Gold Mark: An Anion Gap Mnemonic For The 21st Century
A Lancet Editorial1 in 1977, referring to an article entitled “Clinical use of the anion gap”2 opined: “In an age when all too often plasma-electrolyte measurements are ordered without any deliberate judgment being made as to the likely usefulness of the result, it is refreshing to have a reminder of the subtleties involved in the interpretation of this commonest set of clinical-chemistry tests”. We have discovered some new twists over the past 30 years and would like to share an easily remembered mnemonic aid. The metabolic acidoses are generally separated into two categories on the basis of an anion gap calculation (Na+[Cl−HCO3−]): the high-anion-gap metabolic acidoses, and the normal-anion-gap, or hyperchloraemic, metabolic acidoses. Two popular mnemonics are often used to remember the major causes of the high-gap metabolic acidoses. The first is KUSMALE (a useful misspelling of Adolph Kussmaul's name), which represents Ketoacidosis, Uraemia, Salicylate poisoning, Methanol, Aldehyde (paraldehyde), Lactate, and Ethylene glycol. The second is MUD PILES, representing Methanol, Uraemia, Diabetes, Paraldehyde, Iron (and Isoniazid), Lactate, Ethylene glycol, and Salicylate. Metabolic acidosis due to excessive paraldehyde use has become exceedingly rare. Iron and isoniazid are just two of many drugs and toxins that cause hypotension and lactic acidosis (isoniazid can also generate a component of ketoacidosis). Three “new” organic anion-gap-generating acids and acid precursors have been recognised in recent years. They are D-lactic acid, which can occur in some patients with short bowel syndromes; 5-oxoproline (or pyroglutamic acid) associated with chronic paracetamol use, often by malnourished women; and the anion-gap acidosis generated by high-dose propylen Continue reading >>
Metabolic Acidosis With An Elevated Anion Gap.
Abstract Determining the cause of metabolic acidosis with a high anion gap may present a diagnostic challenge. Possible causes include ketoacidosis, certain toxic ingestions, renal failure and lactic acidosis. Many of these entities present with nausea, vomiting and changes in mental status; however, there are specific hallmarks in the signs, symptoms and laboratory findings that help to differentiate among them. Continue reading >>
Recurrent Severe Anion Gap Metabolic Acidosis Secondary To Episodic Ethylene Glycol Intoxication.
Abstract Acute ethylene glycol toxicity and its attendant metabolic derangement is a well described clinical entity. Recurrent severe anion gap metabolic acidosis consequent to episodic ingestion of ethylene glycol has not been previously reported. We present a patient who developed severe anion gap metabolic acidosis with no osmolar gap and hypokalemia, consequent to episodic ethylene glycol ingestion. Modest artifactual elevation of the serum lactic acid level and rapid response to intravenous bicarbonate infusion may serve as diagnostic clues. Consideration of these aberrant features should be included in the clinical assessment of severe anion gap metabolic acidosis. Continue reading >>
High Anion Gap Metabolic Acidosis Induced By Cumulation Of Ketones, L- And D-lactate, 5-oxoproline And Acute Renal Failure.
Abstract INTRODUCTION: Frequent causes of high anion gap metabolic acidosis (HAGMA) are lactic acidosis, ketoacidosis and impaired renal function. In this case report, a HAGMA caused by ketones, L- and D-lactate, acute renal failure as well as 5-oxoproline is discussed. CASE PRESENTATION: A 69-year-old woman was admitted to the emergency department with lowered consciousness, hyperventilation, diarrhoea and vomiting. The patient had suffered uncontrolled type 2 diabetes mellitus, underwent gastric bypass surgery in the past and was chronically treated with high doses of paracetamol and fosfomycin. Urosepsis was diagnosed, whilst laboratory analysis of serum bicarbonate concentration and calculation of the anion gap indicated a HAGMA. L-lactate, D-lactate, β-hydroxybutyric acid, acetone and 5-oxoproline serum levels were markedly elevated and renal function was impaired. DISCUSSION: We concluded that this case of HAGMA was induced by a variety of underlying conditions: sepsis, hyperglycaemia, prior gastric bypass surgery, decreased renal perfusion and paracetamol intake. Risk factors for 5-oxoproline intoxication present in this case are female gender, sepsis, impaired renal function and uncontrolled type 2 diabetes mellitus. Furthermore, chronic antibiotic treatment with fosfomycin might have played a role in the increased production of 5-oxoproline. CONCLUSION: Paracetamol-induced 5-oxoproline intoxication should be considered as a cause of HAGMA in patients with female gender, sepsis, impaired renal function or uncontrolled type 2 diabetes mellitus, even when other more obvious causes of HAGMA such as lactate, ketones or renal failure can be identified. Continue reading >>
Approach To The Adult With Metabolic Acidosis
