An Unusual Cause For Ketoacidosis
Abstract Introduction In our continuing series on the application of principles of integrative physiology at the bedside, once again the central figure is an imaginary consultant, the renal and metabolic physiologist, Professor McCance, who deals with data from a real case. On this occasion his colleague Sir Hans Krebs, an expert in the field of glucose and energy metabolism, assists him in the analysis. Their emphasis is on concepts that depend on an understanding of physiology that crosses subspecialty boundaries. To avoid overwhelming the reader with details, key facts are provided, but only when necessary. The overall objective of this teaching exercise is to demonstrate how application of simple principles of integrative physiology at the bedside can be extremely helpful for clinical decision-making (Table 1). Principle Comment 1. A high H+ concentration per se is seldom life-threatening The threat to survival is usually due to the cause for the acidosis rather than the pH per se 2. Finding a new anion means a new acid was added Look in plasma (anion gap) and urine (net charge) to identify the new anions 3. Identify the acid by thinking of the properties of the anion Rate of production, rapidity of clearance from plasma, and unique toxic effects may all provide clues 4. Metabolic acidosis develops when the kidney fails to add new HCO3 to the body The kidney generates HCO3− by excreting NH4+, (usually with Cl−), in the urine 5. Ketoacids are brain fuels, produced when there is a prolonged lack of insulin The usual causes are diabetic ketoacidosis, alcoholic ketoacidosis, starvation or hypoglycemia-induced ketoacidosis, or that associated with salicylate overdose 6. Ketoacids are produced in the liver from acetyl-CoA, usually derived from fatty acids A low net in Continue reading >>
Starvation Ketoacidosis: Treatment Pitfalls
Dear Editor, Yeow et al.1 describe a case of non-diabetic euglycaemic acidosis resulting from post op dysphagia and poor intake of approximately six weeks duration. We have seen a similar case of ‘starvation ketoacidosis’ in a patient undergoing percutaneous endoscopic gastrostomy feeding tube replacement. We think that intravenous (IV) glucose should be the initial treatment, with the addition of insulin only if required. The correspondence from Frise and Mackillop2 states this strategy is effective for treating ketoacidosis in pregnancy; however, there are also some other pitfalls in treatment of starvation ketoacidosis which must be considered, and some overlap with alcoholic ketoacidosis. Unlike patients with diabetic ketoacidosis, patients with starvation ketosis release insulin when carbohydrate is administered. They are also producing high levels of glucose elevating hormones such as glucagon and have depleted glycogen stores. These hormones cause the lipolysis which helps generate ketones for fuel. The addition of exogenous insulin in this state risks hypoglycaemia. Once provided with adequate carbohydrate the insulin levels will rise and counter-regulatory hormone levels will fall, resolving the ketosis. Alcoholics are another group prone to ketosis (alcoholic ketoacidosis (AKA)) and are particularly prone to hypoglycaemia; administration of insulin to those patients would have to be with caution and literature3 on AKA reports resolution without insulin administration, although there is little evidence outside of case reports. Starved patients and alcoholics are also both at risk of thiamine deficiency. Depletion of body thiamine stores can occur within four weeks. It is important to consider this, as administration of IV glucose in thiamine deficiency can Continue reading >>
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 >>
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 >>
Ketosis
Not to be confused with Ketoacidosis. Ketosis is a metabolic state in which some of the body's energy supply comes from ketone bodies in the blood, in contrast to a state of glycolysis in which blood glucose provides energy. Ketosis is a result of metabolizing fat to provide energy. Ketosis is a nutritional process characterised by serum concentrations of ketone bodies over 0.5 mM, with low and stable levels of insulin and blood glucose.[1][2] It is almost always generalized with hyperketonemia, that is, an elevated level of ketone bodies in the blood throughout the body. Ketone bodies are formed by ketogenesis when liver glycogen stores are depleted (or from metabolising medium-chain triglycerides[3]). The main ketone bodies used for energy are acetoacetate and β-hydroxybutyrate,[4] and the levels of ketone bodies are regulated mainly by insulin and glucagon.[5] Most cells in the body can use both glucose and ketone bodies for fuel, and during ketosis, free fatty acids and glucose synthesis (gluconeogenesis) fuel the remainder. Longer-term ketosis may result from fasting or staying on a low-carbohydrate diet (ketogenic diet), and deliberately induced ketosis serves as a medical intervention for various conditions, such as intractable epilepsy, and the various types of diabetes.[6] In glycolysis, higher levels of insulin promote storage of body fat and block release of fat from adipose tissues, while in ketosis, fat reserves are readily released and consumed.[5][7] For this reason, ketosis is sometimes referred to as the body's "fat burning" mode.[8] Ketosis and ketoacidosis are similar, but ketoacidosis is an acute life-threatening state requiring prompt medical intervention while ketosis can be physiological. However, there are situations (such as treatment-resistant Continue reading >>
