5.11 Chemistry - Clinical Chemistry Problem Solving

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A blood sample is left on a phlebotomy tray for 4.5 hours before it is delivered to the laboratory. Which group of tests could be performed?

Uric acid, BUN, creatinine Glucose in serum is metabolized by cells at a rate of about 7% per hour. Bilirubin levels will fall if the sample is exposed to sunlight. Transaminases should be measured within 4 hours and ALP within 2 hours if the sample is stored at room temperature. Uric acid, BUN, and creatinine are least likely to be affected.

A chromatogram for blood alcohol (GC) gives broad trailing peaks and increased retention times for ethanol and internal standard. This is most likely caused by:

Water contamination of the column packing Increased oven temperature or gas flow rate will shorten retention times and decrease peak widths. Syringe contamination may cause the appearance of ghost peaks. Water in a PEG column such as Carbowax used for measuring volatiles causes longer retention times and loss of resolution.

A gastric fluid from a patient suspected of having taken an overdose of amphetamine is sent to the laboratory for analysis. The technologist should:

Dilute 1:10 with H2O and filter; perform TLC for amphetamines The gastric sample can be measured by TLC, but such a sample should not be used in place of serum or urine without documentation of acceptability by the reagent manufacturer or laboratory. A positive amphetamine result by a screening test such as TLC or immunoassay may be caused by a related drug which interferes, and therefore, the result should be confirmed by GC-MS if there is a medicolegal implication.

SITUATION: A serum osmolality measured in the emergency department is 326 mOsm/kg. Two hours later, chemistry results are: Na = 135 mmol/L BUN = 18 mg/dL glucose = 72 mg/dL measured osmolality = 318 mOsm/kg What do these results suggest?

Drug or alcohol intoxication The osmolal gap is the difference between calculated and measured osmolality. Here, the osmolal gap is 38 mOsm/kg. When the osmolal gap is greater than 10 mOsm/kg, an unmeasured solute is present or an analytical error occurred when measuring the osmolality, electrolytes, urea, or glucose. The reference range for serum osmolality is 280-295 mOsm/kg. Both osmolality measurements are above the URL. These results point to the presence of an unmeasured solute. A significant osmolal gap in samples from emergency department patients usually results from alcohol or drug consumption. The difference in osmolality between the two samples is 8 mOsm/kg and can be explained by alcohol metabolism during the 2 hours between samples.

When calibrating a pH meter, unstable readings occur for both pH 7.00 and 4.00 calibrators, although both can be set to within 0.1 pH unit. Select the most appropriate course of action.

Examine the reference electrode junction for salt crystals Noise in pH measurements often results from a blocked junction between the reservoir of the reference electrode and test solution. This occurs when salt crystals collect at the junction or when KCl concentration in the reservoir increases due to evaporation of water. The fluid in the reference electrode should be replaced with warm deionized water. After the crystals have dissolved, the water is replaced with fresh reference electrolyte solution.

SITUATION: Results of an iron profile are: serum Fe = 40 μg/dL ferritin = 40μg/L (reference range 15-200) TIBC = 400 μg/dL transferrin = 300 mg/dL These results indicate:

Excess release of ferritin caused by injury Serum ferritin levels fall before iron or TIBC in iron deficiency, and a low level of serum ferritin is diagnostic. However, low tissue levels of ferritin may be masked by increased release into the blood in liver disease, infection, and acute inflammation. Although this patient's serum ferritin is within reference limits, serum iron is low and percent saturation is only 10%. Note that the TIBC and transferrin results are both elevated and agree. TIBC can be estimated by multiplying the serum transferrin by 1.4. These results point to iron deficiency.

An HPLC assay for procainamide gives an internal standard peak that is 15% greater in area and height for sample 1 than sample 2. The technologist should suspect that:

Less recovery from sample 2 occurred in the extraction step The internal standard compensates for variation in extraction, evaporation, reconstitution, and injection volume. The same amount of internal standard is added to all samples and standards prior to assay. Increased column pH or pressure usually alters retention time, and may not affect peak quantitation.

SITUATION: A patient's biochemistry results are: Na = 125 mmol/L Cl = 106 mmol/L K = 4.5 mmol/L TCO2 = 19 mmol/L chol = 240 mg/dL triglyceride = 640 mg/dL glucose = 107 mg/dL AST = 16 IU/L ALT = 11 IU/L amylase = 200 U/L Select the most likely cause of these results.

