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How Are Ketones Produced In Dka?

9/5/10

9/5/10

Ketoacidosis PY GENERAL - ketoacidosis is a high anion gap metabolic acidosis due to an excessive blood concentration of ketone bodies (keto-anions). - ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone) are released into the blood from the liver when hepatic lipid metabolism has changed to a state of increased ketogenesis. - a relative or absolute insulin deficiency is present in all cases. CAUSES The three major types of ketosis are: (i) Starvation ketosis (ii) Alcoholic ketoacidosis (iii) Diabetic ketoacidosis Starvation Ketosis - when hepatic glycogen stores are exhausted (eg after 12-24 hours of total fasting), the liver produces ketones to provide an energy substrate for peripheral tissues. - ketoacidosis can appear after an overnight fast but it typically requires 3 to 14 days of starvation to reach maximal severity. - typical ketoanion levels are only 1 to 2 mmol/l and this will usually not alter the anion gap. - the acidosis even with quite prolonged fasting is only ever of mild to moderate severity with ketoanion levels up to a maximum of 3 to 5 mmol/l and plasma pH down to 7.3. - ketone bodies also stimulate some insulin release from the islets. - patients are usually not diabetic Alcoholic ketoacidosis Presentation - a chronic alcoholic who has a binge, then stops drinking and has little or no oral food intake for a few days (ethanol and fasting) - volume depletion is common and this can result in increased levels of counter regulatory hormones (eg glucagon) - levels of FFA can be high (eg up to 3.5mM) providing plenty of substrate for the altered hepatic lipid metabolism to produce plenty of ketoanions - GIT symptoms are common (eg nausea, vomiting, abdominal pain, haematemesis, melaena) - acidaemia may be severe (eg pH down to 7.0) - plasma glucose Continue reading >>

Understanding And Treating Diabetic Ketoacidosis

Understanding And Treating Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is a serious metabolic disorder that can occur in animals with diabetes mellitus (DM).1,2 Veterinary technicians play an integral role in managing and treating patients with this life-threatening condition. In addition to recognizing the clinical signs of this disorder and evaluating the patient's response to therapy, technicians should understand how this disorder occurs. DM is caused by a relative or absolute lack of insulin production by the pancreatic b-cells or by inactivity or loss of insulin receptors, which are usually found on membranes of skeletal muscle, fat, and liver cells.1,3 In dogs and cats, DM is classified as either insulin-dependent (the body is unable to produce sufficient insulin) or non-insulin-dependent (the body produces insulin, but the tissues in the body are resistant to the insulin).4 Most dogs and cats that develop DKA have an insulin deficiency. Insulin has many functions, including the enhancement of glucose uptake by the cells for energy.1 Without insulin, the cells cannot access glucose, thereby causing them to undergo starvation.2 The unused glucose remains in the circulation, resulting in hyperglycemia. To provide cells with an alternative energy source, the body breaks down adipocytes, releasing free fatty acids (FFAs) into the bloodstream. The liver subsequently converts FFAs to triglycerides and ketone bodies. These ketone bodies (i.e., acetone, acetoacetic acid, b-hydroxybutyric acid) can be used as energy by the tissues when there is a lack of glucose or nutritional intake.1,2 The breakdown of fat, combined with the body's inability to use glucose, causes many pets with diabetes to present with weight loss, despite having a ravenous appetite. If diabetes is undiagnosed or uncontrolled, a series of metab Continue reading >>

Diabetic Ketoacidosis (dka)

Diabetic Ketoacidosis (dka)

