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Lab Medicine Conference : Serum Electrolytes & Chemistries
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Serum Sodium Concentrations
60 % of sodium is in extracellular fluid (ECF) & 40 % is inactive in bone Normal value is 135 to 145 meq/L In normal patient, rarely varies by > 2 meq/L Sx occur if level < 130 or > 150 Patient at risk for seizures or coma if < 115 Onset & degree of Sx related to rapidity of change in concentration Renin - angiotensin - aldosterone and ADH are main modulators of sodium concentration
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Serum Sodium Measurement
Sample can be in either red top tube (no preservative) or green top (lithium heparinate) & measurement is run on serum after the specimen clots Measurement methods : Flame photometry Ion selective electrode Electrical potential of electrode proportional to activity of sodium ions in solution Results are 2 % higher than by flame photometry
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Causes of Pseudohyponatremia (Artifactual Hyponatremia)
Due to % of specimen volume taken up by non-water components & measurement technique using set specimen volume Is problem only with flame photometry method Occurs in marked hyperlipidemia & hyperproteinemias (protein > 11 g/dl) Also hyperglycemia causes hyponatremia (1.6 meq/L decrease per 100 mg/dl increase in glucose)
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Causes of Hyponatremia with Low Total Body Sodium (Hypovolemia)
Extrarenal losses Vomiting / NG suction Diarrhea Third space losses GI fistulas Renal losses Excess diuretic use Salt - losing nephropathies Osmotic diuretics Adrenal insufficiency
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Causes of Hyponatremia with Normal Total Body Sodium
SIADH "Sick cell" syndrome Hypothyroidism Meds & drugs (see next slide)
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Drugs & Meds Causing Hyponatremia (most via SIADH)
Phenothiazines Carbamazepine Chlorpropamide Narcotics Barbiturates Acetominophen Indomethacin Tolbutamide Clofibrate Cyclophosphamide Vincristine Isoproterenol Nicotine
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Causes of SIADH CNS disease Head trauma Intracranial bleed Meningitis
Encephalitis Brain abscess Brain tumor Stroke Porphyria Pulmonary disease Pneumonia Tuberculosis Mycoses Lung abscess Mechanical ventilation Carcinomas Pain Stress
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Causes of Hyponatremia with High Total Body Sodium
Cardiac failure Cirrhosis Nephrotic syndrome Acute & chronic renal failure
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Differential Diagnosis of Hyponatremia
Medical Condition BUN Hematocrit Urine Sodium Urine Osmolality Extrarenal fluid loss High High < 10 meq/L Hypertonic Renal sodium wasting (loss) Mildly elevated Normal or high > 20 meq/L Variable SIADH < 10 Normal or low > 20 meq/L Inappropriate hypertonic Water intoxication Normal or decreased Normal or low Variable < 100 mOsmol / kg "Sick cell" syndrome Normal Normal Variable Variable Cirrhosis or heart failure Variable Normal < 10 meq/L Hypertonic Renal failure High Normal or low > 20 meq/L Isosthenuric
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Causes of Hypernatremia with Low Total Body Sodium
Diarrhea Profuse sweating Osmotic diuresis Mannitol Hyperglycemia
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Other Causes of Hypernatremia
With normal total body sodium : Central diabetes insipidus Nephrogenic diabetes insipidus With high total body sodium : Exogenously administered sodium bicarbonate Hypertonic dialysate for renal dialysis Saline - induced abortions Ingestion of excessive salt tablets Drowning in the Dead Sea
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Serum Potassium (K+) Concentrations
K+ is major intracellular cation Total body amount about 50 meq/kg Normal ECF level is 3.6 to 5.0 meq/L K+ influences water distribution between intracellular & extracellular fluid Also is obligate activator of many enzymes Serum level is 0.5 meq/L higher than in whole blood or plasma
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K+ Turnover and Renal Handling
Usual intake is 50 to 150 meq per day Usual minimum daily losses are 10 meq each in stool, sweat, & obligatory renal Acidosis shifts K+ from intracellular to extracellular fluid Each pH change by 0.1 changes K+ by 0.6 meq/L in opposite direction Secreted & reabsorbed in distal nephron
