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What is Ketoacidosis? + Causes, Signs & Symptoms

Written by Carlos Tello, PhD (Molecular Biology) | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by Carlos Tello, PhD (Molecular Biology) | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Characterized by high glucose, ketone, and acid levels in the blood, ketoacidosis is a life-threatening condition that mainly occurs as a complication of poorly managed diabetes. Keep reading to learn more about this condition, its effects on the body, and how it is diagnosed.

What Is Ketoacidosis?

Ketoacidosis is a medical condition that is mainly characterized by the 3 following abnormalities [1]:

  • High blood concentration of glucose
  • High blood and urine concentration of ketone bodies
  • High blood acid levels

The most common type of ketoacidosis occurs as a complication of diabetes. In diabetic ketoacidosis, the low level of insulin and the excess of its opposing hormones cause the buildup of glucose in the blood and the breakdown of fatty molecules into ketone bodies in the liver [2].

Death rates from ketoacidosis in adults are below 1% in developed countries, but developing countries have higher rates (e.g., 30% in Kenya) [3, 4].

In a study on 275 children under 5 years old with newly diagnosed type 1 diabetes, 28% had ketoacidosis. This condition is the leading cause of death among children with type 1 diabetes [5, 6].

Although diabetic ketoacidosis is more common in people with type 1 diabetes, it can also occur in those with type 2 diabetes. Its frequency is higher in those of African, African-American, or Hispanic origin [7].

Other types of ketoacidosis include:

  • Starvation ketoacidosis: caused by prolonged fasting periods [8]
  • Alcoholic ketoacidosis: caused by long-term alcohol abuse [9]
  • Salicylate ketoacidosis: caused by intoxication with salicylate (found in painkillers) [10]
  • Inborn ketoacidosis: caused by genetic mutations in proteins used for ketone body production and breakdown [11]
  • Lactation ketoacidosis: May spontaneously appear in breastfeeding women [12]
Ketoacidosis is a life-threatening condition characterized by high blood sugar, high blood and urine concentration of ketones, and high blood acidity. It is most commonly caused by diabetes.

Ketoacidosis vs. Nutritional Ketosis

Nutritional ketosis is the physical state when the body uses fat instead of carbohydrates for energy production as a result of fasting or a ketogenic diet [13].

Ketogenic diets are defined by low carbohydrate (typically below 50 g/day) and high fat intake and lead to the increased production of ketone bodies and fatty acids [13].

It’s important to note that eating a ketogenic diet or fasting for a controlled time period will lead to ketosis but not to ketoacidosis:

  • Blood glucose levels remain normal during ketosis because the liver starts producing this sugar from other sources like lactate, pyruvate, and amino acids after the carbohydrate stores have been exhausted [14]
  • Because ketone bodies can inhibit their own production, blood ketone levels never exceed 8 mmol/l, which is a safe value during nutritional ketosis [15, 16]
  • As opposed to the ketone concentrations reached during ketoacidosis (approximately 20 mmol/l), those of nutritional ketosis do not cause blood acidification [16]

Nevertheless, other strategies such as doing more exercise or reducing your calorie intake are safer and more effective to lose weight. Always discuss with your doctor if the ketogenic diet is recommended in your case.

Ketone bodies in the blood are not always dangerous. The ketogenic diet deliberately produces a state of nutritional ketosis so that the body burns fat instead of glucose for energy.

Negative Impacts of Ketoacidosis

The consequences for children can be serious. In juvenile cases, 1 to 2% of children with diabetic ketoacidosis suffer from dangerous fluid buildup in the brain.

  • In a study of 8 children and adolescents, those with diabetic ketoacidosis performed worse in some types of intelligence tests [17].
  • Children with sudden brain damage caused by diabetic ketoacidosis all suffered from brain stroke in a small study on 5 children [18].
  • A 5-year-old child with diabetic ketoacidosis developed thrombosis in the brain [19].
  • In 2 studies on children and adolescents with severe diabetic ketoacidosis, all of them had signs of fluid buildup in the lungs [20, 21].

Diabetic ketoacidosis can lead to serious complications in adults too:

  • Approximately 20% of people with severe ketoacidosis are admitted in a coma [1].
  • Ketoacidosis can also cause irritation of the protective layers of the brain (meningeal syndrome) [22].
  • A 50-year-old patient with recurrent diabetic ketoacidosis episodes lost vision in one eye due to nerve damage [23].
  • On very rare occasions, diabetic ketoacidosis can cause the obstructive buildup of fluid in the brain (hydrocephalus) [24].
  • Ketoacidosis increases the risk of developing thrombosis since it causes dehydration, reduced blood vessel volume, heart problems, and increased blood thickness [25, 26].