Diabetic ketoacidosis is an acute metabolic complication of diabetes characterized by hyperglycemia, hyperketonemia, and metabolic acidosis. Hyperglycemia causes an osmotic diuresis with significant fluid and electrolyte loss. DKA occurs mostly in type 1 diabetes mellitus (DM). It causes nausea, vomiting, and abdominal pain and can progress to cerebral edema, coma, and death. DKA is diagnosed by detection of hyperketonemia and anion gap metabolic acidosis in the presence of hyperglycemia. Treatment involves volume expansion, insulin replacement, and prevention of hypokalemia. Diabetic ketoacidosis (DKA) is most common among patients with type 1 diabetes mellitus and develops when insulin levels are insufficient to meet the body’s basic metabolic requirements. DKA is the first manifestation of type 1 DM in a minority of patients. Insulin deficiency can be absolute (eg, during lapses in the administration of exogenous insulin) or relative (eg, when usual insulin doses do not meet metabolic needs during physiologic stress). Common physiologic stresses that can trigger DKA include Some drugs implicated in causing DKA include DKA is less common in type 2 diabetes mellitus, but it may occur in situations of unusual physiologic stress. Ketosis-prone type 2 diabetes is a variant of type 2 diabetes, which is sometimes seen in obese individuals, often of African (including African-American or Afro-Caribbean) origin. People with ketosis-prone diabetes (also referred to as Flatbush diabetes) can have significant impairment of beta cell function with hyperglycemia, and are therefore more likely to develop DKA in the setting of significant hyperglycemia. SGLT-2 inhibitors have been implicated in causing DKA in both type 1 and type 2 DM. Continue reading >>

The Pathophysiology Of Diabetic Ketoacidosis

The Pathophysiology Of Diabetic Ketoacidosis

People still die from diabetic ketoacidosis. Poor patient education is probably the mostimportant determinant of the incidence of the catastrophe that constitutes "DKA".In several series, only about a fifth of patients with DKA are first-time presenterswith recently acquired Type I diabetes mellitus. The remainder are recognised diabeticswho are either noncompliant with insulin therapy, or have serious underlying illess thatprecipitates DKA. Most such patients have type I ("insulin dependent", "juvenile onset") diabetes mellitus, but it has recently been increasingly recognised that patients with type II diabetes mellitusmay present with ketoacidosis, and that some such patients present with "typical hyperosmolar nonketotic coma", but on closer inspection have varying degrees of ketoacidosis. DKA is best seen as a disorder that follows on an imbalance between insulin levels andlevels of counterregulatory hormones. Put simply: "Diabetic ketoacidosis is due to a marked deficiency of insulin in the face of high levels of hormones thatoppose the effects of insulin, particularly glucagon. Even small amounts of insulin can turn off ketoacid formation". Many hormones antagonise the effects of insulin. These include: In addition, several cytokines such as IL1, IL6 and TNF alpha antagonise the effects ofinsulin. [J Biol Chem 2001 Jul 13;276(28):25889-93]It is thus not surprising that many causes of stress and/or the systemic inflammatory response syndrome,appear to precipitate DKA in patients lacking insulin. Mechanisms by which these hormones and cytokinesantagonise insulin are complex, including inhibition of insulin release (catecholamines), antagonistic metaboliceffects (decreased glycogen production, inhibition of glycolysis), and promotion of peripheral resistance tothe e Continue reading >>

Diabetic Ketoacidosis

Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is a serious problem that can occur in people with diabetes if their body starts to run out of insulin. This causes harmful substances called ketones to build up in the body, which can be life-threatening if not spotted and treated quickly. DKA mainly affects people with type 1 diabetes, but can sometimes occur in people with type 2 diabetes. If you have diabetes, it's important to be aware of the risk and know what to do if DKA occurs. Symptoms of diabetic ketoacidosis Signs of DKA include: needing to pee more than usual being sick breath that smells fruity (like pear drop sweets or nail varnish) deep or fast breathing feeling very tired or sleepy passing out DKA can also cause high blood sugar (hyperglycaemia) and a high level of ketones in your blood or urine, which you can check for using home-testing kits. Symptoms usually develop over 24 hours, but can come on faster. Check your blood sugar and ketone levels Check your blood sugar level if you have symptoms of DKA. If your blood sugar is 11mmol/L or over and you have a blood or urine ketone testing kit, check your ketone level. If you do a blood ketone test: lower than 0.6mmol/L is a normal reading 0.6 to 1.5mmol/L means you're at a slightly increased risk of DKA and should test again in a couple of hours 1.6 to 2.9mmol/L means you're at an increased risk of DKA and should contact your diabetes team or GP as soon as possible 3mmol/L or over means you have a very high risk of DKA and should get medical help immediately If you do a urine ketone test, a result of more than 2+ means there's a high chance you have DKA. When to get medical help Go to your nearest accident and emergency (A&E) department straight away if you think you have DKA, especially if you have a high level of ketones in Continue reading >>

