Diagnosis And Treatment Of Diabetic Ketoacidosis (dka) In Dogs And Cats
What is DKA in Dogs and Cats? Diabetic Ketoacidosis (DKA) is a serious and life-threatening complication of diabetes mellitus that can occur in dogs and cats. DKA is characterized by hyperglycemia, ketonemia, +/- ketonuria, and metabolic acidosis. Ketone bodies are formed by lipolysis (breakdown) of fat and beta-oxidation when the metabolic demands of the cells are not met by the limited intracellular glucose concentrations. This provides alternative energy sources for cells, which are most important for the brain. The three ketones that are formed include beta-hydroxybutyrate, acetoacetate and acetone. Beta-hydroxybutyrate (BHB) and acetoacetate are anions of moderately strong acids contributing most to the academia (low blood pH). Acetone is the ketone body that can be detected on breath. In a normal animal, glucose enters the cell (with help of insulin) – undergoes glycolysis to pyruvate within cytosol – pyruvate moves into mitochondria (energy generating organelle in the cell) to enter the TCA cycle and ATP is formed. ATP is the main energy source of the body. When glucose cannot enter the cell, free fatty acids are broken down (lipolysis) and move into the cell to undergo beta-oxidation (creation of pyruvate). The pyruvate then moves into the mitochondria to enter the TCA cycle (by conversion to Acetyl-CoA first). However, when the TCA cycle is overwhelmed, the Acetyl-CoA is used in ketogenesis to form ketone bodies. Summary Diabetic Ketoacidosis (DKA) in Dogs and Cats When there is no insulin the body cannot utilize glucose and there is no intracellular glucose. The body then uses ketone bodes as an alternate source. When there is decreased insulin and increased counterregulatory hormones fatty acids are converted to AcCoA and then ketones. In the non-diabetic Continue reading >>
Jaime Moo-young, Md
Diabetic Ketoacidosis (DKA) Pathogenesis · Insufficient insulin for a given carbohydrate load decreased cellular metabolism of glucose · Increased gluconeogenesis, glycogenolysisHyperglycemia · Increased breakdown of free fatty acids as alternative energy source ketone and ketoacid accumulation · Hyperglycemiaserum hyperosmolality osmotic diuresis dehydration and electrolyte derangements (dehydration is most lethal!) · Seen almost exclusively in Type I diabetes; rarely in Type II Definition: Triad of 1. Hyperglycemia (usually between 500 – 800 mg/dL or 27.8-44.4 mmol/L) 2. Anion Gap Metabolic Acidosis (pH usually <7.30) 3. Ketonemia: -hydroxybutyrate, acetoacetate most significant ** Urine ketones do not make the diagnosis, but they can support it** Triggers (the “I’sâ€): Don’t forget to ask about these! · Insulin deficiency: insulin non-compliance, insufficient insulin dosing, new-onset Type I diabetes · Iatrognic: glucocorticoids, atypical antipsychotics, high-dose thiazide diuretics · Infection: UTI, pneumonia, TB · Inflammation: pancreatitis, cholecystitis · Ischemia/infarction: MI, stroke, gut ischemia · Intoxication: Alcohol, cocaine, other drugs Presentation · Symptoms · Polyuria, polydipsia, weight loss · Nausea, vomiting, abdominal pain · Fatigue, malaise · Associated trigger sx (fever/chills, chest pain, etc) · Signs · Volume depletion: skin turgor, dry axillae, dry mucus membranes, HR, BP · Altered mental status: stupor, coma · Kussmaul respirations: rapid, shallow breathing = hyperventilation to counteract metabolic acidosis · Fruity, acetone odor on breath Lab workup and findings · Hyperglycemia: > 250 mg/dL in serum, + glucose on urinalysis · Acidemia (pH <7. Continue reading >>
Diabetic Ketoacidosis And Patho
pathophysiology ketogenesis due to insulin deficiency leads to increased serum levels of ketones anad ketonuria acetoacetate, beta-hydroxybutyrate; ketone bodies produced by the liver, organic acids that cause metabolic acidosis respiration partially compensates; reduces pCO2, when pH < 7.2, deep rapid respirations (Kussmaul breathing) acetone; minor product of ketogenesis, can smell fruity on breath of ketoacidosis patients elevated anion gap Methanol intoxication Uremic acidosis Diabetic ketoacidosis Paraldehyde ingestions Intoxicants (salicyclate, ethylene glycol, nipride, epinephrine, norepinephrine) Lactic acidosis (drug induced; didanosine, iron, isoniazid, metformin, zidovudine) Ethanol ketoacidosis Severe renal failure starvation Blood glucose regulation (6) 1. When blood glucose levels rise above a set point, 2. the pancreas secretes insulin into the blood. 