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  1. 1. Nem’s Notes… Phase 1 NEUROSCIENCE 1 (page 1 of 2) The Nervous System Disorders Common neurological disorders arise from non-neurological events (eg CVA) The cause of “intrinsic” disorders is not known. Disorders arise from either: (a) neuronal degeneration (b) neuronal dysfunction Disorders can show either: (a) loss of function and/or (b) abnormal function Psychiatric disorders involve altered behaviour when no pathological cause can be found. Neurology and Psychiatry may overlap considerably. Major Causes (a) Trauma eg skull fracture, spinal injury (b) Cerebrovascular Accident (CVA) eg stroke (c) Infection eg meningitis (d) Neoplasia (tumour) eg glioma (e) Metabolic disorders eg diabetic neuropathy (f) Genetic disorders eg Down’s syndrome (g) Environmental factors eg heavy metal encepholopathy (h) Immunological factors (eg multiple sclerosis?) Divisions Division Consisting of Function Central Nervous System (CNS) Brain & Spinal Cord “Housekeeping” functions processing sensory and motor information and maintaining internal environment. Also supports higher functions of percpetion, cognition, emotion and personality Peripheral Nervous System (PNS) Peripheral Nerves & Ganglia Provides sensory and motor innervation to the body Autonomic Nervous System (ANS) Parts of CNS & PNS Controls visceral (organ) function and homeostasis Each division has local control of function, but some larger systems have several communicating structures that are apart from one another eg the motor system The cerebral hemispheres of the brain have contralateral control of the body (ie left hemisphere controls right side of body). Some higher functions only exist in one hemisphere (eg language in left hemisphere only) Neurons Neurons are the functional cell units of the nervous system. The generate and conduct electrical impulses releasing chemicals at synpases. They are supported by neuroglia which outnumber neurons by 9:1 Axons of neurones of the PNS can regenerate after injury although recovery may be compromised by non-specific target innervation Axons of the CNS do not regenerate more online at page 1 of 14
  2. 2. Nem’s Notes… Phase 1 NEUROSCIENCE 1 (page 2 of 2) The Nervous System Diagnostic (a) History Taking (i) Presenting complaint Techniques (ii) Other illnesses (iii) Social situation (iv) Patient observation. (b) Neuro Exam (i) Level of consciousness (ii) Speech (iii) Mental State & Cognitive Function (iv) Cranial nerve function (v) Motor function (vi) Sensory function (c) Electrophysiology (i) Electroencephalography (EEG) (ii) Electromyography (EMG) & Nerve Conduction Study (d) Imaging (i) Computerised Tomography (CT) – hard tissues (ii) Magnetic Resonance Imaging (MRI) – soft tissues (iii) Angiography of cerebral vasculature more online at page 2 of 14
  3. 3. Nem’s Notes… Phase 1 NEUROSCIENCE 2 (page 1 of 2) Cells of the Nervous System Neuronal All neurons are essentially the same in structure. The diversity of types of neuron Structure arises from the difference in the number and shape of their processes (a) Cell body (Soma) (i) Metabolic centre of the cell (ii) Large nucleus (iii) Abundant rough endoplasmic reticulum (iv) Well developed Golgi apparatus (v) Numerous mitochondria (vi) Numerous lysosomes (vii) Highly organised metabolically active cell (b) Dendrites (i) Receives incoming information (ii) Branch away from cell body (iii) Greatly increase surface area of neuron (iv) Dendritic spines receive majority of synapses (c) Axon (i) Conducts impulse away from cell body (ii) Emerges as the Axon Hillock (iii) Myelinated or unmyelinated (iv) Nodes of Ranvier (d) Terminals (i) Close to target the axon forms terminal branches (ii) Specialised structures called synpatic terminals (iii) Boutons (end of terminal) or varicosities along terminal SEE Mosby Crash Course p11 Neuronal Morphological Sub-Types Sub-Types (a) Pseudounipolar neuron Two fused processes which are both axonal (b) Bipolar neuron Two axonal processes arising from the cell body (c) Golgi Type I Multipolar neuron Cells that extend long distances (d) Golgi Type II Multipolar neuron Cells that have relatively short axons SEE Bray’s Notes p40 Functional Sub-Types (a) Sensory neuron Conducts impulses from sensory receptors