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Acute complications of diabetes - Diabetic ketoacidosis

Video transcript

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 and 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 if someone has type 1 diabetes well since their pancreas cannot produce 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 truce 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 it 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 pawnshop 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 we'll 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 protea 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 lipolysis 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 neo Genesis 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 free fatty acids from the like pollicis and 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 byproduct known as acetyl co a 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 co way from gluconeogenesis which then undergoes a series of reactions to produce ketones then the last pathway dimension is that of glycogen iliza 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 this 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 two days and the most commonly complained 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 these symptoms occur so now as you have vomiting and abdominal pain are pretty nonspecific 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're normally able to reabsorb all of the glucose in the blood however at a certain point of hyperglycemia the amount of glucose in the blood exceeds the kidneys ability to reabsorb it and glucose begins to spill out into the urine and this is a process called glucose areia and glucose is an osmotically active solute in the urine this means that glucose sucks the water that's in the blood stream 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 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 this 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