Cushing reflex
Cushing reflex (also referred to as the vasopressor response, the Cushing effect, the Cushing reaction, the Cushing phenomenon, the Cushing response, or Cushing's Law) is a physiological nervous system response to increased
Definition
The Cushing reflex classically presents as an increase in
In response to rising intracranial pressure (ICP), respiratory cycles change in regularity and rate. Different patterns indicate a different location of the brain where the injury occurred.
Differential diagnosis
Whenever a Cushing reflex occurs, there is a high probability of death in seconds to minutes. As a result, a Cushing reflex indicates a need for immediate care. Since its presence is a good detector of high ICP, it is often useful in the medical field, particularly during surgery.
It has also been reported that the presence of a Cushing reflex due to an ICP increase could allow one to conclude that ischemia has occurred in the
As first postulated by Harvey Cushing, raised intracranial pressure is the primary cause of the Cushing reflex.
Brain plateau wave changes are also associated with the Cushing reflex. These waves are characterized by acute rises of the ICP, and are accompanied by a decrease of the cerebral perfusion pressure. It has been found that if a Cushing reflex occurs, brain plateau wave changes can be erased due to disappearance of high ICP.[9]
Mechanism
The Cushing reflex is complex and seemingly paradoxical.[15] The reflex begins when some event causes increased intracranial pressure (ICP). Since cerebrospinal fluid is located in an area surrounded by the skull, increased ICP consequently increases the pressure in the fluid itself. The pressure in the cerebral spinal fluid eventually rises to the point that it meets and gradually exceeds the mean arterial blood pressure (MAP). When the ICP exceeds the MAP, arterioles located in the brain's cerebrum become compressed. Compression then results in diminished blood supply to the brain, a condition known as cerebral ischemia.[7]
During the increase in ICP, both the sympathetic nervous system and the parasympathetic nervous system are activated. In the first stage of the reflex, sympathetic nervous system stimulation is much greater than parasympathetic stimulation.[13] The sympathetic response activates alpha-1 adrenergic receptors, causing constriction of the body's arteries.[16] This constriction raises the total resistance of blood flow, elevating blood pressure to high levels, which is known as hypertension. The body's induced hypertension is an attempt to restore blood flow to the ischemic brain. The sympathetic stimulation also increases the rate of heart contractions and cardiac output.[17] Increased heart rate is also known as tachycardia. This combined with hypertension is the first stage of the Cushing reflex.[citation needed]
Meanwhile, baroreceptors in the aortic arch detect the increase in blood pressure and trigger a parasympathetic response via the vagus nerve. This induces bradycardia, or slowed heart rate, and signifies the second stage of the reflex.[18] Bradycardia may also be caused by increased ICP due to direct mechanical distortion of the vagus nerve and subsequent parasympathetic response.[citation needed] Furthermore, this reflexive increase in parasympathetic activity is thought to contribute to the formation of Cushing ulcers in the stomach, due to uncontrolled activation of the parietal cells. The blood pressure can be expected to remain higher than the pressure of the raised cerebral spinal fluid to continue to allow blood to flow to the brain. The pressure rises to the point where it overcomes the resisting pressure of the compressed artery, and blood is allowed through, providing oxygen to the hypoxic area of the brain. If the increase in blood pressure is not sufficient to compensate for the compression on the artery, infarction occurs.[19]
Raised ICP, tachycardia, or some other endogenous stimulus can result in distortion and/or increased pressure on the brainstem. Since the brainstem controls involuntary breathing, changes in its homeostasis often results in irregular respiratory pattern and/or apnea.[20] This is the third and final stage of the reflex.
