Disorders Of Nervous System 2020 PDF

DISORDERS OF NERVOUS SYSTEM S Naghma Rizvi August 2020 Acknowledgement:Muhammad Nisar Objectives Review blood brain barrier and CSF barrier Discuss the basic concepts of brain injury  BBB Two barriers maintain chemical environment of the b...

DISORDERS OF NERVOUS SYSTEM S Naghma Rizvi August 2020 Acknowledgement:Muhammad Nisar Objectives Review blood brain barrier and CSF barrier Discuss the basic concepts of brain injury  BBB Two barriers maintain chemical environment of the brain. 1. Blood-Brain Barrier 2. CSF- Blood Barrier  Blood-Brain Barrier The site of BBB is endothelial cells of the cerebral capillaries Endothelial cells are joined by continous tight junction In addition, the brain capillaries are surrounded by the process of supporting cells of barin called astrocytes. Blood Capillary Astrocytes covering blood vessels forming BB barrier Blood vessels outside and inside CNS Pericytes  Functions of BBB Only water ,carbon dioxide and oxygen enters the brain easily. The BB barrier stops many substances from travelling across it.  Cont… Provide passage of essential substance only Reverse transport system remove material from the brain Large molecules such as protein and peptides are largely excluded BBB prevent many drugs from entering the brain especially water soluble. In contrasts may lipid soluble drugs cross the lipid layers of BBB easily.  Cont… Alcohol ,nicotin, heroin are lipid soluble, can easily enter brain Acute cerebral lesions such as trauma and infection, increase the permeability of the BBB and alter brain concentration of protein ,water and electrolytes. Formation, circulation and reabsorption of CSF  CSF BRAIN BARRIER The ependymal cells covering the choroid plexus are linked together by tight junctions, forming a blood–CSF barrier to diffusion of many molecules from the blood plasma of choroid plexus capillaries to the CSF. Water is transported through the choroid epithelial cells by osmosis.  Choroid Plexus/ CSF brain barrier Choroidal epithelium  CSF BRAIN BARRIER O2 and CO2 moves into CSF by diffusion , maintaining partial pressure roughly equal to plasma Lipid and non peptide hormones diffuse through the barrier easily. Large molecules does not pass through it. The choroids epithelium uses energy in the form of ATP to actively secrets components of CSF.  CSF BRAIN BARRIER Remove toxic material of neuronal activity from CSF to plasma because brain and spinal does not have any lymphatic channels  Brain Injury Brain injury occur Theses conditions involve due to conditions different pathway or which includes mechanism of injury Trauma Hypoxic and ischemic Tumor injury Stroke Injury from excitatory Degenerative disorders amino acids Metabolic Cerebral edema derangement Increase ICP and Infections volume  INCREASED HYPOXIC AND INTRACRANIAL ISCHEMIC INJURY VOLUME & PRESSURE Mechanism of Injury INJURY FROM CERERBRAL EXCITORY EDEMA AMINO ACIDS HYPOXIC AND ISCHEMIC INJURY Brain carries 2% of body weight but consume 20% of 02 The ability of cerebral circulation is to provide O2 is sufficiently high to facilitate metabolism of glucose and generate ATP Hypoxia Ischemia O2 deprived blood but Reduce or interrupted with maintained blood flow blood flow Occur due to exposure to atmospheric pressure, severe anemia, CO poisoning.  Hypoxia is tolerated by. Auto-regulation of brain when the supply cerebral blood flow of O2 is minimal in the (role of nitric oxide??) circulation. In chronic hypoxia neurons become tolerant and start Euphoria, drowsiness, anaerobic metabolism Impaired In sudden hypoxia brain problem solving cell does not become tolerant Unconsciousness and convulsion occur O2  Ischemia Reduce or interrupted blood flow may be: Focal Global Collateral circulation is Collateral circulation is present not present Low level of metabolism Inadequate metabolism Low level of energy Energy source glucose and glycogen exhaust Provide energy by anaerobic mean in 2-4 min Produce lactic acid ATP depleted in 4-5 mins  Ischemia Energy depletion affects ionic gradient because its maintenance require 50-70% of total energy. This results in Influx of sodium Edema Influx of calcium Calcium cascade Release of intracellular Efflux of potassium enzymes that causes cell destruction  Injury from Excitatory amino acids (Ischemic) Injury to neurons is cause by over stimulation of receptors for specific amino acids such as glutamate & aspartate. Glutamate are excitatory neurotransmitters in brain. Glutamate is responsible for memory ,cognition, movement and sensation Action of glutamate coupled with receptor-operated ion channel Uncontrolled opening of NMDA leads to calcium cascade and sodium influx causing neuronal swelling and cellular digestion( N-Methy-D Aspartate NMDA) Increase intra cranial pressure and volume Brain is enclosed with rigid confine of skull. Cranial cavity contains blood 10%, brain tissue 80%,CSF 10%. Each of three volume contribute to ICP. Normal ICP 10-15 mmHg Increase ICP is a common pathway for brain injury in different types of insult. Excessive ICP can obstruct blood flow, destroy brain cell, damage delicate brain structure CSF Blood Volume Brain Matter  Increase intra cranial pressure and volume Abnormal changes in ICP can be because of change in any of the 3 components Increase in tissue volume Brain tumor, edema Increase in blood volume Vasodilatation or venous obstruction Increase in CSF Excessive production, decrease reabsorbtion of CSF Increase intra cranial pressure and volume leads to… Decrease perfusion  Cellular hypoxia Confusion lethargy Stupor Coma Death Cerebral Edema Increase in tissue volume secondary to abnormal fluid accumulation. Types of edema Intersticial cerebral edema Vasogenic Edema CytotoxicEdem a  Vasogenic cerebral edema Due to a breakdown of tight endothelial junctions which make up the blood-brain barrier (BBB). This allows normally excluded intravascular proteins and fluid to penetrate into cerebral parenchymal extracellular space. Once plasma constituents cross the BBB, the edema spreads; this may be quite fast and widespread. As water enters white matter it moves extracellularly along fiber tracts and can also affect the gray matter. This type of edema is seen in response to trauma, tumors, focal inflammation, late stages of cerebral ischemia and hypertensive encephalopathy.  