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Ketoacidosis Pathophysiology

Childhood Ketoacidosis

Childhood Ketoacidosis

Patient professional reference Professional Reference articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use. You may find one of our health articles more useful. Diabetic ketoacidosis (DKA) is the leading cause of mortality in childhood diabetes.[1]The primary cause of DKA is absolute or relative insulin deficiency: Absolute - eg, previously undiagnosed type 1 diabetes mellitus or a patient with known type 1 diabetes who does not take their insulin. Relative - stress causes a rise in counter-regulatory hormones with relative insulin deficiency. DKA can be fatal The usual causes of death are: Cerebral oedema - associated with 25% mortality (see 'Cerebral odedema', below). Hypokalaemia - which is preventable with good monitoring. Aspiration pneumonia - thus, use of a nasogastric tube in the semi-conscious or unconscious is advised. Deficiency of insulin. Rise in counter-regulatory hormones, including glucagon, cortisol, growth hormone, and catecholamines. Thus, inappropriate gluconeogenesis and liver glycogenolysis occur compounding the hyperglycaemia, which causes hyperosmolarity and ensuing polyuria, dehydration and loss of electrolytes. Accelerated catabolism from lipolysis of adipose tissue leads to increased free fatty acid circulation, which on hepatic oxidation produces the ketone bodies (acetoacetic acid and beta-hydroxybutyric acid) that cause the metabolic acidosis. A vicious circle is usually set up as vomiting usually occurs compounding the stress and dehydration; the cycle can only be broken by providing insulin and fluids; otherwise, severe acidosis occurs and can be fatal. Biochemical criteria The biochemical criteria required for a diagnosis of DKA to be made are Continue reading >>

Diabetic Ketoacidosis And Hyperglycaemic Hyperosmolar State

Diabetic Ketoacidosis And Hyperglycaemic Hyperosmolar State

The hallmark of diabetes is a raised plasma glucose resulting from an absolute or relative lack of insulin action. Untreated, this can lead to two distinct yet overlapping life-threatening emergencies. Near-complete lack of insulin will result in diabetic ketoacidosis, which is therefore more characteristic of type 1 diabetes, whereas partial insulin deficiency will suppress hepatic ketogenesis but not hepatic glucose output, resulting in hyperglycaemia and dehydration, and culminating in the hyperglycaemic hyperosmolar state. Hyperglycaemia is characteristic of diabetic ketoacidosis, particularly in the previously undiagnosed, but it is the acidosis and the associated electrolyte disorders that make this a life-threatening condition. Hyperglycaemia is the dominant feature of the hyperglycaemic hyperosmolar state, causing severe polyuria and fluid loss and leading to cellular dehydration. Progression from uncontrolled diabetes to a metabolic emergency may result from unrecognised diabetes, sometimes aggravated by glucose containing drinks, or metabolic stress due to infection or intercurrent illness and associated with increased levels of counter-regulatory hormones. Since diabetic ketoacidosis and the hyperglycaemic hyperosmolar state have a similar underlying pathophysiology the principles of treatment are similar (but not identical), and the conditions may be considered two extremes of a spectrum of disease, with individual patients often showing aspects of both. Pathogenesis of DKA and HHS Insulin is a powerful anabolic hormone which helps nutrients to enter the cells, where these nutrients can be used either as fuel or as building blocks for cell growth and expansion. The complementary action of insulin is to antagonise the breakdown of fuel stores. Thus, the relea Continue reading >>

Diabetic Ketoacidosis: A Current Appraisal Of Pathophysiology And Management

Diabetic Ketoacidosis: A Current Appraisal Of Pathophysiology And Management

This is a current appraisal of new insights into the pathophysiology and management of diabetic ketoacidosis (DKA), including laboratory work-up, monitoring of insulin, and fluid management. This article also discussed the complications of DKA and its treatment, focusing on cerebral edema (CE). The author recommends that fluid deficits be replaced at an even rate over 48 h, not to exceed 4/L/m2/24 h. Regular insulin should be started at 0.1 units/kg/h (no bolus). In general, it is recommended that bicarbonate not be administered unless correction of a pH < 6.9 is necessary. To access this article, please choose from the options below Continue reading >>