Diabetic ketoacidosis can damage the muscles, kidneys, stomach, and other vital organs.

  • Several case studies described the rapid breakdown of damaged muscles (rhabdomyolysis) in patients with diabetic ketoacidosis. In some cases, it was accompanied by a severe reaction that causes fever, muscle stiffness, and fast heart rate (malignant hyperthermia) [27, 28, 29].
  • In a study on almost 300 people with diabetic ketoacidosis, 26 had bleeding in the stomach and upper bowels [30].
  • Severe diabetic ketoacidosis can cause kidney failure [31, 32].
  • In a study of 21 people with severe diabetic ketoacidosis, most non-survivors had developed multiple organ failure [33].
Ketoacidosis is an extremely dangerous condition. Among the possible outcomes is fluid in the brain and lungs, nerve damage, bleeding in the gut, multiple organ failure, coma, and death.

Causes

The 3 main factors that cause ketoacidosis are [34]:

  • Infections, such as pneumonia and urinary tract infections (30 to 50% of cases)
  • Inadequate treatment of diabetes (20 to 40%)
  • Undiagnosed diabetes (20 to 30%)

Additional, less frequent causes include [35]:

  • Stroke
  • Heart attack
  • Blockage of lung vessels
  • Pancreatic inflammation
  • Bowel obstruction
  • Kidney failure
  • Alcohol abuse
  • Severe burns
  • Use of certain medications

In 2 to 10% of cases, no cause can be identified [36].

Mechanism of Ketoacidosis

Diabetics have low blood insulin levels, while certain neurotransmitters (catecholamines) and the following insulin-opposing hormones are found at high concentrations [3]:

In normal conditions, insulin prevents sugar production and fat breakdown. An imbalance between insulin and its opposing hormones triggers the mechanisms of diabetic ketoacidosis [37].

1) Glucose Buildup

Low blood insulin levels, as well as the high concentration of glucagon, cortisol, and neurotransmitters (catecholamines), activate 2 types of sugar (glucose) production pathways [38]:

  • Breakdown of sugar stores in the liver (glycogenolysis)
  • Production of sugar from non-sugar compounds (gluconeogenesis)

Increased cortisol causes more protein breakdown. The resulting amino acids (especially glutamine and alanine) are important for sugar production [39].

Breakdown of sugar stores releases lactate as a byproduct, which is used to make glucose [40].

In these conditions, fats are broken down into glycerol, which also makes glucose. Glucose transport into tissues is reduced, leading to glucose buildup in the blood [41, 2].

Low blood insulin and high glucagon, cortisol, and catecholamines activate multiple glucose production pathways, resulting in a dangerous buildup of glucose in the blood.

2) Ketone Buildup and Acidosis

A combination of low blood insulin levels and high concentrations of opposing hormones breaks down existing fatty molecules and prevents the storage of new fats [42, 3].

The resulting fatty acids build up in the liver, where they are transformed into the following ketone bodies [37]:

  • β-hydroxybutyrate
  • Acetoacetate
  • Acetone

Ketone bodies raise blood acid levels and exhaust the molecules (e.g., bicarbonate) used to neutralize them, making the condition worse [43].

Tissues cannot absorb too many ketone bodies, so eventually, these will begin to build up in the blood. They are found in the form of negatively charged ions (anions) and increase the anion gap [44].

Alternatively, the lactate produced by sugar store breakdown also contributes to blood acidosis [40].

Low blood insulin and high glucagon promotes the breakdown of fatty molecules into ketone bodies. These gradually raise the acidity of the blood, eventually causing acidosis.

3) Water and Electrolyte Imbalance

High glucose levels in bodily fluids cause the movement of water and ions (electrolytes) out of cells [37].

The kidney cannot absorb too much glucose, which is found in the urine when concentrations get too high. This causes more frequent urination, which can lead to a deficiency in water and the following electrolytes [45]:

4) Other Types of Ketoacidosis

In starvation ketoacidosis, prolonged fasting [8]:

  • Exhausts sugar stores in the liver
  • Decreases insulin levels
  • Increases the levels of insulin-opposing hormones
  • Increases the use of ketone bodies for energy

In alcoholic ketoacidosis, long-term alcohol abuse is normally accompanied by malnutrition. The exhaustion of sugar and protein stores increases ketone bodies [9].

Alcohol breakdown consumes a molecule (the coenzyme NAD+) that is also required for the production of glucose [46].

Salicylate intoxication can cause acidosis by [47]:

  • Stimulating lactate production (which is used to produce sugar)
  • Increasing fatty acid breakdown and decreasing blood sugar levels (which causes the build-up of ketone bodies)
  • Increasing blood acid levels

Inborn ketoacidosis is caused by genetic defects in enzymes involved in the production and breakdown of ketone bodies [47].

