Causes of Ketoacidosis

Related Subjects: |Diabetic Ketoacidosis (DKA) Adults |Alcoholic Ketoacidosis |Euglycaemic Ketoacidosis (euDKA) with SGLT2 Inhibitors |Causes of Ketoacidosis

⚠️ Not all ketoacidosis is diabetic ketoacidosis. The three classic causes are diabetic ketoacidosis (DKA), alcoholic ketoacidosis (AKA), and starvation ketoacidosis (SKA). 💡 The key bedside discriminator is usually the combination of glucose level + clinical context + severity of acidosis. A simple memory rule is: Ketones above 1.5 mmol/L is high, above 3 is dangerous. DKA is not just ketones though — it is high ketones plus metabolic acidosis, usually with hyperglycaemia.

📖 Introduction

• Ketoacidosis is a high anion gap metabolic acidosis caused by excess production of ketone bodies — mainly beta-hydroxybutyrate and acetoacetate.
• It develops when the body shifts away from carbohydrate use and towards fat breakdown, with hepatic ketone production exceeding peripheral use.
• The common clinically important forms are:
  • 🍬 Diabetic ketoacidosis (DKA)
  • 🍷 Alcoholic ketoacidosis (AKA)
  • 🥣 Starvation ketoacidosis (SKA)
• All three can produce ketonaemia, anion gap metabolic acidosis, nausea, vomiting, tachypnoea, and abdominal pain — so the diagnosis depends on context as much as chemistry.

🧬 Core Pathophysiology

• Low effective insulin activity and increased counter-regulatory hormones (especially glucagon, catecholamines, cortisol, and growth hormone) drive lipolysis.
• Free fatty acids are transported to the liver and converted into ketone bodies.
• When ketone generation exceeds utilisation and buffering capacity, a metabolic acidosis develops.
• The relative balance between insulin deficiency, starvation, glycogen depletion, alcohol metabolism, and stress hormones determines which form of ketoacidosis occurs.

🍬 Diabetic Ketoacidosis (DKA)

• Occurs because of absolute or relative insulin deficiency, usually in type 1 diabetes, but it can also occur in type 2 diabetes during severe physiological stress.
• Typical triggers include:
  • 🦠 Infection
  • 💉 Missed or interrupted insulin
  • ❤️ Myocardial infarction or stroke
  • 🫁 Major illness, surgery, trauma, pancreatitis
  • 🤰 Pregnancy
  • 💊 Drugs such as SGLT2 inhibitors, corticosteroids, and sympathomimetics
• Usually presents with:
  • 📈 Hyperglycaemia
  • 💧 Dehydration
  • 🫁 Kussmaul breathing
  • 🤢 Nausea, vomiting, abdominal pain
  • 🧠 Confusion or reduced consciousness in severe cases
• There is often marked total body depletion of water, potassium, sodium, and phosphate, even if serum potassium is initially normal or raised.
• ⚠️ Euglycaemic DKA can occur, especially with SGLT2 inhibitors, pregnancy, fasting, or partial treatment before presentation.

🍷 Alcoholic Ketoacidosis (AKA)

• Typically occurs after a period of heavy alcohol intake followed by vomiting, poor oral intake, and abrupt cessation of drinking.
• The classic patient has had an alcohol binge, then stops eating and develops persistent vomiting and abdominal pain.
• Alcohol metabolism increases the hepatic NADH:NAD+ ratio, which impairs gluconeogenesis and promotes ketone production.
• AKA is usually associated with:
  • 📉 Normal or low glucose (though mild hyperglycaemia can occur)
  • 🤢 Severe vomiting
  • 💧 Volume depletion
  • 🧪 High anion gap metabolic acidosis
• Patients may smell of alcohol, but often present after they have stopped drinking because they feel too unwell to continue.
• Thiamine deficiency and mixed acid-base disorders are common in this group.

🥣 Starvation Ketoacidosis (SKA)

• Occurs when carbohydrate intake is markedly reduced for a prolonged period, leading to glycogen depletion and a switch to fat metabolism.
• Causes include:
  • 🚫 Prolonged fasting
  • 🥄 Severe malnutrition
  • 🤰 Pregnancy with hyperemesis or poor intake
  • 🦠 Intercurrent illness with reduced intake
  • 🥗 Very low-carbohydrate states in vulnerable patients
• SKA usually causes:
  • 📉 Normal or low glucose
  • 🧪 Ketonaemia
  • ⚖️ Usually milder acidosis than DKA, though it can become significant in physiologically stressed patients
• Pregnancy lowers the threshold for ketosis, so starvation ketoacidosis can develop faster and be more severe in pregnant patients.

📊 Comparison Table

🩺 Clinical Clues That Help Differentiate Them

• Very high glucose + known diabetes + dehydration → think DKA.
• Recent binge drinking + vomiting + not eating + normal/low glucose → think AKA.
• Prolonged fasting, malnutrition, or hyperemesis + normal/low glucose → think SKA.
• SGLT2 inhibitor use + ketones + acidosis with only mild hyperglycaemia → think euglycaemic DKA.

🔎 Investigations

• 🧪 Capillary glucose
• 🩸 Blood gas — pH, bicarbonate, lactate
• ⚡ Blood ketones (beta-hydroxybutyrate preferred where available)
• 🧂 U&E, creatinine, anion gap
• 🧫 FBC, CRP, cultures if infection is suspected
• ❤️ ECG and additional tests depending on trigger (for example troponin, lipase, pregnancy test, toxicology)

⚕️ Management Principles

• DKA:
  • 💧 IV fluid resuscitation
  • 💉 Fixed-rate IV insulin
  • 🧂 Potassium monitoring and replacement
  • 🔍 Identify and treat the precipitant
• AKA:
  • 💧 IV fluids
  • 🍬 Dextrose-containing fluids to switch off ketogenesis
  • 🧠 Thiamine before or with glucose if deficiency risk is present
  • 🩺 Correct magnesium, phosphate, and other electrolyte deficits
• SKA:
  • 🍞 Carbohydrate replacement
  • 💧 Fluids and electrolyte correction
  • 🩺 Treat the reason for poor intake

⚠️ Common Pitfalls

• Assuming all ketotic acidosis in a patient with diabetes is standard hyperglycaemic DKA.
• Missing euglycaemic DKA because the glucose is not dramatically raised.
• Treating AKA like DKA with insulin when the key problem is starvation + alcohol metabolism.
• Failing to give thiamine in alcohol-related presentations.
• Overlooking mixed acid-base disorders, especially in vomiting and sepsis.

🌟 Makindo memory trick:
DKA = Diabetes + Dehydration + usually high glucose.
AKA = Alcohol + Anorexia/poor intake + vomiting.
SKA = Starvation + Scarce carbohydrate intake.
💡 The question to ask first is not “Are there ketones?” but “Why is this person making ketones?”

📚 References

• NICE NG17 – Type 1 diabetes in adults: diabetic ketoacidosis
• BNF/NICE – Diabetic hyperglycaemic emergencies
• Merck Manual Professional – Acute complications of diabetes mellitus
• StatPearls – Ketoacidosis
• Endotext – Hyperglycemic Crises
• StatPearls – Euglycemic Diabetic Ketoacidosis