UNIT 2 (ch15-20) STUDY GUIDE NU 545 Pathophysiology PDF

UNIT 2 STUDY GUIDE NU 545- Pathophysiology Ch. 15, 16, 17, 18 19, 20 CHAPTER 15- Structure & Function of the Neurologic System Afferent (ascending) is used to describe things like nerves, blood vessels, and arteries that lead TOWARD or bring t...

UNIT 2 STUDY GUIDE NU 545- Pathophysiology Ch. 15, 16, 17, 18 19, 20 CHAPTER 15- Structure & Function of the Neurologic System Afferent (ascending) is used to describe things like nerves, blood vessels, and arteries that lead TOWARD or bring things (like blood, in the case of arteries) to an organ, such as the heart or brain. Efferent (descending) is used to describe parts that carry or lead things AWAY from organs or other parts. 1 Support cells of the Nervous System: CNS: Astrocytes: Form specialized contact between neuronal surfaces and blood vessels Provide rapid transport for nutrient and metabolites Thought to form an essential component of blood brain barrier Appear to have scar-forming cells of CNS, which may be foci for seizures Appear to work with neurons in processing information and memory storage Oligodendroglia (oligodendrocytes) Formation of myelin sheath in CNS Microglia Responsible for cleaning cellular debris (phagocytic properties) and the key immune cell in the CNS Ependymal Cells Serve as a lining for ventricles and choroid plexuses involved in production of CSF Peripheral Nervous System: Schwann cells o Formation of myelin sheath within PNS Nonmyelinating Schwann Cells o Provide neuronal metabolic support and regeneration in PNS Satellite glial cells o Surround sensory, sympathetic and parasympathetic nerve cell bodies and ganglia to provide protection and promote cellular communication (similar to astrocytes in CNS) What nerves are capable of regeneration? Mature neurons do not divide and injury in the CNS causes permanent loss of damaged neurons. Crushed nerves recover better than cut nerves. Myelinated fibers in the PNS can repair themselves through axonal reaction Local changes occur when the axon is severed: 1. Cut ends retract and the axolemma covers the cut ends, diminishing the escape of axoplasm 2. Macrophages and Schwann cells begin to phagocytize damaged tissue 3. The cell body undergoes chromatolysis with swelling, loss of Nissl bodies, and the lateral migration of the nucleus 4. Antegrade (Wallerian) degeneration occurs in the distal axon 5. A characteristic swelling appears in the axon terminal and it degenerates and loses contact with the post synaptic membrane within 7 days 6. Macrophages and Schwann cells phagocytize the remnants of the axon terminal 7. Schwann cells proliferate, forming a column or tube of Schwann cells enclosed by the original basal lamina of the endoneurium. 8. Retrograde changes occur at the proximal end of the injured axon and are similar to antegrade changes but only back to the next node of Ranvier. Approximately 7-14 days after the injury, new terminal sprouts project from the proximal segment guided by Schwann cells and enter the sustaining substrate of a more detailed representation of these events o This process is very slow, about 1mm/day, and is limited to myelinated fibers in the PNS. 2  o The closer the injury is to the cell body of the nerve, the greater the chances that the nerve cell will die and not regenerate o Peripheral nerves injured close to the spinal cord recover poorly and slowly because of the long distance between the cell body and the peripheral termination of the axon. The regeneration of axonal constituents in the CNS is limited by an increased incidence of glial scar formation (gliosis) and the different nature of myelin formed by the oligodendrocyte Nerve regeneration depends on many factors: o Location of the injury o The type of injury: crushing injury allows recovery more fully than does a cut injury § Crushed nerves sometimes fully recover, whereas cut nerves often form connective tissue scars that block or slow regenerating axonal branches o The presence of inflammatory responses o The process of scarring 3 Cranial Nerve Origin & Course Function I. Olfactory Fibers arise from nasal Purely sensory; carries impulses for sniff aromatic substances identify them olfactory epithelium & form sense of smell synapses with olfactory bulbs that transmit impulses to temporal lobe II. Optic Fibers arise from retina of eye Purely sensory; carries impulses for Vision and visual field tested with an eye chart to form optic nerve, which vision and by testing point at which person first sees an passes through sphenoid bone; object (finger) moving into visual field; inside of two optic nerves then form eye is viewed with ophthalmoscope to observe optic chiasma (with partial blood vessels of eye interior crossover of fibers) III. Oculomotor Fibers emerge from midbrain Contains motor fiber to inferior Pupils examined for size, shape, and equality; & exit from skull & extend to oblique & to superior, inferior & pupillary reflex tested with a penlight (pupils eye medial rectus extraocular muscles should constrict when illuminated); ability to that direct eyeball; levator muscles of follow moving objects eyelid; smooth muscles of iris & ciliary body; and proprioception (sensory) to brain from extraocular muscles IV. Trochlear Fibers emerge from posterior Proprioceptor & motor fibers for Tested in common with cranial nerve III relative midbrain & exit from skull to superior oblique muscles of eye to ability to follow moving objects run to eye (extraocular muscles) V. Trigeminal Fibers emerge from pons and Both motor & sensory for face; Sensations of pain, touch, and temperature tested form three divisions that exit conducts sensory impulses from with safety pin and hot and cold objects; corneal from skull and run to face and mouth, nose, surface of eye, and dura reflex tested with a wisp of cotton; motor branch cranial dura mater mater; also contains motor fibers that tested by asking subject to clench teeth, open stimulate chewing muscles mouth against resistance, and move jaw from side to side VI. Abducens Fibers leave inferior pons and Contains motor fibers to lateral rectus Tested in common with cranial nerve III relative exit from skull, and extend to muscle and proprioceptor fibers from to ability to move each eye laterally eye same muscle to brain VII. Facial Fibers leave pons and travel Mixed: (1) supplies motor fibers to Anterior two-thirds of tongue tested for ability to through temporal bone & muscles of facial expression and to taste sweet (sugar), salty, sour (vinegar), and bitter extend to face lacrimal and salivary glands and (2) (quinine) substances; symmetry of face checked; carries sensory fibers from taste buds subject asked to close eyes, smile, whistle, and so of anterior part of tongue on; tearing tested with ammonia fumes VIII. Fibers run from inner ear Purely sensory; vestibular branch Hearing checked by air and bone conduction by Vestibulocochlear (hearing & equilibrium transmits impulses for sense of use of a tuning fork; vestibular tests: Bárány and receptors in temporal bone) to equilibrium; cochlear branch caloric tests enter brainstem just below pons transmits impulses for sense of hearing IX. Glossopharyngeal Fibers emerge from midbrain Mixed: (1) motor fibers serve Gag and swallow reflexes checked; subject asked and leave skull and extend to pharynx (throat) and salivary glands, to speak and cough; posterior one-third of tongue pharynx, salivary glands and and (2) sensory fibers carry impulses may be tested for taste tongue from pharynx, posterior tongue (taste buds), and pressure receptors of carotid artery X. Vagus Fibers emerge from medulla, Fibers carry sensory & motor Same as for cranial nerve IX (IX and X are tested pass through skull, and impulses for pharynx; a large part of in common) because they both serve muscles of descending through neck region this nerve is parasympathetic motor the throat into thorax and abdominal fibers, which supply smooth muscles region of abdominal organs; receives sensory impulses from viscera XI. Spinal Accessory Fibers arise from medulla & Provides sensory & motor fibers for Sternocleidomastoid and trapezius muscles superior spinal cord & extend to sternocleidomastoid and trapezius checked for strength by asking subject to rotate muscles of neck & back muscles of soft palate, pharynx, and head and shrug shoulders against resistance larynx XII. Hypoglossal Fibers arise from medulla & Carries motor fibers to muscles of Subject asked to stick out tongue, and any exit from skull & extend to tongue & sensory impulses from position abnormalities are noted tongue tongue to brain 4 Review the anatomy of the brain. The Brain: allows individuals to reason, function intellectually, express personality and mood, and interact with the environment. Weighs approximately 3 lbs. but receives 15%-20% of total cardiac output THREE MAJOR DIVISIONS OF THE BRAIN PRIMARY VESICLES SECONDARY VESICLES ASSOCIATED STRUCTURES FOREBRAIN (prosencephalon) Cerebral hemispheres Telencephalon Cerebral cortex Rhinencephalon (olfaction) Basal ganglia Epithalamus Diencephalon