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Bio217 F2014 Unit 4

Bio217: Pathophysiology Class Notes Professor Linda Falkow

Unit IV: Disorders Structure and Function of the Nervous System Chap. 12: Structure & Function of the Nervous System Chapter 12 Chap. 13: Pain, Temperature, Sleep, and Sensory Chap. 14: Alterations in Cognitive Systems, Cerebral Dynamics, and Motor Function Chap. 15: Disorders of the Central and Peripheral Nervous Systems

Overview of the Nervous System Overview of the Nervous System • Peripheral nervous system (PNS) • (_____) – Somatic nervous system – ______• Motor (efferent) and sensory (afferent) • Peripheral nervous system (_____) pathways regulating voluntary motor control of – Cranial – (ANS) – Spinal nerves • Motor and sensory pathways regulating – Pathways body’s internal environment through • Afferent (______) involuntary control of organ systems • Efferent (______) – Sympathetic (“______”) – Parasympathetic (“Rest and repose”)

Cells of the Nervous System • Neuron (conducts impulses) • – Variable size and structure – Myelin • Three components • Insulating layer of lipid material – Cell body (soma) • Formed by the Schwann cell • Nuclei = cell bodies in CNS – Endoneurium • Ganglia = cell bodies in PNS are ganglia • Delicate layer of CT around each – Dendrites – Neurilemma • ______impulses • Thin membrane between myelin sheath and endoneurium – Axons • Carry impulses ______from cell body

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Neuron Structural Classification of • Axons –Nodes of Ranvier • Based on number of processes • Regular interruptions of the myelin extending from cell body sheath –Unipolar

– –Saltatory conduction Bipolar • Flow of ions between segments of –Multipolar myelin rather than along entire length of axon

Functional Classification of Neurons Neurons

• Sensory (afferent) – Transmit impulses from sensory receptors to CNS • Associational () – Transmit impulses from neuron to neuron • Motor (efferent) – Transmit impulses from CNS to an effector

Neuroglia Neuroglia

• “Nerve glue” • Support the neurons of the CNS – Astrocytes – Oligodendroglia (oligodendrocytes) – Microglia – Ependemal

A – astrocyte B – oligodendrocyte C – microglia D - ependymal

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Nerve Impulse Synapses • Region between adjacent neurons (pre- and • Neurons generate action potentials by postsynaptic neurons) is called a synapse selectively changing the electrical portion • Impulses are transmitted across synapse by of their plasma membranes and chemical and electrical conduction influencing other nearby neurons by release of (chemicals) • Neurotransmitters – More than 30 substances • (ACh, serotonin, NE, dopamine) – Excitatory or Inhibitory

Forebrain: Central Nervous System Gyri, sulci, and fissures Gray matter and : Cerebral nuclei (basal ganglia)

• – Cerebral hemispheres • – Corpora quadrigemina, , and cerebral peduncles • – , , and medulla

Forebrain Central Nervous System - functional areas • – Thalamus – Hypothalamus

• Midbrain – Corpora quadrigemina • Superior and inferior colliculi – • and substantia nigra ( dopamine  NE) • Cerebral peduncles

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Central Nervous System

• ______• Located in vertebral canal, protected – Cerebellum by vertebral column – Connects the brain and the body – Pons – Conducts somatic and autonomic reflexes – – Modulates sensory and motor function

Spinal Cord Spinal Cord

Reflex Arc • Receptor • Afferent (sensory) neuron • Efferent neuron • Effector

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Protective Structures • Cranium – Eight bones • Frontal, Occipital, Temporal (2), Parietal (2), Sphenoid, Ethmoid – Galea aponeurotica

• Meninges – Protective membranes surrounding brain & SC • Dura mater • Arachnoid • Pia mater

Protective Structures Protective Structures • Cerebrospinal fluid (CSF) • Vertebral column – Clear, colorless fluid similar to blood plasma and interstitial fluid – 33 vertebrae • 7 cervical, 12 thoracic, 5 lumbar, – 125 to 150 mL 5 fused sacral, 4 fused coccygeal