3. Insulin stimulates liver and muscle cells to make glycogen, dropping blood glucose levels. 4. When glucose levels drop below a set point, 5. the pancreas secretes glucagon into the blood. 6. Glucagon promotes the breakdown of glycogen and the release of glucose into the blood. (The pancreas signals distant cells to regulate levels in the blood = endocrine function.) Insulin and Glucagon (Regulation) (10) 1. High blood glucose 2. Beta cells 3. Insulin 4. Glucose enters cell 5. Blood glucose lowered 6. Low blood glucose 7. Alpha cells 8. Glucagon 9. Liver releases glucose from glycogen 10. Blood glucose raised What is the manifestations (symptoms) of Type 1? (10) 1. Extreme thirst 2. Frequent urination 3. Drowsiness, lethargy 4. Sugar in urine 5. Sudden vision change 6. Increased appetite 7. Sudden weight loss 8. Fruity, sweet, or wine like odor on breath 9. Heavy, laboured breathing 10. Stupor, unconscious Continue reading >>
Fasting Ketosis And Alcoholic Ketoacidosis
INTRODUCTION Ketoacidosis is the term used for metabolic acidoses associated with an accumulation of ketone bodies. The most common cause of ketoacidosis is diabetic ketoacidosis. Two other causes are fasting ketosis and alcoholic ketoacidosis. Fasting ketosis and alcoholic ketoacidosis will be reviewed here. Issues related to diabetic ketoacidosis are discussed in detail elsewhere. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Epidemiology and pathogenesis" and "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis" and "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment".) PHYSIOLOGY OF KETONE BODIES There are three major ketone bodies, with the interrelationships shown in the figure (figure 1): Acetoacetic acid is the only true ketoacid. The more dominant acid in patients with ketoacidosis is beta-hydroxybutyric acid, which results from the reduction of acetoacetic acid by NADH. Beta-hydroxybutyric acid is a hydroxyacid, not a true ketoacid. Continue reading >>
> Hyperglycemia And Diabetic Ketoacidosis
When blood glucose levels (also called blood sugar levels) are too high, it's called hyperglycemia. Glucose is a sugar that comes from foods, and is formed and stored inside the body. It's the main source of energy for the body's cells and is carried to each through the bloodstream. But even though we need glucose for energy, too much glucose in the blood can be unhealthy. Hyperglycemia is the hallmark of diabetes — it happens when the body either can't make insulin (type 1 diabetes) or can't respond to insulin properly (type 2 diabetes). The body needs insulin so glucose in the blood can enter the cells to be used for energy. In people who have developed diabetes, glucose builds up in the blood, resulting in hyperglycemia. If it's not treated, hyperglycemia can cause serious health problems. Too much sugar in the bloodstream for long periods of time can damage the vessels that supply blood to vital organs. And, too much sugar in the bloodstream can cause other types of damage to body tissues, which can increase the risk of heart disease and stroke, kidney disease, vision problems, and nerve problems in people with diabetes. These problems don't usually show up in kids or teens with diabetes who have had the disease for only a few years. However, they can happen in adulthood in some people, particularly if they haven't managed or controlled their diabetes properly. Blood sugar levels are considered high when they're above someone's target range. The diabetes health care team will let you know what your child's target blood sugar levels are, which will vary based on factors like your child's age. A major goal in controlling diabetes is to keep blood sugar levels as close to the desired range as possible. It's a three-way balancing act of: diabetes medicines (such as in Continue reading >>
Diabetic Ketoacidosis
