Back To CoursePathophysiology Textbook
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Jen has taught biology and related fields to students from Kindergarten to University. She has a Master's Degree in Physiology.
Diabetic ketoacidosis, sometimes abbreviated as DKA, is a condition in which a high amount of acid in the body is caused by a high concentration of ketone bodies. That definition might sound complicated, but it's really not. Acidosis itself is the state of too many hydrogen ions, and therefore too much acid, in the blood. A pH in the blood leaving the heart of 7.35 or less indicates acidosis. Ketones are the biochemicals produced when fat is broken down and used for energy. While a healthy body makes a very low level of ketones and is able to use them for energy, when ketone levels become too high, they make the body's fluids very acidic.
Let's talk about the three Ws of ketoacidosis: who, when, and why. Type one diabetics are the group at the greatest risk for ketoacidosis, although the condition can occur in other groups of people, such as alcoholics. Ketoacidosis usually occurs in type one diabetics either before diagnosis or when they are subjected to a metabolic stress, such as a severe infection. Although it is possible for type two diabetics to develop ketoacidosis, it doesn't happen as frequently.
To understand why diabetic ketoacidosis occurs, let's quickly review what causes diabetes. Diabetics suffer from a lack of insulin, the protein hormone responsible for enabling glucose to get into cells. This inability to get glucose into cells means that the body is forced to turn elsewhere to get energy, and that source is fat.
As anyone who exercises or eats a low-calorie diet knows, fat metabolism is completely normal. Liver cells break down fatty acids in a process called beta-oxidation. The product of beta-oxidation is acetyl-CoA. Normally, acetyl-CoA moves on to the Krebs (or citric acid) cycle, where it's turned into energy. However, there is a limit to how much acetyl-CoA the Krebs cycle can handle. If this limit is exceeded, then the leftover acetyl-CoA is turned into one of three ketones.
Think of a crowd of people waiting to get on an escalator. If the escalator is consistently full, then some people may get tired of waiting and take the stairs. This is a little like what happens in people who have uncontrolled diabetes. Since the body can't use glucose for energy, the body is forced to break down a lot of fat. A lot of beta-oxidation means a lot of acetyl-CoA, and a lot of acetyl-CoA means the production of ketones.
Again, production of some ketones by the body is normal. Ketones can be used by the heart, the brain, and the liver for fuel. Furthermore, people who eat a diet that is extremely low in carbohydrates or do a lot of endurance exercise make more ketones than these organs can use and sometimes enter into ketosis, the state of elevated ketone levels in the body. These individuals will show the presence of ketones in the blood, or ketonemia, as well as a presence of ketones in the urine, or ketonuria. It is only when the number of ketones in the blood is high enough to cause a drop in blood pH that ketoacidosis occurs.
The symptoms of ketoacidosis we're about to discuss and their causes all make a lot of sense if you think about them as being connected rather than as separate, sort of like small roads that connect to one another, eventually leading to a superhighway. Also, pay close attention to the repeated use of scientific roots like 'uri-' and 'poly.' They mean the same thing every time you see them.
The first signs of ketoacidosis are also the signs of uncontrolled diabetes. As we said earlier, a lack of insulin means that glucose isn't going to be able to get into cells. Instead, it causes a high concentration of glucose in the bloodstream, or hyperglycemia. Normally, as blood passes through the kidneys, the kidney recovers all of the glucose present. In a state of hyperglycemia, though, the kidneys aren't able to absorb it all, and some will spill into the urine. This presence of glucose in urine is called glycosuria, and it causes a whole host of other problems.
Glucose in the urine causes water to move from blood plasma into urine via osmosis. All of this water movement creates a high volume of dilute urine, or polyuria. In order to make up for the loss of water in the blood plasma, the body's thirst mechanism kicks in, causing a frequent need to drink, or polydipsia.
Meanwhile, the body is burning fat to prevent itself from starving to death, and there is too much acetyl-CoA for the Krebs cycle to handle, producing so many ketones that ketonemia and ketonuria are present. These cause even more loss of water to the urine in the same way that hyperglycemia and glycosuria cause water loss. It's no surprise that a major symptom of DKA is dehydration. Dehydration also means loss of the sodium and potassium ions crucial for the nervous system function. These lead to heart arrhythmias like tachycardia (fast heart rate). Dehydration also leads to tissue shrinking and a very low blood pressure (hypotension) - and possibly brain swelling. Even worse, people in DKA suffer from nausea and vomiting and even more fluid loss.
As the ketones travel through the blood, they start to fall apart biochemically. This causes two symptoms. First, some of the ketones degrade into acetone. As blood passes through the lungs, acetone diffuses into the alveolar sacs and is exhaled. Acetone, which is present in some nail polish removers, smells fruity or chemical. This smell, which is also present in the urine, is a classic symptom of DKA.
The second consequence of severe ketonemia is the loss of hydrogen ions from the ketones. Once the body's natural buffering system is overwhelmed, these hydrogen ions cause a drop in pH and acidosis. Acidosis can be mild (7.25 to 7.30 on the pH scale), moderate (7.00 to 7.25), or severe (below 7.00). In an effort to rid the body of excess acid, the body will sometimes start Kussmaul breathing, a form of hyperventilation consisting of increasingly quick and deep breaths trying to expel as much carbon dioxide, which is also acidic, as possible.
Logically, the treatment of this condition leads to doing two things: relieving the most dangerous and immediate symptom and treating the root cause. The former is done by providing hydrating fluids, usually an IV drip that is isotonic with the blood, while carefully monitoring sodium and potassium ions. The latter is solved by insulin injection, sometimes, again, by IV. Finally, if the episode of DKA was initiated by infection, then that should be treated with antibiotics. Lack of treatment of DKA will lead to coma and/or death.
Let's recap what we've learned. Diabetic ketoacidosis is a serious and possibly life-threatening condition in which an increase in the amount of ketones in the body causes a drop in blood pH. DKA usually occurs during periods of metabolic stress, such as infection, in type one diabetics. Because type one diabetics suffer from a lack of insulin, the body turns to burning large quantities of fat for energy. One of the biochemicals produced when fat is broken down and used for energy, ketones, spill into the blood, lose hydrogen ions, and cause acidosis, the state of too much acid in the blood.
Symptoms of DKA include some of the symptoms of poorly controlled diabetes: elevated blood glucose levels, or hyperglycemia, as well as a frequent need to drink and to urinate. These last two, called polydipsia and polyuria, are made worse by the presence of both glucose and ketones in the urine. The most immediate and dangerous symptom of DKA is dehydration, which can lead to heart problems and low blood pressure. Ketonemia, the presence of ketones in the blood, is responsible for an odor of acetone on the breath and in the urine; these ketones also lose their hydrogen ions to make the blood acidic. Treatment includes insulin therapy, careful replacement of fluids, and treating the source of the infection.
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Back To CoursePathophysiology Textbook
20 chapters | 274 lessons