Enhanced Clinical Chemistry PDF

be exhausted through HEPA back into the room or to outside through a c...

be exhausted through HEPA back into the room or to outside through a canopy unit II, A2 100 Similar to II, A1, but has 100 lfm intake Yes When exhausted air velocity and plenums are under outdoors negative pressure to room; exhaust air (formally “B3”) can be ducted to the outside through (minute a canopy unit amounts) II, B1 100 30% recirculated, 70% exhausted. Yes Yes (minute Exhaust cabinet air must pass through amounts) a dedicated duct to the outside Enhanced Clinical Chemistry through a HEPA filter Prepared by: Kristine Cher C. Abril, RMT INTERNAL LABORATORY QUALITY EXTERNAL LABORATORY QUALITY CONTROL CONTROL I. Laboratory Safety and Quality Control Intralab Quality Control Interlab Quality Control Quality control within the laboratory Proficiency testing programs to participating BASE QUANTITY Analyses of control samples and patient laboratories Length Meter specimens Significant in maintaining long-term accuracy of Mass Kilogram Essential for daily monitoring of accuracy the analytical method Time Second and precision Difference >2 in the result means that laboratory Electric current Ampere Detects random and systematic error is not in agreement with other laboratories Thermodynamic temperature Kelvin included in the program Amount of substance Mole Luminous intensity Candela COMPARISON OF BIOSAFETY CABINET CHARACTERISTICS Applications BSC Face Airflow Pattern Nonvolatile Volatile Toxic TRADITIONAL THINKING TOTAL QUALITY MANAGEMENT THINKING Class Velocity Toxic Chemicals and Chemicals and Radionuclides Acceptable quality Error-free quality Radionuclides Department focused Organization focused Quality as expense Quality as means to lower costs I 75 In at front through HEPA to the Yes When exhausted Defects by workers Defects by system outside or into the room through outdoors Management-controlled worker Empowered worker HEPA Status quo Continuous quality improvement I, B2 100 No recirculation; total exhaust to the Yes Yes (small Managed by intuition Managed by fact outside through a HEPA filter amounts) Intangible quality Quality defined II, A1 75 70% recirculated to the cabinet work Yes (minute No We versus they relationship Us relationship area through HEPA; 30% balance can amounts) End-process focus System process 1  Reactive systems Proactive systems ✓ Precision - reproducibility; measure of the closeness of the results obtained when analysis on the same sample is repeated; agreement between replicate measurements ✓ The smaller the %CV value, the greater is the precision ✓ Lean Six Sigma is the combination of Lean principles and Six Sigma methodology ✓ Lean principles work to eliminate the waste such as streamlining a process to reduce wait times. Does this process or step need to exist? ✓ Six Sigma business management strategy seeks to improve a process’s performance by identifying and eliminating cause of defects and errors. How can this process be improved? Quality Management Process of Total Quality Management F – find a problem or process to improve Measure of Center O – organize a team ✓ Mean - commonly called average, most commonly used measure of center C – clarify what is known about the process ✓ Median - middle point of the data and is often used with skewed data U – understand causes of the problem/variation ✓ Mode - most frequently occurring value in a dataset. Although it is seldom used to S – select the way the process is to be improved describe data, it is referred to when in reference to the shape of data, a bimodal distribution Deming Cycle P - plan implementation of improvements to be made D – do what is appropriate to implement ±1SD ±2SD ±3SD 68.3% 95.5% 99.7% C – check data collected from monitoring A – act to maintain and continue the process ABBREVIATION NOMENCLATURE FOR QUALITY CONTROL EVALUATION RULES 12s One observation exceeds ±2SD from the target value. Not recommended ✓ Sensitivity - is the ability of an analytical method to measure the smallest concentration The 12s rule is not recommended because it has been an except for "low of the analyte of interest excessive false alert rate sigma" methods 13s One observation exceeds ±3SD from the target value Imprecision or ✓ systematic bias ✓ Specificity - is the ability of an analytical method to measure only the analyte of interest 22s(22.5s) Two sequential observations or observations for two QC Bias ✓ samples in the same run, exceed ±2SD (or ±2.5SD) from ✓ Positive predictive value - chance of an