WBR0580

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Author [[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Physiology
Sub Category SubCategory::Neurology
Prompt [[Prompt::Experimental studies suggest that age-related dementia may be caused by chronic cerebral ischemia that results from decreased cerebral perfusion. A new investigational drug is being evaluated for its possible role in the prevention of dementia. Cerebral perfusion studies during non-stressful events are performed following the administration of the investigational drug. Studies reveal vasodilation of the cerebral arteries. The vasodilation observed following the administration of the drug is similar to that of which of the following physiological mechanism?]]
Answer A AnswerA::Increase in arterial pCO2 only
Answer A Explanation AnswerAExp::Increase in arterial pCO2 leads to decrease in the cerebral blood pH and subsequent cerebral artery vasodilation.
Answer B AnswerB::Decrease in arterial pCO2 only
Answer B Explanation AnswerBExp::Decrease in arterial pCO2 leads to increase in the cerebral blood pH and subsequent cerebral artery vasoconstriction.
Answer C AnswerC::Increase in arterial pO2 only
Answer C Explanation AnswerCExp::Increase in arterial O2 does not regulate cerebral perfusion.
Answer D AnswerD::Decrease in arterial pO2 only
Answer D Explanation AnswerDExp::Decrease in arterial pO2 does not regulate cerebral perfusion unless the pO2 falls below 50 mmHg.
Answer E AnswerE::Increase in arterial pCO2 and decrease in arterial pO2
Answer E Explanation AnswerEExp::Increase in pCO2 causes vasodilation; decrease in pO2 does not affect cerebral blood flow unless pO2 falls below 50 mmHg.
Right Answer RightAnswer::A
Explanation [[Explanation::Cerebral perfusion is highly regulated by the cerebral blood pH that is mainly driven by the CO2 partial pressure in the cerebral arteries. In fact, cerebral perfusion is closely associated with intracranial volume regulation. CO2 is a potent vasodilator that is thought to act by directly affecting extracellular hydrogen ions on vascular smooth muscles along with induction of local prostanoids and nitric oxide secretion in the cerebral circulation. As such, hyperventilation, which decreases the partial pressure of CO2, is important to decrease the intracranial pressure among patients with cerebral edema. Hypercapnia causes vasodilation of cerebral arteries and leads to increased cerebral blood flow. In contrast, hypocapnia results in vasoconstriction and decreased cerebral blood flow. During ischemia, an increase in CO2 results in an acidic pH that causes vasodilation and consequently leads to an increase in the cerebral blood perfusion. CO2 affects cerebral perfusion until the partial pressure of CO2 reaches 90 mmHg, beyond which CO2 no longer regulates cerebral perfusion. In contrast, cerebral blood flow remains constant until severe hypoxemia is present, where partial pressure of oxygen needs to fall below 50 mmHg for changes in cerebral perfusion to be present. It is thought that acute hypoxia results in a drop of ATP that leads to opening of the K-ATP channels on smooth muscles. As channels open, hyperpolarization and vasodilation ensue.

Educational Objective: Cerebral perfusion is regulated by the pH of the blood, which is mainly driven by pCO2 in the cerebral blood. pCO2 affects cerebral perfusion until pCO2 reaches 90 mmHg, beyond which CO2 no longer regulates cerebral perfusion. pO2 does not affect cerebral perfusion unless it falls below 50 mmHg.
References: Battisti-Charbonney A, Fisher J, Duffin J et al. The cerebrovascular response to carbon dioxide in humans. J Physiol. 2011;589(12):3039-48.
Cipolla MJ. The Cerebral Circulation. San Rafael (CA): Morgan & Claypool Life Sciences; 2009. Chapter 5, Control of Cerebral Blood Flow.
First Aid 2014 page 459]]

Approved Approved::Yes
Keyword WBRKeyword::Cerebral flow, WBRKeyword::Cerebral blood flow, WBRKeyword::Chemoreceptor, WBRKeyword::Hypoxia, WBRKeyword::Cerebral perfusion, WBRKeyword::Perfusion, WBRKeyword::pCO2, WBRKeyword::pO2, WBRKeyword::Partial pressure, WBRKeyword::Vasodilation, WBRKeyword::Vasoconstriction, WBRKeyword::Blood flow
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