Ketoacidosis

Ketoacidosis is a metabolic state caused by uncontrolled production of ketone bodies that cause a metabolic acidosis. While ketosis refers to any elevation of blood ketones, ketoacidosis is a specific pathologic condition that results in changes in blood pH and requires medical attention. The most common cause of ketoacidosis is diabetic ketoacidosis but it can also be caused by alcohol, medications, toxins, and rarely, starvation.

Signs and symptoms

The symptoms of ketoacidosis are variable depending on the underlying cause. The most common symptoms include nausea, vomiting, abdominal pain, and weakness.

Diabetes

The most common cause of ketoacidosis is a deficiency of insulin in type 1 diabetes or late-stage type 2 diabetes. This is called diabetic ketoacidosis and is characterized by hyperglycemia, dehydration and metabolic acidosis. Other electrolyte disturbances such as hyperkalemia and hyponatremia may also be present. A lack of insulin in the bloodstream allows unregulated fatty acid release from adipose tissue which increases fatty acid oxidation to acetyl CoA, some of which is diverted to ketogenesis. This raises ketone levels significantly above what is seen in normal physiology.

Other endocrine conditions

Endocrine diseases that may lead to ketoacidosis include severe forms of hypothyroidism, thyrotoxicosis and adrenal failure. In all cases, the hormone-sensitive lipase in cells is phosphorylated and over-active, resulting in unrestrained lipolysis.

Ketonemia and even ketoacidosis may arise from endocrine (non-diabetic) conditions alone,

Alcohol

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 hepatic glycogen stores and ethanol metabolism further impairs gluconeogenesis. This can reduce glucose availability and lead to hypoglycemia and increased reliance on fatty acid and ketone metabolism. An additional stressor such as vomiting or dehydration can cause an increase in counterregulatory hormones such as glucagon, cortisol and growth hormone which may further increase free fatty acid release and ketone production. Ethanol metabolism can also increase blood lactic acid levels which may also contribute to a metabolic acidosis.

Starvation

Starvation is a rare cause of ketoacidosis, usually instead causing physiologic ketosis without ketoacidosis. Ketoacidosis from starvation most commonly occurs in the setting of an additional metabolic stressor such as pregnancy, lactation, or acute illness.

Medications

Certain medications can also cause elevated ketones, such as SGLT2 inhibitors causing euglycemic ketoacidosis. Overdose of salicylates or isoniazid can also cause ketoacidosis. Inversely, hypothermia and underlying factors (e.g., malnutrition) can also trigger ketoacidosis.

Toxins

Ketoacidosis can be the result of ingestion of methanol, ethylene glycol, isopropyl alcohol, and acetone.

Management

Treatment depends on the underlying cause of the ketoacidosis. Diabetic ketoacidosis is resolved with insulin infusion, intravenous fluids, electrolyte replacement and supportive care.

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.