Diabetic Ketoacidosis (dka) - Topic Overview

Diabetic Ketoacidosis (dka) - Topic Overview

Diabetic ketoacidosis (DKA) is a life-threatening condition that develops when cells in the body are unable to get the sugar (glucose) they need for energy because there is not enough insulin. When the sugar cannot get into the cells, it stays in the blood. The kidneys filter some of the sugar from the blood and remove it from the body through urine. Because the cells cannot receive sugar for energy, the body begins to break down fat and muscle for energy. When this happens, ketones, or fatty acids, are produced and enter the bloodstream, causing the chemical imbalance (metabolic acidosis) called diabetic ketoacidosis. Ketoacidosis can be caused by not getting enough insulin, having a severe infection or other illness, becoming severely dehydrated, or some combination of these things. It can occur in people who have little or no insulin in their bodies (mostly people with type 1 diabetes but it can happen with type 2 diabetes, especially children) when their blood sugar levels are high. Your blood sugar may be quite high before you notice symptoms, which include: Flushed, hot, dry skin. Feeling thirsty and urinating a lot. Drowsiness or difficulty waking up. Young children may lack interest in their normal activities. Rapid, deep breathing. A strong, fruity breath odor. Loss of appetite, belly pain, and vomiting. Confusion. Laboratory tests, including blood and urine tests, are used to confirm a diagnosis of diabetic ketoacidosis. Tests for ketones are available for home use. Keep some test strips nearby in case your blood sugar level becomes high. When ketoacidosis is severe, it must be treated in the hospital, often in an intensive care unit. Treatment involves giving insulin and fluids through your vein and closely watching certain chemicals in your blood (electrolyt Continue reading >>

Diabetic Ketoacidosis

Diabetic Ketoacidosis

Also known as: DKA Severe diabetic ketoacidosis is a medical emergency and requires prompt treatment to correct dehydration, electrolyte disturbances and acidosis. It is a complication of insulin dependent Diabetes Mellitus. DKA is the result of marked insulin deficiency, and ketonaemia and ketoacidosis occur approximately 15 days after insulin concentrations are suppressed to fasting levels. Marked insulin suppression occurs on average 4 days after fasting glucose levels reach 30mmol/L. Many cats with DKA have other intercurrent conditions which may precipitate the condition including: infection, pancreatitis or renal insufficiency. Pathophysiology Insulin deficiency leads to increased breakdown of fat that releases fatty acids into the circulation. Free fatty acids are oxidised in the liver to ketones that are used by many tissues as an energy source instead of glucose. This occurs when intracellular levels of glucose are insufficient for energy metabolism as a result of severe insulin deficiency. In the liver, instead of being converted to triglycerides, free fatty acids are oxidised to acetoacetate, which is converted to hydroxybutyrate or acetone. Ketones are acids that cause central nervous system depression and act in the chemoreceptor trigger zone to cause nausea, vomiting and anorexia. They also accelerate osmotic water loss in the urine. Dehydration results from inadequate fluid intake in the face of accelerated water loss due to glucosuria and ketonuria. Dehydration and subsequent reduced tissue perfusion compounds the acidosis through lactic acid production. There is whole body loss of electrolytes including sodium, potassium, magnesium and phosphate and there is also intracellular redistribution of electrolytes following insulin therapy which may compound p Continue reading >>

Can Serum Β-hydroxybutyrate Be Used To Diagnose Diabetic Ketoacidosis?

Can Serum Β-hydroxybutyrate Be Used To Diagnose Diabetic Ketoacidosis?

Abstract OBJECTIVE—Current criteria for the diagnosis of diabetic ketoacidosis (DKA) are limited by their nonspecificity (serum bicarbonate [HCO3] and pH) and qualitative nature (the presence of ketonemia/ketonuria). The present study was undertaken to determine whether quantitative measurement of a ketone body anion could be used to diagnose DKA. RESEARCH DESIGN AND METHODS—A retrospective review of records from hospitalized diabetic patients was undertaken to determine the concentration of serum β-hydroxybutyrate (βOHB) that corresponds to a HCO3 level of 18 mEq/l, the threshold value for diagnosis in recently published consensus criteria. Simultaneous admission βOHB and HCO3 values were recorded from 466 encounters, 129 in children and 337 in adults. RESULTS—A HCO3 level of 18 mEq/l corresponded with βOHB levels of 3.0 and 3.8 mmol/l in children and adults, respectively. With the use of these threshold βOHB values to define DKA, there was substantial discordance (∼≥20%) between βOHB and conventional diagnostic criteria using HCO3, pH, and glucose. In patients with DKA, there was no correlation between HCO3 and glucose levels on admission and a significant but weak correlation between βOHB and glucose levels (P < 0.001). CONCLUSIONS—Where available, serum βOHB levels ≥3.0 and ≥3.8 mmol/l in children and adults, respectively, in the presence of uncontrolled diabetes can be used to diagnose DKA and may be superior to the serum HCO3 level for that purpose. The marked variability in the relationship between βOHB and HCO3 is probably due to the presence of other acid-base disturbances, especially hyperchloremic, nonanion gap acidosis. Recently published consensus criteria for diagnosing diabetic ketoacidosis (DKA) include a serum bicarbonate (HCO3) Continue reading >>

Feline Diabetic Ketoacidosis

Feline Diabetic Ketoacidosis

Fall 2008 Ketoacidosis is a metabolic imbalance that is most commonly seen as a sequel to unmanaged or poorly regulated diabetes mellitus. It is caused by the breakdown of fat and protein in a compensatory effort for the need of more metabolic energy. The excessive breakdown of these stored reserves creates a toxic by-product in the form of ketones. As ketones build up in the blood stream, pH and electrolyte imbalances proceed. This condition is a potentially life-threatening emergency that requires immediate medical attention. Diabetes mellitus is a common endocrine disease in geriatric felines. It is caused by a dysfunction in the beta cells of the exocrine pancreas resulting in an absolute or relative deficiency of insulin. Insulin has been called the cells' gatekeeper. It attaches to the surface of cells and permits glucose, the cells' primary energy source, to enter from the blood. A lack of insulin results in a build up of glucose in the blood, physiologically causing a state of cellular starvation. In response to this condition the body begins to increase the mobilization of protein and fat storage. Fatty acids are released from adipose tissue, which are then oxidized by the liver. Normally, these fatty acids are formed into triglycerides. However, without insulin, these fatty acids are converted into ketone bodies, which cannot be utilized by the body. Together with the increased production and decreased utilization an abnormally high concentration of ketone bodies develop. These fixed acids are buffered by bicarbonate; however, the excessive amounts overwhelm and deplete the bicarbonate leading to an increase in arterial hydrogen ion concentration and a decrease in serum bicarbonate. This increase in hydrogen ions lowers the body's pH, leading to a metabolic ac Continue reading >>

Diabetic Ketoacidosis

Diabetic Ketoacidosis

As fat is broken down, acids called ketones build up in the blood and urine. In high levels, ketones are poisonous. This condition is known as ketoacidosis. Diabetic ketoacidosis (DKA) is sometimes the first sign of type 1 diabetes in people who have not yet been diagnosed. It can also occur in someone who has already been diagnosed with type 1 diabetes. Infection, injury, a serious illness, missing doses of insulin shots, or surgery can lead to DKA in people with type 1 diabetes. People with type 2 diabetes can also develop DKA, but it is less common. It is usually triggered by uncontrolled blood sugar, missing doses of medicines, or a severe illness. Continue reading >>