Lipemia is causing in vitro interference The triglyceride level is about five times normal, causing the sample to be lipemic. This will cause pseudohyponatremia (unbalanced electrolytes). Lipemia may cause a falsely high rate reaction when amylase is measured by turbidimetry; however, the high amylase may be associated with pancreatitis, which results in hyperlipidemia.

Given the serum protein electrophoresis pattern shown, which transaminase results would you expect?

Mild elevations of both (2-5 fold normal) The protein electrophoresis and densitometric scan show a significantly reduced albumin and polyclonal gammopathy. The densitometric scan shows beta-gamma bridging that supports a diagnosis of hepatic cirrhosis. In this condition one would expect two- to fivefold increases of both transaminases with an ALT:AST ratio below 1.

A quantitative sandwich enzyme immunoassay for intact serum hCG was performed on week 4 and the result was 40,000 mIU/mL (reference range 10,000-80,000 mIU/mL). The physician suspected a molar pregnancy and requested that the laboratory repeat the test checking for the hook effect. Which process would identify this problem?

Perform a serial dilution of the sample and repeat the test The hook effect is the result of excessive antigen concentration and results in a dose response (calibration) curve that reverses direction at very high antigen concentrations. It occurs in two-site double antibody sandwich assays when both the capture antibody and the enzyme-conjugated antibody are incubated with the antigen at the same time. The excess antigen saturates both antibodies preventing formation of a double antibody sandwich. The hook effect can cause results to be sufficiently low to cause misdiagnosis. It can be detected by diluting the sample (antigen) in which case the assay result will be greater than in the undiluted sample. An alternative solution is to perform the test using a competitive binding assay or a sandwich assay in which the enzyme-labeled antibody is not added until after separation of free and bound antigen.

SITUATION: Hgb electrophoresis is performed and all of the Hgbs have greater anodal mobility than usual. A fast Hgb (Hgb H) is at the edge of the gel and bands are blurred. The voltage is set correctly, but the current reading on the ammeter is too low. Select the course of action that would correct this problem.

Prepare fresh buffer and repeat the test Increased mobility, decreased resolution, and low current result from low ionic strength. Reducing voltage will slow migration but will not improve resolution. Diluting the buffer will reduce the current, resulting in poorer resolution.

After staining a silica gel plate to determine the L/S ratio, the technologist notes that the lipid standards both migrated 1 cm faster than usual. The technologist should:

Prepare fresh developing solvent and repeat the assay TLC plates migrate in solvent until the front comes to 1 cm of the top of the plate. Separation of lipids on silica gel is based upon adsorption. Higher Rf values indicate greater solubility of lipids in the developing solvent. This may be caused by evaporation of H2O, lowering the polarity of the solvent.

Serial TnI assays are ordered on a patient at admission, 3 hours, and 6 hours afterwards. The samples were collected in heparinized plasma separator tubes. Following are the results (reference range 0-0.03 μg/L Admission = 0.03 μg/L 3 hours = 0.07 μg/L 6 hours = 0.02 μg/L These results indicate:

Random error with the 3-hour sample Troponin assays produce very little fluorescence or chemiluminescence when plasma levels are within the reference range and near the minimum detection limit of the assay. Fibrin, tube additives, and heterophile antibodies have been known to cause spurious elevations, and this result should be treated as a random error because the result before and after are both normal.

After installing a new analyzer and reviewing the results of patients for 1 month, the lead technologist notices a greater frequency of patients with abnormally high triglyceride results. Analysis of all chemistry profiles run the next day indicated that triglyceride results are abnormal whenever the test is run immediately after any sample that is measured for lipase. These observations point to which type of error?

Reagent carryover Carryover errors are usually attributed to interference caused by a sample with a very high concentration of analyte preceding a normal sample. However, reagent carryover may also occur on automated systems that use common reagent delivery lines or reusable cuvettes. In the case of lipase methods, triglycerides used in the reagent may coat the reagent lines or cuvettes interfering with the triglyceride measurements that directly follow.

SITUATION: A 6-year-old child being treated with phenytoin was recently placed on valproic acid for better control of seizures. After displaying signs of phenytoin toxicity including ataxia, a stat phenytoin is determined to be 15.0 mg/L (reference range 10-20 mg/L). A peak blood level drawn 5 hours after the last dose is 18.0 mg/L. The valproic acid measured at the same time is within therapeutic limits. Quality control is within acceptable limits for all tests, but the physician questions the accuracy of the results. What is the most appropriate next course of action?