to the spinal cord and brain. Usually pseudounipolar with one process dividing into twowith one travelling to the CNS and one to a sensory receptor. (b) Motor neuron Conduct impulses from the brain and spinal cord to effectors such as muscles or glands. Usually multipolar with large cell body. (c) Interneuron Responsible for the modification, coordination, integration, facilitation and inhibition between sensory input and motor output. The cell bodies and processes remain within the CNS. Can be large multipolar or small local bipolar. Neuronal Neurons of the CNS are grouped according to their function Organisation (a) Nucleus Unencapsulated cell bodies within CNS eg Brain Stem (b) Laminae Layers of similar neurons eg Cerbral Cortex, Cerebellum (c) Ganglion Groups of cell bodies in the PNS eg Dorsal Root Ganglia (d) Fibre Tracts Bundles of axons in the CNS eg Corpus Callosum (e) Nerves Bundles of axons outside CNS. Often mixed sensory/motor. more online at page 3 of 14
  4. 4. Nem’s Notes… Phase 1 NEUROSCIENCE 2 (page 2 of 2) Cells of the Nervous System Synaptic Terminal portions of axons form synapses with other neurons which release chemical Organisation transmitters to relay the impulse. Neurons receive multiple inputs which are integrated at the postsynaptic neuron. The types of synapse are: (a) Axodendritic (usually excitory effect) (b) Axosomatic (usually inhibitory effect) (c) Axo-axonic (either to the hillock or terminal and usually modulatory) Neuroglia Support cells of the CNS which perform varying functions. They are in close contact with neurons and are essential for correct functioning. Astroglia Astroglia are the most numerous of the neuroglia in the CNS and are closely (Astrocytes) associated with blood vessels, ventricles, neuronal soma, synapses and nodes of Ranvier Functions: (a) Scaffold for other cell types (b) Forms blood-brain barrier and brain-CSF barrier (c) K+ buffering (d) Removal and degradation of neurotransmitters (GABA) (e) Divides in response to injury (scar tissue formation) Oligodendroglia Myelinating cells of the CNS which are found in rows in axon tracts. They have small spherical nuclei with few processes. Functions: (a) Elaboration and maintenance of neuronal myelin (b) Forms up to 40 myelin nodes for up to 50 neurons (c) Very susceptible to nutritional state, toxins and infections (d) Involved in myelin disease states (eg multiple sclerosis) Microglia Derived from blood monocytes which invade to CNS during fetal development. Relatively small cells with highly branched processes. They turn into large phagocytosing cells during tissue damage. Functions: (a) Resident macrophages of the CNS (b) Antigen Presenting capability (c) Role in tissue modelling Other Glial Cells Ependymal Cells Form the simple cuboidal lining of the ventricles and central cord canal. They are ciliated at the luminal surface and have gap junctions Schwann Cells Envelop the axons of motor and sensory neurons. Produce myelin for cells of the PNS. They also have the same functions as the astrocytes and promote repair. Satellite Cells Perform the functions of astrocytes in the grey matter of the CNS. more online at page 4 of 14
  5. 5. Nem’s Notes… Phase 1 NEUROSCIENCE 3 (page 1 of 2) Neuronal Information Transmission Resting The normal resting potential for a neuron is –70 mV Potential The resting potential is achieved as a result of: (a) The concentration of ions inside and outside the cell (b) The permeability and selective gating of the cell to those ions The resting potential is established by the high concentration of potassium ions inside the cell and of sodium ions outside the cell. Potassium naturally moves down its concentration gradient out of the cell and leaves behind negative ions (which make the cell's interior negative). Movement of sodium into the cell (down it’s concentration gradient) opposes this slightly. It does not oppose it totally since the membrane is more permeable to potassium than sodium. The sodium/potassium pump keeps the gradient relatively constant so there is always movement of ions – otherwise there would be some point at which an equilibrium would be reached and the potential “run- down”. Ion Movement Ions cross cell membranes by a variety of methods including ion channels. These