Module 10 CNS PDF

1 The nervous system functions as a whole but it’s structure & functions have been divided into the: 1. Central nervous system Consists of the brain and the spinal cord Enclosed within protective cranial vault (skull) and vertebral column 2. Peripheral nervous system Comp...

1 The nervous system functions as a whole but it’s structure & functions have been divided into the: 1. Central nervous system Consists of the brain and the spinal cord Enclosed within protective cranial vault (skull) and vertebral column 2. Peripheral nervous system Composed of the cranial nerves & spinal nerves Functions as an input-output system for relaying input (impulses) to the CNS & transmitting output messages that control effector organs (muscles and glands for example) Clinically, the peripheral nervous system can be divided into: Somatic nervous system which consists of motor and sensory pathways that regulate voluntary control of skeletal muscle Autonomic nervous system which also consists of motor and sensory components. But, these are involved with regulation of body’s internal viscera through involuntary control of organ systems which are done through the actions of the sympathetic & parasympathetic systems. 2 There are two basic types of cells that make up nervous system: 1. Neurons primary cell of the nervous system (respond to stimuli & conduct impulses) 2. Supporting cells  also known as neuroglial cells  provide structure, support and nutrition for the neurons 3 Looking at the neuron it has three components - the soma which is the cell body and then the thin processes of the cell – the dendrites and axons (these processes form the connections or synapses with other nerve cells) Dendrites are the multiple branch extensions of the cell body They carry nerve impulses toward the cell body This is the part of the neuron that receives stimulation from other nerves and is the main source of information for the neuron Soma: The neuronal cell bodies located with in CNS are found in groups are called nuclei The neuronal cell bodies in the PNS found in groups are called ganglia or plexuses The neuronal body (soma) is equipped for high level of metabolic activity as it must synthesize the cell components necessary to maintain the function of the axon and its numerous terminals. Neural excitation usually begins with the excitation of the dendrites and the cell body delivers the electrical signal to the next segment, the axon. Axons Long, conductive projections from the cell body that carry impulses away from the cell body Typical neuron has only one axon but many axons will have multiple branchings It transmits the original signal initiated in the dendrite and cell body to another neuron or to a muscle or gland. Neurons classified by structure & function: Structurally they’re classified based on the number of projections extending from the cell body 4  Bipolar  one dendrite, one axon Multipolar  one axon, many dendrites Functionally they’re referred to as: Sensory (afferent) neurons which carry impulses from the peripheral receptors to the CNS Motor neurons (efferent) which transmit impulses away from the CNS to an effector organ 4 Neuroglia (literally meaning “nerve glue”) are the cells that support the neurons of the CNS. They make up approx ½ of the total brain and spinal cord volume Five to ten times more numerous than the neurons Four different types of neuralgia cells: 1. Astrocytes  fill spaces between neurons & surround blood vessels in the CNS Contribute to what is called the blood-brain barrier  refers to the impermeability of the CNS to large or potentially harmful molecules 2. Oligiodendrocytes  function to deposit myelin in the CNS (counterpart to the Schwann cell)  helps increase nerve conduction 3. Microglia  remove debris (phagocytosis) in CNS 4. Ependymal  line the CSF-filled cavities of the CNS 5  The myelin sheath is an important component of the axon. It is a lipid material that covers the axon which acts as an insulating substance. This lipid content gives it a whitish color. Actually, the name “white matter” is given to masses of myelinated fibers of the spinal cord and brain. Schwann cells form and maintain the myelin sheath (in the peripheral nervous system) Oligiodendrites are the cells that do the same but in the central nervous system. Nodes of Ranvier form spaces on either side of the myelin sheath  allows for increase nerve conduction … allows impulses to jump from node to node If the layer is tightly wrapped around the axon many times  it increases conduction velocity This is known as myelination Disorders of the myelin sheath  multiple sclerosis and Guillian – Barre syndrome are examples  the myelin degenerates or is destroyed  axon then dies then leading to the clinical manifestations of the disease 6 Multiple Sclerosis (MS) is a demyelinating disease of the CNS Major cause of neurologic disability among young and middle-aged adults ~ 2/3 of person’s experience their first symptoms between the ages of 20-40 years Incidence among women is almost double that among men Believed to be immune-mediated disorder characterized by both a cell-mediated immune response and a humoral immune response meaning that there is both activated T-cells and antibodies that are produced