individual having a given disease or condition if the target value in the same direction the test is abnormal R4s Range between observations for two QC samples in the Imprecision ✓ Negative predictive value - chance an individual does not have a given disease of same run, or for two sequential observations of the same condition if the test is within the reference interval QC sample, exceeds ±4SD ✓ Accuracy - correctness of a result, freedom from error, or how close the answer is to the 10x or 10m Ten sequential observations for the same QC sample are Not recommended on the same side of the target value (x or mean). "true value" 2  The 10x rule is not recommended because it has an excessive falser alert rate 81s(81.5s) Eight sequential observations for the same QC sample Bias trend exceed ±1SD or (±1.5SD) in the same direction from the target value CUSUM Cumulative sum of SDI for a specified number of previous Bias trend results RANDOM ERROR SYSTEMATIC ERROR EWMA Exponentially weighted moving average with newer Bias trend Error that does not recur in regular pattern; Error that influences observations consistently in results having more influence (weight) no trend or means of predicting it one direction. Recurring error inherent in test procedure; seen as a trend in the data Random Errors Mislabelling a sample Improper calibration Pipetting errors Deterioration of reagents Improper mixing of sample and reagent Sample instability Voltage fluctuations not compensated for Instrument drift Systematic Errors by instrument circuitry and temperature Changes in standard materials fluctuations Abrupt, sudden and 6 or more consecutive daily May be observed with SHIFT sustained change in values that distribute the sudden malfunction one direction in themselves on one side of the of an instrument control sample values mean value line, but maintain a constant level Gradual change in the Values for the control that Progressive problem control sample of continue to either increase or with the testing system TREND results decrease over a period of 6 or control sample, such consecutive days as deterioration of reagents or control Shift Trend specimen 3  ✓ Beer's law states that concentration of a substance is directly proportional to the amount of light absorbed or inversely proportional to the logarithm of the transmitted light.  Spectrophotometry - chemical reaction produces colored substance that absorbs light of PROPORTIONAL Type of systematic error where the magnitude Slope SYSTEMATIC ERROR changes as a percent of the analyte present; error a specific wavelength. Amount of light absorbed is directly proportional to dependent on the analyte concentration concentration of analyte CONSTANT SYSTEMATIC Type of systematic error in the sample direction and Y-intercept Single-beam spectrophotometer - simplest type of absorption spectrometer ERROR magnitude; the magnitude of change is constant and Double-beam spectrophotometer - it splits the monochromatic light into two not dependent on the amount of analyte components - one beam passes through the sample and the other through a reference solution or blank ▪ Double-beam in space - uses two photodetectors, for sample beam and reference beam ✓ T test - is used to determine whether there is a statistically significant difference ▪ Double beam in time - uses one photodetector and alternately between the means of two groups of data. Accuracy, Mean passes the monochromatic light through the sample cuvet and ✓ F test - is used to determine whether there is a statistically significant difference then reference cuvet using a chopper or rotating sector mirror between the standard deviations of two groups of data. Precision, Standard deviation ✓ Criteria for a good standard curve - line is straight, line connects all points and line goes Parts of Spectrophotometer through origin or intersect of the two axes X - axis Horizontal, Abscissa Independent variables 1. Light/Radiant source - it provides polychromatic light and must generate sufficient Y - axis Vertical, Ordinate Dependent variables radiant energy or power to measure the analyte of interest 2. Entrance slit - it minimizes unwanted or stray light and prevents entrance of scattered light into monochromator system II. Instrumentation ✓ Stray light - refers to any wavelengths outside the band transmitted by the monochromator; it does not originate from the polychromatic light source; it ✓ Wavelength - is the distance between two successive peaks and it is expressed in terms causes absorbance error of nanometer (nm) 