– Produced by ______in lateral, third, and – Intervertebral disks fourth ventricles • Annulus fibrosus

– Reabsorbed through ______• Nucleus pulposus

Vertebral Column Blood Supply to the Brain

• 800 to 1000 mL per minute

• CO2 is the primary regulator for CNS blood flow • Internal carotid and vertebral arteries • Arterial circle (circle of Willis)

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Blood Supply to the Brain Blood Supply to the Brain

Peripheral Nervous System

• 31 pairs of spinal nerves – Named for vertebral level from which they exit – Mixed nerves – Arise from gray matter of the spinal cord

• 12 pairs of cranial nerves – Sensory, motor, and mixed

Spinal Nerves Autonomic Nervous System

• Located in both the CNS and PNS • Maintains a homeostasis in visceral (internal) organs • Neurons – Preganglionic (myelinated) – Postganglionic (unmyelinated)

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Autonomic Nervous System Sympathetic Nervous System • Two divisions – Sympathetic • “Fight or flight” response • Thoracolumbar • Sympathetic (paravertebral) ganglia

– Parasympathetic • “Rest or repose” response • Craniosacral • Preganglionic neurons travel to ganglia close to organs they innervate

Neurotransmitters and Parasympathetic Nervous System Neuroreceptors of the ANS

• SNS preganglionic fibers – ACh (______) • SNS postganglionic fibers – NE (______) • PSN preganglionic & postganglionic fibers – ACh

Neurotransmitters and Aging and the Nervous System Neuroreceptors of the ANS • Decrease in the number of neurons – Decreased brain weight and size • Senile plaques • Neurofibrillary tangles • Slowing of neurologic responses

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Concept Check: • 1. One function of somatic NS that is not performed • 3. Which of the following best describes the SC? by the ANS is conduction of impulses: – A. Descends inferior to the lumbar vertebrae – A. To involuntary muscles and glands – B. Conducts motor impulses from the brain – B. To the CNS – C. To skeletal muscles – C. Descends to L4 – D. Between the brain and SC – D. Conducts sensory impulses to the brain

• 2. Neurons are specialized for the conduction of impulses, while neuroglia: • 4. Which is not a protective covering of the CNS? – A. Support nerve tissue – A. Cauda equina – B. Serve as motor end plates – B. Dura mater – C. Synthesize ACh and AChE – C. Arachnoid – D. All of the above – D. Cranial bone

• 5. The SNS: – A. Mobilizes E in times of need – B. Is innervated by cell bodies from T1  L2 – C. Is innervated by cell bodies located in the Pain, Temperature, Sleep, and cranial nerve nuclei – D. Both A and B are correct Sensory Function

• 6. The PSN : Chapter 13 – A. Conserves and stores E – B. Has relatively short postganglionic neurons – C. Both A and B are correct – D. Has paravertebral ganglia

Pain of Pain

• “Pain is whatever the experiencing • Nociception person says it is, existing whenever he – Perception of pain says it does” —McCaffrey • Nociceptors – Free nerve endings in skin, muscle, joints, arteries, and the viscera that respond to chemical, mechanical, and thermal stimuli

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Pathways of Nociception of Pain - Spinothalamic tracts • Neuromodulators – Located in pathways of NS – Triggered by tissue injury and or inflammation – Excitatory neuromodulation • Substance P, glutamate, somatostatin – Inhibitory neuromodulation • GABA, glycine, serotonin, NE, endorphins

Neuromodulation of Pain Endorphin Response • Endorphins (endogenous morphines) – Neuropeptides – inhibit pain transmission in CNS – Bind opioid receptors

• Beta-endorphins (rel. from hypothalamus & pit. gland)

• Enkephalin (weaker than other endorphins)

• Dynorphins (can stimulate pain)

