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Dka Pathophysiology Made Simple

Diabetic Ketoacidosis

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 >>

Diabetic Ketoacidosis

Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is a medical emergency that can happen in people with diabetes mellitus. DKA happens mostly in people with Type 1 diabetes, although it may happen in some people that have Type 2 diabetes. DKA happens when a person does not have enough insulin in their body. All of the cells in the body need glucose (sugar) to survive, because the body needs sugar to make energy. Insulin breaks down glucose into a form that the body can use for energy. Without insulin, sugar stays in the blood and cannot get into the cells. This causes high blood sugar levels and makes it impossible for the cells to use glucose to make energy. DKA can be caused by not having enough insulin, eating too many carbohydrates, and sometimes physical or mental stress. DKA can also be a sign that a person has diabetes that has not been discovered, or is not being controlled well. DKA is diagnosed through blood and urine testing. These tests will show high blood sugar, which does not happen with other forms of ketoacidosis. DKA was first discovered around 1886. Before insulin therapy was first used in the 1920s, DKA almost always caused death. The "3 polys" of DKA: Polydipsia (feeling very thirsty; this is caused by dehydration) Polyphagia (feeling very hungry; the brain realizes the body's cells are not getting enough sugar and triggers hunger, because normally eating would give the cells the sugar they need) Polyuria (urinating a lot; this is the body's way of trying to get rid of the extra glucose in the bloodstream) A "fruity" smell on the breath (acetone breath, caused by the body trying to blow off the acids and waste products created by DKA) Abdominal pain As DKA gets worse, it can cause these symptoms:[2] Confusion, which becomes worse and worse (because the brain is not getti Continue reading >>

Diabetic Ketoacidosis

Diabetic Ketoacidosis

I. Review of normal lipid metabolism Triglycerides in adipose ==lipolysis==> Long-chain FAs Long-chain FAs==hepatic beta-oxidation==>Acetyl CoA Acetyl CoA==hepatic ketogenesis==>ketone bodies Ketone bodies are Beta-hydroxybutyrate and Acetoacetate Beta-OHB is oxidized to AcAc-; their relative concentrations depend on redox state of cell; Beta-OHB predominates in situation favoring reductive metabolism (e.g. decreased tissue perfusion, met. acidosis, catabolic states--like DKA!) Typical ratio Beta-OHB:AcAc- is 3:1; us. increases in DKA II. Hormonal influences on glucose and lipid metabolism Insulin In liver, increases glu uptake from portal blood; stimulates glycogenesis, inhibits glycogenolysis and gluconeogenesis In skeletal muscle, increases glu uptake from blood, stimulates protein synth, inhibits proteolysis In adipose tissue, required for glu and lipoprotein uptake from blood; stimulates lipogenesis, inhibits lipolysis Tissues which don't require insulin to transport glucose into cells: brain, renal medulla, formed blood elements Counterregulatory hormones: glucagon (major player in DKA), epi/norepi, cortisol, growth hormone (no acute effects, only over days-weeks) Glucagon: increases hepatic beta-oxidation, ketogenesis, gluconeogenesis and glycogenolysis; decreases hepatic FA synth. Epi/Norepi: increase hepatic gluconeogenesis & glycogenolysis; increases adipose lipolysis; decreases peripheral glu utilization Cortisol: major effect is decreased peripheral glu utiliz; little effect on production Growth hormone: increases hepatic gluconeogenesis and glycogenolysis; increases adipose lipolysis In high counterreg. hormone states (see above), require high levels of insulin to avoid progressive hyperglycemia and ketoacidosis--glucagon levels in DKA are 5-6 x nl* III. Pa Continue reading >>

Diabetic Ketoacidosis (dka)

Diabetic Ketoacidosis (dka)