3. Monochromator - it isolates specific or individual wavelength of light 400-700nm - visible spectrum a. Prisms 700nm - infrared region c. Filter ✓ Wavelength calibration d. Holographic gratings Holmium oxide glass - narrow-spectral bandwidth instruments Didymium filter - broader bandpass instruments 4. Exit slit - it controls the width of light beam. It allows only a narrow fraction of the spectrum to reach the sample cuvet ✓ Bandpass - total range of wavelengths transmitted 4 5. Cuvet - holds the solution whose concentration is to be measured Mass spectroscopy - it is based on fragmentation and 6. Photodetector - it detects and converts transmitted light into photoelectric energy ionization of molecules using a suitable source of energy Gas Chromatography-Mass Spectroscopy - it is the gold standard for drug testing a. Barrier layer cell/Photocell Tandem Mass Spectroscopy (MS/MS) - can detect 20 inborn b. Phototube errors if metabolism from a single blood spot c. Photomultiplier d. Photodiode 2. Liquid Chromatography - is based on the distribution of solutes between a liquid mobile phase and a stationary phase 7. Meter or read-out device High Performance Liquid Chromatography - it uses pressure for  Flame Emission Photometry - it measures the light emitted by a single atom burned in fast separations, controlled temperature, in-line detectors and flame gradient elution technique o Internal standard: Lithium/Cesium - corrects variations in flame and Liquid Chromatography-Mass Spectroscopy - it is used for atomizer characteristics detecting nonvolatile substances in body fluids o  Fluorometry - it measures the amount of light intensity present over a zero background. Atoms absorb light of specific wavelength and emit light of longer wavelength (lower  Atomic Absorption Spectrophotometry - it measures the light absorbed by atoms energy). It uses 2 monochromators. dissociated by heat. Internal standard is not needed as changes in aspiration have little ✓ the wavelength that is best absorbed by a solution to be measured is effect on the number of ground state atoms selected by the primary filter  Turbidimetry - it measures the reduction in light transmission by particles in suspension. ✓ the incident light is prevented from striking the photodetector by the It depends on specimen concentration and particle size secondary filter  Nephelometry - it is similar to turbidity but light is measured at angle from light source. ✓ Increasing temperature results in more random collision between Light scattering depends on wavelength and particle size molecules by increasing their motion. This causes energy to dissipate as  Electrophoresis - migration of charged particles in an electric field. It separates proteins heat instead of fluorescence. Temperature is inversely proportional to on the basis of their electric charge densities fluorescence  Chromatography - it involves separation of soluble components in a solution by specific ✓ differences in physical-chemical characteristics of the different constituents  Chemiluminescence - chemical reaction that produces light. It usually involves oxidation A. Planar of luminol, acridinium esters or dioxetanes 1. Paper Chromatography  Osmometry - is the measurement of the osmolality of an aqueous solution such as 2. Thin Layer Chromatography - it is a semiquantitative drug screening test serum or urine B. Column ✓ freezing point depression osmometry - is the most commonly used method for measuring the changes in colligative properties of a 1. Gas chromatography - it is useful for compounds that are naturally volatile or solution can be easily converted into a volatile form 5  ✓ Electrochemistry - it involves measurement of current or voltage generated by activity ✓ Centrifugal analyzer - it uses force generated by centrifugation to transfer and then of specific ions contain liquids in separate cuvettes for measurement at the perimeter of a spinning rotor a. Potentiometry - measurement of potential (voltage) between two electrodes ✓ Discrete analyzer - it is the most popular and versatile analyzer. Separation of each in a solution sample and accompanying reagents in a separate container. It has the capability of b. Coulometry - it measures the quantity of electricity (in coulombs) needed to running multiple tests one sample at a time or multiple samples one test at a time convert an analyte to a different oxidation state ADVANTAGES OF AUTOMATION DISADVANTAGES OF AUTOMATION c. Voltammetry - method in which a potential is applied to an electrochemical Increased