Understanding The Presentation Of Diabetic Ketoacidosis

Understanding The Presentation Of Diabetic Ketoacidosis

Hypoglycemia, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar nonketotic syndrome (HHNS) must be considered while forming a differential diagnosis when assessing and managing a patient with an altered mental status. This is especially true if the patient has a history of diabetes mellitus (DM). However, be aware that the onset of DKA or HHNS may be the first sign of DM in a patient with no known history. Thus, it is imperative to obtain a blood glucose reading on any patient with an altered mental status, especially if the patient appears to be dehydrated, regardless of a positive or negative history of DM. In addition to the blood glucose reading, the history — particularly onset — and physical assessment findings will contribute to the formulation of a differential diagnosis and the appropriate emergency management of the patient. Pathophysiology of DKA The patient experiencing DKA presents significantly different from one who is hypoglycemic. This is due to the variation in the pathology of the condition. Like hypoglycemia, by understanding the basic pathophysiology of DKA, there is no need to memorize signs and symptoms in order to recognize and differentiate between hypoglycemia and DKA. Unlike hypoglycemia, where the insulin level is in excess and the blood glucose level is extremely low, DKA is associated with a relative or absolute insulin deficiency and a severely elevated blood glucose level, typically greater than 300 mg/dL. Due to the lack of insulin, tissue such as muscle, fat and the liver are unable to take up glucose. Even though the blood has an extremely elevated amount of circulating glucose, the cells are basically starving. Because the blood brain barrier does not require insulin for glucose to diffuse across, the brain cells are rece 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 >>

Pathophysiology And Treatment

Pathophysiology And Treatment

The Kabod Volume 2 Issue 1 Fall 2015 Article 3 Diabetic Ketoacidosis: Pathophysiology and Treatment Laura E. Mumme Liberty University, [email protected] Follow this and additional works at: Part of the Medical Biochemistry Commons, and the Medical Physiology Commons Recommended Citations MLA: Mumme, Laura E. "Diabetic Ketoacidosis: Pathophysiology and Treatment," The Kabod 2. 1 (2015) Article 3. Liberty University Digital Commons. Web. [xx Month xxxx]. APA: Mumme, Laura E. (2015) "Diabetic Ketoacidosis: Pathophysiology and Treatment" The Kabod 2( 1 (2015)), Article 3. Retrieved from Turabian: Mumme, Laura E. "Diabetic Ketoacidosis: Pathophysiology and Treatment" The Kabod 2 , no. 1 2015 (2015) Accessed [Month x, xxxx]. Liberty University Digital Commons. Running head: DIABETIC KETOACIDOSIS 1 Diabetic Ketoacidosis Pathophysiology and Treatment Liberty University 1 Mumme: Diabetic Ketoacidosis Published by [email protected] University, 2015 DIABETIC KETOACIDOSIS 2 Diabetic Ketoacidosis: Pathophysiology and Treatment Diabetic ketoacidosis (DKA), also known as diabetic acidosis or diabetic coma, is a severe complication of diabetes mellitus (DM; Michel, 2011). More commonly seen in patients with type 1 diabetes (T1D), DKA results when lipid breakdown generates a surplus of acidic ketone bodies (Guven, Matfin, & Kuenzi, 2009). According to Dods (2013), DKA can be defined as a condition with “blood glucose greater than 250 mg/dL, blood bicarbonate less than 15 mEq/L, pH less than 7.35, ketonemia, and increased anion gap†(p. 266). The pathophysiology of DKA in patients with T1D will first be addressed, followed by a discussion of proper emergency treatment for this life-threatening condition. The three main abnormalities of DKA patients include hyperglycemia, Continue reading >>

