The Pathophysiology of Diabetic Ketoacidosis (DKA)
Diabetes mellitus is a condition characterized by high blood sugar levels resulting from dramatically reduced insulin efficacy or quantity. Insulin is important for providing glucose to active cells for metabolic use, thereby lowering blood sugar levels. Insulin dysfunction, characteristic of diabetes mellitus, causes high blood sugar because cellular insulin uptake is compromised. Additionally, cells are unable to obtain insulin and therefore require additional energy sources, including the fat stores of adipose tissue.
Fats, or triglycerides, are composed of a glycerol (3-carbon) backbone attached to three fatty acids (hence the name, triglyceride). Digestive lipases separate the fatty acids from the glycerols. The fatty acids are then catabolized via beta (β) oxidation (diagrammed below).
Notice how the ketone bodies are eventually converted to acetyl CoA, which is an intermediate in the Krebs cycle. This is the method by which ketone bodies are used to harvest ATP.
The acidic byproducts of this process, known as ketone bodies, include acetoacetic acid (which dissociates into acetoacetate and a hydrogen ion) and β-hydroxybutyric acid (which dissociates into β-hydroxybutyrate and a hydrogen ion). The hydrogen ions decrease blood pH, resulting in metabolic acidosis*. (The conjugate bases are weak and therefore have negligible effects on plasma pH, especially considering the relative strength of the hydrogen ions’ acidity.) This subtype of acidosis is called diabetic ketoacidosis (DKA), because it is a metabolic acidosis resulting from diabetes-associated fatty acid hypercatabolism.
*Metabolic acidosis is a type of acidosis (lowered blood pH) that results from overproduction of acidic metabolites. In the case of diabetic ketoacidosis, ketone bodies are the acidic metabolites causing acidosis. This is in contrast with respiratory acidosis, in which the body is unable to remove CO2, and therefore the blood becomes acidic.
Here are some cool sources to further explore this subject:
https://diabetes.org/diabetes/dka-ketoacidosis-ketones - This article briefly explains the pathogenesis of DKA and lists symptoms and diagnostic methods.
https://www.ncbi.nlm.nih.gov/books/NBK493179/ - This article provides a short introduction to ketogenesis, which is the synthesis of ketones by processes such as β oxidation.
https://www.anaesthesiamcq.com/AcidBaseBook/ab8_2.php - This article goes over beta oxidation in the context of bodily acid-base imbalances and ketosis. It also mentions other reasons for pH imbalances, ketosis, and reviews the corresponding homeostatic mechanisms.
https://medlineplus.gov/ency/article/001181.htm - This article reviews the types of acidosis and various causes.
https://pharmaceutical-journal.com/article/ld/how-to-interpret-arterial-blood-gas-results - This article goes in-depth on assessing the origins of a patient’s acidosis or alkalosis based on measuring quantities of certain compounds in the blood. (These compounds are members of the main plasma buffering system in the body, the bicarbonate buffer system.) It’s got some fun case studies to try as well!
