HY USMLE Q#17 Resp/Biochem Step 1
HY USMLE Q#17
Biochem/Resp (Step 1 and Step 2CK inspired by MEHLMAN's Instagram)
A 7-year-old boy is brought to the physician to follow up. He has a long history of recurrent pneumonia, sinusitis, and failure to pass meconium at birth. Which of the following findings are likely to be seen in this patient?
A. X-linked recessive inheritance
B. Decrease ENAC activity
C. Dilated rough endoplasmic reticulum
D. Endocrine pancreatic insufficiency
E. Defective anion channel on the cell surface
✅ Correct answer C = Dilated rough endoplasmic reticulum
Educational Objective:
The chloride channel in normal people is located on the cell surface. However, in cystic fibrosis, the misfolded channel/protein, the chloride channel, gets sequestered in the rough endoplasmic reticulum and dilated RER, implying a defective shuttling process. A defective COP2 antegrade transport from the RER to the Golgi apparatus. COP2 is a coated protein.
❌ A. The patient has cystic fibrosis, which is an autosomal recessive inherited condition.
❌ B. The patient has cystic fibrosis, and we will have increased ENAC. So, the lung and the pancreas will have the chloride remaining in the cells, leading to a very negative charge inside the cells. Hence, ENAC will be upregulated to balance out the charge from the positivity to the inside of the cell, as the sodium was very positive.
❌ D. In cystic fibrosis, we have EXOCRINE pancreatic insufficiency because there are no chloride channels; hence, no water comes into the lumen of the pancreas, leading to thick pancreatic fluid, which leads to destruction of the pancreas by the pancreatic enzymes.
❌ E. In cystic fibrosis, there is a deletion of the phenylalanine (F) at position 508 of the CFTR protein. This protein is misfolded in the RER. Misfolded CFTR is recognized as defective --> retained in the RER, and degraded instead of being transported anterogradely by COP2 vesicles to the Golgi; hence, very little functional CFTR channel makes it to the cell surface.
