Worried about the coronavirus? Here's what you should know. Read more. When your cells don't get the glucose they need for energy, your body begins to burn fat for energy, which produces ketones.
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NCBI Bookshelf. Pranita Ghimire ; Amit S. Authors Pranita Ghimire 1 ; Amit S. Dhamoon 2. During catabolic states, fatty acids are metabolized to ketone bodies, which can be readily utilized for fuel by individual cells in the body.
Of the three major ketone bodies, acetoacetic acid is the only true ketoacid chemically, while beta-hydroxybutyric acid is a hydroxy acid, and acetone is a true ketone. Figure 1 shows the schematic of ketogenesis where the fatty acids generated after lipolysis in the adipose tissues enter the hepatocytes via the bloodstream and undergo beta-oxidation to form the various ketone bodies. This biochemical cascade is stimulated by the combination of low insulin levels and high glucagon levels i.
Low insulin levels, most often secondary to absolute or relative hypoglycemia as with fasting, activate hormone-sensitive lipase, which is responsible for the breakdown of triglycerides to free fatty acid and glycerol. DKA is a potentially life-threatening complication of uncontrolled diabetes mellitus if not recognized and treated early. It typically occurs in the setting of hyperglycemia with relative or absolute insulin deficiency. The paucity of insulin causes unopposed lipolysis and oxidation of free fatty acids, resulting in ketone body production and subsequent increased anion gap metabolic acidosis.
Starvation ketoacidosis occurs after the body is deprived of glucose as the primary source of energy for a prolonged time, and fatty acids replace glucose as the major metabolic fuel. DKA can occur in patients with diabetes mellitus, most frequently associated with relative insulin deficiency. This may be caused by precipitating physiologic stress or in some cases, maybe the initial clinical presentation in patients with previously undiagnosed diabetes. Some of the more common risk factors that can precipitate the development of extreme hyperglycemia and subsequent ketoacidosis are infection, non-adherence to insulin therapy, acute major illnesses like myocardial infarction, sepsis, pancreatitis, stress, trauma, and the use of certain medications, such as glucocorticoids or atypical antipsychotic agents which have the potential to affect carbohydrate metabolism.
AKA occurs in patients with chronic alcohol abuse. Patients can have a long-standing history of alcohol use and may also present following binges.
Acetic acid is a product of the metabolism of alcohol and also a substrate for ketogenesis. As the name implies, starvation ketoacidosis is a bodily response to prolonged fasting hypoglycemia, which decreases insulin secretion, shunting the biochemistry towards lipolysis and the oxidation of the by-product fatty acids to ensure a fuel source for the body.
According to the morbidity and mortality review of the CDC, diabetes itself is one of the most common chronic conditions in the world and affects an estimated 30 million people in the United States. For AKA, the prevalence correlates with the incidence of alcohol abuse without racial or gender differences in incidence. It can occur at any age and mainly in chronic alcoholics but rarely in binge drinkers.
It can be seen in cachexia due to underlying malignancy, patients with postoperative or post-radiation dysphagia, and prolonged poor oral intake. Ketone bodies are fat-derived fuels used by tissues at the time of limited glucose availability. Hepatic generation of ketone bodies is usually stimulated by the combination of low insulin levels and high counter-regulatory hormone levels, including glucagon.
Low insulin levels are seen inherently in as either an absolute or relative deficiency in type I diabetes or a relative deficiency with insulin resistance in type II diabetes. In alcoholic or starvation conditions, low insulin levels are secondary to absolute or relative hypoglycemia. This unfavorable ratio of insulin to glucagon activates hormone-sensitive lipase, which breaks down triglycerides in peripheral fat stores, releasing long-chain fatty acids and glycerol.
The fatty acids undergo beta-oxidation in the hepatic mitochondria and generate acetyl-CoA. With the generation of large quantities of acetyl-CoA in the more severe forms of each of these conditions, the oxidative capacity of the Krebs cycle gets saturated, and there is a spillover entry of acetyl-CoA into the ketogenic pathway and subsequent generation of ketone bodies. An increased anion gap metabolic acidosis occurs when these ketone bodies are present as they are unmeasured anions.
