pathophysiology of brain injury
DESCRIPTION
Pathophysiology of brain injury. F. Della Corte – C. Maestrone Intensive Care Unit – University of Novara -School of Medicine. Objectives. -To describe which are the common pathophysiological features shared by head injury and stroke -To define the mechanisms of hypoxic-ischaemic - PowerPoint PPT PresentationTRANSCRIPT
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F. Della Corte – C. Maestrone
Intensive Care Unit – University of Novara -School of Medicine
Pathophysiology of Pathophysiology of brain injurybrain injury
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F. Della Corte, MD
ObjectivesObjectives
-To describe which are the common pathophysiological features shared by head injury and stroke
-To define the mechanisms of hypoxic-ischaemic damage at neuronal level
-To stress the importance of ischemia in the determination of severity in the outcome in head injured patients
-To define the consequences of ischemic events in the adult
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F. Della Corte, MD
Ischemic stroke vs Head injury
In most of the presentations molecular In most of the presentations molecular mechanisms are basically the same though mechanisms are basically the same though operating in:operating in:
-different sequences-different sequences-different time courses-different time courses-different intensities-different intensities
Peripheral penumbraPeripheral penumbra
Central coreCentral core
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F. Della Corte, MD
Factors contributing to the increase of irreversibly damaged
brain parenchyma
Deterioration of CBF
due to progressive
damage of arterial
blood supply
Activation of cytotoxicActivation of cytotoxic
processes secondary toprocesses secondary to
formation and/or releaseformation and/or release
of neurotoxic mediators of neurotoxic mediators
compound and compound and
developmentdevelopment
of tissue acidosisof tissue acidosis
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F. Della Corte, MD
• Inadequate Energy supplyInadequate Energy supply
Cellular injury during ischemiaCellular injury during ischemia
• Consequences of calcium overloadConsequences of calcium overload
• Deterioration of Ion GradientsDeterioration of Ion Gradients
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F. Della Corte, MD
Mild to moderate ischemiaMild to moderate ischemiaSevere ischemiaSevere ischemiaAdvanced ischemiaAdvanced ischemia
Insufficient oxygenInsufficient oxygenand glucoseand glucose
Inadequate energyInadequate energysupplysupply
Failure of neuronal activityFailure of neuronal activityRegional brain dysfunctionRegional brain dysfunction
Influx of waterInflux of waterNaNa++ Cl Cl--
Loss of functionLoss of functioncauses accumulationcauses accumulation
of glutamate of glutamate and aspartateand aspartatewhich bind towhich bind to
NMDA receptorsNMDA receptorsInflux of CaInflux of Ca2+2+
Influx of waterInflux of waterNaNa++ Ca Ca2+2+
Destruction of cellDestruction of cell
componentscomponents
Formation of Formation of
free radicals,free radicals,
eicosanoids andeicosanoids and
leukotrienesleukotrienes
Accumulation of lactic acid and HAccumulation of lactic acid and H++
compromises neuronal integritycompromises neuronal integrity
AnaerobicAnaerobicmetabolismmetabolism
Cytotoxic edemaCytotoxic edema
Irreversible cellular injuryIrreversible cellular injury
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F. Della Corte, MD
Cellular injury during ischemia - Inadequate energy Cellular injury during ischemia - Inadequate energy supplysupply
Ischemia Ischemia ( O( O22,glucose),glucose)
ATP ATP DepolarisationDepolarisation
Failed homeostatic Failed homeostatic mechanismsmechanisms
Lactic acidLactic acid
Free FeFree Fe2+2+
Free radicalsFree radicals
Glial injuryGlial injury
IRREVERSIBLE INJURYIRREVERSIBLE INJURY
ProteolysiProteolysiss
NO synthesisNO synthesisLipolysisLipolysis
GlutamateGlutamate
Arachidonic acidArachidonic acidAuto-oxidationAuto-oxidation
NA DANA DA
NeurotransmittersNeurotransmitters
[H[H++]][Na[Na++] ] ii [K[K++] ] ii [Cl[Cl--] ] ii
[Ca[Ca2+2+] ] ii
VCRVCR
LCRLCR
Free radicalsFree radicals
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F. Della Corte, MD
Ischemia and brain injury
Prognosis in head injury has been strictly correlated with:Prognosis in head injury has been strictly correlated with:
-the degree-the degree-the duration of the ischemia-the duration of the ischemia
More than 90% of authopsies on HI pts showed ischemicMore than 90% of authopsies on HI pts showed ischemiclesions of different severitylesions of different severity
Graham D.I., Adams J.H. Ischemic brain damage in fatal head injuries. Lancet 1:265-266, 1971
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F. Della Corte, MD
Posttraumatic cerebral ischemiaPosttraumatic cerebral ischemia
IntracranialIntracranial
hypertensionhypertensionArterial Arterial
hypotensionhypotension
Brain edema andBrain edema and
swellingswelling
Focal tissue compressionFocal tissue compression
from intracranial hematomasfrom intracranial hematomas
VasospasVasospasmm
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F. Della Corte, MDMartin NA, Patwardhan RV, et al: Characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and vasospasm. J Neurosurg 87: 9-19, 1997
Day
0 1 2 3 4 5 6 7 8 9 10 11 12 13
CBFml/100g/min
CBFml/100g/min
25
35
40
50
30
45
. .... .
.
.
..
I II IIIPhase
Time course and CBF in head injuryTime course and CBF in head injury
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F. Della Corte, MDBouma GJ, Muizelaar JP, Choi SC, et al: Cerebral circulation and metabolism after severe traumatic brain injury: the elusive role of ischemia. J Neurosurg 75: 685-693, 1991
20
25
30
35
0
10
20
30
40
hours after injury6 12 18 24 30 36 42 48
.
..
....
.
. .
CBFCBFml/100g/minml/100g/min
CBFCBFml/100g/minml/100g/min
40
%%ischemiaischemia
%%ischemiaischemiaTime course and CBF in head injuryTime course and CBF in head injury
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F. Della Corte, MD
Bouma GJ, Muizelaar JP, Choi SC, et al: Cerebral circulation and metabolism after severe traumatic brain injury: the elusive role of ischemia. J Neurosurg 75: 685-693, 1991
hours
3.0
4.0
5.0
6.0
7.0
9.0
8.0
.Motorscore
= 1,2
= 3,4,5
.
...
.
AJDOAJDO22
ml/100mlml/100ml
AJDOAJDO22
ml/100mlml/100ml Time course and CBF in head injuryTime course and CBF in head injury
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F. Della Corte, MD
Martin NA, Patwardhan RV, et al: Characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and vasospasm. J Neurosurg 87: 9-19, 1997
PhaseI II III
%
CBF(ml/100g/min)
> 55
35 to 55
< 35
0
10
20
30
40
50
60
70
80
90
100
Time course and CBF in head injuryTime course and CBF in head injuryTime course and CBF in head injuryTime course and CBF in head injury
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F. Della Corte, MD
SEQUENTIAL ACTIVATION OF SEQUENTIAL ACTIVATION OF CEREBROVASCULAR CEREBROVASCULAR
RESPONSESRESPONSES
CBF CBF (ml/100g/m)(ml/100g/m)
SurvivalSurvival
Ischemic thresholdIschemic threshold
DeathDeath
0 1 2 3 4 5 6 7 8 9 10 days post injury0 1 2 3 4 5 6 7 8 9 10 days post injury
Bullock MR et Al J. Neurotrauma 1996; 13; 643-Bullock MR et Al J. Neurotrauma 1996; 13; 643-55
5050
4040
3030
1010
2020
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F. Della Corte, MD
SEQUENTIAL ACTIVATION SEQUENTIAL ACTIVATION OF INJURY PROCESSESOF INJURY PROCESSES
ICP ICP mechanismsmechanisms
Cytotoxic edemaCytotoxic edema
Vascular engoargementVascular engoargement
Vasogenic edemaVasogenic edema
0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 9 10 days post injurydays post injuryBullock MR et Al J. Neurotrauma 1996; 13; 643-Bullock MR et Al J. Neurotrauma 1996; 13; 643-55
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F. Della Corte, MD
0
5
10
15
20
25
30
35
40
24h day 2 day 3 day 4 day 5 day >5
%desaturations(SjO2 < 50% for ten minutes or more)
Time course of jugular venous desaturationsTime course of jugular venous desaturationsGopinath SP: J Neurol,Neurosurg and Psy 1994; 57:717-723
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F. Della Corte, MD
CBF and incidence of jugular venous desaturations
43
44
45
46
47
48
49
50
51
52
None One Multiple
Gopinath SP: J Neurol,Neurosurg and Psy 1994; 57:717-723
ml/100g/min
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F. Della Corte, MD
Oxygen and glucose metabolism after head injury
0
3
6
9
12
CMRO2 CMRglu Metabolic Ratio
Head injuryNormal values
100
50
0
%
Bergsneider: J Neurosurg 86; 241-251, 1997
Metabolic ratio =CMRO2/CMRglu
Metabolic ratio =CMRO2/CMRglu
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F. Della Corte, MD
29.3 + 16.4Mc Laughlin, 1996
39.9 + 11.2 (Schroeder, 1995)
42.5 + 15.8 (Mc Laughlin, 1996)Vasoreactivity 0.4-9.1%
ContusionContusion
Perilesional edemaPerilesional edema
CT-normal tissueCT-normal tissue
Cerebral Blood FlowCerebral Blood Flow
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F. Della Corte, MD
Brain oxygen tension
Van den Brink, Neurosurgery 46; 868-878, 2000
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F. Della Corte, MD
Glutamate
0
2
4
6
8
10
12
14
16
Day 1 Day 2 Day 3 Day 4
M
Days after injury
Yamamoto: Acta Neurochir S75: 31-34
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F. Della Corte, MD
Potassium
0
0,5
1
1,52
2,5
3
3,5
4
0 20 40 60 80
mM
hours
ContusionContusion No contusionNo contusion
Doppenber EMR: Determinants of cerebral extracellular potassium after severe human head injury. Acta Neurochir 1999; S75: 31-34
PotassiumPotassium
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F. Della Corte, MD
Framework of stroke
Stroke
InfarctionInfarction85%85%
HemorrhageHemorrhage15%15%
CerebrovascularCerebrovasculardiseasedisease
80%80% Cardiogenic Cardiogenic embolismembolism
15%15%Other Other
unusualunusual5%5%
IntracerebralIntracerebral
SubarachnoidSubarachnoid
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F. Della Corte, MD
Atherosclerosis and thrombus formation
Physiological subtypes of thrombotic-related ischemic strokePhysiological subtypes of thrombotic-related ischemic stroke
ThrombosisThrombosis
Primary large vesselPrimary large vesselocclusive diseaseocclusive disease
Primary small vesselPrimary small vesselocclusive diseaseocclusive disease
EmbolismEmbolism
-arterial atherothrombosis-cardiogenic
atrial fibrillationmyocardial infarction/mural thrombuscardiomyopathyprosthetic valves
-”paradoxical” (deep vein thrombosis)
-atherothrombosis-dissection-arteritis-migraine-drug-induced-etc
-”lacunar” (i.e. microatheroma/lipoyalinosis-arteritis-eclampsia-drug-induced-antiphospholipid antibodies
Rotthrock JF In Hemostasis and Thrombosis:Philadelphia, JB Lippincott Company, 1994
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F. Della Corte, MD
Atherosclerosis and thrombus formation
Oxydation of LDL cholesterolOxydation of LDL cholesterol
Monocyte/MacrophageMonocyte/Macrophage Endothelial cellsEndothelial cells Smooth muscle cellsSmooth muscle cells
Free radical releaseFree radical release
Oxidize LDL cholesterolOxidize LDL cholesterol
Foam cell Foam cell formationformation
Recruit monocytesRecruit monocytesInhibit macrophage egressInhibit macrophage egress
Promote endothelialPromote endothelialinjuryinjury
Cytotoxicity
Scave
nger rece
ptor
De Graba TJ in Barnett (eds): Stroke:Pathophysiology, De Graba TJ in Barnett (eds): Stroke:Pathophysiology, Diagnosis and Management - New York - Churchill Davidson, 1992Diagnosis and Management - New York - Churchill Davidson, 1992
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F. Della Corte, MD
Atherosclerosis and thrombus formationAtherosclerosis and thrombus formation
Minimal endothelial injuryMinimal endothelial injury
Role of Monocytes and T Lymphocytes Role of Monocytes and T Lymphocytes in the transformation to foam cellsin the transformation to foam cells
Smooth muscle cell migration Smooth muscle cell migration and proliferationand proliferation
Platelets adhesionPlatelets adhesion
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F. Della Corte, MD
Atherosclerosis and thrombus formation (2)Atherosclerosis and thrombus formation (2)
Plaque fissuring and Formation Plaque fissuring and Formation of platelet thrombusof platelet thrombus
I - Platelets activationII - Platelets adhesionIII - Activation of coagulation cascade
Thrombus formationThrombus formation
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F. Della Corte, MD
Atherosclerosis and thrombus formationAtherosclerosis and thrombus formation
Potential outcome of plaque fissuringPotential outcome of plaque fissuring
1)fibrotic organization1)fibrotic organization
2)intraintimal and intraluminal thrombosis2)intraintimal and intraluminal thrombosis
3)occlusive thrombosis3)occlusive thrombosis
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F. Della Corte, MD
Evolution of Evolution of Cerebral AtherothrombosisCerebral Atherothrombosis
The ischemic penumbraThe ischemic penumbra
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F. Della Corte, MD
Cerebral Embolism formationCerebral Embolism formation
I II III
Cardiac SourcesCardiac Sources
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F. Della Corte, MD
Any question from the floor ?
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• …and to bereplied !!!!
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