- [Voiceover] Diabetes mellitus
and its associated complications
are the 8th leading cause of death worldwide.
Now normally we think of both type 1 and type 2 diabetes
as being more chronic conditions that result
in complications such as kidney disease
and cardiovascular disease over years to decades.
And this is true, but there are also
a couple of very important acute complications
of diabetes mellitus.
And these are known as diabetic ketoacidosis,
or DKA for short, and hyperosmolar
hyperglycemic non-ketotic state,
or HHNS for short.
And unfortunately these acute complications
can be very serious, especially HHNS,
which has a mortality rate of eight to 20%.
In this video, let's discuss hyperosmolar
hyperglycemic non-ketotic state.
Now the name hyperosmolar hyperglycemic
non-ketotic state is pretty descriptive
in regards to the metabolism that underlies the disease.
However, it does not really describe
the clinical presentation of the condition.
So let's start with that.
And most commonly, someone with HHNS
has already been diagnosed with diabetes,
and this occurs sometime after their initial diagnosis.
And since they have diabetes,
they likely will have hyperglycemia,
which is one of the defining characteristics
of diabetes mellitus.
And as we'll discuss in just a minute,
it's this hyperglycemia that's driving a lot of the events
that are occurring in HHNS.
Now over a period of days to weeks,
someone with HHNS is gonna become pretty sick,
and they're gonna have symptoms of fatigue,
maybe some weight loss.
They're gonna have extreme thirst
and frequent urination.
On physical exam they'll have signs of dehydration,
such as a high heart rate, known as tachycardia,
a low blood pressure known as hypotension,
the mucus membranes in their mouth may be dry,
and their skin may have decreased turgor,
meaning if you pinch the skin it may kind of
stick up like a tent.
And if it's severe enough, the individual
may have confusion or an altered mental status.
But why exactly do all of these symptoms occur?
To get a better understanding, let's break down
the name hyperosmolar hyperglycemic non-ketotic state,
and then discuss some of the underlying metabolism.
And we're gonna begin here with the hyperglycemia.
Remember, HHNS is caused by diabetes.
And in diabetes, there's a deficiency
of the hormone insulin.
In type 1 diabetes this deficiency is absolute.
The pancreas is not able to produce the insulin.
But in type 2 diabetes, the deficiency is relative,
meaning the body is not able to adequately
respond to the insulin that is being produced
by the pancreas.
Now one of the functions of insulin is to
pull glucose out of the blood to help store it
in cells throughout the body, such as the liver,
where it can then be used for energy later.
Now in diabetes, this doesn't occur properly.
So glucose builds up in the blood
resulting in hyperglycemia, or high blood sugar.
And since the glucose cannot be used for energy,
it can't be taken up.
This is the reason for the fatigue,
or the decreased energy that someone with HNNS has,
and because they have, they're not able to use this energy,
they may also have some weight loss.
Now this will lead us to the hyperosmolar component
of hyperosmolar hyperglycemic non-ketotic state.
So glucose is an osmotically-active solude.
And this means that wherever it goes in the body,
water likes to follow.
So in this diagram here, we have a blood vessel,
and some cells surrounding it.
Now as the glucose levels in the blood will rise,
the water is pulled out of the cells
in order to keep the concentration of glucose in the blood
at a relatively constant level.
This is what I meant by "osmotically active"
in that the water goes wherever the glucose goes.
Now then as this blood moves to the kidneys,
where it's filtered, under normal situations
the kidneys will filter out very little glucose.
They reabsorb almost all of the glucose
that's in the blood.
However, at a certain point,
the hyperglycemia becomes so severe
that the kidneys are not able to reabsorb
all of the glucose,
and it spills out into the urine.
Now just like before,
glucose is still osmotically active.
So water then follows it out of the blood
and into the urine, so this water's flowing
from cells and into the blood, and then into the urine.
And from this process the body begins
to lose a lot of water, a lot of fluid very quickly.