Since milk production requires high sugar consumption rates, lactation ketoacidosis can occur in breastfeeding women [12, 48, 49].

Starvation, alcohol abuse, salicylate toxicity, genetic defects, and breastfeeding can also cause the depletion of sugar stores and drop in insulin required to result in ketoacidosis.

Symptoms of Ketoacidosis

The main symptoms of ketoacidosis include [50, 35, 37]:

  • Dehydration and excessive thirst
  • Excessive urine production
  • Excessive appetite
  • Weakness
  • Weight loss
  • Nausea and vomiting, ‘coffee-ground’ vomiting
  • Stomach pain, upper bowel, and stomach bleeding
  • Nail polish- or fruity-smelling breath
  • Rapid and deep breathing
  • Dry mucosae and rougher skin
  • High heart rate and low blood pressure
  • Normal to low body temperature
  • Sleepiness, confusion, or coma
  • Blurred vision
  • Leg cramps

Ketoacidosis is a serious condition that may be life-threatening if untreated. If you have several of these symptoms, seek immediate medical attention so that your doctor can effectively diagnose and treat it.

Diagnosis

If emergency nurses detect several of the symptoms listed in the previous section, they must conduct quick bedside testing for blood glucose and blood or urine ketones [51].

The blood chemistry is analyzed to determine [35]:

  • Glucose concentration
  • Ketone concentration
  • Blood osmolality (electrolyte-water balance)
  • C-reactive protein count to detect inflammation
  • Troponin T concentration to detect heart failure
  • Full blood count
  • Coagulation profile to confirm normal blood clotting function
  • Kidney and liver function
  • Toxicology screen for harmful chemicals (e.g., salicylate)

Additionally, urine tests must be performed to analyze [35]:

The subsequent laboratory evaluation must include [37]:

  • Blood gases to assess blood acidosis
  • Chest X-ray to detect infections and breathing complications
  • Electrocardiogram to identify signs of heart disease, especially in patients with ion imbalance
  • Bacterial samples of blood, urine, and sputum to identify infectious organisms and test for the presence of ketone bodies

Diabetic ketoacidosis is diagnosed in the presence of [52]:

  • High urine ketone concentration (above 3 mmol/l)
  • High blood glucose concentration (above 250 mg/dl) or presence of type 1 diabetes
  • Low blood bicarbonate concentration (below 18 mmol/l) or high acidosis (pH below 7.3) in the veins

Additionally, the following conditions confirm the diagnosis [51]:

  • Low sodium levels (below 149 mmol/l)
  • High blood creatinine concentration (above 0.12 mmol/l)
  • High blood osmolality (above 320 mmol/kg)
If a patient presents multiple signs and symptoms of ketoacidosis, an emergency nurse or doctor will run blood and urine tests to detect low blood sugar, ketone bodies, and acidity.

Professional Evaluation of Results

Lab results are commonly shown as a set of values known as a “reference range”, which is sometimes referred to as a “normal range”. A reference range includes the upper and lower limits of a lab test based on a group of otherwise healthy people.

Your healthcare provider will compare your lab test results with reference values to see if your chloride results fall outside the range of expected values. By doing so, you and your healthcare provider can gain clues to help identify possible conditions or diseases.

Remember that some lab-to-lab variability occurs due to differences in equipment, techniques, and chemicals used. Don’t panic if your result is slightly out of range – as long as it’s in the normal range based on the laboratory that did the testing, your value is normal.

However, it’s important to remember that a normal test doesn’t mean a particular medical condition is absent. Your doctor will interpret your results in conjunction with your medical history and other test results.

And remember that a single test isn’t enough to make a diagnosis. Your doctor will interpret this test, taking into account your medical history and other tests. A result that is slightly low/high may not be of medical significance, as this test often varies from day to day and from person to person.

Further Reading

Takeaway

Ketoacidosis is a dangerous condition characterized by high blood sugar, ketone bodies in the blood and urine, and high blood acidity. It is most often caused by diabetes, though infections, alcohol abuse, starvation, salicylate toxicity, or lactation can also cause the condition.

Ketoacidosis develops when insulin is low, either because sugar stores are depleted or (in the case of diabetic ketoacidosis) when insulin cannot be produced in sufficient quantities. These conditions produce a cascade of events that lead to the buildup of ketone bodies and acidification of the blood.

If an emergency nurse identifies the symptoms of ketoacidosis in a patient, they will conduct a number of blood and urine tests to check blood sugar, ketone levels, and blood acidity. If you suspect that you are developing or have developed ketoacidosis, seek medical attention immediately.

About the Author

Carlos Tello

Carlos Tello

PhD (Molecular Biology)
Carlos received his PhD and MS from the Universidad de Sevilla.
Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.

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