- [Voiceover] Oftentimes we
think of diabetes mellitus as a chronic disease that
causes serious complications over a long period of time
if it's not treated properly. However, the acute complications
of diabetes mellitus are often the most serious, and can be potentially
even life threatening. Let's discuss one of the acute
complications of diabetes, known as diabetic
ketoacidosis, or DKA for short, which can occur in individuals
with type 1 diabetes. Now recall that type 1 diabetes is an autoimmune disorder. And as such, there's an
autoimmune destruction of the beta cells in the pancreas, which prevents the pancreas from producing and secreting insulin. Therefore, there is an
absolute insulin deficiency in type 1 diabetes. But what exactly does
this mean for the body? To get a better understanding,
let's think about insulin requirements as a balancing act with energy needs. Now the goal here is to
keep the balance in balance. As the energy requirements
of the body go up, insulin is needed to take
the glucose out of the blood and store it throughout the body. Normally in individuals
without type 1 diabetes, the pancreas is able to
produce enough insulin to keep up with any amount
of energy requirement. But how does this change is
someone has type 1 diabetes? Well since their pancreas
cannot produces as much insulin, they have an absolute insulin deficiency. Now for day-to-day activities, this may not actually cause any problems, because the small amount
of insulin that is produced is able to compensate and
keep the balance in balance. However, over time, as
type 1 diabetes worsens, and less insulin is able to be produced, then the balance becomes slightly unequal. And this results in the
sub-acute or mild symptoms of type 1 diabetes such as fatigue, because the body isn't able to match these energy requirements. But what happens if the body
is placed in a state of stress, such as with an infection? Now these stress situations require a tremendous amount of energy, and the balance ends up
getting tipped to a point where the body is far from
being able to compensate. And this is the situation in which diabetic ketoacidosis occurs. And when this happens,
metabolically speaking, the body goes into a starvation state. Now this is not necessarily
a true state of starvation because someone with type 1 diabetes is still able to eat
and bring in nutrients. However, without an
adequate amount of insulin, the body is not able to utilize
these nutrients for energy. And in this sense, type 1
diabetes can be thought of as a starvation in the face of plenty, as glucose is present, in
fact it's present in excess in the blood, however the body is not able to utilize it for energy. So the body reacts as if it is starving, which in some senses it is. So how does this
starvation metabolism then result in diabetic ketoacidosis? Well, first let's start with the goal of starvation metabolism,
and that is to preserve energy for crucial,
life sustaining organs, and the most important
of which is the brain. And one thing you need
to know about the brain, is that when it comes to
energy, the brain is very picky. The brain can't utilize
many forms of energy. In fact, there are only
two forms of energy the brain can use, and these are glucose and ketones. And if it has to choose between the two, it prefers glucose. So the goal of starvation metabolism is to convert other forms of nutrients such as fat, protein and glycogen
into glucose and ketones. Now in order to understand
the clinical presentation of diabetic ketoacidosis, we need to discuss a
few metabolic pathways that occur throughout the body. So I like to think of metabolism as being similar to a pawn shop. At a pawn shop, the goal is to convert different items of value, such
as precious stones or gold into a usable form of
currency in the form of cash. Now in metabolism, there are
many different forms of energy, such as proteins in muscle, and the triglycerides, or lipids
that are in adipose tissue. However, as I just mentioned, they're not usable by the brain. So they need to be converted
into usable forms of energy, such as glucose and ketones. And this most commonly
occurs within the liver, which can be thought of
as the metabolic pawnshop. And there are a few important pathways for the conversion of these energy sources into glucose and ketones, and these pathways are
driven by the interaction between many different hormones. Now, fortunately, the
names of all these pathways will help give us an idea of what they do. So we'll start with proteolysis, which occurs within muscle cells. If we look at the name, lysis
stands for the breakdown, and proteo stands for protein. So proteolysis is the
breakdown of proteins. And in this process,
proteins are broken down into amino acids, which are then carried through the bloodstream to the liver, where they take part in gluconeogenesis, which we'll discuss in
just a minute, here. And similarly, Lypolysis occurs
in adipose, or fat tissue. Now lipo stands for lipids,
which are another term for fats. And once again, lysis
stands for the breakdown of. And in this process, the triglycerides that are within lipids are broken down into their component
parts, which are glycerol and free fatty acids. And they are then carried
through the bloodstream to the liver to take
part in gluconeogenesis. And it's important to
note that this process also produces some inflammatory cytokines, which will become important
in just a little bit, here. Now let's move on to gluconeogenesis. If we look at the name,
