THE WEEKLY USMLE TIMES
Issue #67
Welcome to this week’s issue of The USMLE Times.
In today’s email, you’ll get:
A High-Yield MSK Question
Video & Audio Training Recommendations
Tweet of the Week
Question Breakdown + Related Step 1 Facts
Let’s dive in!
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 a limited range of motion. Her temperature is 37.5°C (99.5°F), blood pressure is 124/78 mmHg, pulse is 82 beats per minute, and respiratory rate is 16 breaths per minute. Laboratory studies reveal an elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), as well as a positive rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Based on the patient's presentation and laboratory findings, which of the following is the most likely underlying pathophysiologic cause of her condition?
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 (PTHrP)
F. Enhanced activation of the Wnt signaling pathway
The answer & question breakdown is at the bottom of the post.
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💎 ANSWER + QUESTION BREAKDOWN
The patient's clinical presentation and laboratory findings are highly suggestive of Rheumatoid Arthritis (RA). RA is a chronic autoimmune condition characterized by inflammation of the synovial membrane, leading to joint pain, stiffness, swelling, and eventually joint destruction.
Rheumatoid Factor (RF): Antibodies against the Fc portion of IgG are produced to help remove antibodies and immune complexes.
Risk factors include Female sex, smoking, HLA-DR1, and HLA-DR4.
ANSWER BREAKDOWNS:
ANSWER CHOICE A: Overexpression of type II collagen leading to joint destruction
Overexpression of type II collagen is more related to cartilage formation and is not directly associated with the pathophysiology of RA.
Overexpression or abnormal accumulation of type II collagen, along with other extracellular matrix components, can contribute to the pathogenesis of osteoarthritis. This can lead to cartilage degradation, joint space narrowing, and ultimately, joint destruction.
In conditions like RA, antibodies against self-antigens, including type II collagen, can lead to chronic inflammation and joint damage. The immune response against type II collagen contributes to the erosive damage seen in RA (overexpression of type II collagen is not the underlying cause of RA).
ANSWER CHOICE B: Accumulation of immune complexes in the synovial membrane
RA is characterized by the formation and deposition of immune complexes (rheumatoid factor and anti-CCP antibodies) in the synovial membrane, leading to inflammation and joint damage. This is the correct answer.
ANSWER CHOICE C: Infiltration of activated neutrophils into the synovium
While neutrophil infiltration does occur in RA, the most characteristic feature is the formation of immune complexes that drive inflammation. Thus, this answer is partially correct but not the most accurate.
In conditions like RA, the synovium becomes inflamed due to the infiltration of immune cells, including neutrophils. This leads to synovitis, characterized by swelling, pain, and reduced movement.
ANSWER CHOICE D: Deposition of monosodium urate crystals within the joint space
Hyperuricemia is a prerequisite for forming monosodium urate (MSU) crystals. It can result from increased uric acid production or decreased kidney excretion.
When phagocytosed by leukocytes (particularly neutrophils), MSU crystals trigger an inflammatory response that is mediated by the activation of the NLRP3 inflammasome, which releases pro-inflammatory cytokines like interleukin-1β (IL-1β).
ANSWER CHOICE E: Overproduction of parathyroid hormone-related protein (PTHrP)
The most common cause of PTHrP overproduction is humoral hypercalcemia of malignancy, which is often associated with certain cancers, particularly squamous cell carcinoma of the lung, renal cell carcinoma, breast cancer, and ovarian cancer.
The main effect of PTHrP overproduction is hypercalcemia, which occurs due to increased osteoclast activity and increased renal tubular reabsorption of calcium, mimicking the effects of high PTH levels but without the elevation of PTH itself.
ANSWER CHOICE F: Enhanced activation of the Wnt signaling pathway
Wnt signaling is crucial for embryonic development, including cell fate determination, cell migration, and organogenesis. Defects in this pathway can lead to developmental defects.
Enhanced Wnt signaling is also implicated in various cancers, especially colorectal cancer. Mutations in APC or β-catenin genes lead to constitutive activation of the pathway, promoting uncontrolled cell proliferation.
THE VERDICT: Given the patient’s clinical symptoms, the most likely diagnosis is rheumatoid arthritis.
FINAL ANSWER: B: Accumulation of immune complexes in the synovial membrane
That’s all for this week’s issue of The USMLE Times!
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