Recommend measurement of free phenytoin using the last specimen Phenytoin levels must be monitored closely because toxic drug levels can occur unexpectedly due to changing pharmacokinetics. Phenytoin follows a nonlinear rate of elimination, which means that clearance decreases as blood levels increase. At high blood levels, saturation of the hepatic hydroxylating enzymes can occur, causing an abrupt increase in the blood level from a small increase in dose. The drug half-life estimated from the two drug levels is approximately 15 hours, which is within the range expected for children, so decreased clearance is not likely the problem. Valproic acid competes with phenytoin for binding sites on albumin. Free phenytoin is the physiologically active fraction and is normally very low, so small changes in protein binding can cause a large change in free drug. For example, a 5% fall in protein binding caused by valproic acid can increase the free phenytoin level by 50%. This patient's free phenytoin level should be measured, and the dose of phenytoin reduced to produce a free drug level that is within the therapeutic range.

SITUATION: The following lab results are reported. Which result is most likely to be erroneous? Arterial blood gases: pH = 7.42 pCO2 = 38.0 mm Hg pO2 = 90 mm Hg bicarbonate = 24 mmol/L Plasma electrolytes: Na = 135 mmol/L K = 4.6 mmol/L Cl = 98 mmol/L TCO2 = 33 mmol/L

TCO2 The pH, pCO2, and bicarbonate are normal, and therefore, agree. The electrolytes are normal also, but the TCO2 is increased significantly. The reference range for venous TCO2 is 22-28 mmol/L. Although TCO2 is the sum of bicarbonate and dissolved CO2, the venous TCO2 is determined almost entirely by the bicarbonate, since dCO2 is lost as CO2 gas when the venous blood is exposed to air during processing. A TCO2 value of 32 mmol/L would be expected in a person with metabolic alkalosis.

Quality control results for uric acid are as follows: Run 1 QC1: 3.5 mg/dL QC2: 6.8 mg/dL Run 2 QC1: 3.8 mg/dL QC2: 7.2 mg/dL Run 3 QC1: 4.1 mg/dL QC2: 7.4 mg/dL Run 4: QC1: 4.2 mg/dL QC2: 7.5 mg/dL Mean: QC1: 3.6 mg/dL QC2: 7.0 mg/dL s QC1: 0.40 QC2: 0.25 Results should be reported from:

Runs 1, 2, and 3 Although no single result exceeds the 2s limit, the 41s rule is broken on Run 4. This means that both QC1 and QC2 exceeded +1s on Run 3 and Run 4.

SITUATION: A plasma sample from a person in a coma as a result of an automobile accident gave the following results: Total CK 480 IU/L Myoglobin 800 μg/L CK-MB 8 μg/L Troponin I 0.02 μg/L What is the best interpretation of these results?

The accident caused traumatic injury, but no heart attack occurred The automobile accident caused both brain damage (coma) and muscle damage (myoglobin). The sandwich assay for MB uses antibodies to both the M and B subunits of CK-MB and therefore, is not subject to interference from CK-BB that could have resulted from brain injury. The CK relative index is 1.6, which is lower than would be expected if the CK-MB were derived from heart damage. Since the TnI is within normal limits, the slight increase in CK-MB is due to the gross release of CK from skeletal muscle.

SITUATION: Laboratory results on a patient from the emergency department are: glucose = 1,100 mg/dL Cl = 115 mmol/L Na = 155 mmol/L TCO2 = 3.0 mmol/L K = 1.2 mmol/L What is the most likely explanation of these results?

Sample drawn above an IV These results are consistent with dilution of venous blood by intravenous fluid containing 5% dextrose and normal saline. The intravenous fluid is free of potassium and bicarbonate, accounting for the low level of these electrolytes (incompatible with life).

SITUATION: A blood sample in a red-stoppered tube is delivered to the laboratory for electrolytes, calcium, and phosphorus. The tube is approximately half full and is accompanied by a purple-stoppered tube for a complete blood count that is approximately three-quarters full. The chemistry results are as follows: Na: 135 mmol/L K: 11.2 mmol/L Cl: 103 mmol/L HCO3: 14 mmol/L Ca: 2.6 mg/dL InP: 3.8 mg/dL What is the most likely explanation of these serum calcium results?

