Pathophysiology - Type I diabetes

- Now Diabetes Mellitus is a group of disorders that's caused by improper function of insulin which is a hormone responsible for regulating blood sugar or blood glucose. And this results in Hyperglycemia. But since Diabetes is a group of disorders there's many different underlying pathophysiological mechanisms that can cause the disease. And depending on which mechanism is occurring in someone the presentation of the disease can actually be very different. So before we get started, I want to briefly talk about the Pancreas. Now you can see here we have the esophagus coming down and it dives behind the liver here. And then it goes into the stomach and then the stomach goes back behind the liver and comes out as the small intestine. And in yellow here, nestled in next to the small intestine and behind the stomach is the Pancreas. Now, the Pancreas is frequently referred to as being comma shaped and you can kind of get that. Oh, if you kind of turned it on its side it might look like a comma. But the way I like to remember how the Pancreas looks is by thinking about my favorite professional football team which is the Minnesota Vikings. And I kind of think the Pancreas maybe it looks like the horns on the side of the Minnesota Vikings helmet. So whatever helps you remember what the Pancreas looks like. But regardless, the Pancreas has two main functions. And the first function is Exocrine. What this means is that the Pancreas secretes Enzymes into the digestive tract which then chemically digests food and help your body absorb the nutrients we eat. So it helps with digestion. But the Pancreas also has some Endocrine function. And what this means is that it produces Hormones. And specifically for the Pancreas these Hormones help the body with Metabolism. But what does all this have to do with Diabetes? Well, I mentioned earlier that Diabetes Mellitus is caused by dysfunction of insulin which is one of these Hormones that the Pancreas produces. And in Type 1 Diabetes, certain areas of the Endocrine portion of the Pancreas are destroyed so that the Pancreas cannot produce insulin. And Type 1 Diabetes is actually a relatively uncommon disease. It affects about three out of every 1,000 people in the United States. Now, let's dive a little bit closer into the Pancreas to get a better understanding of what's going on. So the cells that are responsible for the Endocrine function of the Pancreas are located in regions of the Pancreas that are known as the Islets of Langerhans. So let's just draw those in here. So in these Islets of Langerhans there are two main cell types types that are responsible for producing Hormones. So in blue here, we have the Alpha cells. And the Alpha cells are responsible for secreting glucagon. Then in green we have the Beta cells. And they're responsible for secreting insulin. And as I've mentioned before, these two Hormones are responsible for regulating much of the bodies metabolism. And one specific component of this is our Blood glucose or our Blood sugar level. So what happens is if someone, just say, you pretend you just had a meal and your body starts absorbing the sugar from that meal. What's going to happen is your Blood sugar levels or your Blood glucose levels are going to increase. And this increase in Blood sugar is sensed by the Beta cells in the Pancreas and they'll secrete insulin into the blood. And what it does is that insulin is then going to lower the Blood glucose level by causing the cells all over the body to take up and absorb the glucose so that they can then use it for energy. Or it could be stored in the liver. And either way, the glucose comes out of blood so the Blood sugar level lowers. Now if insulin where to act on its own, the Blood sugar level or Blood glucose level would get too low. It would start to decrease from its normal level. And luckily the Pancreas senses this too in the Alpha cells or the blue cells here and secretes glucagon. And what happens then is glucagon causes the Blood glucose level to raise, going back to normal. And it does this by causing the liver to release the glucose that's stored there. So what does this all have to do with Diabetes or specifically Type 1 Diabetes? Well, in Type 1 Diabetes there is destruction of these Beta cells in the Pancreas so the body can't produce the insulin. And if the body can't produce insulin it's not able to lower its Blood glucose level and you have an unbalanced glucagon response. Which results in this raising of the Blood sugar and this is known as Hyperglycemia. Hyper for high, glycemia for blood sugar. But what is the underlying cause of this destruction of the Beta cells? I'm going to just slide this over so we can get a little more room to work on