Snap Shot A 12 year old boy, previously healthy, is admitted to the hospital after 2 days of polyuria, polyphagia, nausea, vomiting and abdominal pain. Vital signs are: Temp 37C, BP 103/63 mmHg, HR 112, RR 30. Physical exam shows a lethargic boy. Labs are notable for WBC 16,000, Glucose 534, K 5.9, pH 7.13, PCO2 is 20 mmHg, PO2 is 90 mmHg. Introduction Complication of type I diabetes result of ↓ insulin, ↑ glucagon, growth hormone, catecholamine Precipitated by infections drugs (steroids, thiazide diuretics) noncompliance pancreatitis undiagnosed DM Presentation Symptoms abdominal pain vomiting Physical exam Kussmaul respiration increased tidal volume and rate as a result of metabolic acidosis fruity, acetone odor severe hypovolemia coma Evaluation Serology blood glucose levels > 250 mg/dL due to ↑ gluconeogenesis and glycogenolysis arterial pH < 7.3 ↑ anion gap due to ketoacidosis, lactic acidosis ↓ HCO3- consumed in an attempt to buffer the increased acid hyponatremia dilutional hyponatremia glucose acts as an osmotic agent and draws water from ICF to ECF hyperkalemia acidosis results in ICF/ECF exchange of H+ for K+ moderate ketonuria and ketonemia due to ↑ lipolysis β-hydroxybutyrate > acetoacetate β-hydroxybutyrate not detected with normal ketone body tests hypertriglyceridemia due to ↓ in capillary lipoprotein lipase activity activated by insulin leukocytosis due to stress-induced cortisol release H2PO4- is increased in urine, as it is titratable acid used to buffer the excess H+ that is being excreted Treatment Fluids Insulin with glucose must prevent resultant hypokalemia and hypophosphatemia labs may show pseudo-hyperkalemia prior to administartion of fluid and insulin due to transcellular shift of potassium out of the cells to balance the H+ be 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 >>

Management Of Diabetic Ketoacidosis In Adults

Management Of Diabetic Ketoacidosis In Adults

Diabetic ketoacidosis is a potentially life-threatening complication of diabetes, making it a medical emergency. Nurses need to know how to identify and manage it and how to maintain electrolyte balance Continue reading >>

Diabetic Ketoacidosis And Cerebral Edema

Diabetic Ketoacidosis And Cerebral Edema

Elliot J. Krane, M.D. Departments of Pediatrics and Anesthesiology Stanford University Medical Center Introduction In 1922 Banting and Best introduced insulin into clinical practice. A decade later the first reported case of cerebral edema complicating diabetic ketoacidosis (DKA) was reported by Dillon, Riggs and Dyer writing in the pathology literature. While the syndrome of cerebral edema complicating DKA was either not seen, ignored, or was unrecognized by the medical community until 3 decades later when the complication was again reported by Young and Bradley at the Joslin Clinic, there has since been a flurry of case reports in the 1960's and 1970's and basic and clinical research from the 1970's to the 1990's leading to our present day acceptance of this as a known complication of DKA, or of the management of DKA. In fact, we now recognize that the cerebral complications of DKA (including much less frequent cerebral arterial infarctions, venous sinus thrombosis, and central nervous system infections) are the most common cause of diabetic-related death of young diabetic patients (1), accounting for 31% of deaths associated with DKA and 20% of all diabetic deaths, having surpassed aspiration, electrolyte imbalance, myocardial infarction, etc. Furthermore, diabetes mellitus remains an important cause of hospitalization of young children. The prevalence rate of diabetes continues to grow in all Western developed nations, nearly doubling every decade, resulting in 22,000 hospital admissions in children under 15 years of age for diabetes in the United States in 1994, the majority of which were due to ketoacidosis. With approximately 4 hospital admissions of children for DKA per 100,000 population per year (2), every PICU located in a major metropolitan center will conti Continue reading >>

Diabetic Ketoacidosis

Diabetic Ketoacidosis

Diabetic ketoacidosis is a medical emergency that typically occurs as a complication of type 1 diabetes. It can occur in people with undiagnosed type 1 diabetes or in diabetics with: decreased insulin intake intercurrent illness stress of any form (e.g.infection, surgery, MI) Pathophysiology The pathophysiology (see image) of diabetic ketoacidosis must be considered to help understand its presentation and the necessary management. There are 3 main biochemical features: hyperglycaemia hyperketonaemia metabolic acidosis Firstly, lack of insulin causes glucose to remain in the blood rather than be transferred into cells for utilisation. The body therefore responds as if it were in starvation and hepatic glucose production becomes increased. Osmotic diuresis occurs as a consequence of this glucose rich blood being filtered by the kidneys. Glucose is normally reabsorbed by the proximal tubule but in DKA the amount of glucose filtered exceeds the renal threshold for reabsorbtion. The presence of glucose in the tubules causes water retention in the lumen, thus increasing urine output and decreasing reabsorption into the body, leading to dehydration and electrolyte depletion. Secondly, an absence of insulin together with elevated stress hormones such as catecholamines, leads to lipolysis, resulting in numerous free fatty acids available for hepatic ketogenesis. Consequently, there is increased ketone body formation by fatty acid oxidation in the liver, leading to an elevated level in the blood. These ketones give a distinct smell to the urine and breath. Thirdly, the ketone bodies lower the pH of the blood resulting in metabolic acidosis. This causes nausea and vomiting resulting in further dehydration. The body compensates for the acidosis by hyperventilation (Kussmals respira Continue reading >>

Diabetes: Mechanism, Pathophysiology And Management-a Review

Diabetes: Mechanism, Pathophysiology And Management-a Review

Anees A Siddiqui1*, Shadab A Siddiqui2, Suhail Ahmad, Seemi Siddiqui3, Iftikhar Ahsan1, Kapendra Sahu1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi (INDIA)-110062. School of Pharmacy, KIET, Ghaziabad U.P. SGC college of Pharmacy, Baghpat(UP) Corresponding Author:Anees A Siddiqui E-mail: [email protected] Received: 20 February 2011 Accepted: 02 May 2011 Citation: Anees A Siddiqui, Shadab A Siddiqui, Suhail Ahmad, Seemi Siddiqui, Iftikhar Ahsan, Kapendra Sahu “Diabetes: Mechanism, Pathophysiology and Management-A Review” Int. J. Drug Dev. & Res., April-June 2013, 5(2): 1-23. Copyright: © 2013 IJDDR, Anees A Siddiqui et al. This is an open access paper distributed under the copyright agreement with Serials Publication, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Related article at Pubmed, Scholar Google Visit for more related articles at International Journal of Drug Development and Research The prevalence of diabetes is rapidly rising all over the globe at an alarming rate. Over the last three decades, the status of diabetes has been changed, earlier it was considered as a mild disorder of the elderly people. Now it becomes a major cause of morbidity and mortality affecting the youth and middle aged people. According to the Diabetes Atlas 2006 published by the International Diabetes Federation, the number of people with diabetes in India currently around 40.9 million is expected to rise to 69.9 million by 2025 unless urgent preventive steps are taken. The main force of the epidemic of diabetes is the rapid epidemiological transition associated with changes in dietary patterns and decreased physical activity a 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 >>

Diabetes And Hypoglycemia Video Classroom

Diabetes And Hypoglycemia Video Classroom

Diabetes Overview Beginning Signs of Diabetes Pathophysiology of Diabetic Nephropathy Glucose Insulin and Diabetes (Kahn) Juvenile Diabetes Research Foundation Animation about Diabetes Subtle Warning Signs of Diabetes Diabetes Animation Diabetes Made Simple A Day Living with Diabetes Pathophysiology of Diabetes Mellitus Be Diabetes Prepared Health and Science in Diabetes Role of Insulin in Body Living with Diabetes: Documentary What is Diabetes? Diabetes Type 2: Animation Diabetes Symptoms in Men Glucose Animation Diabetes Emergencies 1 Managing Diabetes Insulin Resistence Diabetes: Foot Care Complications of Diabetes Diabetes Emergencies 2 Type 1 Diabetes Medical Science on Type 2 Diabetes Exercise in Diabetics Type 1 Diabetes Animation Diabetes Emergencies 3 Type 2 Diabetes Board Review: Type 1 and 2 Diabetes Diabetes: Excercise: Reverse Resistence 2 Diabetes Animation Treating Hypoglycemia Quickly What is Type 1 Diabetes Management of Diabetes Diabetes: Excercise as Medicine Metformin Medication Hypoglycemia Pathophysiology of Diabetes Pathophysiology of Diabetes 2 Made Easy Diabetes Animation Metformin for Diabetes Diabetic Ketoacidosis Diabetes: Progress in Stem Cell Research Diabetic Nephropathy for the Non-Nephrologist Diabetes Education Diabetes Medications Diabetic DKA Embryonic Stem Cell Diabetes Research Diabetic Retinopathy Insulin, Glucose and You Metformin Still the Best! Inpatient Diabetes Management Diabetes Basics Diabetic Eye Disease Insulin: Synthesis and Secretion 1 Understanding Diabetes Type 2 Hyperglycemic Crises: Part 1 Diabetes Symptoms Obesity and Diabetes Insulin: Synthesis and Secretion 2 Diabetes Update 2010 Hyperglycemic Crises: Part 2 Diabetes: Complications Metabolism and Nutrition: Diabetes Insulin: Synthesis and Secretion 3 Juvenile Dia 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 >>

Diabetic Ketoacidosis (dka)

Diabetic Ketoacidosis (dka)