Thalamus Hypothalamus Subthalamus MIDBRAIN Mesencephalon Tectum (corpora quadrigemina) Connects the Pons to the Tegmentum diencephalon Red nucleus Substantia nigra Cerebral peduncles HINDBRAIN Mentencephalon Cerebellum (rhombencephalon) Pons Myelencephalon Medulla Oblongata BRAINSTEM Comprised of the midbrain, pons, and medulla oblongata Connects the left / right hemispheres, cerebellum, and spinal cord Reticular formation / reticular activating system SPINAL CORD Spinal cord 5  THE CEREBRAL HEMISPHERE The Cerebral Hemispheres. A) Left hemisphere of cerebrum, lateral view B) Functional areas of cerebral cortex, midsagittal view C) Functional areas of the cerebral cortex, lateral view 6  FOREBRAIN (prosencephalon) Telencephalon Frontal Lobe Prefrontal area 1. Goal-oriented behavior 2. Short term memory 3. Concentration 4. Elaboration of thought 5. Inhibition on limbic area (emotional region of the brain) 6. Executive attention functions (problem solving, planning) Premotor area 1. Programs motor movement: (Brodmann area 6) a. Contains cell bodies that form part of the basal ganglia system - extrapyramidal system 2. Controls eye movement a. Brodmann area 8 b. Middle frontal gyrus Primary motor area 1. Primary voluntary motor = somatotopic organization (Brodmann area 4) (Homunculus = little man) 2. Cerebral cortex à central impulses control the opposite side of the body = contralateral control Broca speech area 1. Motor aspect of speech (Brodmann area 44, 45) 2. Speech and language processing area **most important in the 3. Dysfunction (damage from CVA) may result in inability left hemisphere to form words à expressive aphasia or dysphasia Parietal Lobe Somatic sensory input 1. Provides communication between motor and sensory (Brodmann areas 3, 1, 2) areas 2. Storage, analysis, and interpretation of stimuli Temporal Lobe Primary auditory cortex (Brodmann area 41) Wernicke area 1. Sensory speech area (Brodmann area 22) 2. Reception and interpretation of speech (superior temporal gyrus) 3. Dysfunction / damage may result in receptive aphasia or dysphasia 4. Secondary function of balance Memory consolidation and smell Occipital Lobe Primary visual cortex Receives input from the retinas (Brodmann area 17) Remainder of lobe Visual association (Brodmann areas 18, 19) Corpus Callosum Bundle of myelinated fibers that connects the two cerebral hemispheres (conveying contralateral projection) which is essential in coordinating activities between hemispheres Limbic System Located between the 1. Mediates emotion and long-term memory through connections in telencephalon and the prefrontal cortex diencephalon and 2. Primitive behavioral responses and visceral reaction to emotion, surrounding the corpus feeding behaviors, biologic rhythms and sense of smell callosum 3. Expression of affect (emotion and behavioral state) à mediated by connections with limbic system and prefrontal cortex 4. Consolidation of memory à reverberating circuit 7  Diencephalon (Interbrain) Surrounded by the cerebrum and sitting on top of the brainstem; has four divisions Epithalamus Forms the roof of the 3rd 1. Controls vital functions and visceral activities ventricle; composes the 2. Closely associated with the limbic system most superior portion Thalamus Largest component of the 1. Major center for afferent (SENSORY) impulses to the cerebral diencephalon; surrounds cortex the third ventricle 2. Cortical processing = interpretation of sensations 3. Relay center for information from the basal ganglia and cerebellum to appropriate motor area Hypothalamus Forms ventral part 1. Main functions: (a) Maintains constant internal environment (b) Implements behavioral patterns 2. Visceral and somatic responses 3. Affectual responses 4. Hormone synthesis (endocrine function) 5. Sympathetic / Parasympathetic control (autonomic nervous system function) 6. Body temperature regulation 7. Feeding responses 8. Regulation of physical expression of emotions 9. Sexual behavior 10. Pleasure-punishment centers 11. Level of arousal or wakefulness Subthalamus Lateral to hypothalamus Important basal ganglia center for motor activities MIDBRAIN (mesencephalon) Connects the frontal lobe with the hindbrain; composed of 3 structures Tectum (corpora Roof of the midbrain; 1. Superior colliculi – voluntary and involuntary visual motor quadrigemina) includes superior colliculi movements and inferior colliculi a. Ability for the eyes to track moving objects in the visual field 2. Inferior colliculi – similar motor activities but involve movements affecting the auditory system (positioning the head to improve hearing) a. Major relay center along the auditory pathway Tegmentum Floor of the midbrain; 1. Provides communication between motor and sensory areas includes red nucleus and 2. Storage, analysis, and interpretation of stimuli substantia nigra Red nucleus 1. Receives ascending sensory information from the cerebellum and projects a minor motor pathway (rubrospinal tract) to the cervical spinal cord Substantia nigra 1. Synthesizes dopamine 2. Dysfunction of dopaminergic neurons in the substantia nigra is associated with: a. Parkinson disease and schizophrenia Cerebral peduncles Anterior midbrain; made 1. Contains nuclei of the cranial nerves III & IV up of fibers that link to 2. Cerebral aqueduct (aqueduct of Sylvius) = carries CSF cortex of the brainstem between 3rd and 4th ventricles àobstruction of the aqueduct is common cause of hydrocephalus 8  HINDBRAIN Mentencephalon Cerebellum Composed of two lobes 1. Responsible for reflexive, involuntary fine-tuning of of gray and white motor control (conscious and unconscious muscle matter; divided by energy) central fissure; 2. Maintaining balance and posture (via connections with connected by the vermis the medulla and the midbrain) 3. Control of the body = ipsilateral (same side) 4. Damage to the cerebellum is characterized by loss of equilibrium, balance, and motor coordination on the same side Pons “bridge” 1. Transmits information from the cerebellum to the below the midbrain and brainstem (between the two hemispheres) above the medulla 2. Contains nuclei of the 5th-8th (V-VIII) cranial nerves 3. Aids in controlling respirations Myelencephalon Medulla Oblongata Lowest portion of the 1. Aids in controlling reflex activity: brainstem a. Heart rate b. BP c. Respirations d. Coughing e. Sneezing f. Swallowing g. Vomiting 2. Contains nuclei of the IX through XII cranial nerves 3. Sleep-wake rhythms BRAINSTEM Comprised of the midbrain, pons, and medulla oblongata Connects the two hemispheres, cerebellum, and spinal cord Reticular Large network of 1. Controls vital reflexes: Formation diffuse nuclei that a. Cardiovascular connect the brainstem to b. Respiration function the cortex 2. Vomiting, yawning, and hiccups = reflex-like motor responses “Reticular Reticular formation + 1. Essential for maintaining consciousness/wakefulness Activating Cerebral cortex and attention System” 9 Which portion is responsible for keeping you awake, controlling thought, speech, emotions and behavior, maintaining balance and posture? Reticular Formation Prefrontal area Broca speech area Wernicke area (Brainstem) (Forebrain) (Forebrain) (Forebrain-temporal lobe) Regulates vital reflexes Goal-oriented behavior Motor aspects of speech Reception and (cardiovascular function (i.e. ability to (usually on left interpretation of speech and respiration) concentrate) hemisphere); (superior temporal gyrus) RAS: Short-term or recall Damage to this area (ex. Secondary function of Essential for maintaining memory CVA) results in inability balance wakefulness. to form words, called Elaboration of thought expressive aphasia or Damage to this area dysphasia. results in difficulty Inhibition on the limbic understanding words or (emotional) areas of the written language, called CNS. receptive aphasia or Limbic system Hypothalamus Cerebellum (Hindbrain) dysphasia. (Forebrain) (Forebrain) Primitive behavioral Maintenance of a Conscious and responses constant internal unconscious muscle environment synergy Visceral reaction to emotion Implementation of Maintaining balance and behavioral patterns posture Feeding behaviors Integrative centers Damage to the Biologic rhythms control function of the cerebellum is ANS characterized by Sense of smell ipsilateral (same side) Regulation of body loss of equilibrium, Expression of affect temperature balance, and motor (emotional and coordination behavioral states) Regulation of endocrine system Consolidation of memory Regulation of emotional expression 10 What part of the brain must be functioning for cognitive operations? The neural systems essential to cognitive function are: o Attentional systems that provide arousal and maintenance of attention over time o Memory and language systems by which information is communicated o Affective or emotive systems that mediate mood, emotion, and intentions. Cognitive cerebral functions require a functioning reticular activating system à regulates aspects of attention, information processing, and maintains consciousness. Awareness (content of thought) encompasses