What is Ketoacidosis?
Ketoacidosis is a condition where the body has an unusually high amount of certain substances, called ketone bodies, in the blood and urine. These substances – acetone, acetoacetate, and beta-hydroxybutyrate – are produced when the body breaks down fats for energy. This process typically happens when the body is in a state of breakdown, which is often due to low levels of the hormone insulin and high levels of the hormone glucagon.
Among these ketone bodies, only acetoacetic acid is a true ketoacid by chemical standards. Beta-hydroxybutyric acid is a hydroxy acid, and acetone is a true ketone. This process of creating ketone bodies starts when fats, released during the breakdown of fat tissues, enter the liver cells through the bloodstream. Here, they go through beta-oxidation, leading to the creation of these ketone bodies.
This process happens more when insulin levels are low. This often occurs because of low blood sugar levels, such as during fasting. At these times, an enzyme called hormone-sensitive lipase activates, breaking down fat molecules into free fatty acid and glycerol.
Ketoacidosis is particularly significant when discussing diabetic ketoacidosis (DKA), alcoholic ketoacidosis (AKA), and starvation ketoacidosis. DKA may occur as a severe complication of uncontrolled diabetes and could be life-threatening if not detected and treated early. It usually happens when blood sugar levels are high and insulin levels are low, triggering a series of reactions that increase the production of ketone bodies and acid levels in the body.
Alcoholic ketoacidosis may occur in chronic alcohol consumers, those with liver disease, or following acute alcohol ingestion. Starvation ketoacidosis occurs when the body, deprived of glucose or sugar as the primary energy source for a long time, resorts to using fats as the main energy source.
What Causes Ketoacidosis?
Diabetic ketoacidosis, or DKA for short, can happen to people with diabetes, especially when there is not enough insulin in their bodies. This can occur because of physical stress or could be the first sign in people who didn’t know they had diabetes. Certain factors make it more likely for people to develop extremely high blood sugar levels and subsequently DKA. These include infections, forgetting to take insulin, severe illnesses such as heart attack or pancreatitis, stress, trauma, and certain medications like steroids or certain types of anti-psychotic drugs, which can interfere with how the body processes carbohydrates.
Alcoholic ketoacidosis (AKA) tends to occur in people who drink alcohol excessively over a long period of time. It can also happen after heavy drinking sessions. How does this happen? Well, when the body breaks down alcohol, it produces a compound called acetic acid. This compound can form part of the processes that produce ketones. Ketones are substances produced when the body burns fat for energy, and having too many ketones in the blood is toxic. The balance of insulin to other hormones in the body determines whether acetic acid goes into these processes.
Ordinarily, our cells use the sugar in our blood as their primary source of energy. This is achieved with the help of insulin, glucagon, and a hormone called somatostatin. Starvation ketoacidosis happens when the body doesn’t have enough sugar to use for energy because of long periods of fasting where the blood sugar levels are low. This causes the body to produce less insulin, which in turn makes the body use fat for energy and lead to an overproduction of ketones.
Risk Factors and Frequency for Ketoacidosis
DKA, or diabetic ketoacidosis, happens more often in people with type 1 diabetes, but about 10% to 30% of cases also occur in those with type 2 diabetes, especially when they are under extreme stress or dealing with an acute illness. Diabetes is a prevalent chronic condition that affects about 30 million people in the United States. Although hospitalization rates for DKA were declining in the 2000s, they have been steadily increasing since then at an average annual rate of 6.3%, even though in-hospital death rates have been declining during the same period.
AKA, alcoholic ketoacidosis, often occurs in people who regularly abuse alcohol, and the frequency is the same among different genders and races. It can happen at any age but mostly in chronic alcoholics, and is rarely seen in those who only occasionally binge drink.
Starvation ketosis is a condition that usually begins after a person fasts for 12 to 14 hours. If a person doesn’t have access to food, as can happen with severe poverty or eating disorders, the body will move from a state of ketosis to a state of ketoacidosis. This process is seen in patients with wasting syndrome due to cancer, difficulty swallowing after surgery or radiation, and prolonged periods of poor eating.