What Is It? Diabetic ketoacidosis is a potentially fatal complication of diabetes that occurs when you have much less insulin than your body needs. This problem causes the blood to become acidic and the body to become dangerously dehydrated. Diabetic ketoacidosis can occur when diabetes is not treated adequately, or it can occur during times of serious sickness. To understand this illness, you need to understand the way your body powers itself with sugar and other fuels. Foods we eat are broken down by the body, and much of what we eat becomes glucose (a type of sugar), which enters the bloodstream. Insulin helps glucose to pass from the bloodstream into body cells, where it is used for energy. Insulin normally is made by the pancreas, but people with type 1 diabetes (insulin-dependent diabetes) don't produce enough insulin and must inject it daily. Your body needs a constant source of energy. When you have plenty of insulin, your body cells can get all the energy they need from glucose. If you don't have enough insulin in your blood, your liver is programmed to manufacture emergency fuels. These fuels, made from fat, are called ketones (or keto acids). In a pinch, ketones can give you energy. However, if your body stays dependent on ketones for energy for too long, you soon will become ill. Ketones are acidic chemicals that are toxic at high concentrations. In diabetic ketoacidosis, ketones build up in the blood, seriously altering the normal chemistry of the blood and interfering with the function of multiple organs. They make the blood acidic, which causes vomiting and abdominal pain. If the acid level of the blood becomes extreme, ketoacidosis can cause falling blood pressure, coma and death. Ketoacidosis is always accompanied by dehydration, which is caused by high Continue reading >>
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 >>
Ketosis
There is a lot of confusion about the term ketosis among medical professionals as well as laypeople. It is important to understand when and why nutritional ketosis occurs, and why it should not be confused with the metabolic disorder we call ketoacidosis. Ketosis is a metabolic state where the liver produces small organic molecules called ketone bodies. Most cells in the body can use ketone bodies as a source of energy. When there is a limited supply of external energy sources, such as during prolonged fasting or carbohydrate restriction, ketone bodies can provide energy for most organs. In this situation, ketosis can be regarded as a reasonable, adaptive physiologic response that is essential for life, enabling us to survive periods of famine. Nutritional ketosis should not be confused with ketoacidosis, a metabolic condition where the blood becomes acidic as a result of the accumulation of ketone bodies. Ketoacidosis can have serious consequences and may need urgent medical treatment. The most common forms are diabetic ketoacidosis and alcoholic ketoacidosis. What Is Ketosis? The human body can be regarded as a biologic machine. Machines need energy to operate. Some use gasoline, others use electricity, and some use other power resources. Glucose is the primary fuel for most cells and organs in the body. To obtain energy, cells must take up glucose from the blood. Once glucose enters the cells, a series of metabolic reactions break it down into carbon dioxide and water, releasing energy in the process. The body has an ability to store excess glucose in the form of glycogen. In this way, energy can be stored for later use. Glycogen consists of long chains of glucose molecules and is primarily found in the liver and skeletal muscle. Liver glycogen stores are used to mai Continue reading >>
Bicarbonate Therapy In Severe Metabolic Acidosis
Abstract The utility of bicarbonate administration to patients with severe metabolic acidosis remains controversial. Chronic bicarbonate replacement is obviously indicated for patients who continue to lose bicarbonate in the ambulatory setting, particularly patients with renal tubular acidosis syndromes or diarrhea. In patients with acute lactic acidosis and ketoacidosis, lactate and ketone bodies can be converted back to bicarbonate if the clinical situation improves. For these patients, therapy must be individualized. In general, bicarbonate should be given at an arterial blood pH of ≤7.0. The amount given should be what is calculated to bring the pH up to 7.2. The urge to give bicarbonate to a patient with severe acidemia is apt to be all but irresistible. Intervention should be restrained, however, unless the clinical situation clearly suggests benefit. Here we discuss the pros and cons of bicarbonate therapy for patients with severe metabolic acidosis. Metabolic acidosis is an acid-base disorder characterized by a primary consumption of body buffers including a fall in blood bicarbonate