ketoacidosis

Ketoacidosis is a type of metabolic acidosis which is caused by 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 an extreme and uncontrolled form of ketosis, which is a normal response to prolonged fasting. 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.

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. Fasting leads to ketosis but not 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. Ketosis may also smell, but the odour is usually more subtle due to lower concentrations of acetone.

Pathophysiology

Ketoacidosis occurs when the body is producing high levels 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 high blood sugar levels (hyperglycemia) caused by the lack of insulin can lead to further acidity in the blood.

In healthy individuals this normally does not occur because the pancreas produces insulin in response to rising ketone/blood sugar levels.

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

Etiology

Two common types are diabetic and alcoholic ketoacidosis.

 diabetic 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 production) potentially leading to dangerous glucose and ketone levels in the blood.

Hyperglycemia results in glucose overloading the nephron 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.

 alcoholic ketoacidosis

In alcoholic ketoacidosis, alcohol causes dehydration and blocks the first step of gluconeogenesis. 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.

See also

 ketone bodies (ketone)
 ketone acids