USMLE PRACTICE QUESTION #49
TOPIC: Rheumatoid arthritis.
Today’s question will test your understanding of the underlying pathology associated with rheumatoid arthritis.
A 56-year-old woman presents to her primary care physician with a 6-month history of gradually worsening pain and stiffness in her hands and wrists. She also reports experiencing fatigue, mild weight loss, and occasional low-grade fevers. On physical examination, her wrists are swollen, tender, and warm to the touch, with limited range of motion. Her temperature is 99.5°F (37.5°C), blood pressure is 124/78 mmHg, pulse is 82/minute, and respiratory rate is 16/minute. Laboratory studies reveal elevated ESR and anti-CCP antibodies. Which of the following is her condition's most likely underlying pathophysiologic cause?
A. Overexpression of type II collagen leading to joint destruction
B. Accumulation of immune complexes in the synovial membrane
C. Infiltration of activated neutrophils into the synovium
D. Deposition of monosodium urate crystals within the joint space
E. Overproduction of parathyroid hormone-related protein
F. Enhanced activation of the Wnt signaling pathway
G. Autoimmune destruction of the synovial membrane by autoreactive T cells
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
The mental model for this question comes from our detailed test-taking skills masterclass (If you want to elevate your USMLE test-taking skills, check it out). Here’s how to think through this question:
Step 1. Determine what the question is asking: Identify the underlying pathophysiologic cause of the patient’s condition.
Step 2: Is this a first-, second-, or third-order question?
Answer: 2nd order (1st. Diagnose, 2nd. Name the pathophysiology).
Step 3. Read the vignette and make a diagnosis.
Step 4. With a diagnosis in hand, ask yourself the underlying pathophysiologic cause.
Step 5. Look at the answer choices and select the option most closely resembling your thoughts from “Step 4” above.
GENERAL ANALYSIS
This question describes a 56-year-old woman with symptoms and laboratory findings consistent with rheumatoid arthritis. The symptoms include pain, stiffness, and swelling in her hands and wrists, along with systemic symptoms such as fatigue, weight loss, and low-grade fever. Laboratory tests show elevated inflammatory markers (ESR) and positive anti-CCP antibodies. The task is to identify the primary underlying pathophysiologic mechanism responsible for her condition.
ANSWER CHOICES:
ANSWER CHOICE A: Overexpression of type II collagen leading to joint destruction
Type II collagen is a major component of cartilage. Overexpression could theoretically lead to joint issues, but it is not the primary mechanism in RA.
ANSWER CHOICE B: Accumulation of immune complexes in the synovial membrane
Immune complexes can cause inflammation, but this is more characteristic of other conditions like systemic lupus erythematosus (SLE).
ANSWER CHOICE C: Infiltration of activated neutrophils into the synovium
Neutrophils can be present in the synovial fluid, but they are not the primary drivers of RA.
ANSWER CHOICE D: Deposition of monosodium urate crystals within the joint space
This is the mechanism for gout, not RA.
ANSWER CHOICE E: Overproduction of parathyroid hormone-related protein
PTHrP is involved in calcium regulation and is not related to RA.
ANSWER CHOICE F: Enhanced activation of the Wnt signaling pathway
The Wnt pathway is involved in bone and cartilage development, but it is not the primary mechanism in RA.
ANSWER CHOICE G: Autoimmune destruction of the synovial membrane by autoreactive T cells
RA is an autoimmune disease where T cells attack the synovium, leading to inflammation, joint damage, and systemic symptoms.
FINAL VERDICT…
In RA, the immune system mistakenly targets the synovium, leading to an influx of immune cells, including autoreactive T cells. These T cells release cytokines that perpetuate inflammation, causing synovial proliferation (pannus formation), cartilage destruction, and bone erosion. The presence of anti-CCP antibodies supports the diagnosis of RA. Systemic symptoms such as fatigue, fever, and weight loss are due to the widespread inflammatory response. The autoimmune nature of RA distinguishes it from other types of arthritis, such as osteoarthritis or gout, which have different pathophysiological mechanisms.
CORRECT ANSWER: G) Autoimmune destruction of the synovial membrane by autoreactive T cells
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