Urinalysis and Drug Testing Notes
Urinalysis and Drug Testing
Urinalysis
Frequently performed screening test for:
Metabolic disorders
Kidney disorders
UTIs
Many tests based on a single collection, some require collection over time.
Dipstick reagent strip:
Commonly used for chemical evaluation of urine
Microscopic evaluation:
Yields additional data.
Dipstick Testing
Specific Gravity
Measure of dissolved substances in urine.
Expression of concentration.
Color
Not explicitly detailed, but assumed to be a visual assessment.
Clarity
Measures scattered light passing through sample.
Reported as: clear, turbid, or extremely turbid.
pH
Freshly voided urine pH: 5.0–6.0
Glucose
Usually indicative of hyperglycemia due to diabetes.
Also renal tubular dysfunction and pregnancy (increased glomerular filtration).
Protein
Mostly indicative of renal disease.
Strip primarily sensitive to albumin.
Bilirubin
Can be a sign of liver disease, or extrahepatic/intrahepatic biliary obstruction.
Urobilinogen
Increased amounts appear in hemolytic anemias and liver dysfunction.
Blood
Trauma, irritation, very dilute/alkaline urine can lyse cells.
Equally specific for RBCs, Hgb, or myoglobin present.
Blood on dipstick, no RBCs on microscopy?
Hemoglobinuria: lysis of RBCs in the urinary tract, intravascular hemolysis, or transfusion reactions; check bilirubin.
Myoglobinuria: muscular destruction from hypothermia, convulsions, or extensive exertions; check creatine kinase.
Ketones
Ketonuria appears when there is increased use of fat instead of carbohydrate for metabolism.
Observed in DM, vomiting, and inadequate intake of carbohydrates.
Nitrite
Suggests bacteriuria caused by nitrate-reducing bacteria.
Leukocytes
Indicator of inflammation.
Detects lysed and intact WBCs.
Dipstick Testing - Reference Ranges
Specific gravity: 1.005-1.030
pH: 4.6-8.0
Protein: Negative
Glucose: Negative
Ketone: Negative
Bilirubin: Negative
Occult blood: Negative
Nitrite: Negative
Urobilinogen: Normal
Leukocyte esterase: Negative
WBC: 0-2/HPF
RBC: 0-2/HPF
Hyaline casts: 0-2/LPF
Bacteria: None
Dipstick Testing - Causes of False Results
Specific Gravity
False-positive causes: High protein concentrations (100-500 mg/dL), presence of keto acids.
False-negative causes: >1 g/dL glucose and urea concentrations.
pH
False-positive causes: No interferences known.
False-negative causes: Ascorbic acid, high specific gravity, captopril.
Blood
False-positive causes: Menstrual contamination, microbial peroxidases, strong oxidizing agents (soap, detergents).
False-negative causes: High specific gravity, increased glucose/protein, strong oxidizing agents, drugs (gentamicin, cephalosporins), presence of lymphocytes.
Leukocyte Esterase
False-positive causes: Dehydration, exercise.
False-negative causes: Ascorbic acid, various factors that inhibit nitrite formation despite bacteriuria.
Nitrite
False-positive causes: Highly colored substances mask results, beets, drugs (phenazopyridine), vaginal contamination of urine, improper storage with bacterial proliferation, exposure of dipstick to air.
False-negative causes: Highly colored substances mask results, beet ingestion, drugs (phenazopyridine), alkaline urine/drugs, improperly preserved specimen, contamination with quaternary ammonium compounds.
Protein
False-negative causes: Presence of protein other than albumin.
Glucose
False-negative causes: Ascorbic acid, improperly stored specimens (glycolysis).
Ketones
False-negative causes: Improper storage, resulting in volatilization, bacterial breakdown.
Bilirubin
False-negative causes: Ascorbic acid, high nitrite concentrations, improper storage resulting in oxidation/hydrolysis to nonreactive biliverdin and free bilirubin, light exposure, chlorpromazine (Thorazine), selenium.
Urobilinogen
False-negative causes: Formalin, improper storage resulting in oxidation to urobilin. Atypical colors caused by sulfonamides, p-aminobenzoic acid, p-aminosalicylic acid, substances that induce color mask results, beet ingestion, elevated nitrite levels.
Microscopic Urinalysis
Further identifies:
Cells
Organisms
Casts
Crystals
Leukocytes / WBCs
Men < 2 WBCs / high power field (HPF); women < 5 WBCs / HPF
Erythrocytes / RBCs
Can be seen in trauma (including urinary stone disease).
Heavy exercise (usually weight-bearing); should clear within 72 hours.
Dysmorphic erythrocytes: odd shapes due to passage through abnormal glomerulus, suggest glomerular disease.