against self-antigens Autoimmune response leads to destruction of neurons in the CNS (the peripheral nervous system is unaffected). The pathophysiology of MS involves the demyelination of nerve fibers in the white matter of the brain, spinal cord and optic nerve. Symptoms depend on the location and duration of the lesion Lesions are hard, demyelinated or sclerotic patches throughout the white matter of the CNS Lesions are seen in optic nerve, periventricular white matter, brain stem , cerebellum, spinal cord white matter … axons die with demyelination Cause of MS is unknown though there appears to be a genetic tendency towards developing this and other autoimmune diseases. There is suggestion that a childhood viral infection may initiate the immune response: Infection leads to breakdown of the blood brain barrier during viral infection leading to a B-cell lymphocyte developed against the virus to enter the brain and colonize it. 7  An IgG clone (IgG from one B-cell line) is often present in the CSF of an individual with MS Guillian-Barre Syndrome is also a demyelination disease (but of the ventral spinal roots – a peripheral nervous system disease). Cause is unknown 2/3 cases often follow a viral infection (question if it is a result of an altered immune response to the viral antigen) 80-90% of patients will achieve a spontaneous recovery Characterized by progressive ascending muscle weakness of the limbs producing a symmetric flaccid paralysis 7 Functions of the brain, spinal cord and PNS can be impaired because of injury. Mechanisms of injury can vary and may result from trauma, hypoxia, response to neurotransmittors, or pressure changes. Mature neurons do not divide…important fact to consider when neurons are injured as new neurons are not generated to replace those that have lost function through damage or death Metabolic requirements of CNS are very high. The brain comprises 2% of body weight…receives 15% of cardiac output … consumes 20% of its oxygen. It cannot store oxygen…nor participate in anaerobic metabolism If there is interruption in blood or oxygen: Without oxygen brain cells function ~10seconds Unconsciousness with cardiac arrest Death of brain cells within 4 to 6 minutes Glucose major fuel source  no provision for storing glucose The brain as an organ about 3 pounds and has the consistency of tofu or custard. There are three major divisions based on embryologic origin: Forebrain  formed by the two cerebral hemispheres Midbrain  cerebral peduncles Hindbrain  cerebellum, pons and medulla (The midbrain, the medulla and the pons  make up the brain stem). A collection of nerve cell bodies within the brain stem make up the reticular formation Large network of connected tissue that regulate vital reflexes (cardiac & respiratory) Essential for maintaining wakefulness Some nuclei involved in motor movements 8 The Forebrain (telencephalon) Consists of the cerebrum  which includes the cerebral cortex and basal ganglia Cerebral cortex contains the cell bodies & dendrites of the neurons  gray matter White matter lies beneath the cortex  composed of myelinated nerve fibers Hippocampus  located in temporal lobe controls impulses of emotion, hunger, sexual arousal & aggression Amygdala  temporal lobe  produces and responds to nonverbal signs of anger, avoidance, fear 9 Diencephalon (still part of the forebrain) Surrounded by the cereberum Largest component is the thalamus About the size of the thumb (from tip to the first joint) Major integrating center for afferent impulses to the cerebral cortex Perception of various sensations occur here but require cortical processing for interpretation Hypothalamus Maintains constant internal environment Regulation of body temp, endocrine, regulation of emotional expression 10 11 Hindbrain (major structures are the cerebellum and pons) Cerebellum Two hemispheres Responsible for both conscious & unconscious ability to maintain balance and posture Damage is characterized by ipsilateral (same side) loss of equilibrium, balance & motor coordination Cerebellum has ipislateral control of body…in contrast to cerebral cortex…which has contralateral (opposite side) control of body hint, hint! Be careful on quiz questions – don’t confuse cerebellum damage with cortex (cerebrum) damage Pons Important center for control of respiration Medulla Makes-up myelencephalon Lowest portion of the brain stem (autonomic nervous system) Reflex activities such as HR, RR, BP, cough, swallowing & vomiting controlled in this area 12 Parkinson’s is an example of disease of the basal ganglia It’s a chronic progressive disorder Degeneration of the pathway leads to a reduction in the neurotransmittor dopamine As it is the cells of the substania nigra that secrete dopamine Which modulates balance between excitatory and inhibitory neural motor pathways Neurons atrophy and develop Lewy bodies  which are protein aggregates as the cell atrophies Unfortunately clinical manifestations result when ~ 80-90% of the cells that make up the substania negra are lost 13 No specific mechanism for PD has been found. Some theories include: Neuronal injury from oxidative damage (free radical injury) that leads to impaired mitochondrial function and impaired antioxidant protection of the neurons Is it related to a decline in endogenous defense mechanisms associated with aging? Depigmentation of the neurons may lead to an inflammatory response which causes the damage Genetic etiology?  eight genetic loci have been identified in familial PD Check out the web-site below for nice brief summary of Parkinson’s and links to other PD sites: http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_d isease.htm 14 Alzheimer’s disease is another neurodengenerative disorder It is the most common neurodegenerative disorder in the US It is the most frequent cause of dementias in the elderly Affects more that 4 million people in the US…and the numbers will increase as the “boomers” start to age ***while the incidence increases with age…it is NOT considered a normal consequence of aging*** (A study of the incidence of AD of 1200 volunteers in a longitudinal study of aging showed that the risk of developing the disease was 0.8% 60-65 year-old range to 6% in those 85 or older …but… the odds of developing AD were 27% less for individuals with some college education and 36% for those with graduate school education…..so…see there is an advantage to being in school… there’s hope for us  Characterized by the presence of senile plaques and neurofibrillary tangles Senile plaques  caused by accumulation of proteins surrounding deposits of beta-amyloid protein which are surrounded by inflammation Tangles  made up of the protein tau. Tau is found in the degenerating nerve terminals in the plaques. These tau fibers become twisted  forming tangles Cellular changes result in brain atrophy caused by the loss of neurons in the hippocampus and cortex: As plaque development continues brain cell-to-cell communication becomes disrupted Specific mechanism not clear  influence of neurotransmittors and inflammation are under study  are these agents neurotoxins that are promoting neurodegeneration? 15 Graphic of Beta-amyloid plaques in Alzheimer’s disease 16 Picture of atrophy of the hippocampus in Alzheimer’s disease. Severe atrophy of the hippocampus causes the gaping fissures seen. 17 Meninges: The brain and spinal cord are protected by several connective tissue sheaths called the meninges. Three layers: 1. Pia mater (literally means “delicate mother”) Innermost layer which covers the surfaces of the spinal cord and brain Surface blood vessels are encased in this protective layer 2. Arachnoid Nonvascular and waterproof layer that encloses the entire CNS Named for its spider web appearance Cerebrospinal fluid (CSF) is contained in the subarachnoid space 3. Dura ( tough mother) Outer layer is a sheath of continuous sheath of strong connective tissue Provides the major protection for the brain and spinal cord Has two layers – outer layer serves as periosteum of the inner surface of skull Inner layer –has folds that separate the hemisphere (tentorium) Cerebral hemispheres & diencephalons are supratentorial Infratentorial (pons, cerebellum, medulla) Extreme trauma sharp edges of these folds can damage the brain Space-occupying lesions such as tumors or hematomas can squeeze the brain against these edges  herniation. Brian tissue can be compressed, contused, destroyed 18 Blood-Brain Barrier is another protective CNS mechanism Permits passage of essential substances (water, proteins, electrolytes) Cerebral capillaries more permeable at birth than in adulthood Acute cerebral lesions (such as trauma and infection) alter blood-brain barrier Prevents many drugs from entering the brain: Highly water-soluble compounds are excluded from the brain (such as catecholamines) Lipid-soluble molecules cross with ease  Alcohol, nicotine, heroin are all very lipid soluble & rapidly enter the brain 19 Blood supply Blood flow to brain supplied by the two internal carotid arteries anteriorly and the vertebral arteries posteriorly Distal branches of internal carotid and vertebral arteries communicate at the base of the brain through the Circle of Willis Anastomosis of arteries provide continued circulation if blood flow through one of the main vessels is disrupted 20 Regulation of cerebral blood flow Cerebral blood flow is ~750ml/minute or 1/6 cardiac output Regulation of blood flow is largely controlled by autoregulation Autoregulation is the ability to maintain constant cerebral blood flow despite changes in systemic arterial pressure This mechanism is efficient within a range of MAP 60-140 mmHg If blood pressure MAP is 140 – flow increases rapidly & overstretches the cerebral vessels making them prone to rupture Metabolic factors affect cerebral blood flow: Increases in carbon dioxide concentration and/or hydrogen ion concentration will increase cerebral blood flow. Acidosis will depress neuronal activity. So the increased blood flow is the body’s attempt to “wash out” toxins (lactic acid) Decreased oxygen concentration  increases cerebral blood flow as an attempt to provide more oxygen to the site. Remember neural cells function only with aerobic metabolism Increases in carbon dioxide or hydrogen ion (acidosis) increases cerebral blood flow decreased oxygen  increases cerebral blood flow Because increases in H concentration greatly depresses neural activity Increased blood flow is protective as it washes away the hydrogen and other acidic materials away from the