Diabetic Ketoacidosis: Pathophysiology, Management And Complications

Diabetic Ketoacidosis: Pathophysiology, Management And Complications

Diabetic ketoacidosis (DKA) is a common and potentially life-threatening complication of diabetes mellitus, the second most common chronic childhood disease [1]. Prior to the introduction of insulin to clinical medicine by Banting and Best in 1922, DKA had a mortality rate greater than 60% [2]. As insulin was introduced into clinical practice, there was a gradual decrease in mortality associated with DKA over the subsequent 30 years. Recent epidemiological data reveal current mortality varies from 0 to 19% [3,4]. DKA continues to be the most common cause of death in patients younger than 24 years of age; it accounts for as many as 50% of deaths of young diabetic patients [5–7]. In elderly diabetics who have coexisting diseases, DKA carries a high mortality [8]. Despite many advances in the care of diabetic patients, the prevalence of DKA is not declining; it accounts for 14% of all diabetes-related hospital admissions [3, 4, 9]. The incidence of insulin-dependent diabetes mellitus continues to increase worldwide and has roughly doubled in each recent decade [10–13]. Because insulin-dependent diabetes mellitus is increasing, and preventative measures to avoid DKA in diabetic patients have not been successful, the incidence of DKA can also be expected to increase in coming years. Prevention of DKA is the ultimate goal (80% of hospital admissions for DKA occur in treated diabetics) [3,8]. It is necessary for clinicians to understand the pathophysiology and treatment of DKA to care for this increasing diabetic population. We discuss the pathophysiology of diabetic ketoacidosis, its management, and its complications. Continue reading >>

Diabetic Ketoacidosis

Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus.[1] Signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion, and occasionally loss of consciousness.[1] A person's breath may develop a specific smell.[1] Onset of symptoms is usually rapid.[1] In some cases people may not realize they previously had diabetes.[1] DKA happens most often in those with type 1 diabetes, but can also occur in those with other types of diabetes under certain circumstances.[1] Triggers may include infection, not taking insulin correctly, stroke, and certain medications such as steroids.[1] DKA results from a shortage of insulin; in response the body switches to burning fatty acids which produces acidic ketone bodies.[3] DKA is typically diagnosed when testing finds high blood sugar, low blood pH, and ketoacids in either the blood or urine.[1] The primary treatment of DKA is with intravenous fluids and insulin.[1] Depending on the severity, insulin may be given intravenously or by injection under the skin.[3] Usually potassium is also needed to prevent the development of low blood potassium.[1] Throughout treatment blood sugar and potassium levels should be regularly checked.[1] Antibiotics may be required in those with an underlying infection.[6] In those with severely low blood pH, sodium bicarbonate may be given; however, its use is of unclear benefit and typically not recommended.[1][6] Rates of DKA vary around the world.[5] In the United Kingdom, about 4% of people with type 1 diabetes develop DKA each year, while in Malaysia the condition affects about 25% a year.[1][5] DKA was first described in 1886 and, until the introduction of insulin therapy in the 1920s, it was almost univ Continue reading >>

Pathophysiology Of Diabetic Ketoacidosis : Animation

Pathophysiology Of Diabetic Ketoacidosis : Animation

When the rate of synthesis of ketone bodies exceeds the rate of utilization, their concentration in blood increases, this is known as ketonemia. This is followed by ketonuria – excretion of ketone bodies in urine. The overall picture of ketonemia and ketonuria is commonly referred to as ketosis. Mechanism: Hyperglycaemia occurs due to decreased glucose uptake in fat and muscle cells due to insulin deficiency Lipolysis in fat cells now occurs promoted by the insulin deficiency releasing Free fatty acids (FFA) into the blood which provide substrate to the liver A switch in hepatic lipid metabolism occurs due to the insulin deficiency and the glucagon excess, so the excess FFA is metabolised resulting in excess production of acetyl CoA The excess hepatic acetyl CoA (remaining after saturation of TCA cycle) is converted to ketone bodies which are released into the blood Ketoacidosis and hyperglycaemia both occur due to the lack of insulin and the increase in glucagon and most of the clinical effects follow from these two factors 1. ↓ Insulin, ↑Glucogon (glycogen à glucose) - Glucose 500-700 mg/dl 2. Glucose-derived osmotic diuresis 3. ↑ Glucagon - ↑ FFA esterfied à ketone bodies à acidosis Diagnostic tests: Blood glucose greater than 250 mg/dL Blood pH less than 7.3 Blood bicarbonate less than 15 mEq/L Ketones present in blood (exceeds 90 mg/dl) Ketones excreted in urine exceeds 5000 mg/24 hrs Signs and Symptoms: Kussmal's respiration Fruity odor of breath Nausea and abdominal pain Dehydration Lethargy Coma Polydipsia, polyuria, polyphagia Read more Ketone bodies, Ketosis and Ketoacidosis | Medchrome Continue reading >>

