Ketoacidosis

from Wikipedia, the free encyclopedia
Classification according to ICD-10
E87.2 Ketoacidosis
ICD-10 online (WHO version 2019)

The ketoacidosis is a form of metabolic acidosis , particularly frequently as a complication of diabetes mellitus occurs in absolute insulin deficiency. The cause is too high a concentration of ketone bodies in the blood.

Causes and origins

When ketoacidosis develops, the organic acids acetoacetic acid and β-hydroxybutyric acid (ketone bodies) accumulate in the blood and reduce its pH value , caused by a long-term absolute insulin deficiency .

This disinhibits lipolysis and gluconeogenesis , resulting in acetyl-CoA and NADH being produced by lipolysis . The acetyl-CoA can now not (as "normal") be used in the citrate cycle , because this is inhibited on the one hand by the high NADH concentration, on the other hand, there is no oxaloacetate , the reaction partner of acetyl-CoA, since the uninhibited gluconeogenesis is oxaloacetate Substrate used for glucose production. As a result, the high-energy acetyl-CoA accumulates in the cell, and it cannot be used for fatty acid synthesis , as this is not sufficiently stimulated by the lack of insulin. In order to still be able to utilize the acetyl-CoA, the mitochondria of the hepatocytes now synthesize ketone bodies. When β-hydroxybutyrate and acetoacetate are formed, a proton is given off because they are weak organic acids. This lowers the pH.

The most common cause of the accumulation of organic acids in the blood is the catabolic metabolic situation in insulin deficiency in the context of derailed diabetes mellitus (diabetic ketoacidosis) . Another typical cause is the massive increase in β-hydroxybutyric acid in the blood as a result of alcohol consumption (alcoholic ketoacidosis) . Alcohol also inhibits gluconeogenesis and the oxidation of free fatty acids in the liver by increasing the NADH level (2 mol NADH and 1 mol acetyl-CoA are formed per mol of ethanol when completely oxidized). Also, genetic disorders like congenital lack of succinyl-CoA transferase acetoacetates (SCOT syndrome) may trigger.

In mid-May 2015, the US drug safety authority FDA warned of the occurrence of severe ketoacidosis during therapy with SGLT2 inhibitors such as canagliflozin, dapagliflozin and empagliflozin.

Clinical appearance

Clinically, ketoacidosis manifests itself through unspecific symptoms such as difficulty breathing, nausea, vomiting, abdominal pain, polyuria , thirst and weakness. In the further course of the disease ( ketoacidotic coma ) it comes to clouding of consciousness to the loss, the Kussmaul breathing with acetone odor of breath and dehydration ( dehydration ). The clinical picture is fatal if left untreated.

examination

Anamnesis, clinical appearance and a frequently occurring acetone odor in the breath provide valuable information in emergency medicine . The pioneering investigation under stationary conditions is the blood gas analysis (pH <7.25, reduced pCO 2 , HCO 3 - <15 mmol / l and negative BE). In the case of diabetic-induced ketoacidosis, there is a significantly increased blood sugar level (over 240 mg / dl); in the case of alcoholic ketoacidosis, it can be decreased, normal or slightly increased. The determination of the acetone in the urine or blood shows a greatly increased value.

treatment

Therapeutically, the end of the causal, catabolic metabolic process by correcting blood sugar (administration of insulin ) as well as sufficient fluid intake due to the accompanying desiccosis are in the foreground. In addition to general medical emergency or intensive care measures to maintain vital functions , consistent laboratory monitoring of those affected is necessary in order to be able to recognize further potentially life-threatening changes early enough. In particular, significant deviations in blood sugar and potassium levels in the blood often require prompt intervention in the early phase.

Individual evidence

  1. ↑ Duale series Biochemie, Rassow et al., Thieme
  2. ↑ Orphanet: SCOT deficiency , online here
  3. ↑ Diabetes: Ketoacidosis due to SGLT2 inhibitors , Dt. Ärzteblatt from May 19, 2015, accessed May 21, 2015
  4. ↑ FDA Warns Medicines May Result in a Serious Condition of Too Much Acid in the Blood (English)
  5. ↑ a b Walter G. Guder, Jürgen Nolte (Hrsg.): The laboratory book for clinic and practice . Urban & Fischer Verlag, Munich 2005, ISBN 3-437-23340-8 , pp. 255ff. here online
  6. ↑ a b Fritz Koller (greeting), Nikolaus E. Gyr (ed.): Internal emergency. Safe through the acute situation and the following 48 hours . 7th edition. Thieme Verlag, Stuttgart 2003, ISBN 3-13-510607-1 , p. 490 here online .
  7. ↑ ketone test (Azetontest) .