The Brain Hypometabolism Hypothesis Part 52: Secondary Brain Injury and Carbon Dioxide

Model Brain

Sekhon, Ainslie and Griesdale discuss the effect of Carbon Dioxide levels on outcome in secondary brain injury after Hypoxic Ischaemic Brain Injury (HIBI) following cardiac arrest.

It is useful to talk about Carbon Dioxide during cardiac arrest in the first place. The respiratory cycle involves inhalation (Oxygen is approximately 21% of the atmosphere by volume) and exhalation. Exhaled Carbon Dioxide is measured with capnometry and the typical values for Carbon Dioxide in exhaled air are between 4 and 5.5% (e.g (Han et al, 1997)).

Cardiac arrest is effectively cardio-respiratory arrest and the absence of exhalation of Carbon Dioxide would be expected to lead to the retention of Carbon Dioxide. There are many causes of a cardiac-arrest and these different causes can differentially affect the Carbon Dioxide levels in the period leading up to the cardiac arrest. Nevertheless in one study, arterial Carbon Dioxide levels were checked during out of hospital cardiac arrest and Hypercapnia was identified in 94% of cases and Hypocapnia in 6% of cases (Spinelboeck et al, 2016). Therefore in terms of modelling it can be assumed that during the period of Hypoxic injury there is associated Hypercapnia.

In secondary injury after Hypoxic Ischaemic Brain Injury (HIBI), Sekhon and colleagues note that there is a complex relationship between subsequent Carbon Dioxide levels and clinical outcomes (Sekhon et al, 2017). They note the physiological effects of Carbon Dioxide on vascular smooth muscle tone. This in turn affects resistance and Cerebral Blood Flow (CBF). Hypercapnia leads to Cerebral Vasodilatation and Hyperemia which the authors note can lead to reduced CBF.

Following HIBI the authors note that there has been a lot of discussion about the optimal Carbon Dioxide levels in terms of clinical outcomes. They identify that multiple lines of evidence show that Normocapnia is associated with good neurologic outcomes compared to Hypocapnia and Hypercapnia. They also suggest future studies to examine physiological values which in turn would be helpful for modelling.

Interestingly one study found a correlation between Near Death Experiences and Carbon Dioxide levels in survivors of out-of-hospital cardiac arrest (Klemenc-Ketis, Kersnik and Grmec, 2010).

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.

1024px-Acetyl-CoA-3D-vdW

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 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.

References

Han JN, Stegen K, Simkens K, Cauberghs M, Schepers R, Van den Bergh O, Clément J, Van de Woestijne KP. Unsteadiness of breathing in patients with hyperventilation syndrome and anxiety disorders. Eur Respir J. 1997 Jan;10(1):167-76.

Klemenc-Ketis Z, Kersnik J, Grmec S. The effect of carbon dioxide on near-death experiences in out-of-hospital cardiac arrest survivors: a prospective observational study. Critical Care. 2010;14(2):R56. doi:10.1186/cc8952.

 

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.

Index: There are indices for the TAWOP site here and here

Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link.

TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link.

Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk.

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”

Information and Technology for Better Care: Making Better Use of Health and Care Information

computer-keyboard-1380475577zzm

The fifth part of the strategy ‘Information and Technology for Better Care’ is about ‘Making Better Use of Health and Care Information’. NHS Digital is developing

  • An increasing use of Open Data
  • Data extraction services that will reduce burden on care providers to collect data
  • The use of personal apps
  • The use of wearable devices

The vision is for the UK to be

  • A global leader in research
  • A global leader in utilising care data to contribute towards services.

What is the ‘Information and Technology for Better Care’ Paper?

NHS Digital (formerly known as The Health and Social Care Information Centre) published a 5 year strategy in 2015 titled ‘Information and Technology for Better Care’. This document covers a number of areas.

References

https://digital.nhs.uk/article/249/Our-Strategy, accessed 20.4.17

Index: There are indices for the TAWOP site here and here

Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link.

TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link.

Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk.

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”

Information and Technology for Better Care: Supporting Health and Care Organisations with Technology, Data and Information

computer-keyboard-1380475577zzm

The NHS Digital Strategy has five parts. The fourth part focuses on supporting health and care organisations with ‘technology, data and information’. In the strategy it is noted that technology can be used to reduce the funding gap. The HSCIC (now NHS Digital) will support organisations to make use of technology and make expertise available to support organisations with issues such as interoperability. They will develop enabling technology, work with digital champions and establish an innovation centre amongst other actions.

What is the ‘Information and Technology for Better Care’ Paper?

NHS Digital (formerly known as The Health and Social Care Information Centre) published a 5 year strategy in 2015 titled ‘Information and Technology for Better Care’. This document covers a number of areas.

References

https://digital.nhs.uk/article/249/Our-Strategy, accessed 20.4.17

Index: There are indices for the TAWOP site here and here

Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link.

TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link.

Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk.

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”

The Brain Hypometabolism Hypothesis Part 51: Anaemia in Secondary Brain Injury After Hypoxia

 

Model Brain

Sekhon, Ainslie and Griesdale discuss anaemia as another factor relevant to the pathophysiology of secondary brain injury after hypoxia. This is not involved in a causal chain of events resulting from hypoxia but instead it is suggested that it influences the pathophysiology. The authors reference various observational studies that identify an association between Haemoglobin levels and clinical outcomes following hypoxia secondary to hypoxic ischaemic brain injury (HIBI).

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.

1024px-Acetyl-CoA-3D-vdW

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 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.

Index: There are indices for the TAWOP site here and here

Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link.

TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link.

Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk.

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”

The Brain Hypometabolism Hypothesis Part 50: Acetyl CoA

1024px-Acetyl-CoA-3D-vdW

 

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.

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

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.

Index: There are indices for the TAWOP site here and here

Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link.

TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link.

Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk.

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”

Information and Technology for Better Care: National Services to Meet Local Needs

computer-keyboard-1380475577zzm

The NHS Digital Strategy has five parts. The third part focuses on national services to meet local needs. This part of the strategy references key services including

  • The NHS spine
  • National e-mail services
  • National network services
  • NHS Choices
  • The Summary Care Record
  • NHS referrals
  • The Electronic Prescription Service

In this part of the strategy there is a focus on developing national standards to ensure universal access and a seamless integration of the key services as well as an extension of these services into social care.

What is the ‘Information and Technology for Better Care’ Paper?

NHS Digital (formerly known as The Health and Social Care Information Centre) published a 5 year strategy in 2015 titled ‘Information and Technology for Better Care’. This document covers a number of areas.

References

https://digital.nhs.uk/article/249/Our-Strategy, accessed 20.4.17

Index: There are indices for the TAWOP site here and here

Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link.

TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link.

Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk.

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”