Welcome to USMLE practice question #147! Today’s topic is hematology/pathology.
I’m Paul Ciurysek, MD, founder of The USMLE Guys! This daily newsletter aims to provide super high-yield USMLE concepts commonly tested on exam day. All content is FREE! If you’d like more help with your USMLE preparation, please see the options at the bottom of today’s newsletter. Please share the newsletter with a friend if you’d like to support our efforts!
A 58-year-old man with a history of rheumatoid arthritis presents with fatigue and pallor. Laboratory findings show:
• Hemoglobin: 9.5 g/dL
• Mean corpuscular volume (MCV): 82 fL
• Serum iron: Low
• Ferritin: High
• Total iron-binding capacity (TIBC): Low
Bone marrow biopsy shows normal erythroid precursors with increased iron stores in macrophages. Which of the following best explains the pathogenesis of this patient’s anemia?
A) Autoimmune destruction of erythrocyte precursors in the bone marrow
B) Suppression of erythropoiesis by pro-inflammatory cytokines
C) Reduced erythropoietin production by the kidneys due to chronic inflammation
D) Inhibition of ferroportin-mediated iron release from macrophages
E) Hemolysis of erythrocytes mediated by complement activation
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
It’s important to adopt the correct MENTAL MODEL when answering USMLE questions; it saves time and increases accuracy. The mental model outlined below is a foundational component of our test-taking skills masterclass (check it out if you want to elevate your skills). Here’s how to think through this question:
Step 1. Read the last line to get to the heart of the question: “Which of the following best explains the pathogenesis of this patient’s anemia?”
Step 2: Is this a first-, second-, or third-order question?
Answer: 2nd order. 1st: Diagnose the type of anemia, 2nd: Identify the underlying cause.
Step 3: Read the vignette carefully and ask yourself: “Based on the type of anemia present, the cause is __________________.”
Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.
GENERAL ANALYSIS
This 58-year-old man with rheumatoid arthritis (RA) presents with anemia, fatigue, and pallor, along with laboratory findings consistent with anemia of chronic disease (ACD). Key findings include low serum iron, high ferritin, low total iron-binding capacity (TIBC), and increased iron stores in macrophages, which are characteristic of ACD.
ANSWER CHOICES:
CHOICE A: Autoimmune destruction of erythrocyte precursors in the bone marrow
Explanation: Autoimmune destruction of erythrocyte precursors occurs in conditions like pure red cell aplasia or aplastic anemia, leading to a profound reduction in red blood cell production. This patient’s bone marrow biopsy shows normal erythroid precursors, ruling out autoimmune destruction as the cause of anemia.
CHOICE B: Suppression of erythropoiesis by pro-inflammatory cytokines
Explanation: In chronic inflammatory conditions like rheumatoid arthritis, pro-inflammatory cytokines (e.g., IL-6) suppress erythropoiesis by reducing erythropoietin responsiveness and impairing red blood cell production. These cytokines also increase hepcidin levels, which sequester iron in macrophages and reduce its availability for erythropoiesis.
CHOICE C: Reduced erythropoietin production by the kidneys due to chronic inflammation
Explanation: Reduced erythropoietin production is a feature of anemia associated with chronic kidney disease (CKD), where kidney damage impairs erythropoietin secretion. This patient does not have evidence of CKD (e.g., no mention of elevated creatinine or uremia). The anemia is due to inflammation rather than reduced erythropoietin production.
CHOICE D: Inhibition of ferroportin-mediated iron release from macrophages
Explanation: Hepcidin, an acute-phase reactant upregulated by IL-6 during inflammation, inhibits ferroportin-mediated iron release from macrophages. This reduces serum iron levels despite adequate iron stores.
CHOICE E: Hemolysis of erythrocytes mediated by complement activation
Explanation: Complement-mediated hemolysis occurs in conditions like paroxysmal nocturnal hemoglobinuria (PNH) or autoimmune hemolytic anemia (AIHA). These conditions present with hemolysis markers such as elevated LDH, reticulocytosis, and low haptoglobin. This patient has no evidence of hemolysis.
FINAL VERDICT…
CORRECT ANSWER: B) Suppression of erythropoiesis by pro-inflammatory cytokines
Key findings include low serum iron, high ferritin, low total iron-binding capacity (TIBC), and increased iron stores in macrophages, which are characteristic of ACD. The pathogenesis of ACD is primarily driven by pro-inflammatory cytokines (e.g., IL-6, TNF-α, IFN-γ), which suppress erythropoiesis and alter iron metabolism.
KEY CONCEPTS:
Pathophysiology of Anemia of Chronic Disease (ACD):
Chronic inflammation leads to increased production of pro-inflammatory cytokines:
IL-6: Stimulates hepcidin production, which inhibits ferroportin and sequesters iron in macrophages.
TNF-α and IFN-γ: Suppress erythroid progenitor cells and reduce responsiveness to erythropoietin.
Result: Impaired iron utilization and reduced red blood cell production.
Laboratory Findings in ACD:
Normocytic or mildly microcytic anemia.
Low serum iron and TIBC.
High ferritin (reflecting increased iron stores).
Bone marrow biopsy: Increased macrophage iron stores.
Management of ACD:
Treat underlying inflammatory condition (e.g., rheumatoid arthritis).
Erythropoiesis-stimulating agents (e.g., epoetin alfa) may be used in severe cases.
Iron supplementation is generally not effective unless concurrent iron deficiency exists.