all cognitive functions (including awareness of self, environment, and affective states – moods) Awareness is mediated by the core networks (selective attention and memory) under the guidance of executive attention networks (the networks that involve abstract reasoning, planning, decision making, judgment, error correct, and self-control) Each attentional function is not localized in a single brain area but is a network of interconnected brain circuits. Prefrontal cortex is involved in cognitive functions such as planning and evaluating outcomes, and consequences for actions o The prefrontal area mediates several cognitive functions (executive attention functions – planning, problem solving, goal-setting) It is responsible for goal-oriented behavior (i.e., ability to concentrate), short-term or recall memory, and elaboration of thought and inhibition on the limbic (emotional areas of the CNS) Which part of the brain controls movement of the eye? Six extrinsic eye muscles (attached to the outer surface of each eye) allow gross eye movements and permit the eyes to follow a moving object. o These muscles arise from the common tendinous ring in the orbit, the eye cavity, and attach to the eyeball. o The six muscles are: 1. Lateral rectus muscle 2. Medial rectus muscle 3. Inferior rectus muscle 4. Superior rectus muscle 5. Inferior oblique muscle 6. Superior oblique muscles o When muscles contract it causes movement of the eyeball, by pulling the eyeball towards the muscle. The frontal eye fields (lower portion of Brodmann area 8): o Controlling eye movements, are in the middle frontal gyrus The superior colliculi of the midbrain: o Voluntary and involuntary visual motor movements o e.g. the ability of the eyes to track moving objects in the visual field Abnormal ocular movements occur because of oculomotor, trochlear, or abducens cranial nerve dysfunction (e.g., strabismus, nystagmus, and paralysis of individual extraocular muscles) o Oculomotor: fibers emerge from midbrain (oculomotor nucleus) 11  o Trochlear: fibers emerge from posterior midbrain (trochlear nucleus) o Abducens: fibers leave inferior pons (abducens nucleus) Occipital lobe lies caudal to the parietooccipital sulci and superior to the cerebellum. Primary visual cortex (Brodmann area 17) is in this region and receives input from the retinas. Much of the remainder of this lobe is involved in visual association (Brodmann areas 18, 19). Discuss the types of mid-brain dysfunction and its physical symptoms. Midbrain: a relay center for some motor and sensory tracts, as well as a center for auditory and visual reflexes, temperature control, sleep-wake cycles, arousal, and attention. o Damage to the midbrain can result in: § A wide variety of movement disorders § Difficulty with vision and hearing § Trouble with memory Tectum (Corpora Quadrigemina) (roof of the midbrain): o Disorders of selective attention related to visual orienting behavior are produced by disease that involves portions of the midbrain § Superior colliculi: responsible for involuntary and voluntary visual motor movements (i.e. ability to track moving objects in the visual field); disease manifests as slowness in orienting attention § Inferior colliculi: responsible for movement affecting the auditory system (i.e. positioning head to improve hearing); relay center along the auditory pathway Tegmentum (floor of the midbrain): o Red nucleus: receives ascending sensory information from the cerebellum à minor motor pathway (rubrospinal tract) à cervical spinal cord o Substantia nigra (inferior portion of the basal ganglia): § Synthesizes dopamine (neurotransmitter and precursor of norepinephrine) § Dysfunction of this structure is associated with Parkinson’s disease Schizophrenia Huntington’s disease Drug addiction Multi-system atrophy o Damage to tegmentum near hypothalamus and third ventricle à akinetic mutism (neither to move [akinesia] nor speak [mutism]) Cerebral peduncles (anterior midbrain): o Made up of efferent fibers of the corticospinal, corticobulbar, and corticopontocerebellar tracts (tracts that link the cortex to the brainstem) o Cerebral aqueduct (aqueduct of sylvius): § Carries CSF between 3rd / 4th ventricle à obstruction à hydrocephalus Because the midbrain houses the hypothalamus, it also plays a major role in automatic body functions. Other notable structures include: o Nuclei of the third and fourth cranial nerves (pupils) à mid-position pupils 12  o CNS damage or disease affecting lower midbrain àCentral reflex hyperpnea (brainstem breathing pattern) o Severe damage to midbrain/upper pons à decerebrate (abnormal posturing – internal rotation with hyperpronation of forearms) Syndromes associated with midbrain pathology include the Weber, Claude, Benedikt, Nothnagel, and Parinaud syndromes o Parkinsonism is a neurologic condition characterized by tremors, rigidity, hypokinesia, and postural instability because of degeneration of the corpus striatum or substantia nigra. What is the function of the CSF? CSF is a clear, colorless fluid like blood plasma and interstitial fluid. Intracranial and spinal cord structures float in the CSF and are thereby partially protected from jolts and blows, and the buoyant properties of CSF also prevent the brain from tugging on meninges, nerve roots, and blood vessels. Where is CSF produced? Where is CSF absorbed? CSF is produced by the choroid plexus (rich network of blood vessels supplied arising from the pia mater) function to produce cerebrospinal fluids (CSF) o Lies in close contact with ventricular ependymal cells o Tight junctions of the choroid blood vessel providing a limiting barrier between the CSF and blood that functions similarly to the Blood-Brain Barrier CSF does not accumulate and is reabsorbed by means of a pressure gradient between the arachnoid villi and the cerebral venous sinuses. CSF is derived from the blood, and after circulating throughout the CNS, it returns to the blood Know the function of the arachnoid villi. Protrude from the arachnoid space, through the dura mater, and lie within the blood flow of the venous sinuses. The villi function as one-way valves, directing CSF outflow into the blood but preventing blood into the subarachnoid space CSF reabsorbed between arachnoid villi & cerebral venous sinuses 13 Review blood flow to the brain. The brain receives approx. 20% of the cardiac output or 800 to 1000 mL of blood flow per minute CO2 serves as the primary regulator for blood flow (CO2 = powerful vasodilator that effects ensures adequate blood supply) Brain derives arterial blood supply from two systems: Internal carotid arteries (anterior circulation) o Greater amount of blood flow (80% of blood blow to brain) o Originate from common carotid arteries à enter through cranium (base of skull) àcavernous sinus à divide into: § Anterior cerebral artery § Middle cerebral artery Vertebral arteries (posterior circulation) (supplies 20% of blood flow to brain) o Originate at subclavian àpass through the transverse foramina of the cerebral vertebrae àentering the cranium (through the foramen magnum)à join at the junction of the pons and medulla oblongata àform the basilar artery o Basilar artery divides at the midbrain to form three paired posterior cerebral arteries (perfuse cerebellum and brainstem): § Posterior inferior cerebellar artery § Anterior inferior cerebellar artery § Superior cerebellar arteries o Basilar artery also gives rise to small pontine arteries The larger arteries on the surface of the brain and their branches are called the superficial arteries (or conducting arteries), with the small branches that project into the brain called projecting arteries (or nutrient arteries) Circle of Willis (arterial circle) provides alternative route for blood flow when a contributing artery is obstructed and is comprised of: posterior cerebral arteries posterior communicating arteries internal carotid arteries anterior cerebral arteries anterior communicating artery 14 15  CHAPTER 16- Pain, Temperature Regulation, Sleep, and Sensory Function What is the gate control theory of pain? Gate control theory (GCT): o Integrates and builds upon features of other theories (specificity theory, pattern theory, etc.) to explain the complex multidimensional aspects of pain perception and pain modulation Pain transmission is modulated by a balance of impulses conducted to the spinal cord where cells in the substantia gelatinosa function as a “gate” – spinal gate that regulates pain transmission to higher centers in the CNS Nociceptive transmission (mechanical, thermal, and chemical) à opening of the gateà transmit the perception of pain o Large myelinated A-delta fibers and small, unmyelinated C fibers terminate on interneurons in the substantia gelatinosa (laminae in the dorsal horn of the spinal cord) Non-nociceptive stimulation (from touch sensors in the skin; rubbing a painful area) à closure or partial close of the spinal gates à decreased pain perception: o Larger A-beta fibers Know the type of nerve fibers that transmit pain impulses. Nociceptors (primary order neurons): o Free