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Pathophysiology of
traumatic brain injuryBy Amir Rezagholizadeh
Reference
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Outline
• Introduction• Etiology• Classification• Symptoms• General pathophysiology of TBI• Specific pathophysiology of TBI• References
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Introduction
• Traumatic brain injury (TBI) is physical injury to brain tissue that temporarily or permanently impairs brain function.
TBITBI
PDPDADAD HIVHIV
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Etiology
5 Top Causes
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ClassificationTBITBI
moderate
Occurrence
Location
mild moderate severe Primary
severity
Secondary DiffuseFocal
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• 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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• Head Injuries are commonly the basis of Occurrence categorized (a) primary damage, mechanical damage
(b) secondary damage, delayed non-mechanical damage
Classification
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• TBI are the basis of location classified as (a) focal brain damage
(b) diffuse brain damage
Classification
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Diffuse axonal injury
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Symptoms
SLEEP DYSREGULATIONTrouble falling asleep
Overnight awakening
Too much/too little sleep
MOOD DISRUPTIONIrritabilitySadnessAnxiety
PhysicalHeadaches
Dizziness
Light/noise sensitivity
Fatigue/tiredness
COGNITIVEFogginess
Concentration
Memory deficits
Cognitive fatigue
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• The first stage of the pathophysiological cascade
Direct tissue damage impaired Direct tissue damage impaired regulation ofregulation of
CBF and metabolismCBF and metabolism ‘‘Ischaemia-like’ patternIschaemia-like’ pattern
Accumulation of lactic acidAccumulation of lactic acidIncreased membrane Increased membrane permeabilitypermeability
Oedema formationOedema formation
General pathophysiology of TBI
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• The second stage of the pathophysiological cascade
General pathophysiology of TBI
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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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Specific pathophysiology of TBI
ischemic Uncoupling CBF and
metabolism
Increase ICP
Decrease CPP
Decrease CBF
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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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Specific pathophysiology of TBI
depolarization of vascular
smooth muscle
reduced nitric oxide
prostaglandincyclic GMPdepletion
Release endothelin
vasospasm
The mechanisms by which vasospasm occurs
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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
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release of excitatory neurotransmitter
over-stimulation of receptor
CaCa2+2+, Na, Na++, and, andKK++-fluxes-fluxes
trigger catabolicprocesses
increases Na+K+ATPase activity
flow–metabolismuncoupling
Specific pathophysiology of TBI
Excitotoxicity
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Oxidative stress
•Oxidative stress relates to the generation of reactiveoxygen 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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Oedema
Specific pathophysiology of TBI
Cytotoxic brain oedema
increased cell membrane permeability for ions, ionicpump failure due to energy depletion
Vasogenic brain oedema
functional breakdown of the endothelial cell
layer
Increase ICP21
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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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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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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Thank you for your attention
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