ASCP - Clinical Chemistry

Oxycodone - clearance organ

Liver

Oxycodone metabolism - major pathway enzyme + metabolite

CYP3A4 into noroxycodone

Oxycodone metabolism - minor pathway enzyme + metabolite

CYP2D6 into oxymorphone

HbCC, HbSS disease - test for long-term glucose management

Fructosamine (non-enzymatic glucose binding to protein)

IV contamination of CMP would result in falsely high or low results?

Falsely low due to dilution

Which treatment can interfere with accuracy of a glucometer using glucose oxidase-based test strips

Vitamin C (ascorbic acid) > low glucose reading

Disease associated with elevated Alk phos, elevated urinary excretion of pyridinium collagen cross-links (deoxypyridinoline, Dyd), vision changes

Paget disease

Tumor marker assays from different manufactuers can or cannot be directly compared

Cannot - assays are not standarized

Which pre-analytical factor is important to know to establish the correct time of collection AFTER dosing for a new drug

Volume of distribution (has be be achieved before collection, esp for drugs with high Vd - digoxin, cyclosporin, lithium)

Which spectrophotometric technique is depicted in the diagram

Nephelometry (measures scattered light at an angle away from the incident light path)

Obesity leads to ___ cystatin C levels which then can ____ GFR

increased; underestimate

Serum concentration of thyroglobulin (Tg) is normal in which thyroid condition?

PTC

Which 3 medications can cause an acute increase in fT4 or fT3 and why?

Carbamazepine, phenytoin, furosemide

Compete with binding of T4 and T3 to serum proteins like thyroxine binding globulin > can cause decrease in TSH in some instances
Chronic administration eventually leads to system re-equilibrium

Diagnosis: Elevated serum cortisol + urinary free cortisol > not suppressed by high-dose dexamethasone > low plasma ACTH

Adrenal Cushing’s syndrome

Diagnosis: Elevated serum cortisol + urinary free cortisol > not suppressed by high-dose dexamethasone > high plasma ACTH

Cushing’s syndrome from ectopic ACTH secreting tumor

Procalcitonin - clearance organ

Kidneys (impaired renal function causes falsely elevated serum levels)

Which technique should be used to measure testosterone levels in females, children, and hypogonadal males?

Mass spectrometry - precise quantification of testosterone concentrations as these populations have much lower testosterone levels (vs immunoassay)

Diagnosis: Macrocytic anemia with elevated homocysteine and normal MMA

Folate deficiency

Diagnosis: Macrocytic anemia with elevated homocysteine and MMA

Vitamin B12 deficiency

Blood gas specimen is exposed to air - are the levels of PO2, PCO2, and pH increased/decreased/unchanged?

PO2 + pH > increased (PO2 air > PO2 blood; decreased PCO2 leads to less H+ ions)

PCO2 > decreased (PCO2 air < PCO2 blood)

Etiologies of pseudohypokalemia (not including hemolysis)

Traumatic phlebotomy, thrombocytosis, leukocytosis, collection in improper anti-coagulant (K2 EDTA)

High-sensitivity cardiac troponin (hs-cTn) level should be above what percentile in order to help diagnose acute MI

99th percentile

Which components of a lipid panel are affected by eating prior to collection

Triglycerides and calculated LDL

After fatty meal, chylomicrons (made up of 80% TGs) enter blood stream via lymphatics and can increase TG levels for up to 10 hours
Calculated LDL = TC - HDL - (TG/5); increasing TG decreases calculated LDL

For a new moderate or high complexity test (CLIA non-waived test), which assay performance specifications must be evaluated prior to implementing the new test

Precision, accuracy, reportable range, reference intervals

For a CLIA waved test, which assay performance specifications must be evaluated prior to implementing the new test

No performance evaluation is required - lab only needs to adhere to manufacturer’s instructions

For non-waived tests that are modified FDA-approved or non-FDA approved, what additional criteria must be established prior to implementation of the new test

Analytical sensitivity and specificity

Serum and urine bone markers are _____ (elevated/decreased) in fractures

Elevated - remain high for up to 1 year

Serum and urine bone markers are _____ (elevated/decreased) in pregnancy

Elevated - peak at term

Serum and urine bone markers are _____ (elevated/decreased) with use of corticosteroids

Elevated

Serum and urine bone markers are _____ (high/low) in winter and _____ (high/low) in summer

High; low (due to vitamin D exposure)

Serum and urine bone markers are at _____ (peak/nadir) in the morning and _____ (peak/nadir) in the afternoon

Peak; nadir

Delta bilirubin level calculation formula

Delta bilirubin = total bilirubin - (unconjugated bili + conjugated bili)

Delta bilirubin is bound to which protein

Albumin

Delta bilirubin is metabolically _____ (active/inactive)

