After five minutes of hypoxia due to stroke or circulatory failure, irreversible damage to vulnerable regions of the brain begins. These include the pyramidal cells of the hippocampus and neocortex and the Purkinje cells of the cerebellum, as well as other neurons located in watershed areas.
Hypoxic-ischemic encephalopathy results because the bulk of the energy for function of cells in the CNS is derived from oxidative phosphorylation, thus oxygen is critical. Even brief drops in perfusion can result in damage to brain tissue via cessation of oxidative phosphorylation, failure of membrane pumps, glutamate discharge into the synapse and calcium entry into the cell, causing irreversible cell damage. Moreover, without circulation there is no removal of toxic metabolites. In addition to its relation to stroke and cardiopulmonary arrest, hypoxic-ischemic encephalopathy also occurs in the newborn period in about 3.7/1000 births due to numerous intrapartum causes.
Bernheisel et al. discuss the subacute management of ischemic stroke, which may cause neuronal damage similar to that described due to cardiac arrest, but in more localized territories. These patients must be hospitalized and undergo cardiac and neuroimaging in order to determine the cause of the stroke. Diagnostic studies include magnetic resonance angiography, carotid artery ultrasound, and echocardiography are employed to determine the cause of the ischemic stroke.
Vadeboncoeur et al. studied a series of 593 consecutive out of hospital cardiac arrests distributed between two EMS agencies and found that survivors had experienced significantly greater depth of chest compressions (53.6mm) than non-survivors (48.8mm). This is consistent with 2010 AHA guidelines which recommend compression of at least 51mm. Increases in chest compression depth also showed a relationship with improved functional outcomes.
Illustration A is a gross specimen showing damage to the left hippocampus (smaller in size than right) resulting from ischemia.
Illustration B is a pathway depicting the sequence of events leading to neuronal injury caused by ischemia.
Answers 1-4: These regions are less susceptible to ischemia than the hippocampus, with the spinal cord generally being the last to be affected.
Bernheisel CR, Schlaudecker JD, Leopold K. Subacute management of ischemic stroke. Am Fam Physician. 2011 Dec 15;84(12):1383-8. Review. PubMed PMID: 22230273
PMID:22230273 (Link to Abstract)
Vadeboncoeur T, Stolz U, Panchal A, Silver A, Venuti M, Tobin J, Smith G, Nunez M, Karamooz M, Spaite D, Bobrow B. Chest compression depth and survival in out-of-hospital cardiac arrest. Resuscitation. 2013 Oct 12. doi:pii: S0300-9572(13)00769-7. 10.1016/j.resuscitation.2013.10.002. [Epub ahead of print] PubMed PMID: 24125742
PMID:24125742 (Link to Abstract)
USMLE World Step 1 QBank Question #18. Copyright © USMLEWorld, LLC 2012