Signs and Symptoms of Ketoacidosis
Diabetic ketoacidosis (DKA) is a severe condition that can cause numerous symptoms typically within hours of a triggering event. These symptoms include increased urination (polyuria), increased thirst (polydipsia), unintended weight loss, vomiting, weakness, and changes in mental function. Dehydration and metabolic imbalances can intensify, leading to tiredness, confusion, and more severe outcomes like respiratory failure, coma, and even death. A common complaint in DKA is abdominal pain. Alcoholic ketoacidosis (AKA), on the other hand, typically involves abdominal pain and vomiting after suddenly stopping alcohol consumption.
Upon physical examination, most patients with either DKA or AKA show signs of dehydration from fluid and electrolyte loss through the gastrointestinal tract or kidneys. In severe cases, patients might have abnormally low blood pressure and shock. They may also have fast and deep breathing as a way to compensate, known as Kussmaul breathing. Their breath might have a distinctive fruity odor, primarily due to the production of acetone. While neurological issues can occur in DKA, they are less common in AKA. Patients with AKA may show signs of alcohol withdrawal, like high blood pressure and rapid heart rate. Starvation ketoacidosis can lead to signs of muscle wasting like low muscle mass, minimal body fat, visible bone structures, wasting of the temporal muscle, tooth decay, thin and dry hair, and low blood pressure, pulse, and temperature.
Testing for Ketoacidosis
If your doctor suspects you have diabetic ketoacidosis (DKA), a dangerous complication of diabetes, they will need to conduct several laboratory tests. These tests involve checking your blood and urine levels for different substances, including glucose (sugar), ketones (chemicals your body produces when there’s not enough insulin), blood urea nitrogen, creatinine (waste product from your muscles), electrolytes (minerals necessary for your body to function), and anion gap (the difference between the measured and calculated ions in the blood).
Other tests may include measuring the gases in your arteries, osmolality (a blood test to check the balance of electrolytes, chemicals, and water in your body), complete blood count (the number and types of cells in your blood), and blood cultures (test to check for infections in the blood). Additional examination may include a chest X-ray and an electrocardiogram (test that checks your heart’s electrical activity).
Patients with DKA usually have high blood sugar, but the levels can vary. Moreover, although ketone levels are typically high in DKA, initially they might be negative, which does not rule out the diagnosis. Increased anion gap and leukocytosis (high white blood cell count) may indicate an infection. Despite the high glucose levels, your serum sodium (a type of electrolyte) might be relatively low due to the redistribution of water in the body. Patients might also present with high serum potassium levels due to acid accumulation in the body.
Another form of ketoacidosis – alcoholic ketoacidosis (AKA) – can lead to liver inflammation, represented in the blood tests by increased liver enzymes and bilirubin (a yellow compound that occurs in the normal catabolic pathway, it helps break down red blood cells). The presence of these issues doesn’t require the alcohol level to be elevated. The most severe ketoacidosis usually occurs once the alcohol level decreases. As in DKA, hypokalemia (low potassium levels) and increased anion gap are expected.
Common problems in the tests done for AKA are low magnesium and phosphate levels, due to decreased dietary intake and higher losses. As noted earlier, testing for serum beta-hydroxybutyrate, a type of ketone, is more specific than urine ketones. Patients suffering from starvation ketoacidosis may have several electrolyte issues because of long-term malnutrition, along with vitamin deficiencies. In these cases, the pH levels may not be as low as in DKA or AKA, and the glucose levels may be relatively normal.
Treatment Options for Ketoacidosis
Diabetic ketoacidosis (DKA) is a serious condition that affects people with diabetes. It’s often treated first by ensuring the patient has a stable blood flow, can breathe easily, and has a secure airway. After that, the treatment focuses on several areas:
1. Lowering high blood sugar levels with intravenous (given through a vein) insulin.
2. Regularly checking and replacing electrolytes, particularly potassium, which are essential minerals that help the body function.