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Methods of K+ Concentration Measurement
Flame photometry Dual channel type measures Na & K Ion selective electrode Uses cyclic antibiotic valinomycin (a selective K+ binder) on the liquid ion exchange membrane Nuclear magnetic resonance can measure intracellular K+
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Causes of Pseudohyperkalemia (Artifactual)
Traumatic hemolysis from mechanical forces of blood aspiration Extreme leucocytosis (> 600,000 cells/mm3) Platelet counts > 1,000,000 / mm3 Forearm exercise prior to blood draw (causes a 20 % increase) Use of cork instead of rubber stopper on collection tubes
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Causes of Hypokalemia Inadequate intake GI losses Vomiting, NG suction
Diarrhea, laxative abuse Villous adenoma Ureteroenterostomy Renal losses Diuretics Osmotic diuretics Iatrogenic Glucose in DKA Hyperaldosteronism Glucocorticoid excess Bartter's Syndrome Licorice ingestion Renal tubular acidosis Renal artery stenosis Postobstructive diuresis Alkalosis Familial hypokalemic paralysis DKA treatment with insulin Artifactual / lab error
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Causes of Hyperkalemia
Excessive intake Transfusion of old blood Acute or chronic renal failure Potassium-sparing diuretics Hypoaldosteronism Adrenal failure Sickle cell disease S. L. E. Obstructive uropathy Amyloidosis Renal transplant Acidosis Rhabdomyolysis Tumor lysis syndrome Hyperkalemic periodic paralysis Digitalis Succinylcholine Glucagon Arginine Artifactual
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EKG Findings with Altered K+ Levels
Hypokalemia (< 3.0 meq/L) Flattening & inversion of T waves U waves PAC's, PVC's, 1st & 2nd degree block Hyperkalemia (> 6.5 meq/L) High peaked T waves (in all leads) Prolonged QRS & PR intervals Wide complex tachycardias Sine wave
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Bicarbonate (HCO3-) Background Physiology
80 % of carbon dioxide transported from tissues to lungs as plasma bicarbonate 15 % of CO2 transported as carbamino groups in RBC's & 5 % is dissolved as CO2 or H2CO3 (carbonic acid) Carbonic anhydrase catalyzes CO2 + H2O to H2CO3, which then dissociates to H+ and HCO3- HCO3- is exchanged from RBC's for chloride (Cl-) Acute rise in bicarbonate causes biphasic pulmonary response : first hyper- , then hypo- ventilation
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Renal Handling of Bicarbonate
80 to 90 % of filtered HCO3- is reabsorbed in proximal tubule Also reabsorbed from distal tubule In systemic acidosis, normally no HCO3- will appear in final urine Kidney is very efficient at eliminating acute bicarb loads
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Bicarbonate Measurement
The value reported on ABG's is usually just calculated Total CO2 content = sum of dissolved CO2 + total carbonic acid (H2CO3) + bicarbonate (HCO3-) + carbamino CO2 95 % of total CO2 content contrbuted by HCO3- Bicarb level acts as measure of blood buffering capacity
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Reference Ranges for Total CO2 Concentration
Specimen Type Reference Range meq/L Reference Range mMol/L Venous blood, whole 22 to 26 22 to 26 Arterial blood, whole 19 to 24 19 to 24 Venous plasma, serum 23 to 29 23 to 29 Capillary plasma, premie 14 to 27 14 to 27 Cap. plasma, newborn 13 to 22 13 to 22 Capillary plasma, infant 20 to 28 20 to 28 Capillary plasma, child 20 to 28 20 to 28 Capillary plasma, adult 22 to 28 22 to 28 Umbilical cord blood 14 to 22 14 to 22
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Potentiometric Method for Total CO2 Measurement
Measures electrical potential difference between 2 identical ion-selective electrodes in contact with sample solution & reference solution Interfered with by Hypaque (radiographic contrast media) or the anticoagulant sodium fluoride
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Colorimetric Method for Total CO2 Measurement
All CO2 forms are converted to HCO3- via an alkaline buffer HCO3- then reacts with phosphoenolpyruvate to form oxaloacetate & inorganic phosphate Reduction of oxaloacetate to maleate then causes decrease in NADH measureable by change in absorbance at 340 nm, & this is proportional to bicarb in specimen Interfered with by fluoride, EDTA, or mercury
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Beckman / ASTRA Method for Total CO2 Measurement