neogenesis stands for the creation of, and
glucose represents glucose. So gluconeogenesis is
the creation of glucose, which as you recall, is
one of the primary goals of starvation metabolism. So how does this work? Well, the amino acids from
proteolysis in the muscle cells and the glycerol and the
free fatty acids from the lipolysis in the adipose tissue undergo a series of metabolic
reactions within the liver, that produce glucose. But this process is not
perfect, and in order to create glucose from free
fatty acids and glycerol, a by-product known as
acetyl CoA is produced, and then utilized later in
the ketogenesis pathway. So we mentioned that the purpose of starvation metabolism is to
produce glucose and ketones. So the ketogenesis is
where ketones come in here. And it's the metabolic
pathway for the creation of, or the genesis of ketones. And it utilizes the acetyl
CoA from gluconeogenesis, which then undergoes a series of reactions to produce ketones. Then the last pathway to mention
is that of glycogenolysis, which is the lysis, or
breakdown of glycogen. So glycogen is a storage form of glucose. And essentially all it is, is a polymer of many different glucose molecules, or a chain of glucose molecules that are linked to one another. And in glycogenolysis, glycogen
is broken down into glucose, which is once again,
one of the primary goals of starvation metabolism. Now as you can see, there's
a lot going on here, but by understanding
these metabolic pathways, we can gain a clearer understanding of the clinical presentation
of diabetic ketoacidosis. So what is this clinical presentation? First off, someone in DKA is very sick, and likely became sick over a
fairly short period of time, maybe just a few hours to days. And they most commonly complain of abdominal pain, nausea, and vomiting. In addition, they are severely dehydrated, and therefore their skin
may appear cool and clammy. Then lastly, and most
alarming, many individuals in diabetic ketoacidosis will
have an altered mental status, meaning they may be confused
or even unconscious. So why do all of these symptoms occur? So nausea, vomiting and abdominal pain are pretty non-specific symptoms, but they are very common
in diabetic ketoacidosis, and these symptoms occur because of these inflammatory cytokines that
are released from lipolysis, and other metabolic processes. And then these cytokines irritate the gastrointestinal tract,
resulting in these symptoms. Now, unfortunately, the
loss of fluid from vomiting leads to the next clinical
symptom, which is dehydration. However, the dehydration that occurs in diabetic ketoacidosis
is extremely severe, and much more severe than what's caused by the vomiting alone. But why exactly is this? Well, we discussed earlier that the goal of starvation metabolism
is to produce glucose. So what's the problem here? Well, remember, the patient has diabetes. And if there's a deficiency of insulin, then the body is not able
to pull all of this glucose out of the blood to either store it or utilize it for energy. So the body is acting like it's starving, and it continues to
produce all this glucose despite its not being able to use it. And the glucose then builds
up and builds up in the blood, resulting in hyperglycemia,
or high blood sugar levels. Now when the kidneys are filtering blood, they are normally able to reabsorb all of the glucose that's in the blood. However, at a certain
point of hyperglycemia, the amount of glucose in the blood exceeds the kidney's
ability to reabsorb it, and glucose begins to
spill out into the urine. And this is a process called glucosuria. And glucose is an osmotically
active solute in the urine. This means that glucose sucks the water that's in the bloodstream
out into the urine with it, and this is known as osmotic diuresis, or the loss of water due to an osmotically active solute. And it's this osmotic diuresis
that causes the severe fluid loss and dehydration
in diabetic ketoacidosis that can lead to an altered mental status. Now once again, it's
not just the dehydration that causes the altered mental status in diabetic ketoacidosis. It is made worse because
of the consequences of ketogenesis. So ketones, or ketone bodies,
are an important source of energy for the brain and heart during times of starvation. However, they come at a trade-off, and that is that ketone bodies are acids, so they lower the pH of the blood, a process known as acidosis. And the body is able to buffer
this effect to an extent, however, in DKA, the ketones are produced in such large quantities that it overcomes the buffering ability of the body, and results in acidosis. And since it's due to a metabolic process, it is known as a metabolic acidosis. And metabolic acidosis
worsens altered mental status, and also if it's severe
enough, it may even cause cardiac arrhythmias, or
abnormal heart rhythms, that can be fatal. So you can see here that
the clinical presentation of diabetic ketoacidosis is directly tied to the underlying metabolism that's caused by the starvation state, or perhaps, as we said
earlier, better put, the starvation in the face of plenty that occurs in type 1 diabetes. And anytime someone with type 1 diabetes presents with abdominal
pain, altered mental status, and signs of dehydration, DKA, or diabetic ketoacidosis,
should be very high in the differential for
the cause of their illness. And they will need to be
treated quickly and aggressively with intravenous fluids and insulin, because if it's left untreated, diabetic ketoacidosis can be fatal.