Some anticoagulated blood was added to the red-stoppered tube The potassium and the calcium results are above and below physiological limit values, respectively. Although hemolysis could explain the high potassium, hemolysis does not cause a significant change in serum calcium. The wrong order of draw could result in the falsely low calcium value but would not be sufficient to cause a result that is incompatible with life (and does not explain a grossly elevated potassium). The results and the condition of the tubes indicate that blood from a full tube collected in K3 EDTA was added to the clot tube, chelating the calcium and increasing the potassium.

A method calls for extracting an acidic drug from urine with an anion exchange column. The pKa of the drug is 6.5. Extraction is enhanced by adjusting the sample pH to:

8.5 Extraction of a negatively charged drug onto an anion exchange (positively charged) column is optimal when more than 99% of the drug is in the form of anion. The extraction pH should be 2 pH units above the pKa of an acidic drug. When pH = pKa the drug will be 50% ionized, and when pH is greater than pKa the majority of drug is anionic.

Which of the following procedures can be used to detect proportional error in a new method for glucose?

Add 5.0 mg of glucose to 1.0 mL of a serum of known concentration and measure Proportional error is percentage deviation from the expected result, and affects the slope of the calibration curve. It causes a greater absolute error (loss of accuracy) as concentration increases. It is measured by a recovery study in which a sample is spiked with known amounts of analyte. In the example, the concentration should increase by 500 mg/dL.

A biochemical profile routinely performed bimonthly on a renal dialysis patient showed a decreased serum calcium and decreased PTH level. Such a lab result may be explained by which of the following circumstances?

Aluminum toxicity Aluminum present in medications and dialysis bath fluid can cause aluminum toxicity in patients receiving dialysis. Renal failure patients often display high PTH levels owing to poor retention of calcium, and are at risk of developing osteitis fibrosa (soft bones) as a result. Excess aluminum causes osteomalacia by inhibiting release of parathyroid hormone. The finding of low PTH would not be expected with low serum calcium unless aluminum poisoning was present. Malignancy, hypervitaminosis D, and acidosis are associated with high serum calcium.

SITUATION: A digoxin result from a stable patient with a normal electrocardiogram (EKG) is reported as 7.4 ng/mL (URL 2.6 ng/mL) using an immunofluorescent method. Renal function tests were normal and the patient was not taking any other medications. The assay was repeated and results were the same. The sample was frozen and sent to a reference laboratory for confirmation. The result was 1.6 ng/mL measured by a competitive chemiluminescent procedure. Which best explains the discrepancy in results?

An interfering substance was present that cross-reacted with the antibody in the fluorescent immunoassay An error was suspected because there was a discrepancy between the test result and the patient's clinical status (i.e., signs of digoxin toxicity such as ventricular arrhythmia were not present.) Some substances called DLIFs (digoxin-like immunologic factors) can cross-react with antibodies used to measure digoxin. The extent of interference varies with the source of anti-digoxin used. In addition, falsely elevated digoxin results may result from accidental ingestion of plant poisons such as oleandrin and from administration of Digibind, a Fab fragment against digoxin that is used to reverse digoxin toxicity.

Which set of the following laboratory results is most likely from a patient who has suffered an AMI? Reference intervals are in parenthesis.

Answer is B Total CK (10-110 U/L): 170 U/L CK-MB (1-4 μg/L): 14 μg/L CK Index (1%-2.5%): 8.2% Results shown in C and D can be excluded because the CK-MB is not increased. Results shown in A and B have CK-MB levels above the URL. However, patient A has a CK index under 2.5% and a 5- to 10-fold elevation of total CK. These results indicate release of a small of amount of CK-MB from skeletal muscle rather than from cardiac muscle. To maximize the sensitivity of CK-MB, laboratories use an URL of 4 or 5 μg/L. This cutoff can detect about two-thirds of AMI cases within 3 hours of the infarct, but requires the use of a conservative CK index and other cardiac markers to avoid a high number of false positives.

A patient presents to the emergency department with symptoms of intoxication including impaired speech and movement. The plasma osmolality was measured and found to be 330 mOs/kg. The osmolal gap was 40 mOsm/Kg. A blood alcohol was measured by the alcohol dehydrogenase method and found to be 0.15% w/v (150 mg/dL). Electrolyte results showed an increased anion gap. Ethylene glycol intoxication was suspected because the osmolal gap was greater than could be explained by ethanol alone, but gas chromatography was not available. Which of the following would be abnormal if this suspicion proved correct?

Arterial blood gases Ethylene glycol is sometimes used as a substitute for ethanol by alcoholics. It is metabolized to formic acid and glycolic acid by the liver, resulting in metabolic acidosis and an increased anion gap. Lactic acid, glucose, and urinary ketones would be useful in ruling out other causes of metabolic acidosis, but would not be abnormal as a result of ethylene glycol intoxication.

SITUATION: A peak blood level for orally administered theophylline (therapeutic range 8-20 mg/L) measured at 8 a.m. is 5.0 mg/L. The preceding trough level was 4.6 mg/L. What is the most likely explanation of these results?

Blood for peak level was drawn too soon Sample collection time is critical for accurate therapeutic drug monitoring. Blood for trough levels must be collected immediately before the next dose. Blood collection time for peak levels must not occur prior to complete absorption and distribution of drug. This usually requires 1-2 hours for orally administered drugs. The therapeutic range for theophylline is 8-20 mg/L. These results are most consistent with a peak sample having been drawn prior to complete absorption of the drug.

SITUATION: A patient breathing room air has the following arterial blood gas and electrolyte results: pH = 7.54 HCO3 = 18 mmol/L Cl = 98 mmol/L PCO2 = 18.5 mm Hg Na = 135 mmol/L TCO2 = 20 mmol/L PO2 = 145 mm Hg K = 4.6 mmol/L The best explanation for these results is:

Blood gas sample was exposed to air A patient breathing room air cannot have an arterial PO2 greater than 105 mm Hg because alveolar PO2 is 110 mm Hg when breathing 20% O2. Exposure to air caused loss of CO2 gas and increased pH.

A quantitative urine glucose was determined to be 160 mg/dL by the Trinder glucose oxidase method. The sample was refrigerated overnight. The next day, the glucose is repeated and found to be 240 mg/dL using a polarographic method. What is the most likely cause of this discrepancy?

C Urine often contains high levels of ascorbate and other reducing substances. These may cause significant negative bias when measuring glucose using a peroxidase-coupled method. The reductants compete with chromogen for H2O2.

A stat plasma lithium determined using an ion-selective electrode is measured at 14.0 mmol/L. Select the most appropriate course of action.

Call for a new specimen Lithium in excess of 2.0 mmol/L is toxic (in some laboratories 1.5 mmol/L is the upper therapeutic limit). A level of 14 mmol/L would not occur unless the sample were contaminated with lithium. This would most likely result from collection in a green-stoppered tube containing the lithium salt of heparin.

SITUATION: A patient has the following electrolyte results: Na = 130 mmol/L Cl = 105 mmol/L K = 4.8 mmol/L TCO2 = 26 mmol/L Assuming acceptable QC, select the best course of action.

Check the albumin, total protein, Ca, P, and Mg results; if normal, repeat the sodium test The anion gap of this sample is <4 mmol/L. This may result from laboratory error, retention of an unmeasured cation (e.g., calcium), or low level of unmeasured anion such as phosphorus or albumin. The sodium is inappropriately low for the chloride and bicarbonate and should be repeated if no biochemical cause is apparent.

SITUATION: A 22S QC error occurs for serum calcium by atomic absorption. Fresh standards prepared in 5.0% w/v albumin are found to be linear, but repeating the controls with fresh material does not improve the QC results. Select the most likely cause of this problem.

Chemical interference caused incomplete atomization Poor recovery of calcium by atomic absorption is often caused by failure to break thermostable bonds between calcium and phosphate (a form of chemical interference). This may be caused by failure to add lanthanum to the diluent or by low atomizer temperature. The use of 5.0 % w/v albumin in the calibrator produces viscosity and protein-binding characteristics similar to plasma, helping to eliminate matrix interference.

Analysis of normal and abnormal QCs performed at the beginning of the evening shift revealed a 22s error across levels for triglyceride. Both controls were within the 3s limit. The controls were assayed again, and one control was within the acceptable range and the other was slightly above the 2s limit. No further action was taken and the patient results that were part of the run were reported. Which statement best describes this situation?

Corrective action should have been taken before the controls were repeated Quality control limits are chosen to achieve a low probability of false rejection. For example, a 22s error occurs only once in 1,600 occurrences by chance. Therefore, such an error can be assumed to be significant. However, this does not mean the error will occur if the controls are repeated again. The error detection rate (power function) of the 22s rule is only about 30% for a single run. This means that there is a greater chance the repeated controls will be within range than outside acceptable limits. Therefore, controls should never be repeated until the test system is evaluated for potential sources of error. Calibration should have been performed prior to repeating the controls, and patient samples should have been evaluated to determine the magnitude of the error before reporting.

The results shown in the table above are obtained from three consecutive serum samples using an automated random access analyzer that samples directly from a bar-coded tube. Calibration and QC performed at the start of the shift are within the acceptable range, and no error codes are reported by the analyzer for any tests on the three samples. Upon results verification, what is the most appropriate course of action?

D BUN is elevated 5- to 10-fold for three consecutive patients in the absence of any other laboratory evidence of renal disease. The glucose results show conclusively that the samples are not from the same patient. Therefore, the BUN results must be caused by a systematic error, and should not be reported. Further testing for BUN should cease until the analytical components of the BUN assay are completely evaluated and the cause of these results identified and corrected. This is demonstrated by successful recalibration and performance of controls within acceptable limits. Following this, the BUN assay should be repeated on the three samples along with all other specimens with a spurious BUN result that have occurred since the start of the shift.

Hemoglobin electrophoresis performed on agarose at pH 8.8 gives the following results: A2 position: 35% S position: 30% F position: 5% A position: 30% All components of the Hgb C, S, F, A control hemolysate were within the acceptable range. What is the most likely cause of this patient's result?

Hgb SC disease post-transfusion HemoglobinLepore results from a hybridization of the β and δ genes and produces a pattern that is similar to Hgb S trait (AS), except that the quantity of HgbLepore at the Hgb S position is below 20%. Hemoglobin S-β-thalassemia minor results in an increase in Hgb A2 (and possibly Hgb F) because there is reduced transcription of the structurally normal β chain. However, the Hgb S should be greater than the Hgb A, and the amount at the Hgb A2 is far too high. The concentration of Hgb at the A2 position is too high to result from contamination or to be considered as Hgb A2. This pattern appears to express two abnormal Hgbs (Hgb S and C) as well as the normal adult Hgb A. Because inheritance of two abnormal β genes prohibits formation of normal Hgb A, this pattern would occur only if the patient has been transfused with normal RBCs. Hemoglobin SC disease usually produces almost equal amounts of Hgb C and S (and usually a slight increase in Hgb F), and is the most likely cause of these results. This could be confirmed by acid agar electrophoresis or isofocusing to identify the abnormal Hgbs, and review of the patient's medical record for evidence of recent blood transfusion.

SITUATION: Results of an iron profile are: Serum Fe = 40 μg/dL TIBC = 400 μg/dL ferritin = 50 μg/L All of the following tests are useful in establishing a diagnosis of Fe deficiency except:

Hgb electrophoresis Electrophoresis may show an elevated β-globulin (transferrin) characteristic of iron deficiency, or inflammation that would help explain a normal ferritin. Zinc protoporphyrin is elevated in iron deficiency and in lead poisoning. Hemoglobinopathies and thalassemias are not associated with iron deficiency.

An AFP measured on a 30-year-old pregnant woman at approximately 12 weeks gestation is 2.5 multiples of the median (MOM). What course of action is most appropriate?

Repeat the serum AFP in 2 weeks The analytical sensitivity of immunochemical AFP tests is approximately 5 ng/mL. The maternal serum AFP at 12 weeks' gestation is barely above the analytical detection limit. Therefore, to achieve the needed sensitivity, the test should be repeated at 14 weeks. If the result is still equal to or greater than 2.5 MOM, then ultrasound should be performed to verify last menstrual period dating. AFP normally first becomes detectable in maternal serum at week 12 and increases by 15% per week through the 26th week. Levels of 2.5 MOM or greater are associated with spina bifida but also occur in ventral wall and abdominal wall defects, fetal death, Turner's syndrome, trisomy 13, congenital hypothyroidism, tyrosinemia, and several other fetal conditions. A positive serum test should always be repeated, and if positive again, followed by ultrasound. If ultrasound does not explain the elevation, amniotic fluid testing including AFP and acetylcholinesterase is usually recommended.

SITUATION: Results of biochemistry tests are: Na = 138 mmol/L Cl = 94 mmol/L glucose = 100 mg/dL BUN = 6.8 mg/dL albumin = 4.8 g/dL K = 4.2 mmol/L TCO2 = 20 mmol/L T bili = 1.2 mg/dL creat = 1.0 mg/dL T protein = 5.1 g/dL What should be done next?

Repeat the total protein All results are normal except total protein. The albumin level cannot be 94% of the total protein, and a random error in total protein measurement should be assumed.