work capacity per unit of time Initial costs cell and the resulting current is measured Minimized variability Discontinuity of product Reduced errors caused by manual Technical skill required d. Amperometry - measurement of the current flow produced by an oxidation- manipulations reduction reaction Reduced sample volumes Reduced consumable costs Automatic Pipets 1. Air displacement pipet - piston-operated devices; a disposable, one-time use III. Specimen Collection polypyrene tip is attached to the pipet barrel. The pipet tip is placed into the liquid to be aspirated and is drawn into and dispensed from this tip ✓ Venipuncture - 15° to 30° (15°) ✓ Arterial puncture - 45° to 60° (90° for femoral artery) 2. Positive displacement pipet - use a capillary tip that may be siliconized glass, glass or ✓ Modified Allen Test to determine whether the ulnar artery can provide collateral plastic. This type of pipet is useful if a reagent reacts to plastics. Positive displacement circulation to the hand after the radial artery puncture. pipets use a Teflon-tipped plunger that fits tightly inside the capillary. These capillary ✓ Central Venous Access Devices - provide ready access to the patient's circulation, tips are reusable and carry-over is negligible if the pipet is properly maintained eliminating multiple phlebotomies and are especially useful in critical care and surgical 3. Dispenser/Dilutor pipet - it obtains liquid from a common reservoir and dispensed it situations. Indwelling catheters are surgically inserted into the cephalic vein or into the repeatedly internal jugular, subclavian or femoral vein and can be used to draw blood products, administer drugs or blood products and provide total parenteral nutrition ✓ Glass pipet - most basic pipet ✓ Neonatal screening program - filter paper collection or blood spot collection ✓ Automatic pipet - most routinely used pipet ✓ Point-of-care testing - a.k.a. Bed-side, near-patient, physician's office, extra-laboratory, ✓ Batch testing - all samples are loaded at the same time and a single test is conducted on off-site, satellite, kiosk, ancillary decentralized, alternative site testing each sample o Majority of POCT is performed by non-laboratory personnel. Persons ✓ Parallel testing - more than one test is analyzed concurrently on a given clinical performing POCT are called operators and are usually primary patient specimen providers. Operators include phlebotomists, nurse, physicians, ✓ Random access testing - any test can be performed on any sample in any sequence respiratory therapists, radiographers, medical and nursing assistants, ✓ Sequential testing - multiple tests analyzed after another on a given specimen ambulance personnel, patient-care technicians, medical laboratory ✓ Continuous flow analyzer - liquids are pumped through a system of continuous tubing. scientist and patients Samples flow through a common reaction vessel of pathway 6  ✓ Capillary blood samples - for glucose testing and for other assays are used PREANALYTICAL (PREEXAMINATION) PHASE ✓ Stat for the latin word of Statim meaning immediately Test order accuracy Some drug levels such as Theophylline Patient identification Amylase in suspected pancreatitis Blood culture contamination Creatine kinase in suspected MI Test system/Preanalytical (Preexamination) Adequacy of specimen information Hematocrit ANALYTICAL (EXAMINATION) PHASE Blood gases Accuracy of point-of-care testing Potassium Cervical cytology/biopsy correlation ✓ Chain of Custody/Evidence - processing steps for specimens Test system/Analytical (Examination) o initial collection, transportation, storage and analytical testing Diabetes monitoring o must be documented by careful record keeping. Documentation Hyperlipidemia screening ensures that there has been no tampering with the specimen by any POST ANALYTICAL (POST EXAMINATION) PHASE interested parties that the specimen has been collected from the Critical value reporting appropriate person and that the results reported are accurate Turnaround time Test system/Postanalytical (Post-examination) SKIN PUNCTURE Clinician satisfaction Length of the lancet: 1.75mm Clinician follow-up The depth of the incision should be 240 mg/dL 30-39 y/o ✓ it is the cholesterol bound to fatty acid Serum cholesterol: moderate risk >240 mg/dL, high risk >260 mg/dL 40 and over ✓ approximately 70% of total plasma cholesterol 13 I. Chemical Methods ✓ comprise 95% of all fats stored in adipose tissue a. One-step Method ✓ Acetyl coenzyme A: intermediary in the metabolism of TAG through the process