
meaning to say that your patient is severely
and extensively filtering all these glucose
into the urine, drawing in all this water…
welcome to osmotic diuresis.
You might be losing up to six litres of water
or urine per day, what’s your next step
Keep that in mind, we’ll talk about this
Lipolysis taking place resulting in beta oxidation;
you have ketoacidosis… metabolic.
Now, here, when there’s metabolic acidosis
and your bicarbs maybe 18 or 16 or whatnot
and then immediately minutes thereafter, what
is your breathing rate?
Your respiratory rate would be increased because
you’re trying to compensate by decreasing
How did you decrease your carbon dioxide?
You blow off your… you blow it off in a
rapid rate, whooh, whooh, whooh, whooh.
And when you do so, this breath that you’re
smelling from patient with diabetic ketoacidosis...
sweet odour, huh, sweet odour, why?
Because of that acetone, we call this kussmaul’s
Important here more biochemistry as to integration.
First and foremost, you want to keep in mind
for pathology, three different lipases that
we have in our body.
In gastro, we talked about the three different
lipases, we definitely talked about them in
In the pancreatic lipase, we have lipoprotein
lipase, we have hormone-sensitive lipase…
Make sure that you know each and every single
one of those and its clinical significance.
The pancreatic lipase as you know is used
as a marker as far as you’re concerned for
pancreatic damage specifically pancreatic
Then we have lipoprotein lipase which is our
Lipoprotein lipase is found within the peripheral
blood… in the blood.
What’s the third type of lipase that I mentioned?
Hormone sensitive lipase.
Do you remember these?
Keep all three separate.
At this point, our discussion is lipoprotein
lipase also called capillary lipoprotein lipase
located in your blood vessel.
It’s responsible for doing what?
It’s responsible for metabolising your triglycerides
into the respective free lipids and what that
means is that if you’re taking up lipid
from the diet, you’re forming chylomicron.
The chylomicron is then put into circulation
and guess who works upon your chylomicron?
Your lipoprotein lipase so you can then extract
Number two, if you’re moving from the liver
out towards your tissue, that’s VLDL and
that also is worked upon by or acted upon
by lipoprotein lipase.
So, extracting all the triglycerides… lipoprotein
lipase is… what’s my point?
In a diabetic patient, especially DKA, what
do you expect their triglyceride levels to
Really high, really high, really high.
So, what I’m trying to say is if you don’t
have the insulin, you have decreased activity
of your lipoprotein lipase, you’re not able
to properly extract your triglycerides from
the respective packages or vessels, chylomicron
or VLDL, this would then remain back in your
circulation contributing to hypertriglyceridemia;
increased chylomicron, increased VLDL leading
into clinical significance or finding of hypertriglyceridemia.
Each one of these points here with complications
that we find with diabetes mellitus, extremely
important from a biochemical point of view.
It’s a beautiful overview of things that
you want to keep in mind and integrate.
If you feel weak at any point here, please
go back and refer to biochem, physio whatnot…
make sure you know the normal first so you
can understand the abnormal.
So, DKA is more common in type I characterized
by hyperglycemia and anion gap metabolic acidosis.
What is the anion gap?
The formula is one major cation clinically,
one major cation.
“What about potassium, Dr. Raj?”
Hmm, 3.5 to 5.0; use it if you wish, clinically
though, you will be using sodium 135 to 145.
From this, you subtract your anions… there
are two of them, you’re going to take both
These then include your chloride 95 to 105
plus what’s the other major anion?
Bicarb, between 22 to 26.
If you’re weak in this area, I’d recommend
that you go back and take a look at your acid-base
Ketonemia, of course, and anion gap.
Fatigue, blurred vision and polydipsia, polyuria…
yeah, lots of polyuria… lots.
Nausea, vomiting, abdominal pain; kussmaul’s
respiration and fruity breath.
What does that even mean?
Remember this is compensation, you’re trying
to blow off the carbon dioxide.
The common precipitants… new onset diabetes,
inadequate insulin use or infections.
What’s happening, what’s predisposing
the patient into DKA?
The patient just started developing diabetes,
completely exhausted insulin either from type
II perhaps rarely, but could happen especially
under stressful situations and definitely
Remember, you could be in your 20’s and
still develop type I diabetes mellitus.
New - onset, the patient doesn’t know that
he or she is suffering from it, all of a sudden
resulting in DKA; inadequate insulin use,
Let’s talk about management.
First step, make sure that you replenish the
Oftentimes three to six litres, that’s how
much this patient is urinating all over the
Add dextrose to IVF when glucose is less than
200 and what that means is the following.
What’s occurring is the fact that you’re
giving fluids and initially with all of that
fluid that is then being given, there’s
every possibility that along with this obviously
you’re going to give insulin infusion, right?
Now, as you give insulin, what then happens
to this glucose?
It rapidly, rapidly, rapidly decreases and
if at any point in time if you so desire to
also control the glucose.
Remember, you want to monitor your glucose
at all times when you’re giving insulin…
an IV resuscitation is important and dextrose
becomes an important component.
When you start finding your glucose levels
dropping below 200, but that is not how the
patient is presenting initially.
Is that clear?
Your patient is presenting initially with
ridiculously high levels of glucose.
“So, Dr. Raj, what’s causing the decrease
Oh yes, IV fluid is being given along with
insulin, obviously that insulin is going to
decrease that glucose rapidly.
In certain patients, you definitely want to
be careful; close monitoring of not only their
glucose but then also electrolytes… do not
What does insulin do with potassium?
It takes it up into the cell, it technically
stimulates the sodium-potassium ATPase pump
and with that pump, you’re going to pump
the potassium into the cell, your patient
is now rendered hypokalemic and that is really
dangerous for the heart, isn’t it?
Because now you’re causing hyperpolarization
of the resting membrane potential… not good.
In addition, also pay attention magnesium
Magnesium… remember, if your magnesium levels
start dropping, that is not good either.
Your patient is now predisposed to seizures
and perhaps even long QT syndrome; once again,
Subcutaneous insulin administration before
discontinuing insulin infusion completely.
Always make sure that you’re able to properly
wean your patient off.