The role of the central chemoreceptors in the Cushing reflex is unclear. In most normal pressure responses the chemoreceptors and baroreceptors work together to increase or decrease blood pressure. In the Cushing reflex, the central chemoreceptors are likely involved in the detection of ischemia, contributing to the sympathetic surge and hypertension in the first phase of the reflex, and work in opposition to the baroreceptors, contributing to the combined high sympathetic and parasympathetic activation.[21]
Function
Raised intracranial pressure can ultimately result in the shifting or crushing of
Cushing's triad
Cushing's triad refers to when all of these symptoms are seen together:[22]
- Irregular, decreased respirations (caused by impaired brainstem function)
- Bradycardia
- Systolic hypertension (widening pulse pressure)[23]
History
Cushing's reflex is named after
Experimental setup and results
Cushing began experimenting once he obtained approval from Kocher. His experimental setup was a modified version of
This research clearly displayed the cause and effect relationship between intracranial pressure and cerebral compression.[25] Cushing noted this relationship in his subsequent publications. He also noted that there must exist a specific regulatory mechanism that increased blood pressure to a high enough point such that it did not create anemic conditions.[3] Cushing's publications contain his observations and no statistical analysis. The sample size of the experiment is also not known.[25]
Other researchers
Several notable figures in the medical field, including Ernst von Bergmann,[26] Henri Duret,[27] Friedrich Jolly,[28] and others experimented with intracranial pressure similarly to Cushing. Some of these researchers published similar findings concerning the relationship of intracranial pressure to arterial blood pressure before Cushing had begun experimenting. Cushing studied this relationship more carefully and offered an improved explanation of the relationship.[4]
Some controversy concerning plagiarism does surround some of Cushing's research. Bernhard Naunyn, a German pathologist and contemporary of Cushing, made remarks claiming that Cushing neither cited him in Cushing's research nor expanded on any of the results that he had found in his original experiments.[29]
Research directions
Although a lot of progress has been made since 1901 when
The nature of receptors mediating the Cushing response is also unknown.[30] Some research suggests the existence of intracranial baroreceptors to trigger specific Cushing baroreceptor reflex.[31] Experiments by Schmidt and his fellow researchers showed that the Cushing reflex is directed by autonomic nervous system, since its physiological change has to do with the balance of the sympathetic nervous system and parasympathetic nervous system.[31] However, the specific relation between the autonomic nervous system response and the Cushing reflex and its symptoms has yet to be identified.[31]
It has been determined that rate of
Some researchers have also suggested a long-term effect of the Cushing reflex.[7] Thus far it has only been observed as an immediate acute response, but there has been some evidence to suggest that its effects could be prolonged, such as a long-term raise in blood pressure.[7] Heightened sensitivity of neurological response systems leading to arterial hypertension is also possible, but has not been examined.[30]
Although the Cushing reflex was primarily identified as a physiological response when blood flow has almost ceased, its activity has also been seen in
The underlying mechanisms of the reflex on a cellular level are yet to be discovered, and will likely be the next area of research if scientists and or doctors chose to do so.[citation needed]
See also
References
- ^ PMID 12224233.
- PMID 3435736.
- ^ a b c d Cushing, H (1901). "Concerning a definite regulatory mechanism of the vasomotor centre which controls blood pressure during cerebral compression". Bull Johns Hopkins Hosp. 12: 290–2.
- ^ PMID 17143247.
- S2CID 6025444.
- ^ PMID 3375974.
- ^ PMID 2176941.
- ^ PMID 3813470.
- ^ S2CID 43225467.
- PMID 2643847.
- PMID 19100373.
- PMID 9227698.
- ^ S2CID 1449385.
- PMID 15805143.
- PMID 9102186.
- PMID 2887122.
- ^ Per Brodal (2004). The Central Nervous System: Structure and Function. Oxford University Press US. pp. 369–396.
- PMID 4402639.
- ISBN 978-0-7216-0240-0.
- ISBN 9780397511600.
- ISBN 9781455770052, retrieved 2019-11-10
- ISBN 978-1-60535-962-5.
- ISBN 978-1-4496-4151-1.
- ^ Leonard Hill (1896). Physiology and Pathology of the Cerebral Circulation. London: J & A Churchill.
- ^ a b Mitchell Fink; Michelle Hayes; Neil Soni (2008). Classic Papers in Critical Care. London, England: Springer. pp. 89–90.
- PMID 1584389.
- ^ Duret H (1878). Anatomic Studies of the Cerebral Circulation. Paris, Bailliere. p. 642.
{{cite book}}
: CS1 maint: location missing publisher (link) - ^ Friedrich Jolly (1871). About Intracranial Pressure and Blood Circulation Inside the Cranium. Medical Thesis (Thesis). Wurzburg, Germany.
- ^ JF Fulton (1946). Harvey Cushing. A biography. Springfield: Charles C. Thomas. pp. 176–193.
- ^ PMID 1102170.
- ^ )