channels can be (a) voltage gated (b) chemically gated (c) mechanically gated Action Potential An action potential is the sudden change in voltage across a cell membrane due to the rapid movement of ions through ion channels. It is usually due to a synaptic or neural impulse. The action potential is due to voltage gated Na+ channels opening which causes inward flow of ions and positive feedback on depolarisation. K+ channels also open outwards during depolarisation but at a slower rate. Na+ channels quickly inactivate causing the membrane potentials to swing back to the resting potential (briefly becoming more negative before stabilising when channels K+ close) Refractory The sodium channels will not open until the resting membrane potential has been Periods reached This is the Absolute Refractory Period. After this period, the lingering permeability to K+ ions means that sodium channels will only open to much higher voltages. This is the Relative Refractory Period. Channels The main differences between the Na+ and K+ ion channels are: (a) They are selective for either Na+ or K+ (b) K+ channels react more slowly than Na+ channels (c) K+ channels stay open longer than Na+ channels The Threshold Potential is the potential at which an action potential is elicited. more online at page 5 of 14
  6. 6. Nem’s Notes… Phase 1 NEUROSCIENCE 3 (page 2 of 2) Neuronal Information Transmission Propagation At any one time only a portion of an axon is depolarised. This causes adjacent areas to also depolarise. Since there is a refractory period after depolarisation the wave of propagation of the action potential is in one direction only. Propagation velocity is faster in (a) axons of larger diameter (reduced resistance) (b) myelinated axons In myelinated axons the propagation can only occur in between myelin sheaths (ie at the nodes of Ranvier) since the myelin increases membrance resistance. This increases the distance between adjacent areas depolarised by an action potential and therefore the velocity of propagation. This means the nerve fibre can be of smaller diameter and it also increases metabolic efficiency since the energy required to repolarise the axon is less (because it only occurs around the nodes of Ranvier). This type of conduction is known as saltatory conduction. Disorders In multiple sclerosis demyelination of axons of the CNS causes slowed or blocked action potentials. This is due to the fact that sodium channels are only present at the nodes of Ranvier. Since there is no more myelin to conduct the current to the next node the current dissipates throuhg the membrane. This leads to numbness, tingling, wekness, blindness or paralysis. Local Anaesthetics block propagation of the action potential by inhibiting the voltage dependent opening of sodium channels. more online at page 6 of 14
  7. 7. Nem’s Notes… Phase 1 NEUROSCIENCE 4 (page 1 of 1) Neurotransmitters Neurotransmitter (a) Action Potential reaches nerve terminal opening Ca2+ channels. Release (b) Ca2+ ions enter terminal and activates neurotransmitter vesicles (c) Vesicles dock on the presynaptic membrane (d) Vesicles fuse to membrane and form pore (e) Transmitter is released by exocytosis (f) Vesicle is recycled back into the membrane (g) Vesicle is filled with more neurotransmitter Fast/Slow Fast acting neurotransmitter systems are Ligand-Gated Ion Channels. They act in a Systems space of milliseconds and use amino acids as the neurotransmitter including: (a) GABA (γ-amino butyric acid) (b) Glutamate (Glu) (c) Aspartate (Asp) (d) Nicotinic (nACh) Slow acting systems are G-Protein Linked Receptors. They act in seconds or minutes and use monamines or neuropeptides as neurotransmitters including: (a) Acetylchloine (ACh) (b) Dopamine (DA) (c) Noradrenaline (NA) Inhibition/ Neurotransmitters can have either an inhibitory or an excitatory effect on the post- Excitation synaptic membrane. Inhibition occurs when the membrane potential is moved away from the threshold potential by the neurotransmitter (usually by increasing permeability to Cl- ions). Excitation occurs when the membrane potential is moved towards the threshold value (usually by increasing sodium and potassium permeability). Diffuse/Precise A diffuse system is one in which the impulse is spread to numerous