Diabetic ketoacidosis

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Diabetic ketoacidosis

ICD-10 ICD-9 DiseasesDB MedlinePlus eMedicine

E10.1, E11.1, E12.1, E13.1, E14.1 250.1 3709 000320 emerg/135

Diabetic ketoacidosis (DKA) is one consequence of severe, out-of-control diabetes mellitus (chronic high blood sugar, or hyperglycemia). In a diabetes sufferer, DKA begins with relative deficiency in insulin. In the most common cases, this is due to failure to take prescribed insulin. Insulin requirements may rise due to 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.

Contents

1.1 Muscle Wasting 1.2 Ketone Body Production 1.3 Brain 2 Treatment 3 See also
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4 External links

Mechanism
This process is vastly more common in type 1 diabetes than in type 2. A key component of DKA is that there is essentially no circulating insulin. Normally, the balance between storing energy 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 absence of insulin leads to 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 instead to secrete non-carbohydrate sources that can be used to make glucose, on which red blood cells are absolutely dependent and the brain mostly dependent for energy. Some amino acids can be converted to glucose (by gluconeogenesis), so those sources are typically locally available protein.

Muscle Wasting
If muscles cannot absorb glucose, their only source of energy is protein. Since amino acids are not stored as raw materials for metabolism, they must come from protein currently being used for other purposes. Muscles will begin to break down their structural proteins and secrete the raw amino acids into the blood stream. These amino acids travel to the liver, where they are converted to glucose. This explains the thin, wasted appearance of those that have been starved: even in the face of adequate fat stores, muscle will be broken down to make glucose.

Ketone Body Production

Despite high circulating levels of plasma glucose, the liver will act as though the body is starving since insulin levels are so low. In such starvation situations, the liver must produce another form of fuel to feed the brain. In these conditions, the liver uses the "glycerol backbone" of triglycerides to make glucose the brain can use. The fat processing, lipolysis, makes ketones from the fatty acids attached to that backbone, one result of which is ketone bodies, which enter the bloodstream and are available as fuel as well.

Brain
Normally, ketone bodies are produced in minuscule quantities, feeding only part of the energy needs of the heart and brain. However, in DKA, the body thinks it is starving. In order to reduce glucose production via muscle breakdown, the brain switches from using glucose to using ketone bodies. Ketone bodies rapidly become a major component of the brain's fuel. As a result, the bloodstream is filled with an increasing amount of glucose that it cannot use (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 produced, 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
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 levels. Most patients require admission to step-down unit or intensive care unit (ICU) so that vital signs, urine output, and blood tests can be monitored on an hourly basis. In patients with severe alteration of mental status, intubation and mechanical ventilation is required. Survival is dependent on how badly-deranged the metabolism is at presentation to a hospital, but the process is only occasionally fatal. DKA occurs more commonly in type 1 diabetes because the insulin deficiency is more severe, though it can occur rarely in type 2 diabetes. In about a quarter of young people that develop type 1 diabetes, the insulin deficiency and hyperglycemia lead to ketoacidosis before the disease is recognized and treated. This can occur at the onset of type 2 diabetes as well, especially in young people. When a person is known to have diabetes and is being adequately treated, DKA usually results from omission of insulin, mismanagement of acute gastroenteritis (the "flu"), or an overwhelming new health problem (e.g., bacterial infection, myocardial infarction). Insulin deficiency switches many aspects of metabolic balance in a catabolic direction. The liver becomes a net producer of glucose by way of gluconeogenesis (from protein) and glycogenolysis (from glycogen). Fat in adipose tissue is reduced to triglycerides and fatty acids by lipolysis. Muscle is degraded to release amino acids for gluconeogenesis. The rise of fatty acid levels is accompanied by increasing levels of ketone bodies (acetone, acetoacetate and betahydroxybutyrate; only one, acetone, is actually a ketone). As the ketosis worsens, it produces a metabolic acidosis, with anorexia, abdominal distress, and eventually vomiting. The rising level of glucose increases the volume of urine produced by the kidneys (an osmolar diuresis). The high volume of urination (polyuria) also produces increased losses of electrolytes, especially sodium, potassium, chloride, phosphate, and magnesium. Reduced fluid intake from vomiting combined with amplified urination produce dehydration. As the metabolic acidosis worsens, it induces obvious hyperventilation (termed Kussmaul respiration). On presentation to hospital, the patient in DKA is typically dehydrated and breathing both fast and deeply. Abdominal pain is common and may be severe. The level of consciousness is normal until late in the process, when obtundation (dulled or reduced level of alertness or consciousness) may progress to coma. The dehydration can become severe enough to cause shock. Laboratory tests typically show hyperglycemia, metabolic acidosis, normal or elevated potassium, and severe ketosis. Many other tests can be affected.

At this point the patient is urgently in need of intravenous fluids. The basic principles of DKA treatment are: Rapid restoration of adequate circulation and perfusion with isotonic intravenous fluids Gradual rehydration and restoration of depleted electrolytes (especially sodium and potassium) Insulin to reverse the ketosis and lower the glucose Careful monitoring to detect and treat complications Treatment usually results in full recovery, though death can result from inadequate treatment or a variety of complications, such as thrombosis http://en.wikipedia.org/wiki/Diabetic_ketoacidosishttp://en.wikipedia.org/wiki/Di abetic_ketoacidosis