brain tissue 21 CVA (stroke – brain attack) Is an acute focal deficit from a vascular disorder that injures brain tissue Known risk factors: Age  risk increases with age; increases 1%/yr in persons 65-75 yrs-old Incidence is 19% greater in men than women African-Americans exhibit a 60% greater risk of death & disability from stroke than whites Heart disease  especially atrial fibrillation & other conditions that predispose to clot formation on the wall of the heart or valve leaflets Polycythemia, sickle cell predispose to clot formation Alcohol contributes to stroke is several ways: Induction of cardiac arrhythmias Induction of hypertension Reduction of cerebral blood flow Cocaine Causes both ischemic and hemorrhagic strokes Vasospasms Increased HR, BP , body temp, metabolic rate Induces increased platelet activity Two main types of strokes: Ischemic and Hemorrhagic 22 Horizontal section of the brain depicting expansion and softening in the cortex from an occluded middle cerebral artery. 23 Ischemic Stroke is caused by cerebrovascular obstruction by thrombus or emboli During the evolution of an ischemic stroke there is usually a central core of dead or dying cells These cells are surrounded by a band or area of minimally perfused cells  called penumbra (halo) While, these cells receive marginal blood flow & metabolic activities are impaired…the structural integrity of the cells is maintained and the survival of these cells depends on the successful timely return of adequate circulation Thrombotic (large vessel) stroke is the most common cause of ischemic strokes Usually occurs in atherosclerotic blood vessels in the brain  usually found at arterial bifurcations Common sites of plaque formation occur at internal carotid and vertebral arteries Often affect the cortex  causing aphasia or neglect, visual field abnormalities Thrombotic stroke not associated with activity  can occur when person at rest Transient Ischemic Attack (TIA) are focal ischemic cerebral deficits that last for less than 24 hrs (usually only 1-2 hrs) Equivalent to “heart angina”  reflects a temporary disturbance in cerebral blood flow which reverses before infarction occurs Causes are the same as thrombotic stroke Important as they provide warning of impending stroke 4-8% risk of stroke within one month… 12-15% within one year after experiencing a TIA Embolic (cardiogenic) stroke is caused by moving blood clot that travels from its origin to the brain Most frequent site of embolic strokes in middle cerebral artery  it follows the path of least resistance (blood flow) Most cerebral emboli originate from a thrombus in the left heart Usually have a sudden onset with immediate maximum deficit Hemorrhagic stroke (most fatal of the strokes) Spontaneous hemorrhage into the brain substance Results in edema  compression of brain contents, spasm of adjacent blood vessels Occurs suddenly, usually when active Most common predisposing factors are age and hypertension Other causes of hemorrhage include: Aneurysms AVM Vasculitis Drugs 24 Lacunar Infarcts (small vessel strokes) Small 10mm have a 50% chance of bleeding Rupture occurs with acute increases in ICP Cause is unknown: Thought to arise from a congenital defect in wall Family hx seems a significant risk factor People with inheritable connective tissue disorders at risk  Marfan’s Classification based on shape & size: 1. Saccular (berry) Occur in 2% of poplation Result of congenital abnormalities in the media of arterial wall 2. Fusiform (giant) Larger than 25mm in diameter Occur as a result of diffuse arteriosclerotic changes Commonly found in basilar arteries 3. Mycotic Result of arteritis (inflammation of the artery) caused by bacterial emboli 4. Traumatic Caused by weakening of arterial wall by a fracture line, penetrating missile, or after angiography procedures 27 Subarchnoid hemorrhage is bleeding into the subarchnoid space. It is a dreaded complication of a ruptured cerebral aneurysm Manifestations include: 1. Atypical HA 50% have a hx of HA occurring days to weeks before onset of hemorrhage  small leak These can easily be mistaken for migraines Can also present as a sudden, severe HA  “worse HA of my life” HA may be accompanied by collapse & loss of consciousness 2. Meningeal irritation Nuchal rigidity Photopobia 3. Cranial nerve deficit especially cranial nerve II & III (diplopia & blurred vision) Complications can include: 1. Rebleeding  highest incidence on first day after the initial rupture. This leads to catastrophic neurologic deficits or death 2. Vasospam is a dreaded complication in that it is difficult to treat and is associated with high morbidity and mortality. Usually develops within 7 days of aneurysm rupture Involves focal narrowing of cerebral artery or arteries Neuro status gradually deteriorates as blood supply to the area is decreased (in the complication of rebleeding you see a rapid deterioration) Treatment of vasospasm not very successful but includes the use of: Calcium channel blockers  used to prevent or reverse vasospasm Volume expansion  used to increase cerebral perfusion 3. Hydrocephalus Obstruction of arachnoid villi from the irritation and scarring from blood leads to the build-up of CSF within the ventricles, usually requires placement of a shunt. 28 29