• Endomorphins (cause VD due to NO2 released from endothelial cells)

Acute Pain Acute Pain • Referred pain – Pain present in an area removed or distant • Manifestations from point of origin – Fear and anxiety – Area of referred pain is supplied by same • Tachycardia, hypertension, fever, spinal segment as the actual site diaphoresis, dilated pupils, outward • Myocardial pain behaviors, elevated BG, infarction pain decreased gastric acid secretion and intestinal motility, and a general decrease in blood flow

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Chronic Pain Neuropathic Pain • May be sudden or develop insidiously • Result of trauma or disease of nerves • Usually defined as lasting at least 3 to 6 months • Peripheral • Produces significant behavior and psychologic changes – Painful diabetic neuropathy • Types: • Central – Low back pain – Phantom limb – Myofascial pain syndromes – Chronic postoperative pain – Cancer pain

Temperature Regulation Heat Loss • Peripheral & central thermoreceptors • Hypothalamic control (range ~37o + 0.7o) • Radiation, Conduction, Convection • Vasodilation • Heat production • Decreased muscle tone – Metabolism • Evaporation – Skeletal • Increased respirations – Chemical thermogenesis • Voluntary measures • Heat conservation • Adaptation to warmer climates – Vasoconstriction – Voluntary mechanisms

Temperature Regulation Fever • Resetting of the hypothalamic thermostat • Aging

– Slow blood circulation, vasoconstrictive response, and metabolic rate • Activate heat production and conservation – Decreased sweating and perception of heat measures to a new “set point” and cold • ______(exogenous or endogenous) toxins from pathogens  PG (which reset thermostat)

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Fever Benefits of Fever

• Kills many microorganisms • Decreases serum levels of Fe, Zn, and Cu • Promotes lysosomal breakdown and autodestruction of cells • Increases lymphocytic transformation and phagocyte motility • Augments antiviral interferon production

Hyperthermia Hypothermia

• Not mediated by pyrogens (no resetting of thermostat) o • 41o C (105.8o F): nerve damage produces convulsions • Body temperature less than 35 C • 43o C (109.4o F): death results • Produces: • Forms – VC, alterations in the microcirculation, –Heat cramps (abdom. pain, incr. sweat, coagulation, and ischemic tissue damage loss Na+) – Ice crystals, which form inside the cells, –Heat exhaustion (collapse, profuse sweat, causing them to rupture and die high core temp. –Heatstroke ( death, brain cannot tolerate temperatures >40.5o C (104.9o F)

Hypothermia Sleep

• Accidental hypothermia • Infants : 16-17 hours /day; about half in REM – Commonly the result of sudden immersion in • Elderly: decrease in sleep time, longer to fall cold water or prolonged exposure to cold asleep; increase in sleep apnea

• Therapeutic hypothermia REM = rapid eye movement sleep; 90 minute – Used to slow metabolism and preserve ischemic cycles after non-REM sleep tissue during surgery or limb reimplantation – May lead to ventricular fibrillation and cardiac arrest

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Sleep Disorders The Eye • Insomnia – not able to fall asleep or stay asleep – idiopathic, abuse of drugs or alcohol, chronic pain, depression, or certain drugs, age, obesity

• Obstructive sleep apnea – Upper airway blockage –  snoring – Apneic episodes > 10 sec.

Vision External Eye Disorder

• Blepharitis • Conjunctivitis – Inflammation of the eyelids – Inflammation of the conjunctiva • Hordeolum (stye) – Acute bacterial conjunctivitis (pinkeye) – Infection of the sebaceous glands of the eyelids • Highly contagious • Chalazion • Mucopurulent drainage from one or both eyes – Infection of the meibomian (oil-secreting) gland – Viral, Allergic, or Trachoma (chlamydial) conjunctivitis • Keratitis – Infection of the cornea

