Pathophysiology of Central Nervous System Brain pathophysiology Stroke Craniotrauma Spinal cord pathophysiology Intracranial Compatments, Intracranial Pressure and Cerebral Perfusion Pressure Brain is enclosed in the skull… … an advantage before trouble occurs… … big problem after trouble occurs. Intracranial compartments • Brain • Cerebrospinal fluid (CSF) • Blood Intracranial pressure (ICP) • Pressure inside the skull Cerebral perfusion pressure • The pressure gradient through which blood flows to the brain CPP = MAP - ICPCPP = MAP - ICP Cerebral perfusion pressure Mean arterial pressure Intracranial pressure http://ars.els-cdn.com Causes of Intracranial Hypertension Brain compartment • Edema • Tumor • Hemorrhage • Infection CSF compartment • Hydrocephalus Compartment of blood • Venous sinus thrombosis • Acidosis - ischemia Causes of Intracranial Hypertension Brain Edema Cytotoxic (intracellular) • Na/K ATPase failure • Na or Ca influx • H2O • Mainly occurs in first 24 h. following insult Vazogenic (extracellular) • Damage of endothelial cells and Blood – Brain barrier • Extravasation of proteins and electrolytes into Interstitial space • Mainly occurs at 24 h. after insult and later • Neovascularization of tumor – imperfect vessels Interstitial • Obstruction of CSF circulation • Mechanical damage of CSF- brain barrier • Infiltration of CSF into intersticial space Causes of Intracranial Hypertension Hydrocephalus Abnormal accumulation of CSF in liquor space CSF production • Choroid plexus (CP) • 450-750 ml/day CSF resorption • Archnoid granulations (AG) Hydrocephalus • Obstructive (Non- communicating) ✓Impaired CSF circulation due to obstruction ✓For example: ventricular obstruction • Non – obstructive (Communicating) ✓Impaired CSF resorption Acute X Chronic http://www.control.tfe.umu.se CP AG Causes of Intracranial Hypertension Hydrocephalus http://drugline.org Compression of adjacent tissue • Ischemization Infratentorial lesions • Allvays acute • Risk of brain • stem compression Cerebral herniation • Subfalcine • Transtentorial • Tonsillar • Central ✓ Permanent damage of brain ✓ Risk of brain stem compression Consequences of Intracranial Hypertension http://slideshare.net http://edutoolanatomy.wikispaces.com Central Herniation Stroke http://wikipedia.org Stroke Stroke is an acute neurological dysfunction due to vascular disturbance resulting in rapid loss of brain functions Vascular pathologies • Disturbance of vessel wall permeability • Disturbance of vessel contractility • Vessel occlusion ✓ Thrombosis ✓ Embolism • Vessel rupture Atherosclerosis Types o f stroke • Ischemic (70%) • Hemorrhagic (30%) ✓ Intracerebral hematoma ✓ Subarachnoid hemorrhage Ischemic Stroke Critical parameters ➢ Extent of ischemia ➢ Duration of ischemia Atherosclerosis Focal ischemic stroke • Transient ✓Transient ischemic attack (TIA) ✓Prolonged reversible neurological deficit • Permanent ✓Cerebral infarction ❖Embolism ❖Thrombosis Global ischemic stroke • Transient ✓Syncope • Permanent ✓Hypoxic ischemic encephalopathy Why is brain sensitive to ischemia? High metabolic activity • Membrane potential maintaining – repolaristion (Na/K pumps) • Almost exclusivelly oxidative phosphorylation • Consumption ✓Oxygen- 20% of body consumption ✓Glucose – 25% of body consumption Small amount of energy reserves http://assassinscreed.ubi.com Ischemic Stroke Core of infarction (centre of ischemia) • Ireversible neuronal damage • Primary injury Penumbra (periphery of ischemia) • Reversible neuronal