Alcoholic Ketoacidosis
Background In 1940, Dillon and colleagues first described alcoholic ketoacidosis (AKA) as a distinct syndrome. AKA is characterized by metabolic acidosis with an elevated anion gap, elevated serum ketone levels, and a normal or low glucose concentration. [1, 2] Although AKA most commonly occurs in adults with alcoholism, it has been reported in less-experienced drinkers of all ages. Patients typically have a recent history of binge drinking, little or no food intake, and persistent vomiting. [3, 4, 5] A concomitant metabolic alkalosis is common, secondary to vomiting and volume depletion (see Workup). [6] Treatment of AKA is directed toward reversing the 3 major pathophysiologic causes of the syndrome, which are: This goal can usually be achieved through the administration of dextrose and saline solutions (see Treatment). Continue reading >>
Ketoacidosis During A Low-carbohydrate Diet
To the Editor: It is believed that low-carbohydrate diets work best in reducing weight when producing ketosis.1 We report on a 51-year-old white woman who does not have diabetes but had ketoacidosis while consuming a “no-carbohydrate” diet. There was no family history of diabetes, and she was not currently taking any medications. While adhering to a regimen of carbohydrate restriction, she reached a stable weight of 59.1 kg, a decrease from 72.7 kg. After several months of stable weight, she was admitted to the hospital four times with vomiting but without abdominal pain. On each occasion, she reported no alcohol use. Her body-mass index (the weight in kilograms divided by the square of the height in meters) was 26.7 before the weight loss and 21.7 afterward. Laboratory evaluation showed anion-gap acidosis, ketonuria, and elevated plasma glucose concentrations on three of the four occasions (Table 1). She had normal concentrations of plasma lactate and glycosylated hemoglobin. Screening for drugs, including ethyl alcohol and ethylene glycol, was negative. Abdominal ultrasonography showed hepatic steatosis. On each occasion, the patient recovered after administration of intravenous fluids and insulin, was prescribed insulin injections on discharge, and gradually reduced the use of insulin and then discontinued it while remaining euglycemic for six months or more between episodes. Testing for antibodies against glutamic acid decarboxylase and antinuclear antibodies was negative. Values on lipid studies were as follows: serum triglycerides, 102 mg per deciliter; high-density lipoprotein (HDL) cholesterol, 50 mg per deciliter; and calculated low-density lipoprotein (LDL) cholesterol, 189 mg per deciliter. The patient strictly adhered to a low-carbohydrate diet for four Continue reading >>
Diabetic Ketoacidosis: Evaluation And Treatment
Diabetic ketoacidosis is characterized by a serum glucose level greater than 250 mg per dL, a pH less than 7.3, a serum bicarbonate level less than 18 mEq per L, an elevated serum ketone level, and dehydration. Insulin deficiency is the main precipitating factor. Diabetic ketoacidosis can occur in persons of all ages, with 14 percent of cases occurring in persons older than 70 years, 23 percent in persons 51 to 70 years of age, 27 percent in persons 30 to 50 years of age, and 36 percent in persons younger than 30 years. The case fatality rate is 1 to 5 percent. About one-third of all cases are in persons without a history of diabetes mellitus. Common symptoms include polyuria with polydipsia (98 percent), weight loss (81 percent), fatigue (62 percent), dyspnea (57 percent), vomiting (46 percent), preceding febrile illness (40 percent), abdominal pain (32 percent), and polyphagia (23 percent). Measurement of A1C, blood urea nitrogen, creatinine, serum glucose, electrolytes, pH, and serum ketones; complete blood count; urinalysis; electrocardiography; and calculation of anion gap and osmolar gap can differentiate diabetic ketoacidosis from hyperosmolar hyperglycemic state, gastroenteritis, starvation ketosis, and other metabolic syndromes, and can assist in diagnosing comorbid conditions. Appropriate treatment includes administering intravenous fluids and insulin, and monitoring glucose and electrolyte levels. Cerebral edema is a rare but severe complication that occurs predominantly in children. Physicians should recognize the signs of diabetic ketoacidosis for prompt diagnosis, and identify early symptoms to prevent it. Patient education should include information on how to adjust insulin during times of illness and how to monitor glucose and ketone levels, as well as i Continue reading >>
