Pathophysiology of traumatic brain injury

1. Pathophysiology
of
traumatic brain injury
By Amir Rezagholizadeh

2. Reference
2

3. Outline
• Introduction
• Etiology
• Classification
• Symptoms
• General pathophysiology of TBI
• Specific pathophysiology of TBI
• References
3

4. Introduction
• Traumatic brain injury (TBI) is physical injury to brain tissue
that temporarily or permanently impairs brain function.
TBITBI
PDPD
ADAD HIVHIV
4

5. Etiology
5 Top
Causes
5

6. Classification
TBITBI
moderate
Occurrenc
e
Location
mild moderate severe Primary
severity
Secondary DiffuseFocal
6

7. • Traumatic brain injury is graded as mild, moderate, or severe
on the basis of the level of consciousness or Glasgow coma
scale (GCS) .
Classification
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8. • Head Injuries are commonly the basis of Occurrence categorized
(a) primary damage, mechanical damage
(b) secondary damage, delayed non-mechanical damage
Classification
8

9. • TBI are the basis of location classified as
(a) focal brain damage
(b) diffuse brain damage
Classification
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10. Diffuse axonal injury
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11. Symptoms
SLEEP
DYSREGULATION
Trouble falling asleep
Overnight awakening
Too much/too little sleep
MOOD DISRUPTION
Irritability
Sadness
Anxiety
Physical
Headaches
Dizziness
Light/noise sensitivity
Fatigue/tiredness
COGNITIVE
Fogginess
Concentration
Memory deficits
Cognitive fatigue
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12. • The first stage of the pathophysiological cascade
Direct tissue damage impairedDirect tissue damage impaired
regulation ofregulation of
CBF and metabolismCBF and metabolism
Direct tissue damage impairedDirect tissue damage impaired
regulation ofregulation of
CBF and metabolismCBF and metabolism ‘‘Ischaemia-like’ patternIschaemia-like’ pattern‘‘Ischaemia-like’ patternIschaemia-like’ pattern
Accumulation of lactic acidAccumulation of lactic acidAccumulation of lactic acidAccumulation of lactic acidIncreased membraneIncreased membrane
permeabilitypermeability
Increased membraneIncreased membrane
permeabilitypermeability
Oedema formationOedema formationOedema formationOedema formation
General pathophysiology of TBI
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13. • The second stage of the pathophysiological cascade
General pathophysiology of TBI
13

14. Specific pathophysiology of TBI
Cerebral blood flow:
•Studies in laboratory animals and humans have investigated
the effects of TBI on CBF .
•CBF α CPP
•CPP = MAP – ICP
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15. Specific pathophysiology of TBI
ischemic Uncoupling
CBF and
metabolism
Increase ICP
Decrease
CPP
Decrease
CBF
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16. Cerebral vasospasm :
•Vasospasm occurs in more than one-third of patients with
TBI and indicates severe damage to the brain .
•Hypoperfusion occurs in 50% of all patients developing
vasospasm.
Specific pathophysiology of TBI
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17. Specific pathophysiology of TBI
depolarization
of vascular
smooth muscle
reduced
nitric oxide
prostaglandin
cyclic GMP
depletion
Release
endothelin
vasospasm
The mechanisms by which
vasospasm occurs
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18. Cerebral metabolic dysfunction
•Cerebral metabolism and cerebral energy state frequently
reduced after TBI .
•The reduction in post-traumatic cerebral metabolism relates to
intramitochondrial Ca2+
overload , the mitochondrial dysfunction
with reduced ATP-production and reduced availability of the
nicotinic co-enzyme pool .
Specific pathophysiology of TBI
18

19. release of excitatory
neurotransmitter
release of excitatory
neurotransmitter
over-
stimulation of receptor
over-
stimulation of receptor
CaCa2+2+
, Na, Na++
, and, and
KK++
-fluxes-fluxes
CaCa2+2+
, Na, Na++
, and, and
KK++
-fluxes-fluxes
trigger catabolic
processes
trigger catabolic
processes
increases Na+
K+
ATPase
activity
increases Na+
K+
ATPase
activity
flow–metabolism
uncoupling
flow–metabolism
uncoupling
Specific pathophysiology of TBI
Excitotoxicity
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20. Oxidative stress
•Oxidative stress relates to the generation of reactive
oxygen species in response to TBI .
•The excessive production of reactive oxygen species due to
excitotoxicity and exhaustion of the endogenous antioxidant
system .
•Reactive oxygen species induces peroxidation of cellular and
vascular structures, protein oxidation, cleavage of DNA, and
inhibition of the mitochondrial electron transport chain .
Specific pathophysiology of TBI
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21. Oedema
Specific pathophysiology of TBI
Cytotoxic brain
oedema
increased cell membrane
permeability for ions, ionic
pump failure due to energy
depletion
Vasogenic brain
oedema
functional breakdown of
the endothelial cell
layer
Increase ICP
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22. Inflammation
•Damage to the endothelium of blood vessels is a known
pathway for initiation of inflammation .
•Both primary and secondary insults activate the release of
cellular mediators including proinflammatory cytokines,
prostaglandins and free radicals .
•Proinflammatory enzymes such as tumour necrosis factor,
interleukin-1-ß, and interleukin-6 are upregulated within hours
from injury.
Specific pathophysiology of TBI
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23. Necrosis vs apoptosis
• Necrosis occurs in response to severe mechanical or
ischaemic/ hypoxic tissue damage with excessive release of
excitatory amino acid neurotransmitters and metabolic failure.
•The nature of apoptosis generally requires energy supply and
imbalance between naturally occurring pro- and anti-apoptotic
proteins.
•Caspases have been idientified as the most important
mediators of programmed cell death.
Specific pathophysiology of TBI
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24. References
• Werner, C., & Engelhard, K. (2007). Pathophysiology of
traumatic brain injury. British journal of anaesthesia, 99(1), 4-
9.
• Mustafa, Ayman G., and Othaman A. Alshboul.
"Pathophysiology of traumatic brain injury." Neurosciences
18.3 (2013): 222-234.
• Prins, Mayumi, et al. "The pathophysiology of traumatic brain
injury at a glance." Disease models and mechanisms 6.6
(2013): 1307-1315.
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25. Thank you for your attention
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