nerve endings in the afferent PNS that selectively respond to different chemical, mechanical and thermal stimuli o Lateral spinothalmic spinal tract carries the most nociceptive information o When stimulated they cause nociceptive pain. o Categorized according to the stimulus to which they respond and by the properties of the axons associated with them. o Nociception has four phases: 1. Transduction 2. Transmission 3. Perception 4. Modulation A-delta fibers are lightly myelinated, medium-sized fibers that are stimulated by severe mechanical deformation or by mechanical deformation and/or extremes of temperature. o Transmit sharp, well-localized “fast” pain sensations o Cause reflex withdraw of affected body part from the stimulus BEFORE a pain sensation is perceived (i.e. pulling a hand away from a hot stove) Unmyelinated C fibers are smaller, unmyelinated polymodal fibers; stimulated by mechanical, thermal, and chemical nociceptors o Slowly transmit dull, aching, or burning sensations that are poorly localized and longer lasting A-beta fibers are large myelinated fibers o Transmit touch and vibration sensations o DO NOT transmit pain but play a role in pain modulation 16 What are the two types of fibers that transmit the nerve action potentials generated by excitation of any of the nociceptors. Nociceptors are free nerve endings in the afferent peripheral nervous system that selectively respond to different chemical, mechanical, and thermal stimuli. A-delta and C fibers o Comprise the primary, first-order sensory afferents coming into the gate at the dorsal horn of the spinal cord A-delta fibers: o lightly myelinated, medium-sized fibers that are stimulated by severe mechanical deformation (mechanonociceptors) or by mechanical deformation and/or extremes of temperature (mechanothermal nociceptors). o Rapidly transmit sharp, well-localized “fast” pain sensations. o Responsible for causing reflex withdrawal of the affected body part from the stimulus before a pain sensation is perceived. Unmyelinated C fibers: o polymodal; stimulated by mechanical, thermal, and chemical nociceptors. o Slowly transmit dull, aching, or burning sensations that are poorly localized and longer lasting. Pain transmission is the conduction of pain impulses along the A-delta and C fibers into the dorsal horn of the spinal cord and brainstem, thalamus, and cortex. Where in the CNS does pain perception occur? Definition Pain perception: Conscious awareness of pain that occurs primarily in the reticular and limbic systems and the cerebral cortex. Three systems interact to produce the perception of pain and individual responses to pain: 1. Sensory-discriminative system: o Mediated by the somatosensory cortex o Responsible for identifying the: § Presence of pain § Character of pain § Location of pain § Intensity of pain 2. Affective-motivational system: o Mediated through the § Reticular formation § Limbic system § Brainstem with projections to the prefrontal cortex o Determines an individual’s conditioned avoidance behaviors and emotional responses to pain 3. Cognitive evaluative system: o Mediated through the cerebral cortex o Overlies the individual’s learned behavior concerning the experience of pain and can modulate perception of pain 17 Know different clinical descriptions of pain (acute, chronic, neuropathic); pain threshold/tolerance Pain threshold: o point at which a stimulus is perceived as pain o does not vary significantly among people or in the same person over time o Intense pain at one location may increase threshold in another location – perceptual dominance – therefore, pain at one site may mask other painful areas o Generally DECREASED with repeated exposure to pain Pain tolerance: o duration of time or the intensity of pain that an individual will endure before initiating overt pain responses o Generally decreased by person’s § cultural perceptions § expectations § role behaviors § physical and mental health § gender § age § fatigue § anger § boredom § apprehension § sleep deprivation o Tolerance may be INCREASED by alcohol consumption, persistent use of pain medication, hypnosis, warmth, distracting activities, and strong beliefs or faith ACUTE PAIN (nociceptive pain) o Definition: normal protective mechanism that alerts the individual to a condition or experience that is immediately harmful to the body and mobilizes the individual to take prompt action to relieve it o Duration: lasts seconds to days, and sometimes up to 3 months o Patho: relieved after chemical mediators that stimulate pain receptors are removed o S/S: stimulation of ANS à increased HR, HTN, diaphoresis, and dilated pupils o Etiology: arises from cutaneous & deep somatic tissue or visceral organs à classified as: § Somatic: arises from muscle, bone, joints, and skin sharp and well localized (especially fast pain carried by a-fibers) dull, aching, throbbing, and poorly localized (polymodal C fiber transmissions) § Visceral Pain: transmitted by C fibers and refers to pain in internal organs and the lining of body cavities aching, gnawing, throbbing, or intermittent cramping quality; poorly localized; associated with nausea, vomiting, hypotension, restlessness, shock (rare) radiates (spreads away from) the actual site or is referred 18  § Referred Pain: pain felt in an area removed or distant from its point of origin The area of referred pain is supplied by spinal segment as the actual site of pain. Can be acute or chronic CHRONIC PAIN (Persistent pain) o Definition: pain lasting well beyond the expected normal healing time. o Function: serves no purpose; often accompanied by anxiety and depression and causes suffering. It often appears to be out of proportion to apparent tissue injury. o Duration: lasts for more than 3 to 6 months; may be ongoing (low back pain) or intermittent (migraine headaches) o *Changes in PNS and CNS that cause dysregulation of nociception and pain modulation processes (peripheral and central sensitization) are thought to lead to chronic pain o **Persistent pain allows for physiologic adaptation ànormal heart rate and BPà leads to mistakenly conclude that people with chronic pain are malingering because they don’t appear to be in pain NEUROPATHIC PAIN o Definition: chronic pain initiated or caused by primary lesion or dysfunction in the nervous system and leads to long-term changes in pain pathway structures and abnormal processing of sensory information. o Function: amplification of pain without stimulation by injury or inflammation o S/S: burning, shooting, shock-like, tingling; characterized by hyperalgesia (increased sensitivity to a normally painful stimulus – touch, pressure, pinprick, cold, and heat) and allodynia (induction of pain by normally nonpainful stimuli) o Types of Neuropathic pain: § Chronic neuropathic pain: Leads to long-term plastic changes along somatosensory pathways from the periphery to the cortex and abnormal processing of sensory information by the PNS and CNS § Peripheral neuropathic pain: caused by Peripheral nerve trauma Diabetic or alcohol abuse-induced neuropathy Carcinoma Nutritional deficiencies HIV § Central neuropathic pain: caused by a lesion or dysfunction in the CNS, including: Brain or spinal cord trauma Tumors Vascular lesions MS Parkinson disease Postherpetic neuralgia (PHN) Phantom limb pain Sympathetic dystrophy 19  § Deafferentation pain syndromes: Neuropathies that result from lesions in the PNS or CNS that interrupt the spinothalamic pathways at any level of the nervous system and are associated with hyperexcitability of the somatosensory thalamus and cortex § Hemiagnosia pain: Form of central pain associated with stroke that produces paralysis and hypersensitivity/allodynia on one half of the body § Phantom limb pain: Pain in an amputated limb after the stump has completely healed. § Sympathetically mediated pain (SMP) or complex regional pain syndromes (CRPSs): Can occur after peripheral nerve or extremity injuries (usually develop 1-2 weeks after), and include two types: o Type I: associated with injury but no apparent nerve injury. o Type II: evidence of nerve injury. Know endogenous opioids. Definition: family of morphine-like neuropeptides that inhibit transmission of pain impulses in the spinal cord, brain, and periphery Their receptors play a role in various CNS, GI system, immune system, and other organ system disorders. There are 4 types of opioid neuropeptides (substances that act as neurotransmitters by binding to one or more G-protein-coupled opioid receptors): o Enkephalins: best known and most prevalent; 1st endogenous opioids extracted in research § Location: found concentrated in the hypothalamus, the periaqueductal gray (PAG) matter, the nucleus raphe magnus of the medulla, and the dorsa; horns of the spinal cord § Binds to the δ receptors Two types: o Methionine-enkephalin (ratio to leucine-enkephalin is 4:1) o Leucine-enkephalins o Endorphins (endogenous morphine): 1st discovered in the human PAG § Location: produced in the hypothalamus and pituitary gland § Binds to μ receptors in the hypothalamus and pituitary gland § Function: produces the greatest sense of exhilaration or “high” than all other endorphin types; strong mu-receptor agonist and believed to provide substantial natural pain relief o Dynorphins: most potent endogenous neurohormone § Location: found in the hypothalamus, brainstem, PAG-rostral ventromedial medulla (RVM) system, and spinal cord § Binds strongly with the κ receptors § Function: serves to impede pain signals in the brain but can, in certain circumstances, incite pain through mechanisms of up-regulation (paradoxically stimulating chronic pain); plays a role in mood disorders and drug addiction o Endomorphins: potent analgesic, GI, and anti-inflammatory effects § Location: Endomorphins 1 and 2 are peptides isolated from the brain and spinal cord and show highest affinity and selectivity for the (μ) mu-opiate receptor 20  § Binds to almost all tissue in body; receptors throughout the brain, brainstem and GI tract § Function: can modulate stress and anxiety, feeding behavior, cough suppression, immune and inflammatory responses, and alcohol intake What is the relationship between epinephrine and body temperature? Heat production: hypothalamus + endocrine system à hypothalamic hormone called thyroid stimulating hormone release hormone TSH-RH à stimulates anterior pituitary to release TSH à acts on thyroid gland to stimulate release of thyroxine (T4) à acts on adrenal medulla, causing release of epinephrine into the bloodstream Epinephrine causes vasoconstriction (improves thermal regulation), stimulates glycolysis, and increases metabolic rate, thus increasing body heat. Heat is distributed by the circulatory system. Know mechanisms of heat production and heat loss. In human, body temperature is maintained around 37°C (98.6°F) and rarely exceeds 41C. Normal range is 36.2°C to 37.7°C. Temperature regulation (thermoregulation) is mediated by o Hypothalamus o Peripheral thermoreceptors in the skin and abdominal organs (unmyelinated C fibers and thinly myelinated A-delta fibers) o Central thermoreceptors in the spinal cord o Trigeminal ganglia provide the hypothalamus with information about skin and core temperatures HEAT PRODUCTION o Chemical reactions of metabolism: § Chemical reactions that occur during ingestion and metabolism of food and those required to maintain the body at rest (basal metabolism) require energy and produce heat. § These processes occur in the body core (primarily the liver) and are in part responsible for the maintenance of core temperature. o Skeletal muscle contraction: § Produces heat through two mechanisms (both which are controlled by the posterior hypothalamus and occur in response to cold): Gradual increase in muscle tone. Production of muscle oscillations – shiveringà does not occur in neonates o Chemical thermogenesis: § Also called nonshivering or adrenergic thermogenesis § Results from release of epinephrine and norepinephrine à a rapid, transient increase in heat production by raising the body’s basal metabolic rate. § Occurs in brown adipose tissue (rich with mitochondria and blood vessels) and is essential for nonshivering thermogenesis. HEAT LOSS: o Radiation: § Heat loss through electromagnetic waves 21  § These waves emanate from surfaces with temperatures higher than the surrounding air temperature (temperature of the skin is higher than that of air, the skin and the body lose heat to the air) o Conduction: § Heat loss by direct molecule-to-molecule transfer from one surface to another, with warmer surfaces losing heat to cooler surfaces. (skin loses heat through direct contact with cooler air, water, or another surface) o Convection: § The transfer of heat through currents of gases or liquids and occurs passively as warmer air at the surface of the body rises away from the body and is replaced by colder air § Process may be aided by fans or wind à combined effect of conduction and convection by wind is conventionally measured as the wind-chill factor. o Vasodilation: § Peripheral vasodilation increases heat loss by diverting core-warmed blood to the surface of the body. § As the core-warmed blood passes through the periphery, heat is transferred by conduction to the skin surface and from the skin to the surrounding environment. § Occurs in response to autonomic stimulation under the control of the hypothalamus. o Decreased muscle tone: § To decrease heat production, muscle tone may be moderately reduced and voluntary muscle activity curtailed § This may explain in part the “washed-out” feeling associated with high temperatures and warm weather. o Evaporation: § Evaporation of body water from the surface of the skin and the linings of the mucous membranes is a major source of heat reduction. § Insensible water loss accounts for about 600ml of water loss per day. § Sweating may result in 2.2L of fluid lost per hour. § Electrolytes are also lost. § Large volume loss through sweating may result in decreased plasma volume, decreased BP, weakness, & fainting. Heat loss by sweating/evaporation is affected by: Sympathetic neural activity. Favorable temperature difference between the body and the environment. Humidity: when high, sweat does not evaporate and instead remains on the skin or drips, when low, evaporates quickly. o Increased pulmonary ventilation: § Exchanging air with the environment through the normal pulmonary ventilation provides some heat loss, although it is minimal in humans. § This normal process occurs faster at higher body temperatures through and increase in ventilator rates; thus, hyperventilation is associated with hyperthermia. o Voluntary mechanisms: § In response to high body temperatures, people physically “stretch out,” thereby increasing the body surface area available for heat loss 22  § They also “take it easy,” thereby decreasing skeletal muscle work, and they “dress for warm weather” in garments that reflect heat and promote convection, conduction, and evaporation § (light-colored, loose-fitting clothes). o Heat adaptation: § The body of an individual who goes from a cooler to a much warmer climate undergoes a period of adjustment, a process that takes several days to several weeks Heat exhaustion and heat stroke HEAT EXHAUSTION / COLLAPSE: Most common heat related injury; result of prolonged high core or environmental temperatures. o High temperatures cause the appropriate hypothalamic response of profound vasodilation and profuse sweating à (prolonged period) produce dehydration, decreased plasma volumesà hypotension, decreased cardio output, and tachycardia S/S: Individual feels weak, dizzy, nauseated, and faint. o Ceasing activity = decreases muscle work à decreased heat production and lying down redistributes vascular volume. o Should be encouraged to drink warm fluids to replace fluid lost through sweating. HEAT STROKE Rectal temp > 41C or 106F Potentially lethal result of breakdown in control of an overstressed thermoregulatory center Causes/Patho: àoverexposure to environmental heat or impaired physiologic mechanisms for heat loss à sweat cools the person starting with the face and forehead, and fanning the face enhances this mechanism à brain cannot tolerate temperatures greater than 40.5C (104.9F) à cardiovascular and thermoregulatory system stops functioning à body’s heat loss mechanisms fail à sweating ceases (skin becomes dry and flushed; irritability, confusion, stuporous, comatose with possible visual disturbances) Continued progression à high core temperatures and vascular collapse à cerebral edema, degeneration of the CNS, swollen dendrites, renal tubular necrosis, hepatic failure with delirium, multi-system organ failure Coma or death results unless immediate, effective treatment is initiated Treatment: o Remove from warm environment, use cooling blankets or cool water bath, or ice packs on head, neck, axillae, and groin area. o Care must be taken to prevent too rapid cooling of the surface, which causes peripheral vasoconstriction and prevents core cooling. Children more susceptible to heat stroke than adults because: o They produce more metabolic heat when exercising. o They have greater surface area to body mass ratio. o Their sweating capacity is less. 23 Stages of sleep Sleep is an active, multiphase, complex brain process that provides restorative functions and promotes memory consolidation. Major sleep center is located in the Hypothalamus Normal sleep has two phases that can be documented by EEG: o Rapid eye movement (REM) sleep o Non-REM (NREM) or slow-wave sleep Sleep cycle (NREM and REM sleep alternate – each cycle lasting for approximately 9-100 minutes) 1. Awake: wakefulness with eyes closed and predominated by alpha waves. 