Pathophysiology Of Ketoacidosis In Type 2 Diabetes Mellitus.

Pathophysiology Of Ketoacidosis In Type 2 Diabetes Mellitus.

Abstract AIMS: Despite an increasing number of reports of ketoacidosis in populations with Type 2 diabetes mellitus, the pathophysiology of the ketoacidosis in these patients is unclear. We therefore tested the roles of three possible mechanisms: elevated stress hormones, increased free fatty acids (FFA), and suppressed insulin secretion. METHODS: Forty-six patients who presented to the Emergency Department with decompensated diabetes (serum glucose > 22.2 mmol/l and/or ketoacid concentrations > or = 5 mmol/l), had blood sampled prior to insulin therapy. Three groups of subjects were studied: ketosis-prone Type 2 diabetes (KPDM2, n = 13) with ketoacidosis, non-ketosis-prone subjects with Type 2 diabetes (DM2, n = 15), and ketotic Type 1 diabetes (n = 18). RESULTS: All three groups had similar mean plasma glucose concentrations. The degree of ketoacidosis (plasma ketoacids, bicarbonate and anion gap) in Type 1 and 2 subjects was similar. Mean levels of counterregulatory hormones (glucagon, growth hormone, cortisol, epinephrine, norepinephrine), and FFA were not significantly different in DM2 and KPDM2 patients. In contrast, plasma C-peptide concentrations were approximately three-fold lower in KPDM2 vs. non-ketotic DM2 subjects (P = 0.0001). Type 1 ketotic subjects had significantly higher growth hormone (P = 0.024) and FFA (P < 0.002) and lower glucagon levels (P < 0.02) than DM2. CONCLUSIONS: At the time of hospital presentation, the predominant mechanism for ketosis in KPDM2 is likely to be greater insulinopenia. Continue reading >>

Pathophysiology Of Severe Diabetic Ketoacidosis Presenting With Negative Serum Ketones

Pathophysiology Of Severe Diabetic Ketoacidosis Presenting With Negative Serum Ketones

In the paper “Severe diabetic ketoacidosis presenting with negative serum ketones: First case report and a review of the mechanism” [1] is reported a comatose diabetic woman with very low blood-pH and negative serum ketones. Similar case histories have been - unfortunately not noticed - published also earlier, e g [2,3]. To access this article, please choose from the options below Continue reading >>