Epithelial Cells
Squamous epithelial cells suggest contamination.
Organisms
Bacteria
Fungi
Yeast
Trichomonas
Casts
May be used to localize disease to a specific location in the genitourinary tract.
Particles formed from trapped contents of parts of kidney.
Cylindrical shape reflects the tubule in which they were formed and is retained when the casts are washed away.
Predominant cellular elements determine the type of cast.
Urinary Casts & Associated Pathology
Hyaline:
Composition: Mucoproteins
Associated Conditions: May be a normal finding
Erythrocyte:
Composition: Red blood cells
Associated Conditions: Glomerulonephritis, may be a normal finding in patients who play contact sports
Leukocyte:
Composition: White blood cells
Associated Conditions: Pyelonephritis, glomerulonephritis, interstitial nephritis, renal inflammatory processes
Epithelial:
Composition: Renal tubule cells
Associated Conditions: Acute tubular necrosis, interstitial nephritis, eclampsia, nephritic syndrome, allograft rejection, heavy metal ingestion, renal disease
Granular:
Composition: Various cell types
Associated Conditions: Advanced renal disease
Waxy:
Composition: Various cell types
Associated Conditions: Advanced renal disease
Lipid-laden renal tubule cells:
Composition: Fatty
Associated Conditions: Nephrotic syndrome, renal disease, hypothyroidism
Broad:
Composition: Various cell types
Associated Conditions: End-stage renal disease
Urine Drug Screen
Usually conducted on urine, provides presumptive results.
High sensitivity; limitations due to moderate specificity.
Many commercially available tests cross-react with multiple drugs within a class due to the choice of target drug.
Clinicians must be aware of the commercial tests utilized in their laboratory, as cross-reactivities differ between manufacturers and within manufacturers over time.
Cutoff concentrations historically decided w/ reference to federally mandated cutoffs for federal workplace drug testing.
Cutoff concentrations are not generally appropriate for clinical use, since the cutoff values for several drug/drug classes such as opioids are high.
Decreases the likelihood of false-positive results.
Detection of drug abuse rather than legitimate drug use is targeted in this application.
Urine Drug Screen - Detection Times for Various Drugs
Heroin (as morphine): 1-2 days
Cocaine (as metabolites): 3 days
Morphine: 1-2 days
Amphetamine: 1-3 days
3,4-Methylenedioxymethamphetamine (MDMA): 1-2 days
Methadone (as metabolites): 3-7 days
Volatiles: <1 day
Oxycodone: 1-2 days
Gamma-hydroxybutyrate (GHB): 12-24 hours
Phencyclidine (PCP): 1-2 weeks
11-Nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THCA) (marijuana metabolite) (single use): 2-7 days
Barbiturates:
All except phenobarbital: 2 days
Phenobarbital: 1-2 weeks
Benzodiazepines:
All except flunitrazepam: 5-7 days
Flunitrazepam (as metabolites): <3 days
Alcohol metabolites (ethyl glucuronide/ethyl sulfate): Up to 80 hours
Buprenorphine: 1-3 days
Fentanyl: 1-2 days
Zolpidem: 1-3 days
Urine Drug Screen - False Positives
Multiple substances can cause false positives on a urine drug screen:
Foods
OTC Meds
Prescription Meds
Amphetamines
Amantadine (Symmetrel) [Parkinson's dz]
Bupropion (Wellbutrin, Zyban) [Antidepressant; Smoking cessation]
Dextroamphetamine (Dexedrine) [ADHD: Stimulant]
Ephedrine (Ephedra, Ma Huang) [Stimulant]
Labetalol (Trandate) [Hypertension]
Mexiletine [Anti-arrhythmic]
Procainamide [Anti-arrhythmic]
Phentermine (Adipex, Suprenza) [Obesity]
Promethazine (Phenergan) [Nausea]
Propranolol (Inderal) [HTN; Migraines; Anti-arrhythmic; Essential tremor; Stage fright]
Pseudoephedrine (Sudafed) [Nasal decongestant
Ranitidine (Zantac) [GERD; Peptic ulcers]
Selegiline (Zelapar, Eldepryl) [Parkinson's disease]
Trazodone (Desyrel) [Antidepressant; Insomnia; Migraines]
Vick's inhaler
Barbiturates
Ibuprofen, Naproxen [Anti-inflammatories]
Phenytoin (Dilantin) [Seizures]
Primidone (Mysoline) [Seizures]
Benzodiazepines
Chlorpromazine (Thorazine) [Antipsychotic]
Clomipramine (Anafranil) [Antidepressant]
Diphenhydramine (Benadryl) [Antihistamine]
Doxylamine (Unisom) [Insomnia]
Desipramine (Norpramine) [Antidepressant]
Oxaprozin (Daypro) [Arthritis]
Ibuprofen (Advil) [Anti-inflammatory]
Sertraline (Zoloft) [Antidepressant]