damage • Risk of secondary injury development Ischemic Cascade ↓ Oxygen and Glucose Na/K ATPase failure ↑ Glutamate ↑ Ca2+ Na influx Activation of proteolytic and ROS producing enzymes H2O influx ↑ ROS↑ Proteolysis Damage of macromolecules Mitochondrial dysfunctionMitochondrial dysfunction ↓ ATP Respiratory chain leakage ↓ Glutamate reuptake ↓ ATP DepolarizationDepolarization Necrosis Apoptosis according to level of damage Cytotoxic edema NEURONS - Core NEURONS - Penumbra Excitotoxicity Inflammation ROS–reactieveoxygenspecies ↑ Pro-inflammatory cytokines Role of Inflammation in Ischemic Cascade Neuronal damage Mikcoglia, astrocytes Endothelial cell ↑ Pro-inflammatory cytokines ↑ Adhesive molecules Neutrophil and macrophage infiltration ↑ Proteolytic enzymes Endothelial cell death Blood – Brain barrier disruption Vasogenic Edema Tissue damage Ischemia ↑ ROS ROS Mechanisms of Ischemic Damage Excitotoxicity Accumulation of excitatory neurotransmiters in extracellular space • Glutamate • Aspartate Neuronal dmage due to excessive stimulation Cause • Depolarization • Decreased reupteke Consequence • Stimulation of adjacent neurons • Ca overload • Proteolysis • Excessive ROS production • Cytotoxic edema www.nature.com Mechanisms of Ischemic Damage Reactive oxygen species (ROS) ROS are highly reactive particles ROS are mainlu produced during reperfusion Cause • Intracellular ✓ Respiratory chain leakage ❖Disruption of electron transport chains in mitochindria ✓ Ca – overload – activation of ROS producing enzymes • Extracellular ✓ Inflammation Consequence • Lipid peroxidation – damage of membranes • Protein oxidation – damage of enzymes and structural proteins • Oxidation of purin a pyrimidine bases – damage of DNA • Stimulation of inflammatory response Mechanisms of Ischemic Damage Inflammation Cause • Ischemia and tissue damage trigger production of ✓Pro – inflammatory cytokines – activation of leukocytes in periphery ✓Adhessive molecules – attraction of leukocytes to dmaaged area • Infiltrating leukocytes produce ✓Proteolytic enzymes – penetration through tissue ✓Pro – infl. Cytokines ✓ROS Consequence • Damage of ✓Endothelial cells ✓Blood – Brain barrier ✓Neuronal cells http://3.bp.blogspot.com Hemorrhagic Stroke Intracerebral hematoma (ICH) Bleeding into the brain parenchyma (intraaxial) The most often localization • Basal ganglia • Thalamus http://umm.edu Pathophysiology of ICH Hematoma InflammationCytotoxic blood componentsMass effect ↑ ICPMechanical damage of brain parenchyma Complement Etc. Hemoglobin ↑ Pro – infl. cytokines Transient ischemia Fe 2+ ↑ Proteolytic enzymes ↑ ROSInflammation Excitotoxicity ↑ ROS ↑ ROS (Neurons) ↑ Proteolysis (Neurons) Endothelial cell death Blood - Brain barrier disruption Neuronal cell death Edema Hemorrhagic Stroke Subarachnoid Hemorrhage (SAH) Bleeding into the subarachnoid space (extraaxial) The most often cause – cerebral aneurysm rupture The most often localiztion of aneurysm - Willis circle van Gijn J, Rinkel GJ. Subarachnoid haemorrhage: diagnosis, causes and management. Brain.2001;124:249–278. http://chicago.medicine.uic.edu Pathophysiology of SAH Accumulation of blood in subarachnoid space InflammationCytotoxic blood componentsMass effect ↑ ICP Complement Etc. Hemoglobin ↑ Pro – Infl. cytokines Transient Ischemia Fe 2+ ↑ Proteolytic enzymes ↑ ROSInflammation Excitotoxicitÿ ↑ ROS ↑ ROS (Neurons) ↑ Proteolysis (Neurons) Endothelial cell death Blood – Brain barrier disruption Neuronal cell death Edema Cerebral vasospasm