Journal Of The Intensive Care Society
We read with interest the recent case report by Yeow et al.1 of a 65-year-old female who developed starvation ketoacidosis perioperatively following an extended period of poor oral intake. The authors noted that euglycaemic ketoacidosis in non-diabetic patients is very rarely reported and that it is important to be aware of the condition. Perhaps the most common factor that predisposes to starvation ketoacidosis in otherwise healthy individuals is pregnancy, which the authors do not mention. It has long been known that accelerated ketone production following fasting is seen in normal pregnancy.2 We have recently reported a number of cases of starvation ketoacidosis in pregnant women without hyperglycaemia.3 It typically occurs in the third trimester following a short history of reduced oral intake. We have also described this condition in pregnant women with pancreatitis and in one woman after commencement of olanzapine during pregnancy.4,5 Many of these women were admitted to intensive care units and several had emergency deliveries in the absence of a clear diagnosis. On the other hand, in those in whom the diagnosis was recognised, treatment with dextrose alone often appeared to be sufficient to bring about cure. The possible underlying mechanisms are discussed at length elsewhere, but probably involve stimulation of endogenous insulin secretion.3 The authors discuss the difficulty in interpreting the acid-base and electrolyte picture in their patient. A normal anion gap has been reported in ketoacidosis of various aetiologies, not only due to fluid resuscitation but also as a result of disturbed renal electrolyte handling in the setting of ketonuria. This was a finding in many of our obstetric cases. It is essential for clinicians not to be misled by the normal anio Continue reading >>
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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 >>
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 >>
Diabetic, Alcoholic And Starvation Ketoacidosis
Copious amounts of ketones which are generated in insulin-deficient or insulin-unresponsive patients will give rise to a high anion gap metabolic acidosis. Ketones are anions, and they form the high anion gap. Management of DKA and HONK is discussed elsewhere. Meet the ketones Chemically speaking, a ketone is anything with a carbonyl group between a bunch of other carbon atoms. The above are your three typical ketoacidosis-associated ketone bodies. The biochemistry nerds among us will hasten to add that the beta-hydroxybutyrate is in fact not a ketone but a carboxylic acid, but - because it is associated with ketoacidosis, we will continue to refer to it as a ketone for the remainder of this chapter, in the spirit of convention. In the same spirit, we can suspend our objections to acetone being included in a discussion of ketoacidosis, which (though a true ketone) is in fact not acidic or basic, as it does not ionise at physiological pH (its pKa is 20 or so). So really, the only serious ketone acid is acetoacetate, which has a pKa of 3.77. However, beta-hydroxybutyrate is the prevalent ketone in ketoacidosis; the normal ratio of beta-hydroxybutyrate and acetoacetate is 3:1, and it can rise to 10:1 in diabetic ketoacidosis. Acetone is the least abundant. The metabolic origin of ketones The generation of ketones is a normal response to fasting, which follows the depletion of hepatic glycogen stores. Let us discuss normal physiology for a change. You, a healthy adult without serious alcohol problems, are fasting from midnight for a routine elective hernia repair. You will go to be after dinner with a few nice lumps of undigested food in your intestine, as well as about 75g of hepatic glycogen. As you sleep, you gradually digest the food and dip into the glycogen store. At Continue reading >>
Alcoholic Ketoacidosis
