Acute complications of diabetes - Hyperosmolar hyperglycemic nonketotic state

- [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.