Cannabinoids
Dronabinol (Marinol) [Nausea; Appetite stimulant]
Efavirenz (Sustiva) [HIV]
Hemp seed oil, Cannabis seed, Hemp oil, Hemp food
NSAIDS (ibuprofen, naproxen, ketoprofen, piroxicam, etc)
Pantoprazole (Protonix) [GERD; Peptic ulcer dz]
Promethazine (Phenergan) [Nausea]
Cocaine
Amoxicillin (Amoxil) [Antibiotics]
Coca leaf teas
Tonic water
Quetiapine (Seroquel) [Antipsychotic]
Thioridazine (Mellaril) [Antipsychotic]
Verapamil [HTN; Ans-arrhythmic]
Opiates/Opioids
Dextromethorphan (Delsym, Robitussin) [Anti-tussive]
Poppy seeds and oil [Yummy bagels and bread]
Quinine [Antimalarial]
Rifampin [Tuberculosis]
Oxycodone
Hydrocodone, Oxymorphone
Hydromorphone, Codeine,
Amitriptyline (Elavil) [TCA antidepressant]
Dicyclomine (Bentyl) [Anticholinergic for IBS]
Ergotamine [Migraines]
Promethazine (Phenergan) [Nausea/Vomiting]
Sumatriptan (Imitrex) [Migraines] [Congestion]
Phencyclidine (PCP)
Dextroamphetamine (Dexedrine) [ADHD; Stimulant]
Dextromethorphan (Delsym, Robitussin) [Anti-tussive]
Diphenhydramine (Benadryl) [Antihistamine]
Doxylamine (Unisom) [Insomnia]
Ibuprofen (Advil) [Anti-inflammatory]
Imipramine (Tofranil) [TCA antidepressant
Ketamine [General anesthetic]
Meperidine (Demerol) [Pain]
Tramadol (Ultram) [Pain]
Venlafaxine (Effexor) [SNRI Antidepressant]
Diphenhydramine (Benadryl) - LSD [Antihistamine]
Fluoroquinolones (Levaquin, Avelox, Cipro, Floxin)
Chloroquine (Aralen) [Anti-malarial]
Chlorpromazine (Thorazine) [Antipsychotic]
Specimen Validity
Validity refers to the correct specimen identity (i.e., a urine sample is human urine belonging to donor)
Validity issues:
Substituted sample – substance provided in place of the donor’s specimen
drug-free urine (from another individual)
another liquid such as water or commercially available products
Adulterated sample – specimen to which a substance(s) has been added to interfere with the analytical tests utilized to detect drugs
Common additives include:
Household cleaners like bleach, soap
Vinegar, lemon juice, and household cleaners
Commercial products are available to subvert drug tests
Dilution: adding liquids to the sample at the time of collection in order to decrease the concentration of drug below sensitivity
in vivo dilution involves the ingestion of diuretics and other substances to remove the drugs from the body or dilute the urine
Minimizing Specimen Validity Issues:
Specimens are collected under chain of custody
Physical procedures are in place to minimize the likelihood of specimen substitution or adulteration
Witnessing the collection
Not providing access to water in the bathroom
Coloring toilet bowl water
Clothing choices in which a substituted specimen could be hidden
Specimen is sealed in the collection container with tamper-resistant tape
Collector may record the temperature of the specimen (normal between 90–100°F) as well as the urine color
Confirmatory Drug Testing
Confirmation methods are chromatographic and mass spectrometric
Generally require 24–48 hours to complete
Highly sensitive and specific
Quantitative results of a prescribed medication may be useful under certain circumstances (e.g., to assist in differentiating active smoking from passive exposure to nicotine
In general, qualitative identification of the drug is sufficient
Quantitative serum ethanol results are useful in assessing the degree of impairment
Toxicology Issues
Clinical toxicology: treating the poisoned patient
monitoring compliance with medications or drug abstinence
monitoring drug concentrations in order to optimize dosing
A more useful approach clinically, especially in the emergent patient, is knowledge of toxidromes
Forensic toxicology involves the application of toxicology for legal purposes
Results from forensic tox analysis may be used in courts of law
Level of proof is greater in forensic cases
Specimen integrity is essential
Screening results are confirmed by a more specific and usually more sensitive technique
Generally, your role will be patient care
Be careful about providing protected health information to outside entities to include law enforcement
Approach to Toxidromes
To approach to Toxidromes is mentioned as part of the FOUNDATION of emergency medicine. This is a good tool to differenciate what class the patient overdosed/is in toxicity.