Sekhon, Ainslie and Griesdale identify cerebral autoregulation as one of the factors relevant to secondary brain injury after Hypoxic Ischaemic Brain Injury (HIBI). In order to discuss cerebral autoregulation in more detail it is necessary to first discuss mean arterial pressure.
What is Mean Arterial Pressure?
The mean arterial pressure is the average arterial blood pressure in a cardiac cycle (Meaney et al, 2000). This is classically approximated by the use of the formula
MAP = [SP + (2DP)]/3
SP = Systolic Blood Pressure
DP = Diastolic Blood Pressure (Meaney et al, 2000) although there is another approximation mentioned in the same paper.
What is Cerebral Autoregulation?
Cerebral autoregulation refers to the maintenance of cerebral blood flow to meet the metabolic demands of the cerebrum. Cerebral autoregulation requires adaptation of the cerebral blood flow to changes in the Mean Arterial Pressure (MAP).
The Context of Hypoxic Ischaemic Brain Injury (HIBI)
Sekhon, Ainslie and Griesdale have written an open access article on hypoxic ischaemic brain injury titled “Clinical Pathophysiology of Hypoxic Ischemic Brain Injury after Cardiac Arrest:A “two-hit” Model“. This paper can be used as a starting point for discussion of the events that lead to brain injury following hypoxia. This in turn is relevant to the question of energy usage in the Brain Hypometabolism Hypothesis.
Sekhon, Ainslie and Griesdale posit a simple two stage model of brain injury following cardiac arrest in which injury results from
- Primary cerebral hypoxia
- Secondary mechanisms after return of cerebral perfusion
In Sekhon, Ainslie and Griesdale’s model they discuss primary and secondary brain injury following a cardiac arrest.
Primary Brain Injury after Hypoxia
Looking more closely at the primary brain injury they state that with a reduction in cerebral oxygen ATP production decreases and there is a switch to anaerobic respiration. This in turn leads to a reduction in ATP dependent ion channel action. There are three main effects
- Accumulation of Na+ ions
- Accumulation of lactate with acidosis
- An influx of Calcium ions into the cells
Secondary Brain Injury after Hypoxia
Sekhon, Ainslie and Griesdale identify 7 factors associated with secondary brain injury after hypoxia in their two stage model. These 7 factors are
- Microvascular dysfunction
- Cerebral oedema
- Impaired autoregulation
- Carbon Dioxide
Human Metabolism by Frozen Man (CC BY 4.0)
What is Metabolism?
Metabolism can be defined as the chemical processes that occur in living organisms. There are three types of metabolic processes
(a) Generation of energy
(b) Generation of basic chemicals including fatty acids, amino acids and sugars
(c) Elimination of Nitrogen waste products
Brain Hypometabolism Hypothesis
The Brain Hypometabolism Hypothesis focuses on energy metabolism. More specifically the hypothesis states that
‘Energy hypometabolism in the brain leads to neuropathology‘
Glycolysis by Dr Thomas Shafee (CC BY 4.0)
Glycolysis is one of the key pathways for energy metabolism in the human body. In this metabolic pathway the molecule Glucose is converted into Pyruvate. This pathway generates energy in the form of ATP. This pathway however does not use oxygen although the products generated are metabolised using oxygen. This is relevant to the bigger picture of energy metabolism in the brain.
Acetyl CoA Space Filling Molecule by Benjah-bmm27 (Public Domain)
Acetyl Coenzyme A is an important molecule for many pathways involved in energy metabolism. Acetyl Coenzyme A is derived from
(a) Glucose via the Glycolysis pathway
(b) Amino acids via Acetoacetyl-CoA, Pyruvate and directly through multiple pathways
(c) Fatty acids via Beta-oxidation
Vitamin B5 is required for the synthesis of Acetyl CoA.
The Citric Acid Cycle
The Citric Acid Cycle (CC BY 3.0) by,
The Citric Acid Cycle is one of the main energy metabolism pathways in humans. Acetyl Co-A which is generated from other pathways is utilised in the Citric Acid Cycle. The Citric Acid Cycle has a number of properties
- Generation of energy in the form of ATP
- Generating NADH which is utilised in oxidative phosphorylation
- Citric Acid is regenerated
- Carbon Dioxide is produced
The Citric Acid Cycle takes place in the Mitochondria.
The Citric Acid Cycle is important for the discussion of the Brain Hypometabolism Hypothesis where we have already discussed the metabolism of Glucose.
Meaney E, Alva F, Moguel R, Meaney A, Alva J, Webel R. Formula and nomogram for the sphygmomanometric calculation of the mean arterial pressure. Heart. 2000 Jul;84(1):64.
Mypinder S. Sekhon, Philip N. Ainslie and Donald E. Griesdale
Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a “two-hit” model. Critical Care. 2017. 21:90. DOI: 10.1186/s13054-017-1670-9
Spindelboeck W, Gemes G, Strasser C, Toescher K, Kores B, Metnitz P, Haas J, Prause G. Arterial blood gases during and their dynamic changes after cardiopulmonary resuscitation: A prospective clinical study.Resuscitation. 2016 Sep;106:24-9. doi: 10.1016/j.resuscitation.2016.06.013. Epub 2016 Jun 18.
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