Diabetic, Alcoholic And Starvation Ketoacidosis

Diabetic, Alcoholic And Starvation Ketoacidosis

Copious amounts of ketones which are generated in insulin-deficient or insulin-unresponsive patients will give rise to a high anion gap metabolic acidosis. Ketones are anions, and they form the high anion gap. Management of DKA and HONK is discussed elsewhere. Meet the ketones Chemically speaking, a ketone is anything with a carbonyl group between a bunch of other carbon atoms. The above are your three typical ketoacidosis-associated ketone bodies. The biochemistry nerds among us will hasten to add that the beta-hydroxybutyrate is in fact not a ketone but a carboxylic acid, but - because it is associated with ketoacidosis, we will continue to refer to it as a ketone for the remainder of this chapter, in the spirit of convention. In the same spirit, we can suspend our objections to acetone being included in a discussion of ketoacidosis, which (though a true ketone) is in fact not acidic or basic, as it does not ionise at physiological pH (its pKa is 20 or so). So really, the only serious ketone acid is acetoacetate, which has a pKa of 3.77. However, beta-hydroxybutyrate is the prevalent ketone in ketoacidosis; the normal ratio of beta-hydroxybutyrate and acetoacetate is 3:1, and it can rise to 10:1 in diabetic ketoacidosis. Acetone is the least abundant. The metabolic origin of ketones The generation of ketones is a normal response to fasting, which follows the depletion of hepatic glycogen stores. Let us discuss normal physiology for a change. You, a healthy adult without serious alcohol problems, are fasting from midnight for a routine elective hernia repair. You will go to be after dinner with a few nice lumps of undigested food in your intestine, as well as about 75g of hepatic glycogen. As you sleep, you gradually digest the food and dip into the glycogen store. At Continue reading >>

Diabetes And Ketones

Diabetes And Ketones

Tweet The presence of high levels of ketones in the bloodstream is a common complication of diabetes, which if left untreated can lead to ketoacidosis. Ketones build up when there is insufficient insulin to help fuel the body’s cells. High levels of ketones are therefore more common in people with type 1 diabetes or people with advanced type 2 diabetes. If you are suffering from high levels of ketones and seeking medical advice, contact your GP or diabetes healthcare team as soon as possible. What are ketones? Ketones are an acid remaining when the body burns its own fat. When the body has insufficient insulin, it cannot get glucose from the blood into the body's cells to use as energy and will instead begin to burn fat. The liver converts fatty acids into ketones which are then released into the bloodstream for use as energy. It is normal to have a low level of ketones as ketones will be produced whenever body fat is burned. In people that are insulin dependent, such as people with type 1 diabetes, however, high levels of ketones in the blood can result from taking too little insulin and this can lead to a particularly dangerous condition known as ketoacidosis. How do I test for ketones? Ketone testing can be carried out at home. The most accurate way of testing for ketones is to use a blood glucose meter which can test for ketones as well as blood glucose levels. You can also test urine for ketone levels, however, the testing of urine means that the level you get is representative of your ketone levels up to a few hours ago. Read about testing for ketones and how to interpret the results Who needs to be aware of ketones? The following people with diabetes should be aware of ketones and the symptoms of ketoacidosis: Anyone dependent on insulin – such as all people Continue reading >>

Diabetic Ketoacidosis (dka)

Diabetic Ketoacidosis (dka)