Inactive

Why is lipase the preferred marker for acute pancreatitis

Longer elevation in the serum compared to amylase and more specific

Which substances cause a positive interference with Jaffe-based measurement of creatinine

Ketones, glucose, cephalosporins, elevated A1c

The Friedewald equation _____ (underestimates/overestimates) LDL-C when TG concentration is at or above 150 mg/dL (for patients with very high risk ASCVD (<70 mg/mL)

Underestimates

In which three scenarios should the Friedewald equation NOT be used for calculation of LDL-C

Non-fasting patients

TG > 400 mg/dL

Type III hyperlipoproteinemia

Give two examples of drugs where it is important to monitor the free drug concentration

Phenytoin

Valproic Acid

These are highly protein-bound drugs (>70%) and their therapeutic and toxic effects are directly related to their free drug concentration

Secretin stimulation testing is done to evaluate what disease process?

Pancreatic sufficiency

In the secretin stimulation test, what analyte is measured after the stimulation with secretin

Bicarbonate

APAP - major metabolism pathway (>90%) + clearance organ

Glucuronidation and sulfation conjugation pathways; Kidneys

APAP - minor metabolism pathway + metabolite

CYP2E1 (P450); NAPQI (highly toxic)

APAP overdose - mechanism

Accumulation of NAPQI due to saturation of major pathway and decreased elimination from depletion of hepatic glutathione stores

APAP - NAPQI metabolism

Hepatic glutathione rapidly complexes to form non-toxic cysteine or mercapturic acid conjugates

APAP overdose - NAC mechanism of action

Increases production of glutathione (+ possibly sulfate) to inhibit the formation of NAPQI and eliminating formed NAPQI

Which detection technique is the least sensitive for directly detecting a low concentration of an analyte in solution

Absorbance spectrophotometry

Diagnosis: elevated 17-hydroxyprogesterone + salt-wasting crisis

21-alpha-hydroxylase deficiency

Salt-wasting = hyponatremia, hyperkalemia, dehydration

Diagnosis: Elevated DHEA + ambiguous genitalia

3-beta-hydroxysteroid dehydrogenase deficiency

Diagnosis: virilazation without affecting cortisol or aldosterone pathways

Aromatase deficiency

Due to lack of estrogen

Diagnosis: Elevated aldosterone + sexual infantilism + hypertension

17-alpha-hydroxylase deficiency

Diagnosis: Elevated deoxycortisol + virilization + hypertension + hypokalemia

11-beta-hydroxylase deficiency

Bioavailable testosterone is made up of what

Free testosterone (2-3%) + testosterone weakly bound to albumin (33-50%)

Testosterone circulates in the plasma bound to which protein with high affinity

Sex-hormone binding globulin (SHBG, 44-65%)

Initial evaluation of suspected testosterone deficiency should be done by which test and methodology

Total testosterone by immunoassay

Heroin metabolism pathway

Heroin > 6-MAM > morphine > hydromorphone

Codeine metabolism pathways (3)

Codeine > morphine > hydromorphone

Codeine > hydrocodone > hydromorphone

Codeine > hydrocodone > dihydrocodeine

Morphine metabolism pathway

Morphine > hydromorphone

Oxycodone metabolism

Oxycodone > oxymorphone

Diagnosis: Isolated AST elevation in a healthy patient with other normal liver tests (including CK, aldolase, LDH)

Macro-AST = AST forms complexes with Ig’s > delayed clearance and persistent AST elevation

Detect with electrophoresis, polyethylene glycol precipitation, gel filtration chromatography

In acute myocardial injury, the cTn levels _____ (rise/fall or stay stable) over time whereas in chronic myocardial injury, the cTn levels ____ (rise/fall or stay stable) over time

Rise/fall; stay stable

_____ (BNP/NT-proBNP) is degradable by neprilysin

BNP

_____ (BNP/NT-proBNP) is the active form

BNP

_____ (BNP/NT-proBNP) has the longer half-life and is more stable

NT-proBNP

Commercial drug assays detect which benzodiazepine

Diazepam > nordiazepam (+temazepam)

Purpose of the fetal fibronectin asssay

To assess the likelihood of preterm delivery; collected via cervical and vaginal secretions

For each disease, determine if calcium and phosphate levels are increased, decreased, or unchanged

Vitamin D deficiency

Renal osteodystrophy

Paget’s disease

Vitamin D deficiency: decrease calcium, decrease phosphate

Renal osteodystrophy: decreased calcium, unchanged/increased phosphate

Paget’s disease: unchanged calcium and phosphate

Blood specimen with high potassium, low calcium, and low alkaline phosphatase indicate what about specimen collection?

Specimen was collected into potassium-EDTA tube prior to transferring to heparinized tube (specimen has excess potassium and a chelator of divalent cations like Ca and Mg; Alk phos needs Mg as cofactor)

3 major mechanism for hyperkalemia

Decreased aldosterone / aldosterone responsiveness

Reduced distal delivery of sodium

Renal failure

Best laboratory tests to diagnose AL amyloidosis (4)

SPEP

Serum free light chain

Serum IFE

Urine IFE

Best laboratory tests to diagnose monoclonal gammopathy (3)

SPEP

Serum free light chain

Serum IFE

Plasma sodium becomes falsely _____ (low/high) with hyperproteinemia, hyperlipidemia

Plasma sodium becomes falsely _____ (low/high) with hypoproteinemia, hypolipidemia

Low - pseudoHYPOnatremia

High - pseudoHYPERnatremia

Due to indirect ion-selective electrode (ISE) measurement - measures electrolytes after dilution (assuming electrolytes confined to plasma water 93%, and plasma solids 7%)

____ healthy individuals are needed to establish reference interval for a test

____ healthy individuals are needed to establish 95th percentile

300-500

120

____-order kinetics: amount of drug metabolized is independent of parent drug concentration

____-order kinetics: amount of drug metabolized is dependent on parent drug concentration

Zero

First

Drugs administered ____ (route) bypass absorption process

Intravenously

Delayed processing of whole blood specimens causes a/an _____ (acidic/basic) environment

Exposure to air causes a/an _____ (acidic/basic) environment

Acidic

Basic

An acidic (decreased pH) causes _____ (increased/decreased) ionized calcium

A basic (increased pH) causes _____ (increased/decreased) ionized calcium

Increased (H+ ions compete with calcium for albumin binding sites)

Decreased

Ionized calcium is inversely proportional to pH

Which standardized bone turnover marker is used to assess response to anti-resorptive therapies (bisphosphonates/denosumab) in osteoporosis

C-terminal telopeptide of type 1 collagen (CTX)

Decrease > successful therapeutic response

Which standardized bone turnover marker is used to assess response to anabolic therapies (teriparatide, abaloparatide) or formation phase (romosozumab) for osteoporosis

Procollagen type 1 N-terminal propeptide (P1NP)

Which calculation is used to show statistically significant changes between test values obtained on 2 occasions

Reference change value (RCV)

Which calculation is used to evaluate imprecision

% Coefficient of variation (%CV)

Which calculation is a measurement of bias used to compare a laboratory’s mean with peer-group means

SD index (SDI)

Which calculation is used to evaluate the clinical utility of a diagnostic test

Area under the curve (AUC) of receiver-operating characteristic (ROC) curve

Which species of arsenic are toxic

Inorganic species - arsenic III, arsenic V, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA)

Symptoms of acute arsenic toxicity

GI distress

Cardiac arrhythmias

Symptoms of chronic arsenic toxicity

Renal failure

Cardiac arrhythmias

Liver dysfunction

Peripheral neuropathy

True or false: consumption of seafood can result in elevated urinary arsenic levels

True

True or false: consumption of seafood can cause detectable arsenic-DMA and arsenic-MMA

True

Which metabolite of oxycodone is more potent

Oxymorphone

Iron overload (high/low): ____ iron, ____ ferritin, ____ TIBC, ____ transferrin saturation

High, high, low, high

What are the two screening tests used for primary hyperaldosteronism

Aldosterone-to-renin ratio (ARR) and aldosterone-to-direct renin concentration ratio (PAC/DRC)

What are 4 confirmatory tests for primary aldosteronism

Saline infusion test

Fludrocortisone suppression test

Oral sodium loading

Captopril challenge

Confirmatory testing for primary aldosteronism is not required under these 3 circumstances

Spontaneous hypokalemia

Undetectable renin

PAC > 20 ng/dL

Delta check failure definition

Difference between a patient’s current lab result and a previous result that exceeds a predefined limit within a set of time interval

4 common causes of delta check failures

Mislabeling of the specimen

Pre-analytical contamination

Clerical errors

Possible analytical error

Common causes of pseudohyperkalemia

Improper blood collection

Hemolysis

Thrombocytosis - platelets release K during coagulation causing increased serum K (Plt > 500K)

Leukocytosis - plasma K falsely elevated, serum K normal due to leukocyte lysis (WBC > 50K)

Hematologic malignancy

Best initial test to investigate pheochromocytoma

Plasma and urine metanephrines

____-based EGFR calculation should be used in patients with low muscle mass

Cystatin C

Preeclampsia severe features

Thrombocytopenia (<100K)

Elevated LFTs (>2X ULN)

Elevated creatinine (>1.1)

Pulmonary edema

Persistent headache

Visual symptoms

Elevated HVA (homovanillic acid) and VMA (vanillylmandelic acid) in child suggests

Neuroblastoma