it. Well, Type 1 Diabetes is an Autoimmune disease. And as you can imagine by the name it has something to do with the immune system. And what happens is that someone who develops Type 1 Diabetes was born with a genetic predisposition to the disease. Now, this doesn't necessarily mean that he or she had the disease at birth. But they just had something in their genes causing them to be more likely to develop Type 1 Diabetes. Then over time there was some sort of Environmental trigger. And this part of the disease process isn't quite as well understood. And it could be something potentially like a virus, or some sort of toxin, or something else. But regardless, there's some sort of trigger that causes someone with a genetic predisposition to have this Autoimmune response or production of antibodies and T cells that then attack the Beta cells. And this is what causes the destruction of the Beta cells in the absence of the production of insulin. Which is the underlying cause of Type 1 Diabetes. And it's this Autoimmune attack of the Beta cells here that causes the Pancreas to not be able to produce any insulin. And when it can't produce any insulin what happens is that the individual will develop Type 1 Diabetes. Well, let me just move over again so we can get a little more space to go through why symptoms develop in Type 1 Diabetes. All right, so imagine a blood vessel here. And this blood vessel is transporting glucose. And in a normal individual without Diabetes this glucose is going to go to lots of different organs in the body. Such as the brain, and the muscles, and maybe give them a little Popeye tattoo for good measure. As well as the liver, where that glucose can be stored. But unfortunately in Type 1 Diabetes the insulin isn't present to take the glucose out of the blood and help it get to these organs. It gets blocked, almost like the body is starving despite having all of this glucose. And so what happens is that the liver acts like it is starving and it releases its stored glucose back into the blood. And then just like the glucose can't get out of the blood to some of these organs, it also can't get out and be stored in the fat or the adipose tissue, which I'll draw here. And so what the fat does is to also kind of try and help the body create more energy is it breaks down into something known as free fatty acids. Which I'll just abbreviate FFA, which the body can then also use for energy. It's this process here that results in the symptoms of Type 1 Diabetes. And the first one is what I'll call "Starvation in the face of Plenty." And by this I mean, the body almost acts like it's starving even though it has all of this glucose present in the blood. And this results in symptoms like lethargy and fatigue. Because it's trying to maintain the little glucose it thinks it has for the brain and the other organs that are vital and really need it. So someone with Diabetes will be lethargic and fatigued. And then the next thing that happens is, occurs in the kidneys. Now normally the kidneys reabsorb all of the glucose that's in the blood and put it back in the blood when it's, when they're filtering the blood. But when this glucose level gets so high from Diabetes it overwhelms the kidneys. And that glucose spills out in the urine. And this is known as glucosuria or glucose in the urine. And glucose is an osmotically active soluble. What does that mean? Well, what it means is that it tends to draw water with it. So as the body pees out all of this glucose a lot of water comes with it. And this is known as polyuria or poly for kind of lots or many and uria for urine. And this results in dehydration because you're losing all the water and thirst. So, someone with Type 1 Diabetes is frequently going to present with being tired and fatigued, going to the bathroom a lot and dehydrated. And unfortunately, for some individuals, if they get sick when they have Type 1 Diabetes before it's been diagnosed, the body can't compensate for the stress and you can get a life threatening disease that's called Diabetic ketoacidosis or DKA which is a life threatening form of dehydration and acidosis. When it comes to diagnosis about 70% of individuals with Type 1 Diabetes will be diagnosed in this stage before it gets too bad. Bit unfortunately, about 30% of individuals who are diagnosed with Type 1 Diabetes actually have Diabetic ketoacidosis or DKA, as their presenting symptom. So this is just a brief overview of Type 1 Diabetes which is an Autoimmune disease. Meaning that there's antibodies and T cells that destroy the Beta cells of the Pancreas so that the Pancreas can't produce insulin, resulting in Hyperglycemia or high blood sugar. And it's this high blood sugar that results in all of the symptoms of Type 1 Diabetes.