2. NREM sleep a. 75-80% of sleep time b. N1: light sleep with alpha waves interspersed with low-frequency theta waves; slow eye movements cycle lasts 10-12min (3-8% of sleep time) c. N2: further slowing of EEG with the presence of sleep spindles and slow eye movements; cycle lasts 30-60 min; 45-55% of sleep time; temperature drops d. N3: low-frequency high-amplitude delta waves with occasional sleep spindles (known as slow-wave sleep); no slow eye movements; 13-23% of sleep time 3. REM sleep: a. 20-25% of sleep time b. Time of most dreaming c. low-voltage fast activity that occurs for 5-60 min about every 90 minutes REM SLEEP NREM SLEEP Etiology: controlled by the pontine and reticular Etiology: initiated by the withdrawal of neurotransmitters formation; vivid dreaming from the reticular formation and by the inhibition of also known as paradoxic sleep because the EEG pattern arousal mechanisms in the cerebral cortex. is like the normal awake pattern. Patho: Patho: Respiration is DEPENDENT and controlled by Bursts of conjugate rapid eye movement in all metabolic processes. directions Basal metabolic rate is decrease by 10-15%. Atonia of antigravity muscles Temperature decreased 0.5C to 1C. Suppressed temperature regulation HR decreases by 10-30 beats per minute. Alteration in heart rate/blood pressure/respiration Respiration, BP, and muscle tone all decrease, pupils Penile erection in men/clitoral engorgement in women constrict, and knee jerk reflexes are absent. High rate of memorable dreams During N1 and N2 Steroids released in short bursts Cerebral blood flow to brainstem and cerebellum Respiratory control thought to be largely is decreased. INDEPENDENT of metabolic requirements and During N3 oxygen variation. Cerebral blood flow to cortex is decreased and Cerebral blood flow to both hemispheres is increased. growth hormone is released, with depressed levels *Respiratory obstruction common because of loss of of corticosteroids and catecholamines. tongue muscle control **Loss of REM sleep impairs memory and learning. 24 Disorders of the conjunctiva of the eye. Conjunctivitis is an inflammation of the conjunctiva (mucous membrane covering the front part of eyeball). The inflammatory response produces photophobia, visual blurring, redness, edema, pain, and lacrimation (treatment related to cause) Acute bacterial conjunctivitis (“pinkeye”): o Highly contagious o Often caused by gram-positive bacteria (staphylococcus, haemophilus, proteus) o Children ages 6 and under o Haemophilus may lead to otitis media o Onset is acute; disease is often self-limiting, resolving spontaneously in 10-14 day o S/S: mucopurulent drainage from one or both eyes o Tx: preventing spread of organism with handwashing and use of separate towels; Viral conjunctivitis: o Contagious o Caused by an adenovirus (some strains of virus cause conjunctivitis and pharyngitis, and others cause keratoconjunctivitis) o S/S: watering, redness, and photophobia o Tx: symptomatic Allergic conjunctivitis: o Associated with a variety of antigens (pollens) o S/S: Ocular itching, photophobia, burning/gritty feel in eye o Tx: antihistamines, low-dose corticosteroids, mast cell stabilizers, and vasoconstrictors. Chronic conjunctivitis: o Result of any persistent conjunctivitis o Requires identification for effective treatment Trachoma (chlamydial conjunctivitis): o Caused by Chlamydia trachomatis, often associated with poor hygiene and is the leading cause of preventable blindness in the world o S/S: inflammation with scarring of the conjunctiva and eyelids à distorted lashes to abrade the cornea à corneal scarring and blindness o Tx: surgery for in-turned lashes, systemic or local antibiotics, facial cleanliness, and environmental improvement (WHO “SAFE” strategy for treatment) Keratitis: o Inflammation of the cornea that can be noninfectious or caused by bacteria, viruses, or fungi o Bacterial infectionsà corneal ulceration; require intensive antibiotic treatment (staphylococcus aureus is the most common bacterial infection) o Virus (type 1 herpes simplex) can involve the cornea and conjunctiva o Causes: contact use, trauma, and penetrating keratoplasty (corneal grafting) o S/S: photophobia, pain, and lacrimation; severe ulcerations with residual scarring require corneal transplantation. 25  CHAPTER 17-Alterations in Cognitive Systems, Cerebral Hemodynamics, and Motor Function Know the best prognostic indicator of recovery of consciousness and functional outcome after a brain event. Outcomes depend on the cause (etiology) and extent of brain damage and duration of coma (time since onset). The Glasgow Coma Scale (GCS) is used to assess severity of brain injury. The hallmark of a severe TBI is LOC for 6 hours of more. Age and admission GCS score are important diagnostic factors in TBI. TBI classification using the GCS are: o Mild TBI with GCS score of 13 to 15 (associated with mild concussion) o Moderate TBI with GCS score of 9 to 12 (associated with structural injury such as hemorrhage or contusion) o Severe TBI with GCS score of 3 to 8 (associated with cognitive and/or physical disability or death. The Glasgow Coma Score (GCS) is scored between 3 and 15, with 3 being the worst and 15 the best. It is composed of the sum of three parameters: o Best Eye Response, Best Verbal Response, and Best Motor Response GLASSGOW COMA SCORE (GCS) SCORE BEST EYE RESPONSE (4) BEST VERBAL BEST MOTOR REPONSE RESPONSE (5) (6) 1 No eye opening No verbal response No motor response 2 Eye opening to pain Incomprehensible sounds Extension to pain 3 Eye opening to verbal command Inappropriate words Flexion to pain 4 Eyes open spontaneously Confused Withdrawing from pain 5 ---- Oriented Localizing pain 6 ---- Obeys command Know the most critical index of nervous system dysfunction/function. Level of consciousness is the most critical clinical index of nervous system function or dysfunction. Changes can indicate either improvement or deterioration of the individual’s condition and state of awareness. A person who is alert and oriented to self, others, place, and time à functioning at the highest level of consciousness (implies full use of all the person’s cognitive capacities) From this normal alert state, LOCs diminish in stages from confusion to coma 26 Levels of Altered Consciousness: State Definition Confusion Loss of ability to think rapidly and clearly; impaired judgment and decision making; difficulty following instructions Disorientation Beginning loss of consciousness; disorientation to time followed by disorientation to place and impaired memory; lost last is recognition of self Lethargy Limited spontaneous movement or speech; easy arousal with normal speech or touch; may not be oriented to time, place, or person Obtundation Mild to moderate reduction in arousal (awakeness) with limited response to the environment; falls asleep unless stimulated verbally or tactilely; answers questions with minimum response Stupor A condition of deep sleep or unresponsiveness from which the person may be aroused or caused to open eyes only by vigorous and repeated stimulation; response is often withdrawal or grabbing at stimulus Light coma Associated with purposeful movement on stimulation Coma No verbal response to the external environment or to any stimuli; noxious stimuli such as deep pain or suctioning yields motor movement Deep coma Associated with unresponsiveness or no response to any stimulus Know patterns of breathing with head injuries. Breathing Pattern Description Location of Injury Hemispheric Breathing Patterns Normal After a period of hyperventilation that lowers the Response of the nervous system to an arterial carbon dioxide pressure (PaCO2), the external stressor—not associated with injury individual continues to breathe regularly but with a to the central nervous system (CNS) reduced depth. Posthyperventilation Respirations stop after hyperventilation has lowered Associated with diffuse bilateral metabolic apnea (PHVA) the PaCO2 level below normal. Rhythmic breathing or structural disease of the cerebrum returns when the PaCO2 level returns to normal. (Usually, an intact cerebral cortex will trigger breathing within 10 s regardless of PaCO2.) Cheyne-Stokes Breathing pattern has a smooth increase (crescendo) Bilateral dysfunction of the deep cerebral or respirations in the rate and depth of breathing (hyperpnea), which diencephalic structures; seen with peaks and is followed by a gradual smooth decrease supratentorial injury and metabolically (decrescendo) in the rate and depth of breathing to induced coma states unrelated to neurologic the point of apnea when the cycle repeats itself. The dysfunction; may see also in congestive hyperpneic phase lasts longer than the apneic phase heart failure (CHF) (represents an amplitude change). Brainstem Breathing Patterns Central reflex Deep rapid, regular pattern (hyperpnea) occurs, May result from CNS damage or disease that hyperpnea (central with a decreased PaCO2 and a corresponding involves the lower midbrain and upper neurogenic increase in pH and increased PO2. pons; seen after increased intracranial hyperventilation) pressure and blunt head trauma Apneusis A prolonged inspiratory cramp (a pause at full Indicates damage to the respiratory control inspiration) occurs. A common variant of this is a mechanism located at the pontine level; brief end-inspiratory pause of 2 or 3 s, often most commonly associated with pontine alternating with an end-expiratory pause. infarction but documented with hypoglycemia, anoxia, and meningitis Cluster (Biot) A