Vision Changes and Aging Visual Dysfunctions • Alterations in visual acuity • Cornea – ______– cloudy lens due to degeneration • Anterior chamber (age) • Lens • Ciliary muscles – ______– increase in intraocular pressure • – Age-related macular degeneration (AMD) – major cause of blindness in elderly; increased risk due to HT, smoking, DM

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The Ear The Ear

Aging and Hearing Ear Infections

• Cochlear hair cell degeneration • Otitis externa • Loss of auditory neurons in spiral ganglia of – Infection of the outer ear organ of Corti – Commonly caused by prolonged moisture exposure (swimmer’s ear) • Degeneration of basilar conductive membrane of cochlea • Otitis media • Decreased vascularity of cochlea – Acute otitis media • Loss of cortical auditory neurons – Otitis media with effusion

Auditory Dysfunction Concept Check • • 1. Endorphins: Mixed hearing loss – combination of – A. Increase pain sensations conductive and sensorineural loss – B. Decrease pain sensations – C. May increase or decrease pain – D. Have no effect on pain • Functional hearing loss – no known cause • 2. IL -1: – A. Raises hypothalamic set point • Ménière disease – middle ear affected, – B. Is an endogenous pyrogen hearing and balance are impaired – C. Is stimulated by exogenous pyrogens – D. All of the above

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• 3. In heatstroke- Matching: – A. Blood viscosity increases – B. Core temp. increases as regulatory center fails • 8. Blepharitis A. Increase intraocular – C. Stimulates VC pressure – D. Ice crystals form in cells

• Matching: • 9. Vertigo B. Infected eyelid __ 4. Meniere disease A. due to airway obstruction during breathing ___ 5. AMD B. Vestibular & hearing disruption • ___ 6. AOM C. Retinal detachment & loss of 10. Glaucoma C. Inflammation of photoreceptors semicircular canals ___ 7. Sleep apnea D. Effusion behind tympanic membrane

Alterations in Cognitive Networks Alterations in Cognitive Systems, Cerebral Dynamics, • Consciousness & Motor Function –State of awareness of oneself and env.

Chapter 14 –Arousal • State of awakeness –Content of thought

Levels of Consciousness Alterations in Arousal

• Consciousness – alert and aware of person, • Coma is produced by either: place, time – Bilateral hemisphere damage or suppression • Confusion – not able to think – Brain stem lesions or metabolic derangement • Lethargy – limited speech, may/maynot be that damages or suppresses the RAS oriented to PPT • RAS (reticular activating system = maintains • Obtundation – stimulation needed for arousal wakefulness; consists of nuclei in and • Stupor – unresponsive except for vigorous extends to cerebral cortex) stimuli • Coma – no vocalization or arousal – No verbal responses to stimuli – No reaction to deep pain

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Alterations in Arousal Seizures

• Clinical manifestations of Coma • Sudden, transient alteration of brain function – Level of consciousness changes caused by an abrupt explosive, disorderly – Pattern of breathing discharge of cerebral neurons • Posthyperventilation apnea (PHVA) • Motor, sensory, autonomic, or psychic signs • Cheyne-Stokes respirations (CSR) • Convulsion – Vomiting – Tonic-clonic (jerky, contract-relax) movements – Pupillary changes associated with some seizures – Oculomotor responses – Motor responses

Dementia Alzheimer Disease (AD)

• Progressive failure of cerebral • Familial, early and late onset functions that is not caused by an • Nonhereditary (sporadic, late onset) impaired level of consciousness • Theories – Mutation for encoding amyloid protein • Classifications – Alteration in apolipoprotein E – Cortical – Loss of ACh – Subcortical

Alzheimer Disease (AD) Alterations in Movement • Neurofibrillary tangles • Senile plaques • Huntington disease – Also known as “chorea” • Clinical manifestations – Autosomal dominant hereditary- – Forgetfulness, emotional upset, disorientation, degenerative disorder confusion, lack of concentration, decline in abstraction, problem solving, and judgment – Severe degeneration of the basal ganglia (caudate nucleus) and frontal cerebral • Diagnosis is made by ruling out other atrophy causes of dementia • Depletion of gamma-aminobutyric acid (GABA)