Electrode records rate of pH change of reference bicarb solution as CO2 diffuses thru it from specimen pH change is directly proportional to CO2 concentration in specimen False elevations occur from increased temperature or WBC's in sample
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Anion Gap Measurement Anion gap = portion of anions not directly measured by standard tests Defined as serum Na+ concentration minus the sum of the serum bicarb and chloride concentrations Normal anion gap is 8 to 16 meq/L
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Differential Diagnosis of Metabolic Acidosis
Normal anion gap GI loss of bicarb Renal loss of bicarb Addition of hydrochloric acid Elevated anion gap MUDPILES
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Differential Diagnosis of Metabolic Alkalosis
Saline responsive (urine Cl- < 10 meq/L) GI losses - vomiting, NG suction, diarrhea Diuretics Alkali administration Posthypercapnic Non-reabsorbable anion Saline resistant (urine Cl- > 10 meq/L) Mineralocorticoid excess : Hyperaldosteronism, Cushing syndrome Licorice ingestion, Bartter's syndrome Severe hypokalemia
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Physiologic Roles of Chloride Anion
Important determinant of urine concentration Major determinant of ECF volume (with Na+) Factor in acid-base and K+ balance Allows calculation of the anion gap The major anion in the ECF 90 % excreted in urine; some in sweat & stool Reabsorbed in nephron
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Lab Measurement of Chloride
Normal range is 98 to 106 meq/L Pseudohypochloremia caused by : Hemolysis Acute dilutional states Pseudohyperchloremia caused by : Hyperproteinemia Increased bromide or iodide (suspect with very small or negative anion gap)
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Lab Methods for Chloride Measurement
Spectrophotometric Chloride reacted with mercury, thiocyanate, & ferric ion to form a red complex measured at 525 nm Is temperature sensitive Ion selective electrode Beckman / ASTRA Columetric generation of silver ions to form silver chloride ; when all Cl- is titrated, free silver ions detected amperometrically Is method least influenced by other halides
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Causes of Hyperchloremia
Hypoalbuminemia Bromism, Iodidism Unmeasured non-Na+ cations GI losses of bicarb Diarrhea GI tract fistulas Ureterosigmoidostomy Ileal loop conduit CaCl2 or MgCl2 ingestion Cholestyramine ingestion Renal losses of bicarb Renal tubular acidosis Hypoaldosteronism Hyperparathyroidism Carbonic anhydrase inhibitors Miscellaneous Dilutional acidosis Hyperalimentation Sulfur ingestion Compounds with Cl- anion Chronic respiratory acidosis
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Causes of Hypochloremia
NaCl Responsive (urine chloride < 80 meq/L) : Vomiting, NG suction Villous adenoma Diuretics Cystic fibrosis Rapid correction of chronic hypercapnia Massive blood transfusion Non-parathyroid hypercalcemia Large doses of carbenicillin or penicillin NaCl resistant (urine Cl- > 20 meq/L) : Excess mineralocorticoid Hyperaldosteronism Cushing's Syndrome Bartter's syndrome Licorice ingestion Severe K+ depletion Milk-alkali syndrome Alkali administration
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Indications to Obtain Serum Electrolytes
Uncertain hydration status Suspected adrenal insufficiency Suspected new onset renal dysfunction Side effects of meds (digoxin, ACE inhibitors, diuretics, etc.) Suspected SIADH (also need urine Na+) Suspected acid-base disorder New ( only if prolonged postictal or abnormal mental status) or atypical seizures
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Serum Glucose Levels At birth is 70 to 80 % of maternal level
Range 30 to 100, mean 50 mg/dl in first few hours Range 65 to 80 in first few days By 4 to 10 days, same as in adults Normal adult range is 45 to 130 mg/dl (fasting) Although some are symptomatic at levels below 70 mg/dl
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Plasma Versus Whole Blood Glucose Levels
Plasma contains 15 % more water than whole blood So plasma or serum glucose is > whole blood value by factor of 1.15 Deproteinization of plasma yields increased solute concentration with 5 % increase in measured glucose Capillary or arterial values are 10 to 20 mg/dl higher than venous (this effect negligible with fasting)