Alcoholic ketoacidosis  occurs in patients with chronic alcohol abuse and liver disease and usually develops following abrupt withdrawal of alcohol or an episode of acute intoxication. It is not uncommon for the ingested ethanol to have already been metabolized, leading to low or normal serum levels when checked. In addition to this, the increased NADH further suppresses gluconeogenesis and reduces free glucose, perpetuating ketogenesis.
This usually happens after 2 or 3 days of fasting. After several days of fasting, protein catabolism starts, and muscles are broken down, releasing amino acids and lactate into the bloodstream, which can be converted into glucose by the liver.
This biochemical process is responsible for the wasting and cachexia seen during starvation. Patients with DKA may have a myriad of symptoms on presentation, usually within several hours of the inciting event.
Symptoms of hyperglycemia are common, including polyuria, polydipsia, and sometimes more severe presentations include unintentional weight loss, vomiting, weakness, and mentation changes. Dehydration and metabolic abnormalities worsen with progressive uncontrolled osmolar stress, which can lead to lethargy, obtundation, and may even cause respiratory failure, coma, and death. Abdominal pain is also a common complaint in DKA.
AKA patients usually present with abdominal pain and vomiting after abruptly stopping alcohol. On physical exam, most of the patients with ketoacidoses present with features of hypovolemia from gastrointestinal or renal fluid and electrolyte losses.
In severe cases, patients may be hypotensive and in frank shock. They may have a rapid and deep respiratory effort as a compensatory mechanism, known as Kussmaul breathing. They may have a distinct fruity odor to their breath, mainly because of acetone production. AKA patients may have signs of withdrawal like hypertension and tachycardia. The initial laboratory evaluation of a patient with suspected DKA includes blood levels of glucose, ketones, blood urea nitrogen, creatinine, electrolytes, calculated anion gap, arterial blood gases, osmolality, complete blood count with differential, blood cultures and urine studies including ketones, urinalysis, urine culture, chest radiograph, and an electrocardiogram.
Hyperglycemia is the typical finding at presentation with DKA, but patients can present with a range of plasma glucose values. Although ketone levels are generally elevated in DKA, a negative measurement initially does not exclude the diagnosis because ketone laboratory measurements often use the nitroprusside reaction, which only estimates acetoacetate and acetone levels that may not be elevated initially as beta-hydroxybutyrate is the major ketone that is elevated.
The anion-gap is elevated, as mentioned above because ketones are unmeasured anions. Serum sodium is usually relatively low because of shifts of solvent water from the intracellular to extracellular spaces because of the osmotic pull of hyperglycemia. Hence, normal or elevated serum sodium is indicative of severe volume depletion.
Serum potassium levels may be elevated due to shifts from the intracellular compartment for exchange with acids in the absence of insulin and normal or low potassium, indicating an overall depleted body store and subsequent need for correction before initiation of insulin therapy.
In AKA, transaminitis, and hyperbilirubinemia due to concurrent alcoholic hepatitis may also be present. Hypokalemia and increased anion-gap are usually seen with similar mechanisms to those seen in DKA.
Hypomagnesemia and hypophosphatemia are common problems seen in the laboratory evaluation due to decreased dietary intake and increased losses. As mentioned above, the direct measurement of serum beta-hydroxybutyrate is more sensitive and specific than the measurement of urine ketones. Starvation ketoacidoses patients may again have multiple electrolyte abnormalities due to chronic malnutrition, along with vitamin deficiencies.
After initial stabilization of circulation, airway, and breathing as a priority, specific treatment of DKA requires correction of hyperglycemia with intravenous insulin, frequent monitoring, and replacement of electrolytes, mainly potassium, correction of hypovolemia with intravenous fluids, and correction of acidosis.
Aggressive volume resuscitation with isotonic saline infusion is recommended in the initial management of DKA. Volume expansion not only corrects the hemodynamic instability but also improves insulin sensitivity and reduces counter-regulatory hormone levels.
After starting with isotonic saline, the subsequent options can be decided on the serum sodium levels that are corrected for the level of hyperglycemia. Normal or high serum sodium levels warrant replacement with hypotonic saline, and low sodium levels warrant continuation of the isotonic saline. Like mentioned above, potassium levels are usually high because of the transcellular shifts due to the acidosis and the lack of insulin.
