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Ketoacidosis Pathophysiology

Diabetic Ketoacidosis In Type 2 Diabetes Mellitus—pathophysiology And Clinical Presentation

Diabetic Ketoacidosis In Type 2 Diabetes Mellitus—pathophysiology And Clinical Presentation

SN Davis is supported by research grants from the NIH. GE Umpierrez is supported by research grants from the NIH, the American Diabetes Association, and the American Heart Association. The authors declare no competing financial interests. Continue reading >>

Pathophysiology Of Diabetic Ketoacidosis

Pathophysiology Of Diabetic Ketoacidosis

Diabetic ketoacidosis is one of the potentially life-threatening acute complications of diabetes mellitus. In the past, diabetic ketoacidosis was considered as the hallmark of Type I diabetes, but current data show that it can be also diagnosed in patients with type II diabetes mellitus. It is often seen among patients who are poorly compliant to insulin administration during an acute illness. It is commonly precipitated by an acute stressful event such as the development of infection leading to overt sepsis, organ infarction such as stroke and heart attack, burns, pregnancy or intake of drugs that affect carbohydrate metabolism such as corticosteroids, anti-hypertensives, loop diuretics, alcohol, cocaine, and ecstasy. The presence of these stressful conditions incite the release of counter-regulatory hormones such as glucagon, catecholamines and growth hormone. These hormones induce the mobilization of energy stores of fat, glycogen and protein. The net effect of which is the production of glucose. As a result of absent or deficient insulin release, diabetic ketoacidosis present with the following metabolic derangements: profound hyperglycemia, hyperketonemiaand metabolic acidosis. The production of ketones outweighs its excretion by the kidneys. This results in further reduction of systemic insulin, elevated concentrations of glucagon, cortisol, growth hormone and catecholamine. In peripheral tissues, such as the liver, lipolysis occurs to free fatty acids, resulting in further production of excess ketones. Thereby, causing ketosis and metabolic acidosis. Symptoms of diabetic ketoacidosis usually develop within 24 hours. Gastrointestinal symptoms such as nausea and vomiting are very prominent. If these symptoms are present in diabetics, investigation for diabetic keto Continue reading >>

Diabetic Ketoacidosis: Pathophysiology, Management And Complications

Diabetic Ketoacidosis: Pathophysiology, Management And Complications

Abstract 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 >>

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

Diabetic Ketoacidosis

Abbas E. Kitabchi, PhD., MD., FACP, FACE Professor of Medicine & Molecular Sciences and Maston K. Callison Professor in the Division of Endocrinology, Diabetes & Metabolism UT Health Science Center, 920 Madison Ave., 300A, Memphis, TN 38163 Aidar R. Gosmanov, M.D., Ph.D., D.M.Sc. Assistant Professor of Medicine, Division of Endocrinology, Diabetes & Metabolism, The University of Tennessee Health Science Center, 920 Madison Avenue, Suite 300A, Memphis, TN 38163 Clinical Recognition Omission of insulin and infection are the two most common precipitants of DKA. Non-compliance may account for up to 44% of DKA presentations; while infection is less frequently observed in DKA patients. Acute medical illnesses involving the cardiovascular system (myocardial infarction, stroke, acute thrombosis) and gastrointestinal tract (bleeding, pancreatitis), diseases of endocrine axis (acromegaly, Cushing`s syndrome, hyperthyroidism) and impaired thermo-regulation or recent surgical procedures can contribute to the development of DKA by causing dehydration, increase in insulin counter-regulatory hormones, and worsening of peripheral insulin resistance. Medications such as diuretics, beta-blockers, corticosteroids, second-generation anti-psychotics, and/or anti-convulsants may affect carbohydrate metabolism and volume status and, therefore, could precipitateDKA. Other factors: psychological problems, eating disorders, insulin pump malfunction, and drug abuse. It is now recognized that new onset T2DM can manifest with DKA. These patients are obese, mostly African Americans or Hispanics and have undiagnosed hyperglycemia, impaired insulin secretion, and insulin action. A recent report suggests that cocaine abuse is an independent risk factor associated with DKA recurrence. Pathophysiology In Continue reading >>

Chapter 220. Diabetic Ketoacidosis

Chapter 220. Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of diabetes mellitus. The incidence and prevalence of diabetes are rising; as of 2005, an estimated 7% of the U.S. population had diabetes. In patients age 60 or older, the prevalence is estimated to be 20.9%.1 DKA occurs predominately in patients with type 1 (insulin-dependent) diabetes mellitus, but unprovoked DKA can occur in newly diagnosed type 2 (non–insulin-dependent) diabetes mellitus, especially in blacks and Hispanics.2 Between 1993 and 2003, the yearly rate of ED visits for DKA per 10,000 U.S. population with diabetes was 64, with a trend toward an increased rate of visits among the black population compared with the white population.3 Europe has a comparable incidence. A better understanding of pathophysiology and an aggressive, uniform approach to diagnosis and management have reduced mortality to <5% of reported episodes in experienced centers.4 However, mortality is higher in the elderly due to underlying renal disease or coexisting infection and in the presence of coma or hypotension. DKA is a response to cellular starvation brought on by relative insulin deficiency and counterregulatory or catabolic hormone excess (Figure 220-1). Insulin is the only anabolic hormone produced by the endocrine pancreas and is responsible for the metabolism and storage of carbohydrates, fat, and protein. Counterregulatory hormones include glucagon, catecholamines, cortisol, and growth hormone. Complete or relative absence of insulin and the excess counterregulatory hormones result in hyperglycemia (due to excess production and underutilization of glucose), osmotic diuresis, prerenal azotemia, worsening hyperglycemia, ketone formation, and a wide-anion gap metabolic acidosis.4 Insulin deficiency. Patho 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 >>

Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, And Preventable Safety Concern With Sglt2 Inhibitors

Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, And Preventable Safety Concern With Sglt2 Inhibitors

The Case At Hand Recently, the U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication that warns of an increased risk of diabetic ketoacidosis (DKA) with uncharacteristically mild to moderate glucose elevations (euglycemic DKA [euDKA]) associated with the use of all the approved sodium–glucose cotransporter 2 (SGLT2) inhibitors (1). This Communication was based on 20 clinical cases requiring hospitalization captured between March 2013 and June 2014 in the FDA Adverse Event Reporting System database. The scarce clinical data provided suggested that most of the DKA cases were reported in patients with type 2 diabetes (T2D), for whom this class of agents is indicated; most likely, however, they were insulin-treated patients, some with type 1 diabetes (T1D). The FDA also identified potential triggering factors such as intercurrent illness, reduced food and fluid intake, reduced insulin doses, and history of alcohol intake. The following month, at the request of the European Commission, the European Medicines Agency (EMA) announced on 12 June 2015 that the Pharmacovigilance Risk Assessment Committee has started a review of all of the three approved SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) to evaluate the risk of DKA in T2D (2). The EMA announcement claimed that as of May 2015 a total of 101 cases of DKA have been reported worldwide in EudraVigilance in T2D patients treated with SGLT2 inhibitors, with an estimated exposure over 0.5 million patient-years. No clinical details were provided except for the mention that “all cases were serious and some required hospitalisation. Although [DKA] is usually accompanied by high blood sugar levels, in a number of these reports blood sugar levels were only moderately increased” (2). Wit Continue reading >>

Extreme Gestational Starvation Ketoacidosis: Case Report And Review Of Pathophysiology

Extreme Gestational Starvation Ketoacidosis: Case Report And Review Of Pathophysiology

A case of severe starvation ketoacidosis developing during pregnancy is presented. The insulinopenic/insulinresistant state found during fasting in late gestation predisposes to ketosis. Superimposition of stress hormones, which further augment lipolysis, exacerbates the degree of ketoacidosis. In our patient, gestational diabetes, twin pregnancies, preterm labor, and occult infection were factors that contributed to severe starvation ketoacidosis. Diagnosis was delayed because starvation ketosis is not generally considered to be a cause of severe acidosis, and because the anion gap was not elevated. Improved understanding of the complex fuel metabolism during pregnancy should aid in prevention, early recognition, and appropriate therapy of this condition. 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 >>

Ketoacidosis

Ketoacidosis

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 keto-anion 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 keto-anion 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 KETOSIS 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 free fatty acids (FFA) can be high (eg up to 3.5mM) providing plenty of substrate for the altered hepatic lipid metabolism to produce plenty of ketoanions GI symptoms are common (eg nausea, vomiting, abdominal pain, haematemesis, melaena) acidaemia may be severe (eg pH down to 7.0) plasma glucose may be depressed or normal or 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 >>

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 >>

Diabetic Ketoacidosis

Diabetic Ketoacidosis

Print Overview Diabetic ketoacidosis is a serious complication of diabetes that occurs when your body produces high levels of blood acids called ketones. The condition develops when your body can't produce enough insulin. Insulin normally plays a key role in helping sugar (glucose) — a major source of energy for your muscles and other tissues — enter your cells. Without enough insulin, your body begins to break down fat as fuel. This process produces a buildup of acids in the bloodstream called ketones, eventually leading to diabetic ketoacidosis if untreated. If you have diabetes or you're at risk of diabetes, learn the warning signs of diabetic ketoacidosis — and know when to seek emergency care. Symptoms Diabetic ketoacidosis signs and symptoms often develop quickly, sometimes within 24 hours. For some, these signs and symptoms may be the first indication of having diabetes. You may notice: Excessive thirst Frequent urination Nausea and vomiting Abdominal pain Weakness or fatigue Shortness of breath Fruity-scented breath Confusion More-specific signs of diabetic ketoacidosis — which can be detected through home blood and urine testing kits — include: High blood sugar level (hyperglycemia) High ketone levels in your urine When to see a doctor If you feel ill or stressed or you've had a recent illness or injury, check your blood sugar level often. You might also try an over-the-counter urine ketones testing kit. Contact your doctor immediately if: You're vomiting and unable to tolerate food or liquid Your blood sugar level is higher than your target range and doesn't respond to home treatment Your urine ketone level is moderate or high Seek emergency care if: Your blood sugar level is consistently higher than 300 milligrams per deciliter (mg/dL), or 16.7 mill Continue reading >>

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 >>

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