Traumatic Brain Injury Traumatic Brain Injury Introduction The most often causes • Traffic accidents • Falls • Sport injuries Classificarion • Primary ✓ Results from trauma… • Sekundární ✓ Results from reactions initiated by trauma • Focal • Difuse http://www.seattlecaraccidentlawyerblog.com Diffuse Brain Injury Diffuse axonal injury • Structural damage of axons (white matter) • Acceleration – deceleration, rotational forces • No macroscopically detectable pathology • Microscopicly detectable axonal swelling • Wallerian degeneration develops later ✓Degeneration of axon distally to injury ✓No axonal regeneration inCNS Concussion • The mildest grade of diffuse axonal injury • No structural tissue damage • Transient functional damage (loss of consciousness not longer than 10 minutes) http://www.givengain.com Primary Brain Injury Mechanism of production • Contact injury ✓Head hits the object or head is hited by the object ✓Risk skull fracture ❖Impressive – small objects ❖Linear – big objects ✓Gunshot injury ➢ Par coup injury ✓ Contusion close to impact site ➢ Par contre coup • Contusion opposite to impact site • Noncontact injury • Acceleration – deceleration injury http://www.yalescientific.org Focal injury Contusion • Mechanical damage of brain tissue, pia – arachnoid membranes not damaged • Smoot transition between contusion and ICH • The most often localizations ✓Frontal lobe ✓Temporal lobe Laceration • The most severe grade of contusion • Mechanical damage of both brain tissue and pia-arachnoid membranes • Contusion + traumatic subarachnoid (subdural) hemorrhage Secondary Brain Injury Edema • Cytotoxic • Vasogenic Ischemia Brain swelling • Causes ✓ Acidosis - vasodilatation ✓ Diffuse microvascular injury ➢ Vascular autoregulation failure ✓ Damage brain areas responsible for vasoregulation ➢ Thalamus, brain stem ➢ Vasoparalysis Secondary injury results in ICP increase Traumatic Hematomas Intraaxial • Intracerebral Extraaxial • Epidural • Subdural • Subarachnoid www2.aofoundation.org http://cs.wikipedia.org Intracerebral Hemorrhage ➢ Smoot transition between contusion and ICH according to sverity of injury The most often localization • Temporal lobe • Frontal lobe Epidural Hematoma ➢ Blood collection between the skull and dura mater ➢ The most often cause is skull fracture, which leads to damage of meningeal artery (contact injury) ➢ Separation of dura from the skull – convex shape The most often localization • Temporo - basal • Temporo - parietal Subdural Hematoma ➢ Blood collection between dura mater and arachnoidea ➢ The most often results from tears in briding veins which cross subdural space (acceleration – deceleration injury) Acute – fresh blood Chronic – colliquated blood Traumatic Subarachnoid Hemorrhage ➢ Blood collection between arachnoidea and pia mater ➢ Often associates with brain laceration ➢ No vasospasm occurs in traumatic SAH http://cs.wikipedia.org Consequences of Brain Injury ➢ Impairment of consciousness ➢ Cognitive impairment (including executive functions) ➢ Focal neurological deficit Impairment of Consciousness Qualitative ➢ Normal vigility, impairment of content • Disorientation Quantitative ➢ Impairment od vigility • Somnolence – state of near-sleep, responsivnes • Stupor – responsivness only to base stimuli (pain) • Coma - unresponsivness Glasgow Coma Scale Best eye opening Best verbal Best motor 1 - None 1 - None 1 - None 2 – To pain 2 - Incomprehensible 2 – Extensor (decerebrate) 3 – To speech 3 - Inappropriate 3 – Flexion (decorticate) 