postsynaptic neurones (eg some NA, DA systems) whereas a precise system is one where the impulse is spread to few specific neurones. Modulatory systems affect the cortex, brain stem and spinal cord and affect arousal, mood, motivation and sleeping. Drug Treatment Drugs acting on GABA receptor to increase affinity for GABA cause: (a) Sedation, Sleep (b) Anticonvulsant (c) Reduced voluntary muscle tone Drugs acting to block sodium channels are used as antiepileptics since they stop rapid firing of neurones eg Phenytoin and Carbamazepine. Increased GABAergic action also helps prevent seizures. Dopaminergic drugs such as L-DOPA which can pass through the blood-brain barrier are used to treat Parkinson’s which is due to loss of dopaminergic cells more online at page 7 of 14
  8. 8. Nem’s Notes… Phase 1 NEUROSCIENCE 5 (page 1 of 2) The Central Nervous System Divisions The CNS is divided into the following major divisions: (a) Spinal Cord – controls reflex sensori-motor functions and autonomic function (b) Brainstem (medulla, pons, midbrain) – controls vital functions (eg breathing) (c) Cerebellum – controls co-ordination of movement (d) Diencephalon (thalamus, hypothalamus) – interfaces CNS, ANS, endocrine (e) Cerebral hemispheres (cortex, ganglia) – all functions Meninges The CNS is covered by the meninges which are made up of three layers: (a) Dura Mater – tough membrane attached to bone or forming septa (b) Arachnoid Membrane – Thin membrane attached to underside of Dura Mater (c) Pia Mater – Delicate membrane close to brain/spinal cord surface acting as protective cushion against itself and gravity. Between the arachnoid and pia mater is the sub-arachnoid space where cerebro- spinal fluid (CSF) circulates. CSF The Ventricular System of the brain is the space where CSF fluid is formed and circulates. It consists of: (a) Lateral Ventricles (1st & 2nd ) relating to: the cerebral hemispheres (b) Third Ventrcle the diencephalon (c) Aqueduct the midbrain (d) Fourth Ventricle the pons and medulla (e) Central Canal CSF compositon is different from that of blood because: (a) it normally contains few cells (b) it contains far less protein (c) it has a low concentration of Na+ and K+ ions (d) it has a high concentration of Mg2+ and Cl- ions The normal volume of CSF = 150 ml and Flow Rate = 50 ml/day Brain Lobes The brain has distinguishable areas that are responsible for different functions: (a) Frontal Lobe (b) Parietal Lobe (c) Occipital Lobe (d) Temporal Lobes Spinal Cord The spinal cord has various spinal and vertebral levels with nerves arising from each. There are 31 pairs of spinal nerves: (a) Cervical (C1 – C8) 08 (b) Thoracic (T1 – T12) 12 (c) Lumbar (L1 – L5) 05 (d) Sacral (S1 – S5) 05 (e) Coccygeal Nerve 01 31 more online at page 8 of 14
  9. 9. Nem’s Notes… Phase 1 NEUROSCIENCE 5 (page 2 of 2) The Central Nervous System Meningitis This is an infection of the meninges and can be caused by virus or bacteria. Symptoms include: (a) severe headache (b) fever (c) tiredness (d) irritability (e) neck stiffness (f) confusion (g) fits (h) meningococcal rash (75% of cases) Viral form is mild to moderate and self-limiting. Bacterial form can be caused by various bacteria: (a) Neisseria meningitidis – isolated cases/outbreaks, severe (b) Streptococcus pneumoniae – usually isolated in <2 or >60 yrs (c) Haemophilus influenzae – most common cause for <5 yrs Hydrocephalus This is due to increased CSF in the CNS due to blockage of ventricular system Symptoms include: (a) increased head circumference (in children) (b) irritability (c) loss of upward gaze (d) increase cranial pressure (e) headache (f) drowsiness (g) blackouts There are two forms of hydrocephalus: (a) Communicating involves all 4 ventricles and is due to a blockage outside of the ventricular system that leads to decreased CSF absorption in the subarachnoid space. It can be due to: (i) Meningitis (ii) Head injury (iii) Congenital defects (iv) Haemorrhage (b) Non-communicating does not involve all the ventricles and is due to a blockage within the ventricular system (usually in the aqueduct) Possible causes include: (i) Aqueduct stenosis (ii) Ventricular tumour (iii) Paraventricular tumour Treatment can be to remove tumour, to divert CSF with a shunt or to create an alternate pathway for the CSF (ventriculostomy) more online at page 9 of 14
  10. 10. Nem’s Notes… Phase 1 NEUROSCIENCE 6 (page 1 of 2) Vasculature of the CNS Brain The brain requires: (a) 10-20% of cardiac output (b) 20% of oxygen consumption (c) 66% of liver glucose It therefore requires a good blood supply for normal function. CVA / TIA Cerebro-vascular accident (stroke): Rapidly developing focal disturbance of brain function of presumed vascular origin lasting for more than 24 hours Transient Ischaemic Attack: Rapidly developing focal disturbance of brain function of presumed vascular origin that resolves completely with 24 hours Ischaemia Insufficient blood supply to tissue Hypoxia Lack of oxygen Anoxia Absence of oxygen Infarction Death of tissue due to inadequate blood supply Thrombosis Blood clot within a blood vessel Embolism Blood clot which has broken off and lodged somewhere else Haemorrhage Bleeding from a ruptured blood vessel Circle of Willis Neurological Anterior Cerebral Artery Contralateral paralysis leg>arm & face (motor pathway) Deficits Disturbance of intellect and judgement (frontal lobe) Loss of appropriate social behaviour (frontal lobe) Middle Cerbral Artery “Classic Stroke” Contralateral hemiplegia arm>leg (motor pathway) Hemisensory deficits (sensory cortex) Hemianopia (visual function) Aphasia (left sided lesion) (language function) Posterior Cerebral Artery Visual deficits (occipital lobe) more online at page 10 of 14
  11. 11. Nem’s Notes… Phase 1 NEUROSCIENCE 6 (page2 of 2) Vasculature of the CNS Haemorrhage Haemorrhagic Stroke Extradural Trauma, immediate effects Subdural Trauma, delayed effects Subarachnoid Ruptured aneurysm Intracerebral spontaneous hypertension Regulation of The cerebral arteries can be vasodilated by CO2 and NO when blood flow is reduced. Blood Flow This increases cerebral blood flow. The blood flow is also regulated by neural factors: (a) Sympathetic factors cause vasoconstriction (b) Parasympathetic factors cause slight vasodilation (c) Dopaminergic neurones cause vasoconstriction (localised effects) If Cerebral Blood Flow is interrupted for as little as 4 seconds unconsciousness will result. After a few minutes irreversible damage occurs. If blood glucose is interrupted then brain function will be impaired. If it falls below 2 mM it will result in unconsciousness leading to coma and death. Blood-Brain This barrier protects the brain from potentially harmful substances (eg toxins and Barrier hormones such as catecholamines) and wide variations in ion concentration. It does however allow some lipophilic molecules to cross (eg alcohol). It allows certain hydrophilic molecules to enter the CSF by means of specific transport mechanisms: (a) Water aquaporins (AQP1, AQP4) (b) Glucose GLUT1 proteins (c) Amino Acids 3 different transport systems (d) Electrolytes via specific transport mechanisms Some areas of the brain lie outside the blood-brain barrier having fenestrated capillary networks. more online at page 11 of 14
  12. 12. Nem’s Notes… Phase 1 NEUROSCIENCE 7 (page 1 of 1) The Peripheral Nervous System PNS The Peripheral Nervous System consists of the nerves emerging from the brain and spinal cord which innervate the peripheral organs. It is made up of both neurons and glial cells and the axons form bundles which together with glial cells and connective tissue form peripheral nerves. Divisions (a) Efferent – responsible for transmission of information out of the CNS to effectors (i) Somatic motor neurons (innervating skeletal muscle) (ii) Autonomic neurons (innervating glands and viscera) (b) Afferent – responsible for transmitting information from recpetors to the CNS (i) Sensory neurons (innervating skin, joints, viscera) Spinal Nerves A typical spinal nerve supplies one region of the body (a dermatome of skin) They consist of: (a) a ventral root (motor) (b) a dorsal root (sensory) (c) a dorsal root ganglion where they meet The spinal nerves also divide into several branches called rami These are: (a) the dorsal ramus (innervating skin and muscle of the back) (b) the ventral ramus (innervating skin, chest muscles, limbs, pelvis) (c) the rami comunicantes(sympathetic neurons innervating viscera) There are 31 pairs of spinal nerves (SEE p1 Neuroscience 5) The upper limbs are supplied by nerves C5 to T1 via the Brachial plexus The lower limbs are supplied by nerves L2 to S2 via the Lumbo-sacral plexus Each nerve also supplies half the adjacent dermatome so that a lesion in one nerve will not result in complete loss of sensitivity (anaesthesia) but rather a decrease in sensitivity (hypoaesthesia) Peripheral Each peripheral nerve forms bundles called fascicles which divide along its length Nerves supplying various regions of the body. Each part is surrounded by a connective tissue sheath: (a) epineurium loose connective tissue surrounding the whole nerve (b) perineurium dense connective tissue surrounding a fascicle (c) endoneurium loose connective tissue surrounding individual nerves If a peripheral nerve is damaged the can be regenerated by this process: (a) Within 48hrs the axon and sheath beyond the crush/cut is phagocytosed by macrophages (Wallerian degeneration) (b) The cell bodies undergo metabolic changes (Chromatolysis) (c) The proximal axon find Schwann cells and endoneurial sheaths (d) Failure causes trapped axons called a neuroma (e) Otherwise regeneration of the axon is 2-5 mm per day and will be complete from 1 month to 1 year Diagnostic (a) Nerve Conduction Velocity tests can detect peripheral neuropathy Techniques (b) Nerve biopsy of small peripheral nerve can be used to study pathogenesis more online at page 12 of 14
  13. 13. Nem’s Notes… Phase 1 NEUROSCIENCE 8 (page 1 of 2) The Autonomic Nervous System Functions The autonomic nervous system (ANS) is the part of the nervous system that controls involuntary activity (eg homeostasis) Examples include: (a) Blood Pressure Regulation (b) Respiration Regulation (c) Gastrointestinal Motility (d) Temperature Regulation It is divided into two separate systems: (a) Parasympathetic (“Eat and Sleep” functions) Discrete and specific (b) Sympathetic (“Fight or Flight” functions) Diffuse stimulating whole body Baroreceptor This maintains blood pressure. Increased arterial pressure stimulates baroreceptors Reflex which increase afferent nerve activity which in turn decreases sympathetic activity which leads to decreased heart rate and vasodilation which decreases blood pressure Fight or Flight This is a mass Sympathetic discharge in response to stress or alarm and induces: Reflex (a) increased blood pressure (b) increased blood flow to muscle (c) decreased blood flow in other areas (eg splanchnic bed) (d) increased blood glucose (e) increased respiration GI Tract Autonomic innervation of the Gastro-intestinal tract is both sympathetic and parasympathetic: Sympathetic: (a) Decreases motility and tone (b) Stimulates contraction of sphincters (c) Inhibits secretory activity Parasympathetic: (a) Increase motility and tone (b) Cause relaxation of sphincters (c) Stimulates secretory activity Penis Sympathetic: (a) Penile flaccidity (b) Ejaculation Parasympathetic: (a) Erection [Point and Shoot] Eye Muscles Sympathetic: (a) Relaxes ciliary muscles (for distant vision) (b) Contracts radial muscle (dilating pupil) Parasympathetic: (a) Contracts ciliary muscles (for near vision) (b) Contracts pupillary sphincter (contracting pupil) Neurotransmitters (a) Acetylcholine (ACh) (b) Noradrenaline (NA) [Norepinephrine] (c) Adrenaline (A) [Epinephrine] Chemical Parasympathetic: ACh to Nicotinic cholinoceptor; ACh to Muscarinic cholinoceptor Transmission Sympathetic: ACh to Nicotinic cholinoceptor; NA to adrenoceptor Adrenal Medulla: ACh to Nicotinic cholinoceptor; A & NA secreted into blood more online at page 13 of 14
  14. 14. Nem’s Notes… Phase 1 NEUROSCIENCE 8 (page 2 of 2) The Autonomic Nervous System Neurotransmitter (a) ACh is synthesised from choline using acetyl-CoA Synthesis (b) NA synthesis is from tyrosine to DOPA to dopamine to NA (c) A synthesis is from NA to A Sympathetic The sympathetic nerves are from T1 to L3 down the spinal cord Anatomy There are many more post-ganglionic nerves than there are pre-ganglionic. This causes diffuse sympathetic effects. ParasympatheticThe parasympathetic nerves are from either the cranial or sacral outflow. Anatomy There are five main ganglia: (a) Occulomotor nerve (IIIrd Cranial) (b) Facial nerve (VIIth Cranial) (c) Glossopharyngeal nerve (IXth Cranial) (d) Vagus nerve (Xth Cranial) (e) Splanchnic nerve more online at page 14 of 14