What is the biochemical mechanism of ketoacidosis?
Nov 25, 2025
Source: Cainiu Health
Dr. Tian Hongbo
Introduction
The biochemical mechanisms of ketoacidosis generally include absolute or relative insulin deficiency, enhanced fat catabolism, excessive ketone body production, acid-base imbalance, and electrolyte disturbances. Insulin normally inhibits fat breakdown and promotes glucose utilization; when its secretion is sharply reduced or its action impaired, the body cannot effectively utilize glucose and instead turns to fat breakdown for energy, setting the stage for ketoacidosis.
The biochemical mechanisms of ketoacidosis generally include absolute or relative insulin deficiency, enhanced fat catabolism, excessive ketone body production, acid-base imbalance, and electrolyte disturbances. A detailed analysis is as follows:
1. Absolute or relative insulin deficiency: Insulin inhibits fat breakdown and promotes glucose utilization. When insulin secretion drops sharply or its action is impaired, the body cannot effectively use glucose for energy and instead turns to fat breakdown, setting the stage for ketosis.
2. Enhanced fat catabolism: Insulin deficiency activates lipase enzymes, promoting extensive breakdown of fats in adipose cells and releasing large amounts of free fatty acids into the bloodstream, which are transported to the liver and serve as the primary substrate for ketone body formation, leading to abnormally increased fat metabolism.
3. Excessive ketone body production: Upon receiving an influx of fatty acids, the liver converts them via β-oxidation into acetyl-CoA. Due to lack of insulin regulation, acetyl-CoA cannot adequately enter the tricarboxylic acid (TCA) cycle for oxidation, and instead is shunted toward excessive ketone body synthesis, exceeding the body’s metabolic capacity.
4. Acid-base imbalance: Accumulation of excess acidic ketone bodies consumes alkaline substances in the body such as bicarbonate, leading to decreased blood pH and resulting in metabolic acidosis, which impairs normal function of tissues and organs throughout the body.
5. Electrolyte imbalance: During acidosis, potassium ions shift from inside cells to the extracellular space. Additionally, excretion of large amounts of acidic substances through urine results in loss of electrolytes such as sodium, potassium, and chloride. Symptoms like vomiting and polyuria further exacerbate electrolyte depletion and contribute to imbalance.
If symptoms suggestive of ketoacidosis occur—such as increased thirst and urination, nausea, vomiting, or breath with a fruity (acetone-like) odor—immediate medical evaluation is required. Patients with diabetes should regularly monitor blood glucose levels and take insulin or other antidiabetic medications as prescribed, avoiding abrupt discontinuation of treatment.