of beta ✓ Colorimetry oxidation, it enters the Kreb's cycle to be converted to energy ✓ Pearson, Stern and Mac Gavack ✓ it evaluates suspected atherosclerosis ✓ fasting TAG of ≥200 mg/dL is at risk for coronary artery disease b. Two-step Method ✓ very high TAG of ≥500 mg/dL: acute pancreatitis ✓ Extraction + Colorimetry ✓ Bloors Triglyceride Normal Borderline High High Very High mg/dL bone (labile) ✓ it has 2 isoenzyme fractions: cytoplasm and mitochondrial AST ✓ major tissue source: cardiac tissue, liver and skeletal muscle c. Chemical Inhibition test ✓ method: Reitman and Frankel; Karmen (most common) ✓ phenylalanine inhibits placental and intestinal ALP ✓ it uses malate dehydrogenase; requires vitamin B6 as cofactor ✓ synthetic 3M urea inhibits bone ALP ✓ levamisole inhibits liver and bone Enzyme Onset Peak Elevation CKMB 4 to 6 hours 12 to 24 hours 48 to 72 hours d. Bowers and McComb AST 6 to 8 hours 18 to 24 hours 4 to 5 days ✓ szasz modification LD 12 to 24 hours 48 to 72 hours 10 days ✓ it is considered as the most specific method ✓ uses p-nitrophenyl phosphate like Bessy, Lowry and Brock 4. Alanine Aminotransferase/SGPT ✓ the highest concentration is in the live; more liver-specific than AST 2. Acid Phosphatase ✓ major tissue source: liver ✓ it has the same reaction by ALP except that it is active at pH 5.0 ✓ not part of cardiac test ✓ it is significant in the evaluation of hepatic disorders ✓ tissue sources: prostate (major source), RBC, platelets, liver and bone ✓ serum ACP decreases within 1 to 2 hours if left at room temperature ✓ it monitors the course of liver treatment and the effects of drug therapy ✓ if not assayed immediately, serum should be frozen or acidified to a pH lower ✓ method: Reitman and Frankel; Karmen (most common) than 6.5 ✓ with acidification, ACP is stable for 2 days at room temperature Hepatic Disorders ✓ alpha naphthyl PO4 is preferred for continuous monitoring method 1. Acute injury (Hepatitis) and Necrosis Increased: ALT, AST, ALP, Bilirubin (B1 and B2) ✓ thymolphthalein MonoPO4 is the specific substrate; substrate of choice or quantitative endpoint reaction Normal: TPAG 2nd markers: increased LD4, LD5 ACP Other Names Inhibitors Prostatic ACP Specific ACP L-tartrate Nonprostatic ACP Nonspecific ACP 2% formaldehyde + Cupric ions 2. Biliary Tract Obstruction Red Cell ACP Increased: ALP and Bilirubin 2 Slightly increased: ALT, AST Diagnostic Significance Normal: TPAG ✓ for the detection of adenocarcinoma 2nd markers: increased GGT, LAP, 5'NT ✓ useful in forensic clinical chemistry such as in the investigation of rape cases ✓ vaginal washings are examined for seminal fluid-ACP activity which can persist for up to 3. Cirrhosis 4 days Increased: Bilirubin 1 and 2 Slightly increased: ALT, AST, ALP 3. Aspartate Aminotransferase/SGOT Decreased: Total protein, Albumin ✓ it is significant in MI, hepatocellular disorders and skeletal muscle involvement Increased: Globulin 30  2nd markers: increased Ammonia, LD4, LD5 ✓ substrate: 50% olive oil or triolein (pure form of TAG) 5. Amylase b. Tietz and Fiereck ✓ it catalyzes breakdown of starch and glycogen c. Peroxidase coupling ✓ it is the smallest enzyme in size ✓ most commonly used method; does not use 50% olive oil ✓ it is normally filtered in the glomerulus and appears in urine ✓ it is the earliest pancreatic marker 7. Lactate Dehydrogenase ✓ isoenzymes: S type and P type ✓ it is a zinc-containing enzyme that is part of the glycolytic pathway and is found ✓ major tissue source: acinar cells of the pancreas and salivary glands in all cells in the body ✓ it lacks specificity due to various organ sources Methods for Amylase ✓ it is useful in monitoring myocardial, hematological and hepatic disorders Substrate: Starch a. Saccharogenic Tissue Sources ✓ expressed in Somogyi units, measures amount of reducing sugar LD1 and LD2: heart, RBC, kidneys produced LD3: lungs, pancreas, spleen, WBC LD4 and LD5: skeletal muscles, liver, intestine b. Amyloclastic LD6: alcohol dehydrogenase ✓ degradation of starch; measures the decrease in substrate concentration ✓ LD2 is greater than LD1 is seen in healthy sera ✓ LD1 > LD2, flipped pattern; seen in MI and pernicious anemia c. Chromogenic ✓ LD1 and LD2: most abundant, most anodal, heat stable ✓ measures amylase activity by increase in color intensity ✓ LD4 and LD5: least in concentration, least anodal, cold labile ✓ highest elevations of LD: pernicious anemia, hemolytic disorders and d. Coupled-enzyme megaloblastic anemia ✓ measures amylase by continuous monitoring technique 