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Alterations in Movement Parkinson Disease

• Hypokinesia • Severe degeneration of the basal ganglia –Decreased movement (corpus striatum) involves dopamine secreting cells –Akinesia – Parkinsonian tremor –Bradykinesia – Parkinsonian rigidity –Loss of associated movement – Parkinsonian bradykinesia – Postural disturbances

Parkinson Disease Concept Check

Matching: a. No speech or arousal 1. Confusion b. Only responses to strong stimuli 2. Lethargy c. Stimulation necessary for arousal 3. Obtundation d. Speech limited, may or may not be 4. Stupor oriented 5. Coma e. Not able to think straight

• 6. AD a. Autosomal dominant, GABA Disorders of the Central & Peripheral decreased Nervous Systems

• 7. HD b. Decreased dopamine, Chapter 15 resting tremors

• 8. PD c. Neurofibrillary tangles, amyloid proteins

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Brain Trauma Brain Trauma • Closed (blunt, nonmissile) trauma • Major head trauma – Head strikes hard surface or a rapidly moving object – Traumatic insult to the brain physical, strikes the head intellectual, emotional, social, and – The dura intact, brain tissue not exposed to the env. – Causes focal (local) or diffuse (general) brain injuries vocational changes

– Transportation accidents • Open (penetrating, missile) trauma – Falls – Injury breaks dura, exposes cranial contents to env. – – Sports-related event Causes primarily focal injuries

– Violence

Brain Trauma Focal Brain Injury

• Observable brain lesion • Force of impact produces contusions (bruise) • Contusions can cause: – Extradural (epidural) hemorrhages or hematomas – Subdural hematomas – Intracerebral hematomas

Hematomas Subdural Hematomas – collection of blood in closed space

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Mild Concussion Classic Cerebral Concussion • Temporary axonal disturbance  • Grade IV – attention and memory deficits but no loss of – Disconnection of cerebral systems from the brain consciousness stem and reticular activating system • I: confusion, disorientation, and momentary – Physiologic and neurologic dysfunction without amnesia substantial anatomic disruption • II: momentary confusion and retrograde – Loss of consciousness (<6 hours) amnesia – Anterograde and retrograde amnesia • III: confusion with retrograde (events preceding trauma) – Postconcussive syndrome (headaches, anxiety, and anterograde amnesia (unable to form recent insomnia, depression, unable to concentrate) memories)

Spinal Cord Trauma Spinal Cord Trauma

• Most commonly occurs due to vertebral injuries – Simple fracture, compressed fracture, and comminuted fracture and dislocation • Traumatic injury of vertebral and neural tissues as a result of compressing, pulling, or shearing forces Hyperextension of vertebral column fracture or non-fracture w/ SC injury

Spinal Cord Trauma Spinal Cord Trauma

Flexion injury of vertebral column Axial compression injury

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Spinal Cord Trauma Spinal Cord Trauma

• Spinal shock – Normal activity of the SC ceases at and below ______. Sites lack continuous nervous discharges from brain. – Complete loss of reflex function below level of lesion

Flexion-rotation injury

Degenerative Disorders of the Spine Cerebrovascular Disorders • Degenerative disk disease (DDD) • Cerebrovascular accident (CVA) – stroke – Spondylolysis – structural defect of lamina or – Impairment of cerebral circulation vertebral arch (lumbar) – Leading cause of disability – Spondylolisthesis- vertebra slides forward – 3rd leading cause of death in US – Spinal stenosis – ______of spinal canal, puts pressure on nerves (sciatica) • Low back pain – Classified • Global hypoperfusion (as in shock) • Herniated intervertebral disk – protusion of • Ischemia (thrombotic, embolic) nucleus pulposus • Hemorrhagic