cluster of breaths has a disordered sequence with Dysfunction in the lower pontine and high breathing irregular pauses between breaths. medullary areas Ataxic breathing Completely irregular breathing occurs, with random Originates from a primary dysfunction of the shallow and deep breaths and irregular pauses. Often medulla the rate is slow. Gasping breathing A pattern of deep “all-or-none” breaths is Indicative of a failing medullary respiratory pattern (agonal gasps) accompanied by a slow respiratory rate. center 27 Know vomiting with which CNS injuries. Vomiting, yawning, and hiccups are complex reflex motor responses that are integrated by neural mechanisms in the lower brainstem. Most CNS disorders produce nausea and vomiting. These responses may be produced by: o Compression or diseases involving tissues of the medulla oblongata (e.g., infection, neoplasm, infarct, or other more benign stimuli to the vagal nerve). o Direct involvement of the central neural mechanism (e.g., pyloric obstruction) – usually vomiting occurs without nausea. o Injuries that involve the vestibular nuclei or its immediate projections, particularly when double vision is present (diplopia). o Injuries that impinge directly on the floor of the fourth ventricle. o Injuries that produce brainstem compression secondary to increased ICP. Know diagnostic criteria for vegetative state and brain death. Brain death (or total brain death): occurs when irreversible brain damage is so extensive that the brain has no potential for recovery and no longer can maintain the body’s internal homeostasis. State laws define brain death as irreversible cessation of function of the entire brain, including the brainstem and cerebellum. This is to be distinguished from cerebral brain death, which is the death of the cerebral hemispheres exclusive of the brainstem and cerebellum. Clinical criteria for brain death: o Completion of all appropriate and therapeutic procedures with no possibility of brain function recovery. o Unresponsive coma (absence of motor and reflex movements). o No spontaneous respiration (apnea) – a PaCO2 that rises above 60mmhg without breathing efforts, providing evidence of a nonfunctioning respiratory center (apnea challenge). o No brainstem function (ocular responses to head turning or caloric stimulation; dilated fixed pupils; no gag or corneal reflex). o Isoelectric (flat) EEG (electrocerebral silence) for 6-12 hours for patients who are not hypothermic and have not ingested depressant drugs o Persistence of these signs for an appropriate observation period Persistent vegetative state (PVS): complete unawareness of the self or surrounding environment and complete loss of cognitive function (unresponsive wakefulness syndrome) Diagnostic criteria for PVS: o Periods of eye opening (spontaneous or following stimulation). o Potential for subcortical responses to external stimuli, including generalized physiologic responses to pain, such as posturing, tachycardia, diaphoresis, and subcortical motor responses, such as grasp reflex. o Return of vegetative autonomic functions, including sleep-wake cycles and normalization of respiratory and digestive system functions. o Occasional roving eye movements without concomitant visual tracking ability. o There may possibly be random hand, extremity, or head movements. The individual can maintain BP and breathing without support. Brainstem reflexes are intact, but cerebral functions are lost. 28  o No discrete localizing motor responses are present, and the individual does not speak any comprehensive words or follow commands. o Recovery unlikely if persist longer than 12 months Clinical manifestations and presenting signs of Creutzfeldt-Jacob Creutzfeldt-Jakob disease is a progressive, fatal, dementing neurologic illness caused by an infectious protein known as a prion. Prior = composed of misfolded proteins unable to self-replicate à spongiform encephalopathy within grey matter Rare; 1 in 1.5 million annually; 10% of cases are genetic (most cases are sporadic) o Molecular mechanism: PrPsc proteins type 1 and 2 o Causal Genes (Chromosome): Prior (20); up to 15% of cases carry these dominant mutations o Susceptibility Genes: PRNP codon 129 homozygosity for methionine or valine Diagnosis: clinical evaluation, MRI, electroencephalography; CSF fluid shows (14-3-3 protein or human prior protein PrPsc and it is also detected in olfactory epithelium, blood, and/or urine samples) Clinical manifestations: Progressive dementia and at least 2 of the following 4 features: o myoclonus, visual or cerebellar disturbance, pyramidal or extrapyramidal signs, and akinetic mutism Prognosis: fatal – average lifespan of 8 months Treatment: no treatment exists Clinical manifestations and presenting signs of brain abscess Abscesses are localized collections of pus within the parenchyma of the brain or spinal cord and are rare. Immunosuppressed persons are particularly at risk. Brain abscesses are classified as extradural, subdural, or intracerebral. o Extradural brain abscesses (empyemas) are associated with osteomyelitis in a cranial bone. o Subdural brain abscesses (empyemas) arise from a sinus infection or a vascular source. o Intracerebral brain abscesses arise from a vascular source. Progression: localized inflammation to a necrotic core with the formation of a connective tissue capsule, usually within 14 days or longer. Brain abscesses evolve through four stages regardless of infecting microorganism, except in the immunosuppressed host where the process may be incomplete. Stages: 1. Early cerebritis (days 1 to 3): localized inflammatory process develops in which perivascular infiltration and inflammatory cells, composed of neutrophils, plasma cells, and mononuclear cells, surround a central core of coagulative necrosis marked cerebral edema surrounds the area 2. Late cerebritis (days 4 to 9): The necrotic center is surrounded by an inflammatory infiltrate of macrophages and fibroblasts 29  Rapid new blood vessels form around the abscess; a thin capsule of fibroblasts and reticular fibers gradually develops; the area is still surrounded by cerebral edema. 3. Early capsule formation (days 10 to 13): The necrotic center decreases in size the inflammatory infiltrate changes in character and contains an increasing number of fibroblasts and macrophages mature collagen evolves, forming a capsule 4. Late capsule formation (days 14 and longer): A well-formed necrotic center surrounded by a dense collagenous capsule develops. The development of symptoms may be very insidious, often making an abscess difficult to diagnose: o Early manifestations: § low-grade fever § headache (most common symptom) § nausea and vomiting § neck pain and stiffness § confusion § drowsiness § sensory deficits § communication deficits o Later manifestations (associated with an expanding mass): § decreased attention span § memory deficits § decreased visual acuity and narrowed visual fields § papilledema § ocular palsy § ataxia § cognitive deficits § seizures Extradural brain abscesses are associated with localized pain, purulent drainage from the nasal passages or auditory canal, fever, localized tenderness, and neck stiffness; occasionally the individual experiences a focal seizure. Evaluation: suggested based on clinical features and confirmed with MRI or contrast-enhanced CT Treatment: o Stereotactic surgical aspiration à identification of the pathogen and for decompression of the abscess. o Antibiotics are initiated à clinical suspicion of an abscess. o Multiple or surgically inaccessible abscesses are treated with antibiotics (+ corticosteroid therapy to treat the cerebral edema) o In addition, ICP or hydrocephalus, or both, require management. 30 Characteristics of Alzheimer’s disease. Leading cause of severe cognitive dysfunction in older adults (most common in women) GREATEST RISK FACTORS are age and family history PROTECTIVE FACTORS are lifelong activity, the presence of apoE2 and antioxidant substances, omega-3 fatty acids, estrogen replacement at the time of surgical menopause, low-calorie diet, and use of nonsteroidal anti-inflammatory agents Characterized by 3 forms: Nonhereditary sporadic or late onset Alzheimer’s Disease (70-90%): a. Most prevalent, does not have a specific genetic association but cellular pathology is the same as gene associated early and late onset Alzheimer’s Disease. b. Pathologic alterations in the brain: i. Accumulation of extracellular neuritic plaques with a core of abnormally folded amyloid beta and tau proteins ii. Intraneuronal neurofibrillary tangles **neurotic plaques and neurofibrillary tangles are more concentrated in the cerebral cortex and hippocampus** iii. Degeneration of basal forebrain cholinergic neurons with loss of acetylcholine, synapses, and other neurotransmitters contributes to decline in memory, attention and loss of other cognitive functions. c. Failure to process and clear amyloid precursor protein results in the accumulation of amyloid beta protein toxic fragments that leads to formation of diffuse neuritic plaques disruption of nerve impulse transmission death of neurons-result is brain atrophy with decreases in weight and volume d. Aging and injury can cause changes that contribute to the development and progression of Alzheimer’s Disease. Early-onset Familial Alzheimer’s Disease (FAD): a. Autosomal dominant; linked to 3 genes with mutations on chromosome 21 b. Gene-associated late onset- major genetic risk is related to apolipoprotein E gene-allele 4 (apoE4) on chromosome 19 (apoE4 interferes with amyloid beta clearance from the brain and is processed into neurotoxic fragments found in the plaques and tangles in the brain of people with AD) Early-onset Alzheimer’s Disease: a. very rare; genetic susceptibility tests for PSEN1, PSEN2, and APP are used for screening Clinical Manifestations: o Alzheimer’s Disease has a long preclinical and prodromal course. o Progresses from mild short-term memory deficits to total loss of cognition and executive functions Evaluation: diagnosis is made by ruling out other causes. Definitive diagnosis can only be made by autopsy. o Clinical history (including mental status exams, clock drawing, and geriatric depression scale), CSF analysis, brain imaging of structure, blood flow and metabolism; and the course of the illness is used to assess progression of Alzheimer’s Disease o Genetic susceptibility tests for PSEN1, PSEN2, and APP are used to screen for early-onset Alzheimer’s Disease Treatment: o No disease modifying therapies o Treatment is directed at using devices to compensate for the impaired cognitive function § memory aids, maintaining unimpaired cognitive functions; and maintaining or improving the general state of hygiene, nutrition, and health o Cholinesterase inhibitors (used in mild-moderate cases of Alzheimer’s Disease) 31 o NMDA receptor antagonist blocks glutamate activity and may slow the progression of disease in moderate-severe Alzheimer’s Disease o Anti-myeloid drugs are in clinical trials 32 Define seizure and status epilepticus. What is the medical significance? Know benign febrile seizures. SEIZURE STATUS EPILEPTICUS Defined as a sudden, transient alteration of brain In adults, it is a state of continuous seizures lasting function caused by an abrupt explosive disorderly more than 5 minutes OR discharge of cerebral neurons Rapidly recurring seizures before the person has fully Sudden, explosive, disorderly discharge of brain cells regained consciousness from the preceding seizure Types of Seizures see attachment OR S/S: LOC, apnea, hypoxia, acidosis, and lactate A single seizure lasting more than 30 minutes. accumulation with resulting brain tissue injury and Cause: often results from abrupt discontinuation of destruction (overall medical concerns for seizures) antiseizure medications but also may occur in untreated or inadequately treated persons with seizure disorders. **medical emergency d/t resulting cerebral hypoxia, **important to provide oxygen ** aspiration, intellectual disability, dementia, & death Long-term Complications: neuronal death, neuronal injury, and alteration of neuronal networks. Patho: a group of neurons may exhibit a paroxysmal depolarization shift and function as an epileptogenic focus These neurons are hyperexcitable (more easily activated by hyperthermia, hypoxia, hypoglycemia, hyponatremia, repeated sensory stimulation, and certain sleep phases) Epileptogenic neurons fire more frequently and with greater amplitude When the intensity reaches a threshold point, cortical excitation spreads à excitation of the subcortical, thalamic, and brainstem areas: Tonic phase (muscle contraction with increased muscle tone) = loss of consciousness When inhibitory neurons in the cortex, anterior thalamus, and basal ganglia react to the cortical excitation à seizure discharge is interrupted: Clonic phase (alternating contraction and relaxation of muscles) = intermittent; gradually decrease and finally cease à epileptogenic neurons are exhausted During seizure activity – cerebral blood flow increases, oxygen consumption (60% greater than normal) à rapidly depleting O2 and glucose à lactate accumulates in brain tissue à (severe seizure continues) progressive brain injury and irreversible damage **If seizure focus in the brain is active for a prolonged period à a mirror focus may develop in contralateral normal tissue à seizure activity (particularly with focal epilepsy - i.e., temporal or frontal lobe) Etiology: a seizure disorder is a manifestation of disease, NOT a specific disease. 33 Onset of seizures may point to the present of: An ongoing primary neurological disease (including cerebral lesions, biochemical disorders, cerebral trauma, and epilepsy) OR Conditions such as metabolic defects, congenital malformations, genetic predisposition, perinatal injury, postnatal trauma, myoclonic syndromes, infection, brain tumor, and vascular disease OR Hypoglycemia, fatigue, emotional or physical stress, fever, hyponatremia, constipation, blinking lights, use of stimulant drugs, loud noises, certain odors, and withdrawal from drugs/alcohol. Phases of seizures: Two types of symptoms signal the preictal phase of a generalized tonic-clonic seizure: Prodroma: early manifestations occurring hours to days before a seizure (may include anxiety, depression, or inability to think clearly Focal seizure or aura that immediately precedes the onset of a generalized tonic-clonic seizure. Both may become familiar to the person and may enable the person to prevent injuries during the seizure. The ictus is the episode of the epileptic seizure with tonic-clonic activity. Airway maintenance needs to be ensured. The postictal state follows an epileptic seizure and can include signs of headache, confusion, aphasia, memory loss, paralysis and deep sleep that may last hours or a day or two. Diagnosis of seizures: Health history (most critical aspect of diagnosis, establishing the cause and onset) Supplemented with physical exam, lab tests of blood and urine (glucose, serum Ca+, BUN, urine Na+, creatinine clearance) – identify any systemic diseases CT/MRI scans and CSF serology – identify any neurologic diseases EEG – identify the type of seizure and determine its focus MRI + EEF – identify neural networks involved in epileptic activity Treatment of seizures: Correct or control cause (#1) – if not possible… Anti-seizure medications (goal: complete suppression of seizure activity without intolerable side effects or drug resistance) Dietary treatments à Ketogenic diet or modified Atkins diet (60 cause the juvenile form of the disease. o Fathers, but not mothers, with high normal alleles do not develop Huntington disease but are at risk for transmitting potentially penetrant HB alleles (> or = 36) to their offspring, who can develop Huntington disease. o The genetic defect of Huntington disease is on the short arm of chromosome 4. o There is an abnormally long polyglutamine tract in the huntingtin (htt) protein that is toxic to neurons and is caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion (40 to 70 repeats instead of 9 to 34) à produces tangles of protein that collect in brain cells and chains of glutamine on the abnormal molecules that adhere to each other (exact mechanism of neuronal death is unknown) Clinical Manifestations (SLOW PROGRESSION): o Excess of dopaminergic activity = hypotonia and hyperkinesia. o Loss of excitatory glutamate = impaired modulation of movement later during the disease. o Build-up of lactic acid = difficulty producing energy for the brain. o S/S: involuntary fragmentary movements (occur without conscious effort), emotional lability, and progressive dysfunction of cognitive processes (dementia) that may precede motor symptoms. § Chorea is the most common type of abnormal movement § Begins in the face and arms, eventually affecting the entire body § Chorea can be combined with athetosis (twisting and writhing) and ballism (flailing of limbs) 40  § Cognitive deficits à loss of working memory and reduced capacity to plan, organize, and sequence. Thinking is slow, and apathy is present. Restlessness, disinhibition, and irritability are common. Euphoria or depression may be present. Prognosis: FATAL Define dyskinesia. Types? Characteristics? Dyskinesias: unnatural movements or abnormal involuntary movements (and are included in the general category of hyperkinesia, which are excessive movements.) o Paroxysmal dyskinesia: abnormal, involuntary movements that occur as spasms. o Tardive (slow onset) dyskinesia: involuntary movement of face, trunk, and extremities due to § Parkinson disease § Prolonged antipsychotic drug usage d/t increase of dopamine § S/S: rapid, repetitive, stereotypic movements (e.g., continual chewing with intermittent protrusions of the tongue, lip smacking, etc.) o Hypokinesia: decreased amplitude of movement. o Bradykinesia: decreased speed of movement o Akinesia: absence of voluntary movements. Parkinson’s disease is the hallmark of lack of movement Huntington’s disease is the hallmark of excess movement. (i.e. tick-like jerky movements, smacking lips, or flicking the tongue, unsteady gait, rocking back and forth.) What is respon