Also see Pet Diabetes Wiki: Ketoacidosis A Ketone Primer by an FDMB user What are Ketones? Ketones or ketone bodies (acetone, acetoacetic acid, and beta-hydroxybutyric acid) are waste products of fatty acid breakdown in the body. This is the result of burning fat, rather than glucose, to fuel the body. The body tries to dispose of excess ketones as quickly as possible when they are present in the blood. The kidneys filter out ketones and excrete them into the urine. Should you care about ketones? YES! If they build up, they can lead to very serious energy problems in the body, resulting in diabetic ketoacidosis, a true medical emergency. If the condition is not reversed and other systemic stresses are present, ketones may continue to rise and a condition known as diabetic ketoacidosis (DKA) may occur. This condition can progress very quickly and cause severe illness. It is potentially fatal even when treated. Recognition of DKA and rapid treatment by your veterinarian can save your cat's life. Signs of Diabetic Ketoacidosis (DKA) Drinking excessive amounts of water OR no water Excessive urination Diminished activity Not eating for over 12 hours Vomiting Lethargy and depression Weakness Breathing very fast Dehydration Ketone odor on breath (smells like nail-polish remover or fruit) Causes of Diabetic Ketoacidosis (DKA) Insulin dependent diabetes mellitus Inadequate insulin dosing or production Infection Concurrent diseas that stresses the animal Estrus Medication noncompliance Lethargy and depression Stress Surgery Idiopathic (unknown causes) Risk Factors for DKA Any condition that causes an insulin deficiency History of corticosteroid or beta-blocker administration Diagnosis Laboratory tests performed by your vet are necessary for diagnosis. Depending on how sick your c Continue reading >>

Ketone Bodies: A Review Of Physiology, Pathophysiology And Application Of Monitoring To Diabetes.

Ketone Bodies: A Review Of Physiology, Pathophysiology And Application Of Monitoring To Diabetes.

Abstract Ketone bodies are produced by the liver and used peripherally as an energy source when glucose is not readily available. The two main ketone bodies are acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB), while acetone is the third, and least abundant, ketone body. Ketones are always present in the blood and their levels increase during fasting and prolonged exercise. They are also found in the blood of neonates and pregnant women. Diabetes is the most common pathological cause of elevated blood ketones. In diabetic ketoacidosis (DKA), high levels of ketones are produced in response to low insulin levels and high levels of counterregulatory hormones. In acute DKA, the ketone body ratio (3HB:AcAc) rises from normal (1:1) to as high as 10:1. In response to insulin therapy, 3HB levels commonly decrease long before AcAc levels. The frequently employed nitroprusside test only detects AcAc in blood and urine. This test is inconvenient, does not assess the best indicator of ketone body levels (3HB), provides only a semiquantitative assessment of ketone levels and is associated with false-positive results. Recently, inexpensive quantitative tests of 3HB levels have become available for use with small blood samples (5-25 microl). These tests offer new options for monitoring and treating diabetes and other states characterized by the abnormal metabolism of ketone bodies. Continue reading >>

Diabetic Ketoacidosis

Diabetic Ketoacidosis

Diabetic Ketoacidosis Definition Diabetic ketoacidosis is a dangerous complication of diabetes mellitus in which the chemical balance of the body becomes far too acidic. Description Diabetic ketoacidosis (DKA) always results from a severe insulin deficiency. Insulin is the hormone secreted by the body to lower the blood sugar levels when they become too high. Diabetes mellitus is the disease resulting from the inability of the body to produce or respond properly to insulin, required by the body to convert glucose to energy. In childhood diabetes, DKA complications represent the leading cause of death, mostly due to the accumulation of abnormally large amounts of fluid in the brain (cerebral edema). DKA combines three major features: hyperglycemia, meaning excessively high blood sugar kevels; hyperketonemia, meaning an overproduction of ketones by the body; and acidosis, meaning that the blood has become too acidic. Insulin deficiency is responsible for all three conditions: the body glucose goes largely unused since most cells are unable to transport glucose into the cell without the presence of insulin; this condition makes the body use stored fat as an alternative source instead of the unavailable glucose for energy, a process that produces acidic ketones, which build up because they require insulin to be broken down. The presence of excess ketones in the bloodstream in turn causes the blood to become more acidic than the body tissues, which creates a toxic condition. Causes and symptoms DKA is most commonly seen in individuals with type I diabetes, under 19 years of age and is usually caused by the interruption of their insulin treatment or by acute infection or trauma. A small number of people with type II diabetes also experience ketoacidosis, but this is rare give Continue reading >>

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