6. Lipase Methods for LD ✓ most specific pancreatic marker a. Wacker method (Forward/Direct reaction) ✓ it is secreted exclusively in the pancreas; not affected by renal disorders ✓ LD1 prefers the forward reaction ✓ major tissue source: pancreas ✓ most commonly used; lactate is more specific Methods for Lipase b. Wrobleuski La Due (Reverse/Indirect reaction) a. Cherry crandal ✓ LD5 prefers the reverse reaction ✓ reference method ✓ 2x faster, preferred in dry slide technology, smaller specimen volume 31  8. Creatine Kinase 12. Pseudocholinesterase ✓ CK1/CK-BB: brain type ✓ it reflects synthetic function rather than hepatocyte injury ✓ CK2/CK-MB: hybrid type ✓ it is a marker for organophosphate poisoning ✓ CK3-MM: muscle type ✓ CK-BB: rarely seen in serum of adults; only increased in cerebrovascular 13. Angiotensin-Converting Enzyme diseases and severe head trauma ✓ it converts angiotensin I to angiotensin II within the lungs ✓ CK-BB is the most anodal and labile isoenzyme; CK-MM is the least anodal ✓ it is possible indicator of neuronal dysfunction ✓ CK-MM is both abundantly present in cardiac and skeletal muscles ✓ it is a critical target for inhibitory drugs designed to lower blood pressure ✓ it is very sensitive indicator of acute MI and Duchenne disorder 14. Ceruloplasmin Methods for CK ✓ it is a copper-carrying protein and also an enzyme a. Tanzer-Gilvarg (Forward/Direct method) ✓ it is a marker for Wilson's disease b. Oliver-Rosalki (Reverse/Indirect method) 15. Ornithine Carbamoyl Transferase ✓ most commonly used method, faster reaction ✓ it is a marker for hepatobiliary diseases 9. Aldolase 16. Glucose-6-Phosphate-Dehydrogenase ✓ it is significant in skeletal muscle disease ✓ it is part of the newborn screening test ` ✓ it functions to maintain NADPH in the reduced form in the erythrocytes Isoenzymes Aldolase A: skeletal muscles X. Electrolytes Aldolase B: WBC, liver, kidney Aldolase C: brain tissue ✓ these are ions capable of carrying electric charge 10. 5'Nucleotidase Functions of Electrolytes ✓ it is a marker for hepatobiliary disease and infiltrative lesions of the liver a. Volume and Osmotic regulation: Na+, Cl-, K+ ✓ secondary marker for obstructive jaundice b. Myocardial Rhythm and Contractility: K+, Ca++, Mg++ c. Cofactors in enzyme activation: Ca++, Mg++, Zn++, Cl-, K+ 11. Gamma Glutamyl Transferase d. Regulation of ATPase ion pumps: Mg++ ✓ it is a marker used together with ALP to differentiate liver (OJ) from bone e. Neuromuscular excitability: K+, Ca++, Mg++ disorder (Paget's) f. Production and use of ATP: Mg++, PO4-3 ✓ it is a sensitive indicator of alcoholism; most sensitive marker of acute alcoholic g. Acid-Base balance: HCO3-, K+, Cl-, PO4-3 hepatitis h. Replication of DNA: Mg++ 32  1. Sodium Methods for Sodium ✓ it is also known as "Natrium" a. Emission Flame Photometry ✓ it is the major extracellular cation, major contributor of osmolality b. Ion Selective Electrode (Glass Aluminum Silicate) ✓ it is the principal osmotic particle outside the cell c. Atomic Absorption Spectrophotometry ✓ reference value: 135 to 145 mmol/L d. Colorimetry (Albanese-Lein method) Hormones Affecting Sodium Levels: 2. Potassium a. Aldosterone ✓ otherwise known as "Kalium" ✓ it promotes reabsorption of sodium in the distal tubule ✓ it is the major intracellular cation; it permits neural signal to move down the ✓ it promotes sodium retention and potassium excretion nerve fiber ✓ it is the single most important analyte in terms of an abnormality being b. Atrial Natriuretic Factor immediately life threatening ✓ it removes excess sodium ✓ reference value: 3.5 to 5.2 mmol/L A. Hypernatremia A. Hyperkalemia ✓ it is caused by loss of water, gain of sodium or both; it is usually results from ✓ it is almost always due to impaired renal excretion excessive water loss ✓ reduced aldosterone ✓ chronic hypernatremia in an alert patient is indicative of hypothalamic disease ✓ acidosis: plasma increases 0.2 to 1.7 mmol/L for each unit reduction of pH; ✓ thirst is the major defense against hyperosmolality and hypernatremia H+ enters RBC and K+ moves out of the cell ✓ low insulin levels cause high serum potassium B. Hyponatremia ✓ it is the most common electrolyte disorder B. Artifactual hyperkalemia ✓ if renal failure occurs, the kidneys ultimately fail to concentrate the urine, ✓ causes: sample hemolysis, thrombocytosis, prolonged tourniquet application, resulting to hyponatremia fist clenching, blood stored in ice, high blast counts, recentrifugation of SST as ✓ it could lead to neuropsychiatric symptoms,