Ketoacidosis

Ketoacidosis is a metabolic state associated with high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids. The two common ketones produced in humans are acetoacetic acid and β-hydroxybutyrate.

Ketoacidosis is a pathological metabolic state marked by extreme and uncontrolled ketosis. In ketoacidosis, the body fails to adequately regulate ketone production causing such a severe accumulation of keto acids that the pH of the blood is substantially decreased. In extreme cases ketoacidosis can be fatal.^[1]

Ketoacidosis is most common in untreated type 1 diabetes mellitus, when the liver breaks down fat and proteins in response to a perceived need for respiratory substrate. Prolonged alcoholism may lead to alcoholic ketoacidosis.

Ketoacidosis can be smelled on a person's breath. This is due to acetone, a direct byproduct of the spontaneous decomposition of acetoacetic acid. It is often described as smelling like fruit or nail polish remover.^[2] Ketosis may also smell, but the odor is usually more subtle due to lower concentrations of acetone.

Pathophysiology

Ketoacidosis occurs when the body is producing large quantities of ketone bodies via the metabolism of fatty acids (ketosis) and the body is producing insufficient insulin to slow this production. The excess ketone bodies can significantly acidify the blood. The presence of a high concentration of glucose in the blood (hyperglycemia) caused by the lack of insulin can lead to further acidity. In healthy individuals this normally does not occur because the pancreas produces insulin in response to rising ketone/blood glucose concentration.

Acidity results from the dissociation of the H⁺ ion at physiological pH of metabolic ketone bodies such as acetoacetate, and β-hydroxybutyrate.

Acetone has no easily liberated proton, and is thus non-acidic in human biochemical environments.

Etiology

Two common types are diabetic and alcoholic ketoacidosis.

In diabetic patients, ketoacidosis is usually accompanied by insulin deficiency, hyperglycemia, and dehydration. Particularly in type 1 diabetics the lack of insulin in the bloodstream prevents glucose absorption and can cause unchecked ketone body production (through fatty acid metabolism) potentially leading to dangerous glucose and ketone levels in the blood. Hyperglycemia results in glucose overloading the kidneys and spilling into the urine (transport maximum for glucose is exceeded). Dehydration results following the osmotic movement of water into urine (Osmotic diuresis), exacerbating the acidosis.

In alcoholic ketoacidosis, alcohol causes dehydration and blocks the first step of gluconeogenesis by depleting oxaloacetate .^{[citation needed]} The body is unable to synthesize enough glucose to meet its needs, thus creating an energy crisis resulting in fatty acid metabolism, and ketone body formation.

A mild acidosis may result from prolonged fasting or when following a ketogenic diet or a very low calorie diet.^[3][4]

See also

• Diabetic ketoacidosis
• Keto acids
• Kussmaul breathing
• Low-carbohydrate diet
• Very-low-calorie diet

References

External links

• The Merck Manual - Diabetic Ketoacidosis
• Alcoholic Ketoacidosis
• Lancet case study Atkins diet-induced Ketoacidosis