When the potassium levels are low, this means that the total body potassium is low, and hence, insulin therapy should be postponed till at least the level of serum potassium is greater than 3. In the 3. The treatment of the acidosis itself is more controversial.
Treatment with sodium bicarbonate therapy is controversial. It has been studied and found to provide no added benefit when the arterial blood pH is greater than 6. Several studies have found higher potassium requirements in patients receiving bicarbonate. AKA typically responds to treatment with intravenous saline and intravenous glucose, with rapid clearance of the associated ketones due to a reduction in counter-regulatory hormones and the induction of endogenous insulin.
Thiamine replacement is important in alcohol-related presentations, including intoxication, withdrawal, and ketoacidosis, and should be initially done parenterally and after that maintained orally.
Electrolyte replacement is critical. Also of paramount importance is monitoring and replacing the magnesium and phosphate levels, which are usually low in both chronic alcoholism and prolonged dietary deprivation as in starvation. The treatment of starvation ketoacidosis is similar to AKA.
Patients need to be monitored for refeeding syndrome, which is associated with electrolyte abnormalities seen when aggressive feeding is started in an individual starved for a prolonged time. Hyperosmolar hyperglycemic state HHS occurs in the setting of insulin resistance and is more typical of type 2 diabetes. There is sufficient insulin in patients with HHS to suppress lipolysis and production of ketone bodies, but inadequate amounts to prevent the hyperglycemia, dehydration, and hyperosmolality, characteristic of HHS.
An illness or event that leads to dehydration will often precipitate the hyperglycemia associated with HHS.
HHS typically presents with normal or small amounts of urine or serum ketones. Lactic acidosis is an alternative cause of an increased anion gap metabolic acidosis. Lactic acidosis is found with tissue hypoperfusion, hematological malignancies, and various medications. Rhabdomyolysis is a diagnostic consideration in a patient with a history of alcohol use disorder and an anion gap metabolic acidosis, but this condition is frequently associated with hyperkalemia, hyperphosphatemia, hypocalcemia, and a urinalysis positive for blood with no erythrocytes visible on urine microscopy.
Diabetes, once diagnosed, is mostly managed with changes in diet, lifestyle, and medication adherence. The goal is to prevent high glucose levels, which helps prevent diabetic complications. Empowering the patient regarding management is hence of the utmost importance.
Diabetes self-management education DSME and diabetes self-management support DSMS are recommended at the time of diagnosis of prediabetes or diabetes and throughout the lifetime of the patient. DSMS is an individualized plan that provides opportunities for educational and motivational support for diabetes self-management. DSME and DSMS jointly provide an opportunity for collaboration between the patient and health care providers to assess educational needs and abilities, develop personal treatment goals, learn self-management skills, and provide ongoing psychosocial and clinical support.
The diabetic nurse should follow all outpatients to ensure medication compliance, followup with clinicians, and adopting a positive lifestyle. Further, the nurse should teach the patient how to monitor home blood glucose and the importance of careful monitoring of blood sugars during infection, stress, or trauma. The physical therapist should be involved in educating the patient on exercise and the importance of maintaining healthy body weight.
The social worker should be involved to ensure that the patient has the support services and financial assistance to undergo treatment. The members of the interprofessional team should communicate to ensure that the patient is receiving the optimal standard of care.
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DKA (Ketoacidosis) & Ketones
NCBI Bookshelf. Pranita Ghimire ; Amit S. Authors Pranita Ghimire 1 ; Amit S. Dhamoon 2.
PENATALAKSANAAN KETOASIDOSIS DIABETIK (KAD)
NCBI Bookshelf. Endotext [Internet]. Adair R Gosmanov , M. Diabetic ketoacidosis DKA and hyperglycemic hyperosmolar state HHS are acute metabolic complications of diabetes mellitus that can occur in patients with both type 1 and 2 diabetes mellitus. Timely diagnosis, comprehensive clinical and biochemical evaluation, and effective management is key to the successful resolution of DKA and HHS.