Cytotoxic Cerebral Edema In this type of edema the BBB remains intact. This edema is due to the derangement in cellular metabolism resulting in inadequate functioning of the sodium and potassium pump in the glial cell membrane. As a result there is cellular retention of sodium and water. There are swollen astrocytes in gray and white matter. Cytoxotic edema is seen with various intoxications severe hypothermia, early ischemia, encephalopathy, early stroke or hypoxia.  Interstitial Cerebral Edema This form of edema is due to rupture of CSF- brain barrier resulting in trans-ependymal flow of CSF; this permits CSF to penetrate brain and spread in the extracellular space of white matter. Differentiated from vasogenic edema in that fluid contains almost no protein Stroke S Naghma Rizvi September, 2016 Acknowledgement: Muhammad Nisar objectives Review cerebral blood flow Define stroke Discuss type of stroke Discuss risk factors and pathophysiology associated with stroke Cerebral blood flow Stroke Acute focal neurovascular disorder Also previously. called as brain attack A stroke occurs when a part of the brain is damaged. Stroke is characterized by the sudden loss of circulation to an area of the brain, resulting in a corresponding loss of neurologic function. Also called cerebrovascular accident ( CVA) or stroke syndrome Types of stroke 80% of all strokes are Ischemic Hemorrhagic Ischemic stroke stroke Hemorrhagic stroke Bleeding into the Brain tissue Interruption of blood flow in cerebral artery RISK FACTORS Age DM Gender Sedentary life style Race Obesity Heart disease Sickle cell anemia HTN Polycythemia High cholesterol Arterial fibrillation Prior stroke RISK FACTORS Cocaine Increase BP,increase HR Induce cardiac arrhythmias, induction of HTN, Alchohol Reduce cerebral blood flow, enhancement of blood coagulation disorders Pathophysiology of Ischemic Stroke Atherosclerotic plaques ( thrombus) ( Large cerebral arteries) Occlusion of the artery Ischemia of the respective brain area Inadequate delivery of blood ( oxygen + nutrients) to brain tissues Oxygen deprivation for more than 3-4 mins Infarction Edema of the brain tissues Classification of Ischemic stroke: Five stroke sub-types Ischemic Penumbra in evolving stroke Large vessel (Thrombotic) stroke Small Vessel (Lacunar infarct) Cardiogenic Embolic stroke TIA Ischemic Penumbra In the evolution of a stroke ,there is usually central core of dead and dying cells, surrounded by ischemic area of minimally surviving cell called penumbra. Brain cells of penumbra receive marginal blood flow, there metabolic activities are low ISCHEMIC STROKE Cause by cerebro vascular obstruction by thrombus or emboli Cessation of blood supply to brain Large vessel Thrombotic stroke Usually occur in atherosclerotic blood vessel Usually present at bifurcation. It occur gradually, over several days ,during which CNS symptoms may start and then deteriorates Cardiogenic embolic stroke Cause my moving blood clot Usually effect smaller vessels specially at bifurcations. Emboli originate in the heart and travel to brain  Small Vessel LACUNAR INFARCT Lacunars infarct are small Size around 1.5-2 cm to very small 3-4 mm Located mostly in non cortical parts of brain or in the brain stem Result from occlusion of the smaller branch of large cerebral arteries. In process of healing leaves behind a cavity. Cont… Due to size and location it does not cause profound deficit Often produce symptoms such as pure motor hemipligia, pure sensory hemiplegia etc  TIA (Mini stroke, Brain Angina) TIAs are characterized by focal neurological deficit last for less than 24 hours TIAs can lead to stroke Sign and symptoms of TIA based on the artery involve Best described as a zone of penumbra without central infarction TIA A TIA happens when blood flow to part of the brain is blocked or reduced, often by a blood clot. After a short time, blood flows again and the symptoms go away. Cont… A TIA is a warning: It means you are likely to have a stroke in the future. If you think you are having a TIA, call emergency. Early treatment can help prevent a stroke. If you think you have had a TIA but your symptoms have gone away, you still need to call your doctor right away Hemorrhagic stroke Rupture of blood vessel leads to hemorrhage into brain cell resulting in edema. Edema causes compression of brain content that may lead to coma or brain death. Causes of Hemorrhagic Stroke Aneurysm Arteriovenous malformation Hypertension Head injury Hemorrhagic Stroke Pathophysiology B.P rupture of blood vessel Blood escape into surrounding brain tissues expanding hematoma Pressure on brain tissues ICP Compensatory decrease blood circulation Death / Herniation Ruptured Berry Aneurism Intraventricular Hemorrhage: