Clinical Chemistry, Immunology and Laboratory Quality Control

480 Index




Quality control Renal excretion, 254 abnormal patterns in, 397t
Brand-Altman plot, 60 Renal tubular acidosis (RTA), 76 albumin band, 393
delta checks, 56 58 Renin, 70, 198 alpha zone, 393
external, 53 54 Renin-Angiotensin-Aldosterone beta zone, 393 394
internal, 53 system, 70 71, 198 common features of, 396
Levey2Jennings chart, 55 56, 55f, Reports gamma zone, 394
57f clinician, 35 immunofixation studies, 396
linear regression equation, LIS, 35 monoclonal band, identification
interpretations of, 59 60 Respiratory acidosis, 79, 81 of, 394 395
materials, 52 causes of, 81 problems associated with
method validation/evaluation, Respiratory alkalosis, 79, 81 interpretation of, 395 396,
58 59 causes of, 81 395b
implementation steps, 58 59 Respiratory compensation, 78 serum protein components,
receiver2operator curve, 60 61, Retention time, 10 12 392 393
61f principles of, 11 12 Serum separator gel tubes (SSTs)
and reference ranges errors, 61, 62t Reverse-phase chromatography, 10 and therapeutic drug monitoring
six sigma, 61 Reyes’s syndrome, 188, 338 results, 277
t-test, 63 Rheumatoid factors, 28 29 Severe combined immunodeficiency
types of, 52. see also specific types Ribavirin, 122 123 (SCID), 432
Westgard rules, 56, 56t Ribose, 107 Sex hormone-binding globulin
Quantitative plasma amino acid Ritonavir, 270 (SHBG), 145
profile, 225 Rohypnol, 309 310 Sheehan’s syndrome, 150
Quetiapine, 283 Rotor’s syndrome, 184 Short bowl syndrome, 324b
Quinidine, 259, 265 RTA (renal tubular acidosis), 76 Short-chain acetyl CoA
Rufinamide, 264 dehydrogenase deficiency
R (SCAD), 220
Raltegravir, 270 S SIADH (syndrome of inappropriate
Random access analyzers, 14 15 Saccharides, 107 108. see also antidiuretic hormone
Random errors, 51 52 Carbohydrates secretion), 72
Rapid HIV antibody tests, 411 412 Saline suppression test, 162 causes of, 76t
Rave party drugs, 309 311, 310t SAMHSA drugs, 291 292 clinical features of, 72
Reactive hypoglycemia, 117 119, Saquinavir, 270 and plasma osmolality, 72
119t SCAD (short-chain acetyl CoA Sick cell syndrome, 74
Reaven, Gerald, 112 113 dehydrogenase deficiency), 220 Sickle cell disease, 370 372
Receiver2operator curve (ROC), Schwartz-Bartter syndrome. diagnostic tips for, 379 385, 382t
60 61, 61f see Syndrome of inappropriate features of, 372t
Receptors antidiuretic hormone symptoms of, 370 371
for hormones, 145 146 secretion (SIADH) Sickling disorders, 365
polymorphism of, 355 356 Schwartz formula, 201 Silent carriers, 366 367
Red man/neck syndrome, 269 SD (standard deviation), 47 Simmonds’ disease, 150
Reference range, 49 50, 262t Secondary hyperlipidemia, 95 Simvastatin, 101, 259
errors associated with, 61, 62t Secondary hypothyroidism, 154 Single nucleotide polymorphisms
Refractive index detection, 10 Selective glomerular proteinuria, 398 (SNPs), 353
Regression equation. see Linear Sensitivity, clinical, 50 51 Sirolimus, 267 268, 283 284
regression equation Serum bilirubin, 182 183 Six sigma, 61
Regulatory function, kidneys, 197 Serum immunofixation, 391 Smoke inhalation case study, 340b
Remifentanil, 314 Serum protein electrophoresis Smoking, and drug disposition,
Renal disorders, 207t (SPEP), 391 396 259 260

Index 481




SNPs (single nucleotide Steroids, 85 features of, 370t
polymorphisms), 353 Stiripentol, 264 delta, 369 370
Sodium, 67 Storage diagnostic tips for, 379 385, 381t
fractional excretion of, 202 of blood specimens, 35 The Joint Commission (TJC), 38 39
intake by adults, 68 of urine specimens, 42 T helper-mediated activation of
Sodium bicarbonate, 269 Stress, and hormones levels, macrophages, 432 433
Somatostatin, 109, 147 148 146 147 Theophylline
Somatostatinomas, 165 Succinylcholine, 251 252 metabolism, 257
Sorbitol, 115 Sucrose, 107 therapeutic drug monitoring, 266
Specificity, clinical, 50 51 Sufentanil, 314 Therapeutic drug monitoring
Specimens Sulfation, 252 of aminoglycoside antibiotics, 269
blood Sunshine vitamin. see Vitamin D of anti-asthmatic drugs, 266
collection, errors of, 40 41 Syndrome of inappropriate antibiotics, 268 269
handling, 35 antidiuretic hormone anticonvulsants, 260 264
identification, 38 39 secretion (SIADH), 72 of antidepressants, 266 267
labeling, 35 causes of, 76t of antineoplastic drugs, 269 270
non-barcoded, 39 clinical features of, 72 of antiretrovirals, 270
order of draw, 37 38 and plasma osmolality, 72 benefits, 250 251
storage of, 35 Syndrome X. see Metabolic syndrome cardioactive drugs, 264 266
for blood gas determinations, Synthetic marijuana, 313 314 current state, highlights of, 249
43 44 Systematic errors, 51 52 defined, 249
coefficient of variation, 47 48 Systematic lupus erythematosus drugs require, 250
mean value of, 47 (SLE), 438 endogenous factors and, 276 277
standard deviation, 47 free vs. total, 250
transportation, issues with, 42 43 T Gas Chromatography Combined
urine Tacrine, 259 260 with Mass Spectrometry (GC/
issues associated with, 42 Tacrolimus, 259, 267 268, MS), 275
Spectrophotometric detections, 1 3, 2t 283 284 Gas Chromatography (GC) with
atomic absorption, 3 5 Tamm Horsfall protein, 397 Flame Ionization or Nitrogen
colorimetry, 1 2 Tamoxifen, 357 Detection and, 275
enzymatic assays, 5 6 Tangier disease, 96 goal of, 249
immunoassays, 6 Tau protein, 402 immunoassays and, 275 276
nephelometry, 6 Tay 2 Sachs disease, 222 223 of immunosuppressants, 267 268
transmittance in, 2 3 TBG (thyroxine-binding globulin), interferences
turbidimetry, 6 145 digoxin immunoassays,
Sphingolipids, 85 86 TCAs (tricyclic antidepressants), 277 280, 278t
Spice. see Synthetic marijuana 266 267 issues of, 275 276
Spironolactone, 280 T cells, 428 429 of levetiracetam, 264
St. John’s wort, 454 457 defects, 432 of lidocaine, 265
9
pharmacokinetic interaction of, TCH (Δ -Tetrahydrocannabinol), methods, 275 276
455, 456t 294 of pregabalin, 264
Standard deviation (SD), 47 Tests. see Laboratory test results, interpretation of, 261t
Standard error of mean, 48 Thalassemia, 365 results, serum separator gel tubes
Statins, 101 alpha, 365 368 and, 277
Statistics, laboratory. see Laboratory categories, 366 Thin-layer chromatography (TLC), 8
statistics beta, 365 366, 368 369, Thiocarbamate, 343 344
Stercobilinogen, 178 179 380 381, 381t Thioguanine, 356
Steroid hormones, 158 160, 159f categories, 369 Thiopurine, 356

482 Index




Thiopurine S-methyltransferase Transaminases, 179 180 Tubular proteinuria, 206
(TPMT), 355 356 Transferrin, 393 394 Tumor markers. see also specific
Thrombocytopenia, 433 Transient hypothyroidism, 154 155 markers
Thyroid-binding globulin, 393 Transient ischemic heart attack, 37b alpha-fetoprotein, 236 237
Thyroid disease, and drug Transient monoclonal gammopathy, beta-2-microglobulin (β 2 -
metabolism, 258 391 392 microglobulin), 240 241
Thyroid function test, 152 154, 152t Transmittance, 2 3 CA-19-9, 239 240
TSH as, 152 154, 152t Transplant rejection, 436 437 elevation, degree of, 239 240
Thyroid gland, 151 152 Transportation, specimens false positive test results, 240
and hypothyroidism, 154 155 issues associated with, 42 43 levels, serial monitoring of, 240
Thyroid hormone, secretion of, 146 Transporter proteins cancer antigen 125, 235 236
Thyroiditis, 156 polymorphism of, 355 356 concentrations, 236
postpartum, 156 Transrectal ultrasound (TRUS), 233 false positive, 236
Thyroid peroxidase antibody Trastuzumab, 230 231 carcinoembryonic antigen,
(TPOAb), 153 Trazodone, 296 238 239
Thyroid-stimulating hormone (TSH), TRH (thyrotropin-releasing commonly used, 231t
29, 145 146, 154 155 hormone), 145 148, human chorionic gonadotropin,
and hyperthyroidism, 156 151 152 241 242
as thyroid function test, 152 154, Tricyclic antidepressants (TCAs), beta, 241
152t 266 267 false positive test results,
Thyroid storm, 156 analysis, interferences in, 242 243
Thyrotoxicosis. see Hyperthyroidism 282 283, 282t laboratory tests for, 241
Thyrotropin-releasing hormone chromatogram of, 10 12, 11f low level of, causes and
(TRH), 145 148, 151 152 manifestations of, 342 evaluation of, 242 243
Thyroxine (T4), 151 overdose with, 341 342, 342t phantom, 242 243
free, 153 mortality from, 342 pituitary, 242 243
Thyroxine-binding globulin (TBG), Triglycerides, 5 6, 85, 88 level of, 230 231
145 hepatic lipase and, 177 178 elevation, causes of, 231t
Tiagabine, 264 high, and risk of cardiovascular overview, 229
TLC (thin-layer chromatography), 8 disease, 92 prostate-specific antigen, 232 234
Tobramycin, 268 269 Triiodothyronine (T3), 151 active, 232
Tocainide, 265 266 free, 153 complexed, 232
Toll-like receptors, 427 428 reverse analysis, 153 free, 232
Topiramate, 264 Trimipramine, 266 267 as proPSA, 234
Total bilirubin, 190 191 Tripeptide, 151 152 purposes of, 229 230
Total cholesterol-to-HDL cholesterol Troponin I, 29 30, 134 136 uses of, 229 231
ratio, 94 CK-MB isoenzyme vs., 134 135 Turbidimetry, 6
Total drug monitoring, free drug elevation of, 135 Type 1 diabetes mellitus, 110 112,
monitoring vs., 250 high-sensitive assays, 137 115b
Total parenteral nutrition (TPN), 216 Troponin T, 134 136 environmental factors and,
Total protein/creatinine ratio, 206 CK-MB isoenzyme vs., 134 135 111 112
Toxic adenoma, 156 TRUS (transrectal ultrasound), 233 features of, 113t
Toxic nodular goiter, 156 TSH (thyroid-stimulating hormone), genetic susceptibility and,
ToxiLab technique, 8 29, 145 146 111 112
TPOAb (thyroid peroxidase and hyperthyroidism, 156 Type 2 diabetes mellitus, 110, 112
antibody), 153 as thyroid function test, 152 154, features of, 113t
Trace Element Blood Collection 152t and ketoacidosis, 112
Tubes, 38 T-test, 63 Tyrosinemia, 189 190

Index 483




U Urine specimens Warfarin, 259 260
adulterated, in workplace drug pharmacogenomics and, 356
UDP-glucuronosyltransferase
testing, 302 303 Warfarin herb interactions, 454 457
(UGT1A1), 182 183,
issues associated with, 42 Water
189 190, 357
storage of, 42 balance, hormones in, 69 70
UDP-glucuronyl transferase (uridine-
Urobilinogen, 178 179 distribution in human body, 67 68
5-phosphate glucuronyl
UV (ultraviolet) detection, 8 Water deprivation test, 72
transferase), 253 254
Watery diarrhea, 165
UGT1A1 gene, and Gilbert’s
syndrome, 182 183 V Westgard rules, 56, 56t
Ultracentrifugation, 86 87 Valinomycin, 7 WHO (World Health Organization)
Ultra-Rapid Metabolizers (UM), 354 Valproic acid, 260 261 on cardiovascular diseases, 90 91
Ultraviolet-visible (UV-Vis) Vancomycin, 206, 249, 269 Whole blood alcohol, 323 325
spectrophotometry, 10 Variance, 47 Wilcoxon rank sum test, 63
UM (Ultra-Rapid Metabolizers), 354 Vasoactive intestinal polypeptides Wilson’s Disease, 348
Un-assayed control, 52 (VIP), 165 Wilson’s disease, 186
Unconjugated bilirubin, 178 179 Vasoconstriction, 69 70 Window period in HIV infection,
United States Vasopressin, 148. see also Antidiuretic 407 409
abused drugs in, 275 276, 278t hormone (ADH) Winters formula, 80, 82
Urea, 203 205 Verapamil, 265 266 Wiskott Aldrich Syndrome (WAS),
measurement of, 208 Verner 2 Morrison syndrome, 165 432 433
Urea cycle disorders, 218 219 Very-long-chain acetyl-CoA Wiskott Aldrich Syndrome Protein
Uremia, drug metabolism/ dehydrogenase deficiency (WASP), 432 433
disposition in, 256 (VLCAD), 220 Within-run assay precision, 58
Uric acid, 203 205 Very low density lipoprotein (VLDL), Workplace drug testing
measurement of, 208 86 88, 177 178 adulterated urine specimens in,
Uridine-5-phosphate glucuronyl characteristics of, 87t 302 303
transferase (UDP-glucuronyl Vigabatrin, 264 medical drug testing vs., 290 291
transferase), 253 254 VIP (vasoactive intestinal World Health Organization (WHO)
Urinalysis, 42, 208 209 polypeptides), 165 on cardiovascular diseases, 90 91
Urinary protein, 397 VIPomas, 165
Urine Vitamin B 12 , 219 220 X
alcohol determination in, Vitamin D Xanthine, 204 205
326 327 deficiency, 198 X1c, 363 364
drug testing, 292 293 primary source of, 157 158 X-linked disorder, 218 219
galactose in, 122 Vitamin K epoxide reductase X-linked lymphoproliferative disease,
glucose monitoring in, 122 complex (VKORC1), 356 433
protein in, 205 206 VKORC1 (vitamin K epoxide
Urine dipstick analysis, 208 209 reductase complex), 356 Z
Urine electrophoresis, 391 VLCAD (very-long-chain acetyl-CoA Zellweger syndrome, 221
Urine immunofixation studies, dehydrogenase deficiency), 220 Zidovudine, 270
391 392, 399 400 VLDL. see Very low density Zimmerman correction, 4
Urine osmolality, 68 69 lipoprotein (VLDL) Zinc protoporphyrin (ZPP), 345
and cranial diabetes insipidus, 72 Von Gierke’s disease, 217 218 Zollinger 2 Ellison syndrome, 165
Urine protein electrophoresis, Zona fasciculata, 158 160
397 398 W Zona glomerulosa, 158 160
glomerular filtration process in, 397 Waived tests, 53 Zona reticularis, 158 160
24-hour urine analysis, 397 Waldenström’s macroglobulinemia, Zonisamide, 264
of proteinuria, 397 398 396 ZPP (zinc protoporphyrin), 345