concentration. There are many causes (Table 1), and there are multiple mechanisms that minimize the fall in arterial pH. A patient with metabolic acidosis may have a normal or even high pH if there is another primary, contravening event that raises the bicarbonate concentration (vomiting) or lowers the arterial Pco2 (respiratory alkalosis). Metabolic acidosis differs from “acidemia” in that the latter refers solely to a fall in blood pH and not the process. A recent online survey by Kraut and Kurtz1 highlighted the uncertainty over when to give bicarbonate to patients with metabolic acidosis. They reported that nephrologists will prescribe therapy at a higher pH compared with Continue reading >>
Hypoglycemia
Introduction Infants and children produce and use glucose at a higher turnover rate than adults, and are thus unable to maintain a normal plasma glucose concentration even after a short fast of 24-36 hours. In infants, 90% of the glucose is used by the brain, which decreases over time to reach the norm of 40% for adults. Thus, preventing hypoglycemia is very important to avoid developmental deficits. Definition of hypoglycemia <40 mg/dL, regardless of age. This definition is controversial, however, glucose levels below 40 mg/dL produces hunger and excessive catecholamine response. Symptoms Gen: Irritability, anxiety, hunger, fatigue, Neuro: HA, blurred vision, tremors, weakness, confusion, ataxia, stupor, seizures, coma GI: abdominal pain, Heme/CV: pallor, cyanosis, diaphoresis, tachycardia, Resp: tachypnea, lethargy, apnea Most symptoms can be explained through stimulation of sympathetic responses. Recurrent severe hypoglycemic episodes can lead to brain damage and intellectual impairment. History Age Dietary Intake: what types of food (carbohydrates, protein, etc), how soon after eating did hypoglycemia develop, amount of food intake Child’s PMHx Family History: sudden infant deaths, similar problems in family Evaluation of Suspected Hypoglycemia (note: if possible, collect these samples before treatment to offer chances of earlier diagnosis) Venous sample for glucose, BMP (electrolytes, BUN, Cr), LFTs, lactate, insulin level, C-peptide, growth hormone, and cortisol levels. Blood samples for substrates: FFAs, Beta-hydroxybutarate, total and free carnitine, acylcarnitines Immediately begin efforts to collect urine (bagged specimen) and send for urinalysis and urine organic acid analysis. Check urine for ketones and glucose. Differential for Hypoglycemia A good starti Continue reading >>
Ketosis- Causes And Consequences
1. KETOSIS- CAUSESAND 10/21/2012CONSEQUENCES Biochemistry For MedicsBiochemistry for Medicswww.namrata.co 1 2. Ketone Bodies• Ketone bodies can be regarded as water-soluble, transportable form of acetyl units. Fatty acids are released by 10/21/2012 adipose tissue and converted into acetyl units by the liver, which then exports them as ketone bodies.• Acetoacetate, D(-3) –hydroxy butyrate (Beta hydroxy Biochemistry For Medics butyrate), and acetone are often referred to as ketone bodies 2 3. KetogenesisKetogenesis takes place in liver using Acetyl co A as a substrate or a precursor molecule. 10/21/2012 Enzymes responsible for ketone body formation are associated mainly with the mitochondria Biochemistry For MedicsStepsTwo molecules of acetyl CoA condense to form acetoacetyl CoA. This reaction, which is catalyzed by thiolase, is the reverse of the thiolysis step in the oxidation of fatty acids. 3 4. Ketogenesis Acetoacetyl CoA then reacts with acetyl CoA and water to give 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) and 10/21/2012 CoASH. The reaction is catalyzed by HMG co A synthase. Biochemistry For Medics This enzyme is exclusively present in liver mitochondria. There are two isoforms of this enzyme-cytosolic and mitochondrial. The mitochondrial enzyme is needed for ketogenesis while the cytosolic form is associated with cholesterol biosynthesis. 4 5. KetogenesisThis condensation resembles the one catalyzed by citrate synthase. 10/21/2012 This reaction, which has a favorable equilibrium owing to the hydrolysis of a thioester linkage, Biochemistry For Medics compensates for the unfavorable equilibrium in the formation of acetoacetyl CoA. 3-Hydroxy-3-methylglutaryl CoA is then cleaved to acetyl CoA and acetoacetate in the presence of HM Continue reading >>
What Are Ketones And What Do They Have To Do With Diabetes?