Acute Complications Of Diabetes - Diabetic Ketoacidosis

Acute Complications Of Diabetes - Diabetic Ketoacidosis

- [Voiceover] Oftentimes we think of diabetes mellitus as a chronic disease that causes serious complications over a long period of time if it's not treated properly. However, the acute complications of diabetes mellitus are often the most serious, and can be potentially even life threatening. Let's discuss one of the acute complications of diabetes, known as diabetic ketoacidosis, or DKA for short, which can occur in individuals with type 1 diabetes. Now recall that type 1 diabetes is an autoimmune disorder. And as such, there's an autoimmune destruction of the beta cells in the pancreas, which prevents the pancreas from producing and secreting insulin. Therefore, there is an absolute insulin deficiency in type 1 diabetes. But what exactly does this mean for the body? To get a better understanding, let's think about insulin requirements as a balancing act with energy needs. Now the goal here is to keep the balance in balance. As the energy requirements of the body go up, insulin is needed to take the glucose out of the blood and store it throughout the body. Normally in individuals without type 1 diabetes, the pancreas is able to produce enough insulin to keep up with any amount of energy requirement. But how does this change is someone has type 1 diabetes? Well since their pancreas cannot produces as much insulin, they have an absolute insulin deficiency. Now for day-to-day activities, this may not actually cause any problems, because the small amount of insulin that is produced is able to compensate and keep the balance in balance. However, over time, as type 1 diabetes worsens, and less insulin is able to be produced, then the balance becomes slightly unequal. And this results in the sub-acute or mild symptoms of type 1 diabetes such as fatigue, because the body isn 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

Diabetic Ketoacidosis

Practice Essentials Diabetic ketoacidosis (DKA) is an acute, major, life-threatening complication of diabetes that mainly occurs in patients with type 1 diabetes, but it is not uncommon in some patients with type 2 diabetes. This condition is a complex disordered metabolic state characterized by hyperglycemia, ketoacidosis, and ketonuria. Signs and symptoms The most common early symptoms of DKA are the insidious increase in polydipsia and polyuria. The following are other signs and symptoms of DKA: Nausea and vomiting; may be associated with diffuse abdominal pain, decreased appetite, and anorexia History of failure to comply with insulin therapy or missed insulin injections due to vomiting or psychological reasons or history of mechanical failure of insulin infusion pump Altered consciousness (eg, mild disorientation, confusion); frank coma is uncommon but may occur when the condition is neglected or with severe dehydration/acidosis Signs and symptoms of DKA associated with possible intercurrent infection are as follows: See Clinical Presentation for more detail. Diagnosis On examination, general findings of DKA may include the following: Characteristic acetone (ketotic) breath odor In addition, evaluate patients for signs of possible intercurrent illnesses such as MI, UTI, pneumonia, and perinephric abscess. Search for signs of infection is mandatory in all cases. Testing Initial and repeat laboratory studies for patients with DKA include the following: Serum electrolyte levels (eg, potassium, sodium, chloride, magnesium, calcium, phosphorus) Note that high serum glucose levels may lead to dilutional hyponatremia; high triglyceride levels may lead to factitious low glucose levels; and high levels of ketone bodies may lead to factitious elevation of creatinine levels. Continue reading >>

Ketoacidosis Pathophysiology

Ketoacidosis Pathophysiology

Introduction Diabetic ketoacidosis Diabetic ketoacidosis is a serious, life threatening condition - successful treatment requires attention to metabolic consequences. Ketone production In the normal animal free fatty acids (FFA) are released from adipose tissue in the process of lipolysis and are used as fuel or assimilated by the liver in the presence of reduced insulin concentrations and increased glucagon concentrations. They are used to build triglycerides, metabolized in the tricarboxylic acid cycle or converted to ketone bodies. In the face of a relative or absolute insulin deficiency the cells are unable to uptake and utilize glucose. Ketone bodies can be used by peripheral tissues and the liver as an alternative source of energy and are therefore life-saving in the short-term. Production is normally carefully controlled by a homeostatic mechanism. If this balance is disturbed a number of processes are activated which together produce a decompensated state which inevitably progresses towards death unless averting action is taken. As the rate of ketone body production begins to exceed the rate at which they can be used, ketonemia develops with associated acidosis. Once the concentration in the blood exceeds the renal threshold ketonuria Urinalysis: ketone develops and this provides an alternative mechanism for ketone removal from the body. Insulin antagonism Ketoacidosis Diabetic ketoacidosis is often associated with conditions which increase concentrations of diabetogenic hormones: Infection: increases concentrations of cortisol and glucagon. Congestive heart failure: increases concentrations of catecholamines and glucagon. Pyrexia: increases concentrations of cortisol, catecholamines, growth hormone and glucagons. Fasting During fasting the body mobilizes lipid Continue reading >>

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