Diabetic ketoacidosis is a condition that results from when the body is deprived of the ability to use glucose as an energy source. Usually this is due to a lack of insulin. Insulin is used to uptake glucose into the cells to be used for energy. If there is no insulin or the cells are resistant to insulin, the blood sugar levels increase to dangerous levels for the patient. It seems counter intuitive that the patient wouldn't have energy with such high levels of glucose, but this glucose is essentially unusable without insulin. Because your body needs energy to survive, it starts turning to alternative fuel sources (fat). Fat cells start breaking down and, as a result, release ketones (which are acidic) into the bloodstream. Hence the name: diabetic ketoacidosis. “High levels of ketones can poison the body. When levels get too high, you can develop DKA. DKA may happen to anyone with diabetes, though it is rare in people with type 2. Treatment for DKA usually takes place in the hospital. But you can help prevent it by learning the warning signs and checking your urine and blood regularly.” Causes The most common causes of DKA are not getting enough insulin, having a severe infection, becoming dehydrated, or a combination of these issues. It seems like it occurs mainly in patients with type one diabetes. Symptoms Some of the symptoms that people experience with DKA include the following: Excessive thirst and urination (more water is pulled into the urine as a result of high ketone loss in the urine) Lethargy Breathing very quickly (patients have a very high level of acids in their bloodstream and they try to "blow" off carbon dioxide by breathing quickly) A fruity odor on their breath (ketones have a fruity smell) Nausea and vomiting (the body tries to get rid of acid Continue reading >>

Pediatric Diabetic Ketoacidosis

Pediatric Diabetic Ketoacidosis

Pediatric Diabetic Ketoacidosis Authors: Katia M. Lugo-Enriquez, MD, FACEP, Faculty, Florida Hospital Emergency Medicine Residency Program, Orlando, FL. Nick Passafiume, MD, Florida Hospital Emergency Medicine Residency Program, Orlando, FL. Peer Reviewer: Richard A. Brodsky, MD, Pediatric Emergency Medicine, St. Christopher's Hospital for Children, Assistant Professor, Drexel University, Philadelphia, PA. Children with diabetes, especially type 1, remain at risk for developing diabetic ketoacidosis (DKA). This may seem confounding in a modern society with such advanced medical care, but the fact remains that children who are type 1 diabetics have an incidence of DKA of 8 per 100 patient years.1 In fact, Neu and colleagues have noted in a multicenter analysis of 14,664 patients in Europe from 1995 to 2007 that there was no significant change in ketoacidosis presenting at diabetes onset in children.2 In children younger than 19 years old, DKA is the admitting diagnosis in 65% of all hospital admissions of patients with diabetes mellitus.3 This article reviews the presentation, diagnostic evaluation, treatment, and potential complications associated with pediatric DKA. — The Editor Introduction The overall mortality rate for children in DKA is not unimpressive: The range is 0.15% to 0.31%.4 Besides death, one of the most feared repercussions of DKA in children is cerebral edema, an entity that occurs approximately 1% of the time.5,6 Cerebral edema, with the exception of a few case reports in some young adults, has largely been a complication of treatment in the pediatric population, and the exact factors have yet to be completely determined. The mortality associated with cerebral edema may approach 20% to 50%, and the incidence of neurologic morbidity is significant and Continue reading >>

Diabetic Ketoacidosis In Pregnancy

Diabetic Ketoacidosis In Pregnancy

Abstract Diabetic ketoacidosis (DKA) is a life-threatening medical emergency and is characterized by hyperglycemia, acidosis, and ketonemia. DKA is observed in 5–10 % of all pregnancies complicated by pregestational diabetes mellitus. Laboratory findings are as follows: Ketonemia 3 mmol/L and over or significant ketonuria (more than 2+ on standard urine sticks) Blood glucose over 11 mmol/L or known diabetes mellitus Bicarbonate (HCO3 −−) below 15 mmol/L and/or venous pH less than 7.3 Common risk factors for DKA in pregnancy are new-onset diabetes, infections like UTI, influenza, poor patient compliance, insulin pump failure, treatment with β-mimetic tocolytic medications, and antenatal corticosteroids for fetal lung maturity. Patient should be counseled about the precipitating cause and early warning symptoms of DKA. DKA should be treated promptly, and HDU/level 2 facility with trained nursing staff and/or insertion of central line is required during pregnancy for its management. Continuous fetal heart rate monitoring commonly demonstrates recurrent late decelerations. Delivery is rarely indicated as FHR pattern resolves as maternal condition improves. DKA therapy can lead to frequent complication of hypoglycemia and hypokalemia, so glucose and K concentration monitoring should be done judiciously. Maternal mortality is rare now with proper management, but fetal mortality is still quite high ranging from 10 to 35 %. Continue reading >>

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