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Artifactual Causes of Hypoglycemia
Glycolysis from erythrocytes & leucocytes can cause glucose to decrease by 18 % in 30 minutes (even faster in hyperleucocytotic states) Methods to prevent glycolysis in sample : Rapid centrifugation Add glycolysis inhibitor such as fluoride (however this can inhibit enzymes on test strips) Rapid cooling on ice
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Methods of Glucose Measurement in the Lab
Spectrophotometric o-toluidine method being phased out since may be carcinogen Enzymatic (uses hexokinase or glucose oxidase) Glucose oxidized to gluconic acid & H2O2 Peroxidase then oxidizes a chromogen in proportion to the specimen glucose concentration Or, polarographic method measures O2 consumption in oxidizing the glucose (rate of consumption is proportional to glucose concentration)
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Reagent Strip Systems for Rapid Glucose Estimation
Strips are impregnated with glucose oxidase, peroxidase, & chromogen ; dye response is specific for glucose Some use visual comparison to reference color chart & others use reflectance meter Good correlation with lab measurement except at very low or very high values Some are affected by low or high hematocrits Commonly used brands include Dextrostix, Chemstrip bG, Visidex, Stat-Tek, & Glucoscan
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Lab Charges at H.M.C. for Electrolytes and Glucose
Test Routine Stat Electrolyte Panel (Na, K, CO2, Cl) $ 12 $ 35 Any single electrolyte Single lyte, nonblood $ 17 $ 24 $ 26 $ 35 Glucose $ 19 $ 29 Calcium Ionized calcium $ 19 $ 28 $ 29 Osmolality $ 24 $ 36
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Indications to Obtain Serum Glucose Level
Stat bedside test should be done for almost all patients with altered mental status or focal neurologic signs Suspected poorly controlled diabetes New onset glucosuria NOT needed for simple clear-cut insulin induced hypoglycemia (initial & followup bedside tests are sufficient if initial low vaue increases with Rx) Recurrent infections
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Calcium Physiology Most abundant mineral in body 1 to 2 grams
99 % in bone 40 to 45 % of serum calcium bound to plasma proteins, mostly albumin 5 to 10 % is in non-ionized complexes (citrate, phosphate) 40 to 50 % is free ionized the physiologically active form involved in osteogenesis & osteolysis
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Serum Calcium Concentrations
Normal : 8.5 to 10.5 mg/dl Lower in elderly & pregnancy Venous stasis (prolonged tourniquet) raises value 10 % For change in serum protein by 1 gm/dl, serum calcium changes by 0.8 mg % Normal ionized calcium range : 1.0 to 1.38 mmol/L or 4 to 4.8 mg % Acidosis increases ionized fraction pH change by 0.1 causes change in calcium of 0.17 mg %
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Serum Calcium Measurement
Most common methods use : Calcium dialyzed into acid solution of the dye o-cresolphthalein complexone Base then added & absorption at 570 nm measured Automated analyzers : multiple different brands Only 20 microliters of blood needed Only takes 10 minutes or less Many other methods can be used : precipitation, photometry, polarographic, atomic absorption spectroscopy
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Measurement of Serum Ionized Calcium
Calcium ion selective electrode used Membrane impregnated with liquid ion-exchange & is saturated with calcium When serum is pumped thru the electrode, it causes a potential difference between the serum ionized calcium & the liquid ion-exchanger The potential difference is proportional to the serum ionized calcium concentration Precision of this method is +/- 2 %
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Costs of Serum Calcium Tests
Serum calcium at H.M.C. : $15.00 Ionized calcium : $25.00 As part of SMA-12 : $22.50 Increase charge by 50 % for stat
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Indications to Obtain a Serum Calcium
Altered mental status in an ill-appearing patient Clinical signs of tetany (for confirmation) Recurrent nephrolithiasis Known or suspected malignancies involving bone
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Serum Osmolality Free permeability of biologic membranes to water results in osmolal equilibrium throughout body Extracellular fluid osmolality equilibrates with intracellular fluid Normal serum osmolality is 285 to 295 mosmol/kg Osmoreceptors in hypothalamus sense change of less than 2 % ADH (causes resorption of water in distal nephron) secreted to preserve osmolal homeostasis