SITUATION: A patient's biochemistry results are: ALT = 55 IU/L glucose = 87 mg/dL Na = 142 mmol/L Ca = 8.4 mg/dL AST = 165 IU/L LD = 340 IU/L K = 6.8 mmol/L Pi = 7.2 mg/dL Select the best course of action.

Report results along with an estimate of the degree of hemolysis Results indicate a moderately hemolyzed sample. Because sodium, calcium, and glucose are not significantly affected, results should be reported along with an estimate of visible hemolysis. The physician may reorder affected tests of interest.

SITUATION: An amylase result is 550 U/L. A 1:4 dilution of the specimen in NaCl gives 180 U/L (before mathematical correction for dilution). The dilution is repeated with the same results. The technologist should:

Report the amylase as 720 U/L A 1:4 dilution refers to 1 part serum and 3 parts diluent; the result is multiplied by 4 to determine the serum concentration. Serum may contain wheat germ gluten or other natural amylase inhibitors that, when diluted, result in increased enzyme activity. Serum for amylase should always be diluted with normal saline because chloride ions are needed for amylase activity.

Serum protein and immunofixation electrophoresis are ordered on a patient. The former is performed, but there is no evidence of a monoclonal protein. Select the best course of action.

Report the result; request a urine sample for protein electrophoresis An area of restricted mobility should be identified on serum protein electrophoresis before IFE is performed. About one out of four patients with multiple myeloma have monoclonal free λ or κ chains in urine only, and therefore, urine electrophoresis should be included in initial testing.

A lipemic sample gives a sodium of 130 mmol/L on an analyzer that uses a 1:50 dilution of serum or plasma before introducing it to the ion selective electrodes. The same sample gives a sodium of 142 mmol/L using a direct (undiluted) ion selective electrode. Assuming acceptable quality control, which of the following is the most appropriate course of action?

Report the undiluted ion selective electrode result Lipemic samples give lower results for sodium (pseudohyponatremia) when diluted prior to measurement because the H2O phase is mostly diluent and a significant component of the sample volume is displaced by lipid. Direct ISEs measure sodium in the plasma water, more accurately reflecting patient status.

A technologist is asked to use the serum from a clot tube left over from a chemistry profile run at 8 a.m. for a stat ionized calcium (Cai) at 11 a.m. The technologist should:

Request a new sample Cai is pH dependent. Heparinized blood is preferred because it can be assayed immediately. Serum may be used, but the specimen must remain tightly capped while clotting and centrifuging, and analyzed as soon as possible.

SITUATION: A patient who has a positive urinalysis for glucose and ketones has a glycated Hgb of 4.0%. A fasting glucose performed the previous day was 180 mg/dL. Assuming acceptable QC, you would:

Request a new specimen and repeat the glycosylated Hgb The glycated Hgb is at the lowest normal limit (4%-5.5%), but the fasting glucose indicates frank diabetes mellitus. Although the glycosylated Hgb reflects the average blood glucose 2-3 months earlier, the value reported is inconsistent with the other laboratory results. A high probability of sample misidentification or analytical error necessitates that the test be repeated.

SITUATION: A patient previously diagnosed with primary hypothyroidism and started on thyroxine replacement therapy is seen for follow-up testing after 2 weeks. The serum-free T4 is normal but the TSH is still elevated. What is the most likely explanation for these results?

Results are consistent with a euthyroid patient in the early phase of therapy Results of thyroid tests (especially in hospitalized patients) may sometimes appear discrepant because medications and nonthyroid illnesses can affect test results. The pituitary is slow to respond to thyroxine replacement, and 6-8 weeks are usually required before TSH levels fall back to normal. In the early stage of therapy, the patient should be monitored by the free T4 result. This patient's free T4 is normal, indicating that replacement therapy is adequate. The high TSH sometimes seen in treated patients is called pituitary lag.

The following chart compares the monthly total bilirubin mean of Laboratory A to the monthly mean of Laboratory B, which uses the same control materials, analyzer, and method. Level 1 Control Mean: Lab A: 1.1 mg/dL Lab B: 1.4 mg/dL CV Lab A: 2.1% Lab B: 2.2% Level 2 Control Mean: Lab A: 6.7 mg/dL Lab B: 7.0 mg/dL CV Lab A: 3.2% Lab B: 3.6% Both laboratories performed controls at the beginning of each shift using commercially prepared liquid QC serum stored at -20°C. Which of the following conditions would explain these differences?