Now as the body loses all its water in the urine,
the concentration of the soludes in the blood,
such as sodium, potassium and glucose, increases.
And this process, which is ultimately caused
by the underlying hyperglycemia
is known as hyperosmolarity, or a high concentration
of osmotically-active soludes.
And the loss of fluid or the water,
all this water loss in the urine,
because of glucose or an osmotically-active solude,
is known as osmotic diuresis.
And this is the reason for the intense thirst
and frequent urination in HHNS,
as well as the severe dehydration
and altered mental status.
Now up to this point you may be asking yourself,
"So what is the difference between
"diabetic ketoacidosis and hyperosmolar
"hyperglycemic non-ketotic state?"
And that would be a good question,
because so far there has not been a really
significant difference between the two.
However, this is where the non-ketotic portion
of HHNS becomes the differentiator.
So the vast majority of individuals with
hyperosmolar hyperglycemic non-ketotic state
have type 2 diabetes.
This means that their pancreases
are still able to produce insulin.
So the deficiency in the insulin is relative,
because the pancreas is still producing insulin,
it's just the cells throughout the body
can't adequately respond to it.
So how does this difference affect
the underlying metabolism?
Well, in both DKA and HHNS, the body is
in a state of, in a sense, starvation,
or starvation in the face of plenty,
meaning that even though there is plenty of energy present
in the blood, in the form of glucose,
the body is starving for energy
because it can't utilize this energy.
And as such the body's metabolism responds
as if it actually is starving.
And so one of the metabolic processes
that occurs during starvation is a process
known as ketogenesis.
And as its name suggests, this is the process
by which ketones, or ketone bodies are produced.
So genesis means the creation of.
And these ketones are produced from acetyl CoA,
which is a by-product of fat metabolism.
However, these ketones, or ketone bodies,
they also have a third name, and that is ketoacids.
And that's because they're acidic.
And so the production of all of these ketones,
or the ketogenesis, results in a metabolic acidosis.
Hence the name diabetic ketoacidosis.
However, in HHNS, the individual has
type 2 diabetes as we stated.
And the insulin that is present acts to inhibit
this ketogenesis pathway,
and therefore since insulin is present in HHNS,
the creation of these ketone bodies is minimized,
hence the name hyperosmolar hyperglycemic
non-ketotic state.
So now that we understand the physiology
or the metabolism that underlies
the clinical presentation of HHNS,
let's use this knowledge to also understand
how HHNS can be treated.
Now first off, due to how severe HHNS can become,
anyone with HHNS, or anyone even suspected
of having HHNS should really be treated
in the intensive care unit, or the ICU of a hospital.
And there are two major treatments that need to occur.
The first is the administration of IV
or intravenous insulin.
So the administration of insulin overcomes
this underlying relative insulin deficit,
and therefore drives the glucose out of the bloodstream
and into the cells throughout the body.
So this is gonna decrease the hyperglycemia,
which in return is gonna decrease
the osmotic diuresis, and the fluid loss.
And the combination of those two things
are going to decrease the hyperosmolarity of the blood.
And the second treatment is the aggressive rehydration
with intravenous fluids such as normal saline.
And this replenishes the fluid loss
that's caused by that osmotic diuresis.
And it also helps to decrease the osmolality.
Now rehydration will help alleviate
the signs of dehydration,
such as the tachycardia, the hypotension,
and the altered mental status.
So as we mentioned earlier,
hyperosmolar hyperglycemic non-ketotic state
is a very serious, and potentially even life-threatening
complication of type 2 diabetes.
And as such, any individual with type 2 diabetes
who becomes very ill over a period of days to weeks
should really be taken to the emergency room
immediately to be evaluated for HHNS.
And if it's present, they need to be aggressively treated
with IV insulin and fluid resuscitation,
to prevent the potentially fatal outcomes
that are associated with
hyperosmolar hyperglycemic non-ketotic state.