Cerebrovascular Disorders Cerebrovascular Disorders • Cerebrovascular accidents (CVAs) – Thrombotic stroke • Hemorrhagic stroke (intracranial hemorrhage) • Arterial occlusions caused by thrombi formed in –Due to HT, aneurysms arteries supplying the brain –Causes sudden rupture of cerebral artery • Due to obesity, smoking, OC, surgery • Transient ischemic attacks (TIAs) – blood accumulating deep in brain – Embolic stroke => further neural tissue compromise • Fragments that break from a thrombus formed outside brain • Can also be from fat, tumor, bacteria, air • Middle cerebral artery is site of emboli

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TIA (transient ischemic attack) Intracranial Aneurysm

– Recurring episode of neurologic deficit – Lasts seconds to hours (clears in 12-24 hours) – Microemboli  temporary interruption of blood flow – Also small spasms of brain arterioles – Double vision, blindness (unilateral), uncoordinated gait, fall due to weakness in legs, dizzy, slurred speech – Temporary – clears in 12-24 hours – Impending stroke sign – warning of stroke – Aspirin or Anticoagulant is given to minimize blood clots

Infection and Intracranial Aneurysm Inflammation of the CNS • Due to: atherosclerosis, congenital, trauma, inflammation • Meningitis

– • Pathophysiology: no single mechanism Bacterial meningitis – Aseptic (viral, nonpurulent, lymphocytic) • Classified: based on shape meningitis – Fungal meningitis • Clinical manifestations: asymptomatic or various cranial nerve compression, or – Tubercular (TB) meningitis hemorrhage

Demyelinating Disorders Understanding Demyelination • Multiple sclerosis (MS) – MS is a progressive, inflammatory, demyelinating • Myelin (white matter)= ______that disorder of the CNS speeds nerve impulse conduction – Involves optic, oculomotor & spinal tracts • Injury to myelin by hypoxemia, chemicals, or – Ups and downs of MS – exacerbations & autoimmune responses remissions • Leads to inflammation, breakdown of layers – Occurs in women mostly (18-40yrs.) and formation of plaque (scar tissue) – Causes: viral, autoimmune, genetic, stress • Damaged myelin sheath not able to conduct – Symptoms: optic neuritis & sensory impairment AP neurologic dysfunction (paresthesia) – Prognosis varies

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Neuromuscular Junction Disorders NMJ

• Myasthenia gravis (“grave muscular weakness”) • During normal NMJ transmission- motor  – Chronic autoimmune disease neuron AP travels to axon terminal release of ACh (neurotransmitter)  – Antibodies produced against ACh receptors diffuses across cleft and attach to receptor – Weakness and fatigue of muscles head and neck sites on motor end plate  depolarization  diplopia, difficulty chewing, talking, swallowing of muscle fiber. • In MG – antibodies attach to ACh receptors – Causes: unknown, autoimmune, disorders of thymus and block the ACh from attaching  – Symptoms: progressive muscle weakness, respiratory blocked neuromuscular transmission distress (______) – Treatment: AChase drugs, Corticosteroids

• 3. TIAs are: Concept Check A. Neurological deficits that slowly resolve B. Neurological deficits that occur every hour • 1. If an individual struck the car windshield in a car accident, C. Focal neurological deficits that dev. suddenly, last for a few the coup/contrecoup injury would be in the : minutes, and clear in 24 hours A. Frontal/parietal region D. Events that never indicate an impending stroke B. Frontal/occipital region

C. Parietal/occipital region Matching: D. Occipital/frontal region 4. MG a. Autoimmune disorder, antibodies

attack ACh receptors at NMJ 2. Injury of the cervical SC may be life threatening due to:

A. Increased intracranial pressure B. Spinal shock 5. MS b. Protrusion of nucleus pulposus C. Loss of bladder and rectal contrao D. Impairment of the diaphragm 6. Herniated disc c. Demyelination of nerves

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