THE WEEKLY USMLE TIMES
Issue #65
Welcome to this week’s issue of The USMLE Times.
In today’s email, you’ll get:
High-Yield GI Question + Breakdown
Video & Audio Training Recommendations
Popular Tweet of The Week
Reading Recommendation of The Week
Let’s dive in!
A 3-day-old male is brought to the pediatrician by his parents due to concerns about his inability to pass meconium since birth. The infant was born at full term with no complications during pregnancy or delivery. His vital signs are as follows: Heart rate 130/minute, respiratory rate 30/minute, blood pressure 65/45 mmHg, temperature 98.1°F (36.7°C), and oxygen saturation 98% on room air. Physical examination reveals a distended abdomen and digital rectal examination produces a sudden gush of meconium. Which of the following best describes the reason why ganglion cells failed to migrate to the correct location in this infant's colon?
A. Failure of neural crest cell differentiation into ganglion cells
B. Impaired secretion of glial-derived neurotrophic factor (GDNF)
C. Deficient expression of the SRY gene during development
D. Inadequate production of fibroblast growth factor (FGF)
E. Disruption of sonic hedgehog (SHH) signaling pathway
F. Overexpression of Wnt signaling pathway components
G. Insufficient production of bone morphogenetic protein (BMP)
The answer & question breakdown is at the bottom of the post.
📺 WATCH
🎧 LISTEN
💬 TWEET OF THE WEEK 💬
📚 QUICK READ OF THE WEEK - “Becoming A Magician”
This piece is about the perceived ‘magic’ of someone at the top of their game. It’s both inspiring and motivating and if you’re someone who wants to become the best they can be, a must-read! Check it out HERE.
💎 ANSWER + QUESTION BREAKDOWN
The clinical presentation described in the question suggests Hirschsprung's disease, a congenital condition characterized by the absence of ganglion cells in the distal bowel. This absence leads to a failure of relaxation and subsequent functional obstruction, with the most common symptom being a delay in passing meconium within the first 48 hours of life, as observed in the described infant. The distended abdomen and the explosive release of meconium following a digital rectal examination further support this diagnosis.
Let's dissect each option to understand their relevance to the development of ganglion cells in the colon:
A. Failure of neural crest cell differentiation into ganglion cells
Role in Development: Neural crest cells differentiate into various cell types, including the ganglion cells of the enteric nervous system.
Relevance to the Condition: While the failure of these cells to differentiate into ganglion cells could theoretically contribute to Hirschsprung's disease, the question focuses on the migration aspect, which is more directly related to other factors.
B. Impaired secretion of glial-derived neurotrophic factor (GDNF)
Role in Development: GDNF is crucial for the survival and migration of neural crest cells into the gut.
Relevance to the Condition: Impaired secretion or function of GDNF can lead to the failure of neural crest cells to migrate properly into the distal colon, resulting in the absence of ganglion cells characteristic of Hirschsprung's disease.
This is the correct answer!
C. Deficient expression of the SRY gene during development
Role in Development: The SRY gene is responsible for determining male sex in the developing embryo.
Relevance to the Condition: This gene's expression is unrelated to the migration of neural crest cells or the development of the enteric nervous system.
D. Inadequate production of fibroblast growth factor (FGF)
Role in Development: FGFs are involved in a wide range of developmental processes, including cell survival, growth, and differentiation.
Relevance to the Condition: Although FGFs play a role in many developmental processes, they are not explicitly linked to the migration of neural crest cells to the gut or the pathogenesis of Hirschsprung's disease.
E. Disruption of sonic hedgehog (SHH) signaling pathway
Role in Development: SHH signaling is important for many aspects of embryonic development, including patterning of the neural tube, limb, and other structures.
Relevance to the Condition: While important for overall development, disruptions in SHH signaling is not directly implicated in the failure of ganglion cell migration in Hirschsprung's disease.
F. Overexpression of Wnt signaling pathway components
Role in Development: The Wnt signaling pathway plays a key role in cell proliferation, differentiation, and migration during development.
Relevance to the Condition: While Wnt signaling is crucial for development, its overexpression is not typically associated with the failure of ganglion cell migration seen in Hirschsprung's disease.
G. Insufficient production of bone morphogenetic protein (BMP)
Role in Development: BMPs are involved in a broad range of developmental processes, including cell differentiation, growth, and apoptosis.
Relevance to the Condition: BMPs are important for development, but like FGFs, they are not specifically linked to the migration of neural crest cells into the gut or the development of Hirschsprung's disease.
The Correct Answer is B. Impaired secretion of glial-derived neurotrophic factor (GDNF)
GDNF plays a critical role in the survival and proper migration of neural crest cells to the gut, where they differentiate into ganglion cells of the enteric nervous system. A deficiency in GDNF signaling can lead to the failure of these cells to colonize the distal bowel, resulting in the absence of peristalsis and the clinical manifestations of Hirschsprung's disease.
That’s all folks! If you found this week’s edition of The USMLE Times to be helpful, please hit the heart and click the ‘share’ icon below to share it with a friend who could benefit from it.
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Until next time - Dr. Paul