4 - Spontaneous 4 - Confused 4 – Withdraws to pain 5 - Oriented 5 – Localizes pain 6 - Obeys Cognitive Impairment and Focal Neurological Deficit http://www.modernfamilyideas.com Cognitive impairment and Focal Neurological Deficit http://www.modernfamilyideas.com „Dementia“ and Focal Neurological Deficit http://www.modernfamilyideas.com Focal Neurological Deficit http://www.emunix.emich.edu Focal Neurological Deficit http://www.ims.uni-stuttgart.de Focal Neurological Deficit Examples of Ishcemia Arteria cerebri anterior ✓ Contralateral hemiparesis accentes on lower limb (FL) ✓ Behavioral impairment- billateral oclusion (FL) Arteria cerebri media ✓ Contralateral hemiparesis accentes on upper limb (FL) ✓ Impairment of speech functions – left side occlusion (FL, TL) ✓ Impairment of writing, counting, right – left orientation (TL) ✓ Impairment of spatial orientation when non-dominant parietal lobe affected Arteria cerebri posterior ✓ Impairment of vision (OL) ✓ Reading disorders (Corpus callosum, PL) Vertebrobasilar arteries ✓ Cerebellar symptomatology ✓ Brain stem symptomatology ✓ Vertigo, nystagmus, diplopia, bilateral hemiaresis, paresis of cranial nerves respiratory disorders Spinal Cord Injury Spinal Cord Injury The most often causes • Traffic accidents • Work and sports injuries Mechanisms of injury • Extensive Flection, extension or rotation • Direct impact Back injury • Vertebrae ✓ Fracture ✓ Dislocation • Ligaments • Intervertebral disc Spinal cord injury • Streetch • Pressure The most often localization of injury C4-C6 a Th11-L2 www.bodyinmotion.co.uk Spinal Cord Injury Commotion • Transient functional disability • Reversible Contusion • Incomplete spinal cord injury • Complete spinal cord injury ✓ Phase 1 – spinal shock ❖Areflexia and loss of descending facilitation distally from injury ❖Atony of urinary bladder detrusor with retention of urine and ishuria paradoxa ✓ Phase 2 – spinal automatism ❖ Hyperreflexia/spasticity distally from injury, loss voluntary motoric activity and loss of descending facilitation ❖ Spasticity of urine bladder Consequences of Spinal Cord Injury Paralysis ➢ Loss of muscle function most often caused by damage of nervous system Plegia • Total paralysis Paresis • Partial paralysis • Mono-, di-, quadru-, para-, hemi• Central ✓Loss of upper motor neuron ✓First flaccid ❖Spinal shock ✓Then spastic ❖Activity of lower motor neuron • Peripheral ✓Loss of lower motor neuron ✓Flaccid http://medical-dictionary.thefreedictionary.com Spinal cord (SC) and spine (S) segments • Upper cervical: SC=S • Lower cervical and upper thoracic: SC=S+1 • Middle thoracic hrudní: SC=S+2 • Lower thoracic: SC=S+3 • Medulary cone: L1 –L2 Plexus cervicalis: C1-C4 C4 – nervus phrenicus Plexus brachialis: C5 – Th1 Plexus lumbalis: L1-L4 Plexus sacralis: S1-S5 Consequences of Spinal Cord Injury Paralysis http://www.jhu.edu Consequences of Spinal Cord Injury Paralysis C1 – C4 ✓ Spastic quadruplegia ✓ Sphincter function disorders C5 – Th2 ✓ Upper limbs: flaccid paresis/plegia ✓ Lower limbs: spastic paresis/plegia ✓ Sphincter function disorders Th3 – Th10 ✓ Lower limbs: spastic paresis/plegia ✓ Sphincter function disorders Th9 – L2 ✓ Lower limbs: flaccid paresis/plegia ✓ Sphincter function disorders L3 – S5 ✓ Sphincter function disorders http://whyfiles.org Consequences of Spinal Cord Injury Paralysis Hypesthesia ➢ Incomplete loss of sensation For example: Thermal hypestesia, tactile hypestesia Anesthesia ➢ Complete loss of sensation http://www.rci.rutgers.edu THANK YOU