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Scenario 2



Antigen Labelled antigen Antibody
FIGURE 2.1
Competitive immunoassay. (Courtesy of Stephen R. Master, MD, PhD, Perelman School of Medicine, University of Pennsylvania)








Second antibody attached to
an enzyme to generate signal



Capture (first) antibody

Solid support for first antibody

Antigen
FIGURE 2.2
Sandwich immunoassay. (Courtesy of Stephen R. Master, MD, PhD, Perelman School of Medicine, University of Pennsylvania)

Myoglobin
and CK isoforms
50 (large MI)
Troponin
Multiples of the upper limit of normal 20 5 CKMB




10



Troponin

th
0 2 1 (small MI) 10% CV/99 percentile
0 1 2 3 4 5 6 7 8 9
Days after onset of AMI
FIGURE 8.1
Timing of release of various cardiac biomarkers after myocardial injury. r American Heart Association. Reprinted with permission.[3]










LH




Progesterone
Titer Estradiol



FSH





Day 1 Day 14 Day 28
Menstruation Follicular phase Ovulation Luteal phase Menstruation
FIGURE 9.1
Titers of various hormones during menstrual cycle. (Courtesy of Andres Quesda, M.D, Department of Pathology and Laboratory
medicine, University of Teaxs-Houston Medical School.)

Alkaline Gel: Band in C Lane


Acid Gel: Band in C Lane Band in A Lane Band between A and S land


Prominent peak
at appx. 4.9 min Peak at appx. 3.7 Prominent peak
HPLC: with a small peak min (A2 window), between 4.5 and
just before main greater than 10% 5 min
peak (Hgb C1d)


Capillary Peak in Zone 2 Peak in Zone 4 Peak in Zone 3
Electrophoresis:



Hgb C Hgb E Hgb O (Arab)
FIGURE 21.1
Interpretation of hemoglobinopathy when a band is present in the C lane in the alkaline gel. (Courtesy of Andres Quesda, M.D,
Department of Pathology and Laboratory Medicine, University of Texas, Houston Medical School.)




Alkaline Gel: Band in C Lane



Band in S Band in A Band in A Band in A
Acid Gel:
Lane Lane Lane Lane

Peak at Peak at appx.
appx. 3.9 to 3.7min. In
Prominent Peak at appx. 4.2min with Hgb Lepore
HPLC: peak at appx. 3.9 to 4.2min second trait, the
4.5min small neak amount of
at 4.5 to 4.7 Lepore is 5–
min (G2) 15%

Capillary Peak in Zone 5 Peak in Zone 6 Peak in Zone 6 Peak in Zone 6
Electrophoresis:



Hgb S Hgb D Hgb G Hgb Lepore
FIGURE 21.2
Interpretation of hemoglobinopathy when a band is present in the E lane in the alkaline gel. (Courtesy of Andres Quesda, M.D,
Department of Pathology and Laboratory Medicine, University of Texas, Houston Medical School.)

Virological and serological response to acute HBV infection with recovery

HBV DNA


HBsAg

Total anti-HBc
Titer HBeAg IgM anti-HBc Anti-HBe

Anti-HBs








0 4 8 12 16 20 24 28 32 36 52 100
Weeks after exposure
FIGURE 23.1
Virological and serological response to acute hepatitis B infection with recovery. (Courtesy of Andres Quesda, M.D, Department of
Pathology and Laboratory Medicine, University of Texas, Houston Medical School.)