| Ketoacidosis | |
|---|---|
 | |
| Ketone bodies | |
| Specialty | Endocrinology |
| Symptoms | nausea, vomiting, pain, weakness, unusual breath odor, rapid breathing |
| Causes | medications, alcoholic beverages, undiagnosed diabetes |
Ketoacidosis is a metabolic state caused by uncontrolled production ofketone bodies that cause ametabolic acidosis. Whileketosis refers to any elevation of bloodketones, ketoacidosis is a specific pathologic condition that results in changes inblood pH and requires medical attention. The most common cause of ketoacidosis isdiabetic ketoacidosis but it can also be caused byalcohol, medications, toxins, and rarely, starvation.[citation needed]
The symptoms of ketoacidosis are variable depending on the underlying cause. The most common symptoms include nausea, vomiting, abdominal pain, and weakness.[1][2] Breath may also develop the smell of acetone as it is a volatile ketone that can be exhaled. Rapid deep breathing, orKussmaul breathing, may be present to compensate for the metabolic acidosis.[1] Altered mental status is more common in diabetic than alcoholic ketoacidosis.[2]
Ketoacidosis is caused by the uncontrolled production ofketone bodies. Usually the production of ketones is carefully controlled by several hormones, most importantlyinsulin. If the mechanisms that control ketone production fail, ketone levels may become dramatically elevated and cause dangerous changes in physiology such as ametabolic acidosis.[3][4]
The most common cause of ketoacidosis is a deficiency of insulin intype 1 diabetes or late-stagetype 2 diabetes. This is calleddiabetic ketoacidosis and is characterized byhyperglycemia,dehydration and metabolic acidosis. Other electrolyte disturbances such ashyperkalemia andhyponatremia may also be present. A lack of insulin in the bloodstream allows unregulatedfatty acid release from adipose tissue which increases fatty acid oxidation toacetyl CoA, some of which is diverted toketogenesis. This raises ketone levels significantly above what is seen in normal physiology.[1]
Alcoholic ketoacidosis is caused by complex physiology that is usually the result of prolonged and heavy alcohol intake in the setting of poor nutrition. Chronic alcohol use can cause depleted hepaticglycogen stores andethanol metabolism further impairsgluconeogenesis. This can reduce glucose availability and lead tohypoglycemia and increased reliance on fatty acid and ketone metabolism. An additional stressor such as vomiting or dehydration can cause an increase incounterregulatory hormones such as glucagon,cortisol andgrowth hormone which may further increase free fatty acid release and ketone production. Ethanol metabolism can also increase bloodlactic acid levels which may also contribute to a metabolic acidosis.[2]
Starvation is a rare cause of ketoacidosis, usually instead causingphysiologic ketosis without ketoacidosis.[5] Ketoacidosis from starvation most commonly occurs in the setting of an additional metabolic stressor such as pregnancy, lactation, or acute illness.[5][6]
Certain medications can also cause elevated ketones, such asSGLT2 inhibitors causingeuglycemic ketoacidosis.[7] Overdose ofsalicylates orisoniazid can also cause ketoacidosis.[4]
Ketoacidosis can be the result of ingestion ofmethanol,ethylene glycol,isopropyl alcohol, andacetone.[4]
Ketones are primarily produced from free fatty acids in themitochondria ofliver cells. The production of ketones is strongly regulated by insulin and an absolute or relative lack of insulin underlies the pathophysiology of ketoacidosis.Insulin is a potent inhibitor of fatty acid release, so insulin deficiency can cause an uncontrolled release of fatty acids fromadipose tissue. Insulin deficiency can also enhance ketone production and inhibit peripheral use of ketones.[3] This can occur during states of complete insulin deficiency (such as untreated diabetes) or relative insulin deficiency in states of elevated glucagon andcounter-regulatory hormones (such as starvation, heavy chronic alcohol use or illness).[4]
Acetoacetic acid andβ-hydroxybutyrate are the most abundant circulating ketone bodies.Ketone bodies are acidic; however, at physiologic concentrations, the body's acid/base buffering system prevents them from changing blood pH.[3]
Blood tests for the diagnosis of diabetic ketoacidosis measure glycemia (sugar level), pH (blood acidity), and ketone bodies. As urgent medical treatment is often required when DKA is suspected, the tentative diagnosis can be made based on clinical history and by calculating theanion gap from thebasic metabolic panel, which would demonstrate a high anion-gap metabolic acidosis along with high glucose levels. This allows timely treatment with fluids and insulin well before direct serum ketone body testing results arrive. Urine ketone testing is also available but this cannot easily distinguish DKA from other causes of ketonuria without more context.
Diagnostic workup should also include tests to determine any potential infectious trigger for DKA such aspneumonia orUTI.[8]
Treatment depends on the underlying cause of the ketoacidosis.Diabetic ketoacidosis is resolved with insulin infusion, intravenous fluids, electrolyte replacement and supportive care.[1] Alcoholic ketoacidosis is treated with intravenousdextrose and supportive care and usually does not require insulin.[2] Starvation ketoacidosis can be resolved with intravenous dextrose with attention to electrolyte changes that can occur withrefeeding syndrome.[5]
Certain populations are predisposed to develop ketoacidosis including people with diabetes, people with a history of prolonged and heavy alcohol use, pregnant women, breastfeeding women, children, and infants.[citation needed]
People with diabetes that produce very little or no insulin are predisposed to develop ketoacidosis, especially during periods of illness or missed insulin doses. This includes people with type 1 diabetes orketosis prone diabetes.[1]
Prolonged heavy alcohol use is a risk of ketoacidosis, especially in people with poor nutrition or a concurrent illness.[2]
Pregnant women have high levels of hormones including glucagon andhuman placental lactogen that increase circulating free fatty acids which increases ketone production.[6] Lactating women also are predisposed to increased ketone production. These populations are at risk of developing ketoacidosis in the setting of metabolic stressors such as fasting, low-carbohydrate diets, or acute illness.[9]
Children and infants have lower glycogen stores and may develop high levels of glucagon and counter-regulatory hormones during acute illness, especially gastrointestinal illness. This allows children and infants to easily produce ketones and although rare, can progress to ketoacidosis in acute illness.[10]
The dictionary definition ofketoacidosis at Wiktionary