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Effects of Adding Solute Particles
to a Solution (continuous linear effects) Adding one mole (6.02 x particles) to pure water causes : Osmotic pressure increased Freezing point decreased (1.86 C) Vapor pressure decreased (0.3 mm Hg) Boiling point increased (1.86 C) 22 o o
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Osmolality Measurement
Osmotic coefficients are correction factors that index degree of variance of solutes from ideal calculated activity Osmolality then is measure of concentration of particles in solution Defined as : 1 osmolal solution contains 1 mole of solute particles per kg of solvent Osmolarity is measure of concentration of particles per volume 1 osmolar solution contains 1 mole solute particles per liter of solvent Osmolality = osmolarity only when solvent is pure water
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Types of Osmometers in Use
Vapor pressure osmometer Can accurately analyze grossly lipemic specimens But is insensitive to volatile solutes Not preferred for most E.D. needs Freezing point osmometer More useful for E.D.
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Principles of Freezing Point Osmometers
Freezing point = unique temperature at which solid & liquid phases of a substance exist at equilibrium Supercooling is the tendency of a solution to remain liquid despite cooling to temp. below its freezing point (by stirring, etc.) The energy required to preserve the liquid supercooled state can be measured as the heat generated once crystallization occurs This is the "heat of fusion" & is measured by the freezing point osmometer Thermistor coupled to transducer & galvanometer measures liberated heat of fusion when stirring wire rod is stopped
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Freezing Point Osmometer
Can measure samples as small as 0.2 ml Error from hemolysis of sample is small Sample tube must be covered at all times to prevent loss of volatile CO2 Measurements still reliable even if delayed, if sample is covered & refrigerated
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Reported Measurement Units Requiring Standardization for Osmolality Determinations
Nonelectrolytes (glucose, alcohol, etc.) Reported in mg / deciliter Osmolal contribution is then the reported lab value divided by 1/10 of the gross molecular weight of the compound Electrolytes (elemental ions) Reported as meq / liter Reported number requires no modification for osmolal contribution
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Errors in Osmolality Assumptions
Normal serum is 93 % water Lipids & proteins comprise the remaining 7 % So osmolarity of serum does not exactly equal osmolality Hyperlipidemia to a degree sufficient to cause lactescence requires concurrent vapor pressure measurement for accuracy Serum protein content changes (e.g., multiple myeloma) rarely affect calculation significantly
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Standard Formula for Calculated Serum Osmolality
Derived from a study comparing 13 different equations using measurements of different serum components in 705 inpatients Calculated osmolality = 2 X Na + glucose/18 + BUN/2.8
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The Osmolal Gap Represents measured osmolality (by lab) > calculated osmolality (by formula) Represents unmeasured solutes which often could be toxins Always clinically significant if > 20 mosmol/kg Should always be determined for suspected non-ethanol alcohol ingestions or other osmotically active suspected ingestants
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Expected Osmolal Contributions by Different Alcohols
Ethanol measured value in mg/dl divided by 4.6 Ethylene glycol measured value in mg/dl divided by 6 Isopropanol measured value in mg/dl divided by 6.2 Methanol measured value in mg/dl divided by 3.2 Add these values to the standard calculated osmolality equation
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Other Substances Which Can Cause An Osmolal Gap
Glycerol, mannitol Iatrogenic for diuresis Radiographic contrast media Iodine, bromine Low anion gap Very rarely from high dose antibiotics or other meds
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