The Brain Hypometabolism Hypothesis Part 48: Secondary Brain Injury with Hypoxia – Microvascular Dysfunction + Reperfusion Injury (Updated 22.4.17)

Model Brain

In their article Sekhon, Ainslie and Griesdale have identified microvascular dysfunction and reperfusion injury as one of the 7 factors that lead to secondary brain injury after hypoxia. Following the return of spontaneous circulation (ROSC) they identify

  1. A loss of the endothelial functions
  2. Reperfusion injury

The Context of Hypoxic Ischaemic Brain Injury

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

  1. Primary cerebral hypoxia
  2. 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

  1. Accumulation of Na+ ions
  2. Accumulation of lactate with acidosis
  3. 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

  1. Microvascular dysfunction
  2. Cerebral oedema
  3. Anaemia
  4. Impaired autoregulation
  5. Carbon Dioxide
  6. Hyperoxia
  7. Hyperthermia

 

Human_Metabolism_-_Pathways

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

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.

The Citric Acid Cycle

KrebbsCycle
The Citric Acid Cycle (CC BY 3.0) by Narayanese, WikiUserPedia, YassineMrabet, TotoBaggins, Wadester16

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

  1. Generation of energy in the form of ATP
  2. Generating NADH which is utilised in oxidative phosphorylation
  3. Citric Acid is regenerated
  4. 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.

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Disclaimer: The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

Conflicts of Interest: *For potential conflicts of interest please see the About section”

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