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Diabetic ketoacidosis (DKA) is one consequence of severe, out-of-control diabetes mellitus (high blood sugar, or hyperglycemia). In a diabetes sufferer, the spiral begins with a physiologic stress that causes release of catecholamines, glucagon, and cortisol. This stress may be emotional or physical, although the most common cause by far is infection (e.g., pneumonia or urinary tract infection). Simply having uncontrolled hyperglycemia may be sufficient to trigger an attack if significant dehydration occurs.
This process is vastly more common in diabetes mellitus type 1 than in type 2. A key component of DKA is that there is essentially no circulating insulin. Normally, the balance between storing and releasing energy in the body is controlled by the insulin to glucagon ratio. In type 1 diabetics, who do not produce any insulin on their own, the unfortunate effect of one half of a ratio being zero creates DKA.
Without insulin, cells cannot transport glucose out of the bloodstream and into themselves. This occurs because glucagon tells cells not to use glucose from outside, but to instead secrete non-carbohydrate sources that can be used to make glucose, on which red blood cells are absolutely dependent and the brain mostly dependent in order to have energy. Some amino acids can be converted to glucose (by gluconeogenesis), so those sources are typically locally available protein. This is the only source in muscle tissue; the liver can also use the 'glycerol backbone' made available in its fat processing. Since neither protein nor amino acids are stored as 'raw material', amino acids used in glucose production must come from protein currently in use for other purposes. This explains the thin, wasted appearance of those who have been starved: even in the face of adequate fat stores, muscle will be broken down to make glucose.
In starvation situations, then, the liver must produce another form of fuel. The brain, in particular, is protected by the blood-brain barrier which makes it unable to use fats for fuel. If it is to avoid using glucose, it must have a new energy source. The liver provides this by making ketone bodies from fats, then secreting them into the bloodstream. Normally, ketone bodies are produced in minuscule quantities, feeding only part of the energy needs of the heart and brain. In DKA, they rapidly become a major component of the brain's fuel.
As a result, a bloodstream filled with glucose that it cannot use and that is spiraling higher and higher (as the liver continues gluconeogenesis and exporting the glucose so made). This significantly increases its osmolality. At the same time, massive amounts of ketone bodies are being made, which in addition to increasing the osmolal load of the blood, are acidic. As a result, the pH of the blood begins to change. Glucose begins to spill into the urine as the proteins responsible for reclaiming it from urine reach maximum capacity. As it does so, it takes a great deal of body water with it, resulting in dehydration.
Dehydration worsens the increased osmolality of the blood, and forces water out of cells and into the bloodstream in order to keep vital organs perfused. The vicious cycle is now set, and if untreated will lead to coma and death.
Treatment consists of hydration to lower the osmolality of the blood, replacement of lost electrolytes, insulin to force glucose and potassium into the cells, and eventually glucose simultaneously with insulin in order to correct other metabolic abnormalities, such as elevated blood potassium (hyperkalemia) and elevated ketone bodies. Survival is dependent on how badly deranged metabolism is at presentation to a hospital, but the process is only occasionally fatal.
Original version from the public domain NIH Diabetes dictionary. Significantly modified
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