People with Type 1 Diabetes, or people with advanced Type 2 Diabetes, do not produce, enough, or any Insulin at all and Insulin is a pancreas produced hormone that is required to metabolise the blood sugar and when the body has insufficient Insulin, it cannot get glucose from the blood into the body's cells to use as energy. Glucose is the primary fuel that the body uses for energy and a lack of energy makes the body think that you do not have enough glucose present in the blood, so the body starts to burn body fat in order to create more glucose; however, this does not create more Insulin and so the body still cannot get glucose from the blood into the body's cells to use as energy; this creates a vicious circle, in which the body burns even more fat. Unfortunately, when the body burns too much fat, it also creates Ketones, which is an acid that is released into the bloodstream and if there is insufficient Insulin present to help fuel the body’s cells, the Keytones start to build up; therefore, high levels of Ketones are more common in people with Type 1 Diabetes, or people with advanced Type 2 Diabetes. The Symptoms Of Ketoacidosis: Symptoms of Ketoacidosis include Slow, Deep Breathing; Ketones give the breath a sickly, fruity odour like nail varnish remover or pear drops; Confusion; Frequent Urination 'Polyuria'; Poor Appetite and eventually Loss of Consciousness; a good indication is if you can taste nail varnish or pear drops when licking your lips. How Do I Test For Ketones? Ketone testing can be carried out at home; there are several products that test for Ketones in the urine and there are blood glucose meters which can also test for Ketones as well as test the blood glucose levels; although, you will probably only need to use ketone testing if you are ill or Continue reading >>
Diabetic Ketoacidosis
Professor of Pediatric Endocrinology University of Khartoum, Sudan Introduction DKA is a serious acute complications of Diabetes Mellitus. It carries significant risk of death and/or morbidity especially with delayed treatment. The prognosis of DKA is worse in the extremes of age, with a mortality rates of 5-10%. With the new advances of therapy, DKA mortality decreases to > 2%. Before discovery and use of Insulin (1922) the mortality was 100%. Epidemiology DKA is reported in 2-5% of known type 1 diabetic patients in industrialized countries, while it occurs in 35-40% of such patients in Africa. DKA at the time of first diagnosis of diabetes mellitus is reported in only 2-3% in western Europe, but is seen in 95% of diabetic children in Sudan. Similar results were reported from other African countries . Consequences The latter observation is annoying because it implies the following: The late diagnosis of type 1 diabetes in many developing countries particularly in Africa. The late presentation of DKA, which is associated with risk of morbidity & mortality Death of young children with DKA undiagnosed or wrongly diagnosed as malaria or meningitis. Pathophysiology Secondary to insulin deficiency, and the action of counter-regulatory hormones, blood glucose increases leading to hyperglycemia and glucosuria. Glucosuria causes an osmotic diuresis, leading to water & Na loss. In the absence of insulin activity the body fails to utilize glucose as fuel and uses fats instead. This leads to ketosis. Pathophysiology/2 The excess of ketone bodies will cause metabolic acidosis, the later is also aggravated by Lactic acidosis caused by dehydration & poor tissue perfusion. Vomiting due to an ileus, plus increased insensible water losses due to tachypnea will worsen the state of dehydr Continue reading >>
Ketonuria, What Causes It?
Ketonuria is a condition of an abnormal quantity of ketones and ketone bodies in urine. It indicates a possible presence of malignant diabetes mellitus. A diabetic with the risk of ketonuria requires regular urine monitoring to watch out for the buildup of ketone for prompt treatment to prevent sliding into unmanageable condition. Ketonuria is also known as ketoaciduria or acetonuria. KETONURIA CAUSES The human body requires carbohydrates for energy, but the presence of diabetes causing abnormal carbohydrates metabolism is responsible for ketones to build up and accumulation in the blood and passed out in urine. The conditions responsible for Ketones accumulation are acidosis and coma in diabetics. Other enabling factors may include Starvation, Digestive disturbances, Dietary imbalance, Eclampsia, Glycogen storage diseases, Severe, prolonged exercise, Fever, Prolonged exposure to cold temperatures. Ketones are toxic and disrupt uric acid excretion. The cause mild depression of the central nervous system and acidosis. FOOD DIGESTION AND INSULIN In food digestion, the body breaks fat, proteins and carbohydrates into nutrients for the body use. Proteins are converted to amino acid, fat to fatty acid and glucose. All these nutrients get into the blood stream to begin the work of sustenance and nourishment of the body. In food digestion, the body turns proteins, fats, and carbohydrates into nutrients that sustain and nurture it. It converts Fats into fatty acids, Proteins into amino acids and Carbohydrates into glucose (sugar) that enters the bloodstream. Although the body requires glucose to power it, the glucose is only available through insulin. Insulin is the hormone responsible for supplying the body its glucose needs, and it is produced by the pancreas. It is when gluc Continue reading >>
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 >>