The laboratories used a different source of bilirubin calibrator Interlaboratory variation in bilirubin results is often caused by differences in the assigned value of the calibrator used. Bilirubin calibrators are either serum-based material that have been reference assayed or unconjugated bilirubin stabilized by addition of alkali and albumin. Calibrator differences result in bias and should be suspected when the laboratory's mean differs significantly from the peer group's mean. The bias in this example is due to constant rather than proportional error. When bilirubin calibrator error is suspected, the molar absorptivity of the calibrator should be measured and the bilirubin concentration calculated. Photodegradation generally results in a greater loss of bilirubin at higher concentration and also contributes to random error.

SITUATION: Biochemistry tests are performed 24 hours apart on a patient and delta-check flag is reported for inorganic phosphorus by the laboratory information system. Given the results shown in the table above, identify the most likely cause.

The patient was not fasting when the sample was collected on day 2 The delta check compares the difference of the patient's two most recent laboratory results within a 3-day period to a delta limit usually determined as a percentage difference. The purpose of the delta check is to detect sample identification errors. A delta-check flag can also be caused by random analytical errors and interfering substances such as hemolysis, icterus, and lipemia, and by metabolic changes associated with disease or treatment. Therefore, results should be carefully considered before determining the cause. In this case, hemolysis and icterus can be ruled out because enzymes sensitive to hemolysis interference (AST, ALT, and LD) and bilirubin are within normal limits. Tests showing a significant difference are inorganic phosphorus, ALP, triglycerides, and glucose. These four tests are elevated by diet (the ALP from postprandial secretion of intestinal ALP). All other tests show a high level of agreement between days, and the differences are attributable to normal physiological and analytical variation.

The following results are reported on an adult male patient being evaluated for chest pain: Admission Myoglobin (Cutoff = 100 μg/L): 12 μg/L Troponin I (Cutoff = 0.03 μg/L): 1.1 μg/L CK-MB (Cutoff = 4 μg/L): 18 μg/L 3 hours post admission Myoglobin (Cutoff = 100 μg/L): 360 μg/L Troponin I (Cutoff = 0.03 μg/L): 1.8 μg/L CK-MB (Cutoff = 4 μg/L): 26 μg/L 6 hours post admission Myoglobin (Cutoff = 100 μg/L): 300 μg/L Troponin I (Cutoff = 0.03 μg/L): 2.4 μg/L CK-MB (Cutoff = 4 μg/L): 40 μg/L What is the most likely cause of these results?

The wrong sample was assayed for the first myoglobin Myoglobin is the first cardiac marker to rise outside the URL following an MI (2-3 hours) followed by TnI (4-6 hours) and CK-MB (4-8 hours). The admission TnI and CK-MB are both elevated, and they continue to rise in all three samples. Because TnI and CK-MB peak before 24 hours post-AMI, the infarction likely occurred within the last 12-24 hours. The myoglobin can remain elevated for up to 36 hours post-AMI and should have been elevated in the admission sample.

Which of two instruments can be assumed to have the narrower bandpass? Assume that wavelength is accurately calibrated.

Thee instrument giving the highest absorbance for a solution of 0.1 mmol/L NADH at 340 nm Bandpass is defined by the range of wavelengths passed through the sample at the specified wavelength setting. It can be measured using any solution having a narrow absorbance peak (e.g., NADH at 340 nm). The instrument producing the purest monochromatic light will have the highest absorbance reading.

Two consecutive serum samples give the results shown in the table above (at the top of this page) for a metabolic function profile. The instrument is a random access analyzer that uses two sample probes. The first probe aspirates a variable amount of serum for the spectrophotometric chemistry tests, and the second probe makes a 1:50 dilution of serum for electrolyte measurements. What is the most likely cause of these results?

There is a fibrin strand in the probe used for the spectrophotometric chemistry tests Electrolyte results for both patients are within the physiological range but are distinctly different. The first results indicate a high potassium and increased anion gap, and one would expect the BUN, uric acid, and creatinine to be elevated. However, the results for BUN and glucose are unlikely for any patient, and the creatinine and uric acid signals are below the detection limit of the analyzer, indicating that little or no sample was added. This could be caused by a partially obstructed sample probe, or insufficient sample volume. The results for the second sample are below detection limits for all spectrophotometric tests, which may be the result of complete probe obstruction or the inability to generate a detectable signal with the trace quantity of serum that was added. Because all of the low or undetectable signals are for tests sampled by the first probe, the only explanation is that the probe is obstructed or malfunctioning.


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