3. Treating dehydration with intravenous fluids.
4. Correcting acidosis, which is when your body’s fluids contain too much acid.
This condition can be severe and requires regular monitoring for insulin therapy and potential heart rhythm problems. For this reason, patients are often admitted to the intensive care unit. Blood sugar levels and electrolytes should be checked every hour during the initial stage of treatment.
Resuscitation with isotonic saline infusion, a saltwater solution, is recommended at the start of DKA treatment. This helps correct the instability of the patient’s body circulation and improves insulin sensitivity, thereby reducing the levels of hormones that oppose the action of insulin.
After starting with isotonic saline, what fluid will be used next depends on the patient’s sodium levels in their blood, corrected for their high blood sugar levels. Normal or high sodium levels mean the patient should receive hypotonic saline, and low levels mean the patient should continue receiving isotonic saline.
Intravenous glucose should be added to the fluid once the sugar levels drop to around 200 to 250 mg/dl. Along with fluids, the patient should also receive an intravenous infusion of regular insulin to maintain the sugar level between 150 to 200 mg/dl and until high anion-gap acidosis (a type of metabolic acidosis) is resolved in DKA.
Potassium levels are often high due to shifts in cells caused by the acidosis and lack of insulin. If potassium levels are low, it could mean the total potassium in the body is low. In this instance, insulin therapy should be delayed until the potassium level is above 3.3 mEq/L. Continuing with low potassium levels could risk causing heart rhythm problems.
Treating acidosis with sodium bicarbonate therapy is not clear-cut and may not provide any extra benefits when the blood pH level is higher than 6.9.
Alcoholic ketoacidosis (AKA), another type of ketoacidosis often seen in heavy drinkers, usually responds well to treatment with intravenous saline and glucose. This therapy clears excess ketones, compounds produced when the body burns fat for fuel due to fasting, alcoholism, or illnesses that restrict food intake from the body, by reducing counter-regulatory hormones and triggering natural insulin production.
Replacing thiamine, a type of vitamin B that is typically low in people with chronic alcoholism, is also vital in managing AKA, as is replacing lost electrolytes such as potassium, magnesium, and phosphate.
Treatment for starvation ketoacidosis, another type caused by not eating for a long period, is similar to AKA. However, it is essential to monitor for refeeding syndrome. During refeeding syndrome, aggressive feeding in a person who has been starved for a long time can cause significant shifts in cells due to insulin release. Therefore, like in AKA, it’s crucial to monitor and replace the potassium, phosphate, and magnesium levels in these patients.
What else can Ketoacidosis be?
Hyperosmolar hyperglycemic state (HHS) is a condition usually seen in people with type 2 diabetes, due to a resistance to insulin. People with HHS have enough insulin in their bodies to stop the production of ketone bodies, but not enough to prevent high blood sugar levels, dehydration, and hyperosmolality, which are the hallmarks of HHS. The condition is often triggered by an illness or event that causes dehydration, which then results in high blood sugar levels. Unlike diabetic ketoacidosis (DKA), HHS develops over a period of days to weeks and is typically characterized by extreme high blood sugar levels and changes in mental status. In HHS, there are usually normal or small traces of ketones in urine or blood tests, much higher plasma glucose levels than in DKA, and the serum osmolality is highly elevated. The serum bicarbonate level stays above 18 mEq/L (18 mmol/L), and the pH remains above 7.3.
Lactic acidosis is another condition that could lead to an increased anion gap metabolic acidosis. It’s usually seen in cases of reduced tissue blood flow, blood cancers, and as a side effect of certain drugs.
Rhabdomyolysis, a condition that causes muscle breakdown, could also be a consideration in patients with a history of alcohol abuse and anion gap metabolic acidosis. This condition is usually associated with high potassium and phosphate levels in blood, low calcium levels, and a positive urine test for blood without any red blood cells visible under the microscope.
Acute abdominal emergencies, like acute pancreatitis, should always be considered when a patient primarily presents with abdominal pain.
