ABPath - American Board of Pathology Chemical Pathology Questions and Answers 1 — Questions and Answers
Question 1: A 55-year-old male presents to the emergency department with severe headache, palpitations, and sweating. His blood pressure is 210/120 mmHg. A 24-hour urine collection is ordered to screen for a suspected pheochromocytoma. Which of the following analytes provides the highest diagnostic sensitivity for this condition?
- Vanillylmandelic acid (VMA)
- Total catecholamines
- Fractionated metanephrines (Correct answer)
- Homovanillic acid (HVA)
Correct answer: Fractionated metanephrines
Fractionated metanephrines (metanephrine and normetanephrine) in urine or plasma are the metabolites of epinephrine and norepinephrine. Their measurement is recommended for the initial biochemical testing for pheochromocytomas and paragangliomas due to their superior diagnostic sensitivity compared to catecholamines or VMA. Tumors secrete these metabolites continuously, making them less susceptible to fluctuations seen with catecholamine secretion.
Question 2: A 68-year-old female is admitted with chest pain. Serial high-sensitivity cardiac troponin I (hs-cTnI) levels are measured. The first result is 45 ng/L (99th percentile URL: 26 ng/L). A second result 3 hours later is 250 ng/L. According to the universal definition of myocardial infarction, what does this pattern represent?
- Chronic myocardial injury
- A significant rise and fall pattern indicative of acute myocardial infarction (Correct answer)
- Analytic interference in the assay
- A clinically insignificant fluctuation
Correct answer: A significant rise and fall pattern indicative of acute myocardial infarction
The universal definition of myocardial infarction requires a rise and/or fall of cardiac troponin values with at least one value above the 99th percentile upper reference limit. The significant increase from 45 ng/L to 250 ng/L over 3 hours, with the initial value already being elevated, is characteristic of an acute event like a myocardial infarction, differentiating it from chronic, stable elevations.
Question 3: A patient with uncontrolled Type 1 diabetes presents with nausea, vomiting, and altered mental status. Laboratory results are: Na+ 132 mmol/L, K+ 5.1 mmol/L, Cl- 95 mmol/L, HCO3- 10 mmol/L, Glucose 550 mg/dL. What is the calculated serum anion gap, and what is its significance?
- 12 mmol/L, which is a normal anion gap
- 27 mmol/L, indicating a high anion gap metabolic acidosis (Correct answer)
- 5 mmol/L, indicating a low anion gap
- 17 mmol/L, which is borderline high and requires further investigation
Correct answer: 27 mmol/L, indicating a high anion gap metabolic acidosis
The anion gap is calculated as [Na+] – ([Cl-] + [HCO3-]). Using the patient's values: 132 – (95 + 10) = 27 mmol/L. A normal anion gap is typically between 8-12 mEq/L. An anion gap of 27 is significantly elevated, indicating a high anion gap metabolic acidosis. In this clinical context, it is due to the accumulation of unmeasured ketoacids (beta-hydroxybutyrate and acetoacetate) characteristic of diabetic ketoacidosis (DKA).
Question 4: Which of the following laboratory findings is most consistent with hypercalcemia of malignancy?
- Elevated serum calcium, elevated PTH
- Elevated serum calcium, low PTH, elevated PTHrP (Correct answer)
- Low serum calcium, elevated PTH
- Elevated serum calcium, low PTH, low PTHrP
Correct answer: Elevated serum calcium, low PTH, elevated PTHrP
Hypercalcemia of malignancy is a common cause of nonparathyroid hypercalcemia. It is often mediated by the secretion of parathyroid hormone-related peptide (PTHrP) by tumors. PTHrP mimics the action of PTH on bone and kidney, leading to increased calcium levels. However, the high calcium level provides negative feedback to the parathyroid glands, suppressing the secretion of endogenous PTH. Therefore, the characteristic pattern is high calcium, low PTH, and high PTHrP.
Question 5: A 45-year-old patient on long-term phenytoin therapy for a seizure disorder is admitted for pneumonia and found to have a serum albumin of 2.5 g/dL (normal 3.5-5.0 g/dL). The measured total phenytoin level is 15 mcg/mL (therapeutic range 10-20 mcg/mL). Which of the following is the most appropriate interpretation and action?
- The level is therapeutic; no action is needed.
- The patient is likely subtherapeutic due to low albumin; the dose should be increased.
- The patient is at risk for toxicity; the free phenytoin level should be checked or the dose should be reduced. (Correct answer)
- The phenytoin level is invalid and should be redrawn.
Correct answer: The patient is at risk for toxicity; the free phenytoin level should be checked or the dose should be reduced.
Phenytoin is highly protein-bound, primarily to albumin. In states of hypoalbuminemia, the fraction of free (active) drug is increased. A total phenytoin level within the therapeutic range can be misleading, as the biologically active free concentration may be in the toxic range. Therefore, the patient is at risk for toxicity despite the 'normal' total level. The best course of action is to measure the free phenytoin level directly or to calculate an adjusted level and consider a dose reduction.
Question 6: A comatose patient is brought to the emergency room with suspected toxic ingestion. Labs show: measured osmolality 350 mOsm/kg, Na+ 140 mmol/L, BUN 28 mg/dL, Glucose 90 mg/dL. The calculated osmolality is 295 mOsm/kg. Anion gap is 25 mEq/L. What is the most likely cause of the elevated osmolal gap and anion gap?
- Isopropanol ingestion
- Ethanol intoxication
- Diabetic ketoacidosis
- Ethylene glycol poisoning (Correct answer)
Correct answer: Ethylene glycol poisoning
The osmolal gap is the difference between the measured and calculated osmolality (350 - 295 = 55 mOsm/kg). An elevated osmolal gap (>10-15) indicates the presence of unmeasured osmoles. Ethylene glycol is an osmotically active parent compound that causes an initial elevation in the osmolal gap. As it is metabolized by alcohol dehydrogenase to acidic metabolites (e.g., glycolic acid, oxalic acid), the osmolal gap decreases while the anion gap increases. The presence of both a significantly elevated osmolal gap and a high anion gap is highly characteristic of ethylene glycol (or methanol) poisoning. Isopropanol causes an elevated osmolal gap but typically not a significant anion gap.
ABPath - American Board of Pathology Chemical Pathology Questions and Answers 1
A 55-year-old male presents to the emergency department with severe headache, palpitations, and sweating.
His blood pressure is 210/120 mmHg.
A 24-hour urine collection is ordered to screen for a suspected pheochromocytoma.
Which of the following analytes provides the highest diagnostic sensitivity for this condition?