INTRODUCTION On a typical Western diet, approximately 15,000 mmol of carbon dioxide (which can generate carbonic acid as it combines with water) and 50 to 100 mEq of nonvolatile acid (mostly sulfuric acid derived from the metabolism of sulfur-containing amino acids) are produced each day. Acid-base balance is maintained by pulmonary and renal excretion of carbon dioxide and nonvolatile acid, respectively. Renal excretion of acid involves the combination of hydrogen ions with urinary titratable acids, particularly phosphate (HPO42- + H+ —> H2PO4-), and ammonia to form ammonium (NH3 + H+ —> NH4+) . The latter is the primary adaptive response since ammonia production from the metabolism of glutamine can be appropriately increased in response to an acid load . Acid-base balance is usually assessed in terms of the bicarbonate-carbon dioxide buffer system: Dissolved CO2 + H2O <—> H2CO3 <—> HCO3- + H+ The ratio between these reactants can be expressed by the Henderson-Hasselbalch equation. By convention, the pKa of 6.10 is used when the dominator is the concentration of dissolved CO2, and this is proportional to the pCO2 (the actual concentration of the acid H2CO3 is very low): TI AU Garibotto G, Sofia A, Robaudo C, Saffioti S, Sala MR, Verzola D, Vettore M, Russo R, Procopio V, Deferrari G, Tessari P To evaluate the effects of chronic metabolic acidosis on protein dynamics and amino acid oxidation in the human kidney, a combination of organ isotopic ((14)C-leucine) and mass-balance techniques in 11 subjects with normal renal function undergoing venous catheterizations was used. Five of 11 studies were performed in the presence of metabolic acidosis. In subjects with normal acid-base balance, kidney protein degradation was 35% to 130% higher than protein synthesi Continue reading >>
The anion gap is the difference between primary measured cations (sodium Na+ and potassium K+) and the primary measured anions (chloride Cl- and bicarbonate HCO3-) in serum. This test is most commonly performed in patients who present with altered mental status, unknown exposures, acute renal failure, and acute illnesses.  See the Anion Gap calculator. The reference range of the anion gap is 3-11 mEq/L The normal value for the serum anion gap is 8-16 mEq/L. However, there are always unmeasurable anions, so an anion gap of less than 11 mEq/L using any of the equations listed in Description is considered normal. For the urine anion gap, the most prominently unmeasured anion is ammonia. Healthy subjects typically have a gap of 0 to slightly normal (< 10 mEq/L). A urine anion gap of more than 20 mEq/L is seen in metabolic acidosis when the kidneys are unable to excrete ammonia (such as in renal tubular acidosis). If the urine anion gap is zero or negative but the serum AG is positive, the source is most likely gastrointestinal (diarrhea or vomiting).  Continue reading >>
Acid-base And Electrolyte Teaching Case Non–anion Gap Metabolic Acidosis: A Clinical Approach To Evaluation
Acid-base disturbances can result from kidney or nonkidney disorders. We present a case of high-volume ileostomy output causing large bicarbonate losses and resulting in a non–anion gap metabolic acidosis. Non–anion gap metabolic acidosis can present as a form of either acute or chronic metabolic acidosis. A complete clinical history and physical examination are critical initial steps to begin the evaluation process, followed by measuring serum electrolytes with a focus on potassium level, blood gas, urine pH, and either direct or indirect urine ammonium concentration. The present case was selected to highlight the differential diagnosis of a non–anion gap metabolic acidosis and illustrate a systematic approach to this problem. Continue reading >>
Metabolic Acidosis (increased Anion Gap)
metabolic acidosis (increased anion gap) FREE subscriptions for doctors and students... click here You have 3 open access pages. Increased anion gap: diabetic ketoacidosis starvation ketoacidosis lactic acidosis (types A and B) acidosis of renal failure salicylate poisoning methanol poisoning ammonium chloride Links: diabetic ketoacidosis lactic acidosis acute renal failure (ARF) salicylate poisoning This site is intended for the use of healthcare professionals only. A licensed medical practitioner should be consulted for diagnosis and treatment of any and all medical conditions. Copyright 2016 Oxbridge Solutions Ltd®. Any distribution or duplication of the information contained herein is strictly prohibited. Oxbridge Solutions Ltd® receives funding from advertising but maintains editorial independence more... GPnotebook stores small data files on your computer called cookies so that we can recognise you and provide you with the best service. If you do not want to receive cookies please do not use GPnotebook. Continue reading >>
Medical Mnemonics: Causes Of Anion Gap Metabolic Acidosis – “gold Mark”
The classic mnemonic often used to remember the causes of anion gap metabolic acidosis is “MUDPILES” M – Methanol U – Uremia D – Diabetic ketoacidosis P – Propylene Glycol I – Isoniazid L – Lactic Acidosis E – Ethylene Glycol S – Salicylates More recently a new mnemonic has been suggested to update new our understanding of anion-gap generating acids. The updated mnemonic “GOLD MARK” was proposed in a 2008 article in The Lancet. G – Glycols (ethylene glycol and propylene glycol) O – Oxoproline L – L-Lactate D – D-Lactate M – Methanol A – Aspirin R – Renal Failure K – Ketoacidosis As medicine evolves, so do our Mnemonics. This is the fifth medical mnemonic in our series of Monday Mnemonics. Continue reading >>
Clinical Aspects Of The Anion Gap
The anion gap (AG) is a calculated parameter derived from measured serum/plasma electrolyte concentrations. The clinical value of this calculated parameter is the main focus of this article. Both increased and reduced anion gap have clinical significance, but the deviation from normal that has most clinical significance is increased anion gap associated with metabolic acidosis. This reflects the main clinical utility of the anion gap, which is to help in elucidating disturbances of acid-base balance. The article begins with a discussion of the concept of the anion gap, how it is calculated and issues surrounding the anion gap reference interval. CONCEPT OF THE ANION GAP - ITS DEFINITION AND CALCULATION Blood plasma is an aqueous (water) solution containing a plethora of chemical species including some that have a net electrical charge, the result of dissociation of salts and acids in the aqueous medium. Those that have a net positive charge are called cations and those with a net negative charge are called anions; collectively these electrically charged species are called ions. The law of electrochemical neutrality demands that, in common with all solutions, blood serum/plasma is electrochemically neutral so that the sum of the concentration of cations always equals the sum of the concentration of anions . This immutable law is reflected in FIGURE 1, a graphic display of the concentration of the major ions normally present in plasma/serum. It is clear from this that quantitatively the most significant cation in plasma is sodium (Na+), and the most significant anions are chloride (Cl-) and bicarbonate HCO3-. The concentration of these three plasma constituents (sodium, chloride and bicarbonate) along with the cation potassium (K+) are routinely measured in the clinica Continue reading >>
High Anion Gap Metabolic Acidosis
Abstract In the previous chapter, we presented various causes of high anion gap (AG) metabolic acidosis. For discussion purpose, these causes can be conveniently divided into the following categories: 3. 5-Oxoproline (pyroglutamic acid) Continue reading >>
Best Case Ever 56 Anion Gap Metabolic Acidosis
In this month’s Best Case Ever on EM Cases Dr. Ross Claybo and Dr. Keerat Grewal tell the story of a patient with a complicated anion gap metabolic acidosis. We discuss how to sort through the differential diagnosis with a better mnemonic than MUDPILES, the controversy around administering sodium bicarbonate for metabolic acidosis, the indications for fomepizole and the value of taking time to to build a therapeutic relationship with your ED patients. Podcast production and sound design by Anton Helman. Show notes by Anton Helman, March 2017 The MUDPILES mnemonic for anion gap metabolic acidosis is out of date Why? Metabolic acidosis due to paraldehyde overdose is exceedingly rare Iron and isoniazid are just two of many drugs and toxins that cause hypotension and lactic acidosis (isoniazid can also generate a component of ketoacidosis). Three “newer” anion-gap-generating acids have been recognised recently: D-lactic acid, which can occur in some patients with short bowel syndromes. 5-oxoproline (or pyroglutamic acid) associated with chronic acetaminophen use. Propylene glycol infusions – solvent used for several IV medications including lorazepam and phenobarbital. The GOLDMARK mnemonic for anion gap metabolic acidosis is more useful GOLDMARK mnemonic for anion gap metabolic acidosis Glycols (ethylene glycol & propylene glycol) Oxoproline (metabolite of acetaminophen) L-lactate D-lactate (acetaminophen, short bowel syndrome, propylene glycol infusions for lorazepam and phenobarbital) Methanol ASA Renal Failure Ketoacidosis (starvation, alcohol and DKA) Osmolar Gap common differential diagnosis Ketoacids (DKA, AKA, starvation ketosis) Alcohols Sepsis Ischemia Sodium bicarbonate for metabolic acidosis: Still controversial The indcations for sodium bicarb for metab Continue reading >>
Metabolic acidosis is primary reduction in bicarbonate (HCO3−), typically with compensatory reduction in carbon dioxide partial pressure (Pco2); pH may be markedly low or slightly subnormal. Metabolic acidoses are categorized as high or normal anion gap based on the presence or absence of unmeasured anions in serum. Causes include accumulation of ketones and lactic acid, renal failure, and drug or toxin ingestion (high anion gap) and GI or renal HCO3− loss (normal anion gap). Symptoms and signs in severe cases include nausea and vomiting, lethargy, and hyperpnea. Diagnosis is clinical and with ABG and serum electrolyte measurement. The cause is treated; IV sodium bicarbonate may be indicated when pH is very low. Acidemia (arterial pH < 7.35) results when acid load overwhelms respiratory compensation. Causes are classified by their effect on the anion gap (see The Anion Gap and see Table: Causes of Metabolic Acidosis). High anion gap acidosis Ketoacidosis is a common complication of type 1 diabetes mellitus (see diabetic ketoacidosis), but it also occurs with chronic alcoholism (see alcoholic ketoacidosis), undernutrition, and, to a lesser degree, fasting. In these conditions, the body converts from glucose to free fatty acid (FFA) metabolism; FFAs are converted by the liver into ketoacids, acetoacetic acid, and beta-hydroxybutyrate (all unmeasured anions). Ketoacidosis is also a rare manifestation of congenital isovaleric and methylmalonic acidemia. Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. Lactate accumulation results from a combination of excess formation and decreased utilization of lactate. Excess lactate production occurs during states of anaerobic metabolism. The most serious form occurs during the various types o Continue reading >>
How Does Diabetic Ketoacidosis Develop?
Diabetic ketoacidosis, DKA, is a serious, life-threatening condition that can cause a diabetic coma and possibly death. It develops when the body does not get enough sugar in order to produce energy because of a lack of insulin. This causes the body to start using stored fat for energy. According to WebMD, when the body cannot convert the sugar into energy, it stays inside of the bloodstream (WebMD, 2017). This causes the kidneys to filter some of the sugar from the blood into the urine. This causes ketones to be released from the breakdown of fat, making the blood’s pH level to become acidic. DKA is a condition that should not be taken lightly. It can cause several different problems inside of the body. It is very important that you take care of your body in order to prevent the development of DKA. How does DKA start? WebMD said, “Ketoacidosis can be caused by not getting enough insulin, having a severe infection or other illness, becoming severely dehydrated, or some combination of these things” (WebMD, 2017). There are things that you can control. Frequent communication with your doctor will assist you in determining how much insulin you should take and when. If you keep taking it consistently and on time, it will help immensely. It is difficult to control if you get a severe infection or illness. However, you do have control on how you will react. Do not be afraid to go to the doctor. Get the medical treatment that you need so it does not become much worse. DKA can also be caused by dehydration. Drinking water is a great way to prevent dehydration. Also, cutting out beverages like soda can also help a ton! Focusing more on water will also help you to cut out unnecessary sodium, trans fats, and sugars that you do not need. By drinking healthier, it will make yo Continue reading >>
Serum Anion Gap In The Differential Diagnosis Of Metabolic Acidosis In Critically Ill Newborns.
Abstract OBJECTIVES: To determine in critically ill newborn infants (1) the range of the serum anion gap without metabolic acidosis and (2) whether the serum anion gap can be used to distinguish newborns with lactic acidosis from those with hyperchloremic metabolic acidosis. STUDY DESIGN: Umbilical arterial blood gases and serum electrolyte and lactate concentrations were measured simultaneously in 210 samples from 63 infants over the first week of life. Metabolic acidosis was defined as a blood base deficit (BD) >4 mmol/L. The anion gap was calculated as [Na(+)] - [C1(-)] - [TCO (2)]. Lactic acidosis was defined as a serum lactate concentration >2 SD above the mean serum lactate concentration in samples without metabolic acidosis. RESULTS: In 89 blood samples with BD <4 mmol/L, serum lactate concentration decreased with postnatal age (r = 0.51). The upper limit of serum lactate concentration was 3.8 mmol/L at less than 48 hours, 2.4 mmol/L between 48 and 96 hours, and 1.5 mmol/L for infants greater than 96 hours of age. The mean serum anion gap +/- 2 SD in 174 samples without lactic acidosis was 8 +/- 4 mmol/L; in 36 samples with lactic acidosis it was 16 +/- 9 mmol/L (P <.0001). Serum anion gap and lactate concentration were poorly correlated for samples without lactic acidosis (r = 0.04) but highly correlated in those with lactic acidosis (r = 0.81, P <.0001). None of the 85 samples with metabolic acidosis but without lactic acidosis had an anion gap >16 mmol/L; only 4 of 36 samples with lactic acidosis had an anion gap <8 meq/L. However, 25 of 36 samples with lactic acidosis had serum anion gaps of 8 to 16 mmol/L. CONCLUSION: In the presence of metabolic acidosis, a serum anion gap >16 mmol/L is highly predictive of lactic acidosis; a serum anion gap <8 is highly pr Continue reading >>