Alcoholic ketoacidosis is a metabolic complication of alcohol use and starvation characterized by hyperketonemia and anion gap metabolic acidosis without significant hyperglycemia. Alcoholic ketoacidosis causes nausea, vomiting, and abdominal pain. Diagnosis is by history and findings of ketoacidosis without hyperglycemia. Treatment is IV saline solution and dextrose infusion. Alcoholic ketoacidosis is attributed to the combined effects of alcohol and starvation on glucose metabolism. Alcohol diminishes hepatic gluconeogenesis and leads to decreased insulin secretion, increased lipolysis, impaired fatty acid oxidation, and subsequent ketogenesis, causing an elevated anion gap metabolic acidosis. Counter-regulatory hormones are increased and may further inhibit insulin secretion. Plasma glucose levels are usually low or normal, but mild hyperglycemia sometimes occurs. Diagnosis requires a high index of suspicion; similar symptoms in an alcoholic patient may result from acute pancreatitis, methanol or ethylene glycol poisoning, or diabetic ketoacidosis (DKA). In patients suspected of having alcoholic ketoacidosis, serum electrolytes (including magnesium), BUN and creatinine, glucose, ketones, amylase, lipase, and plasma osmolality should be measured. Urine should be tested for ketones. Patients who appear significantly ill and those with positive ketones should have arterial blood gas and serum lactate measurement. The absence of hyperglycemia makes DKA improbable. Those with mild hyperglycemia may have underlying diabetes mellitus, which may be recognized by elevated levels of glycosylated Hb (HbA1c). Typical laboratory findings include a high anion gap metabolic acidosis, ketonemia, and low levels of potassium, magnesium, and phosphorus. Detection of acidosis may be com Continue reading >>
Starvation Ketoacidosis As A Cause Of Unexplained Metabolic Acidosis In The Perioperative Period
Go to: Abstract Patient: Female, 24 Final Diagnosis: Starvation ketoacidosis Symptoms: None Medication: — Clinical Procedure: Lumbar laminectomy Specialty: Orthopedics and Traumatology Besides providing anesthesia for surgery, the anesthesiologist’s role is to optimize the patient for surgery and for post-surgical recovery. This involves timely identification and treatment of medical comorbidities and abnormal laboratory values that could complicate the patient’s perioperative course. There are several potential causes of anion and non-anion gap metabolic acidosis in surgical patients, most of which could profoundly affect a patient’s surgical outcome. Thus, the presence of an acute acid-base disturbance requires a thorough workup, the results of which will influence the patient’s anesthetic management. An otherwise-healthy 24-year-old female presented for elective spine surgery and was found to have metabolic acidosis, hypotension, and polyuria intraoperatively. Common causes of acute metabolic acidosis were investigated and systematically ruled out, including lactic acidosis, diabetic ketoacidosis, drug-induced ketoacidosis, ingestion of toxic alcohols (e.g., methanol, ethylene glycol), uremia, and acute renal failure. Laboratory workup was remarkable only for elevated serum and urinary ketone levels, believed to be secondary to starvation ketoacidosis. Due to the patient’s unexplained acid-base disturbance, she was kept intubated postoperatively to allow for further workup and management. Starvation ketoacidosis is not widely recognized as a perioperative entity, and it is not well described in the medical literature. Lack of anesthesiologist awareness about this disorder may complicate the differential diagnosis for acute intraoperative metabolic acidosi Continue reading >>
Why Dka & Nutritional Ketosis Are Not The Same
There’s a very common misconception and general misunderstanding around ketones. Specifically, the misunderstandings lie in the areas of: ketones that are produced in low-carb diets of generally less than 50 grams of carbs per day, which is low enough to put a person in a state of “nutritional ketosis” ketones that are produced when a diabetic is in a state of “diabetic ketoacidosis” (DKA) and lastly, there are “starvation ketones” and “illness-induced ketones” The fact is they are very different. DKA is a dangerous state of ketosis that can easily land a diabetic in the hospital and is life-threatening. Meanwhile, “nutritional ketosis” is the result of a nutritional approach that both non-diabetics and diabetics can safely achieve through low-carb nutrition. Diabetic Ketoacidosis vs. Nutritional Ketosis Ryan Attar (soon to be Ryan Attar, ND) helps explain the science and actual human physiology behind these different types of ketone production. Ryan is currently studying to become a Doctor of Naturopathic Medicine in Connecticut and also pursuing a Masters Degree in Human Nutrition. He has interned under the supervision of the very well-known diabetes doc, Dr. Bernstein. Ryan explains: Diabetic Ketoacidosis: “Diabetic Ketoacidosis (DKA), is a very dangerous state where an individual with uncontrolled diabetes is effectively starving due to lack of insulin. Insulin brings glucose into our cells and without it the body switches to ketones. Our brain can function off either glucose or fat and ketones. Ketones are a breakdown of fat and amino acids that can travel through the blood to various tissues to be utilized for fuel.” “In normal individuals, or those with well controlled diabetes, insulin acts to cancel the feedback loop and slow and sto Continue reading >>
