Autonomic Nervous System PDF

Autonomic Nervous System Study Unit 8.2 FLG 332 Dr Y Hlophe Lecture 4 Reference: Human Physiology an integrated approach 6th ed D.U. Silverthorn 2012. Chapter 11 2020  Autonomic nervous system (ANS) ▪ ANS is part of the nervous system r...

Autonomic Nervous System Study Unit 8.2 FLG 332 Dr Y Hlophe Lecture 4 Reference: Human Physiology an integrated approach 6th ed D.U. Silverthorn 2012. Chapter 11 2020  Autonomic nervous system (ANS) ▪ ANS is part of the nervous system responsible for homeostasis ▪ Regulates body temperature ▪ Fluid and electrolyte balance ▪ Blood pressure ▪ Innervates visceral organs ▪ Heart ▪ Lungs ▪ Glands (sweat and salivary) ▪ Blood vessels ▪ Bladder ▪ Includes enteric nervous system in gastrointestinal tract ▪ Contains sensory, inter and motor neurons ▪ Contains as many neurons as spinal cord  Autonomic nervous system (ANS) ▪ ANS has two divisions ▪ Sympathetic (excitatory) Antagonistic effect ▪ Parasympathetic (inhibitory) ▪ Each has a preganglionic and a postganglionic division Autonomic nervous system (ANS) Spinal nerves ▪ Four main groupings of spinal nerves ▪ Cervical ▪ C1-C8 ▪ Thoracic ▪ T1-T12 ▪ Lumbar ▪ L1-L5 ▪ Sacral ▪ S1-S5 ▪ 1 Coccygeal nerve Autonomic nervous system (ANS) Sympathetic division  Autonomic nervous system (ANS) Sympathetic division ▪ Sympathetic nervous system (prevail during stress) ▪ Nerve fibres leave CNS ▪ With spinal nerves ▪ (T1-L2) ▪ Thoracolumbar outflow ▪ Preganglionic fibres synapse in paravertebral ganglia ▪ Preganglionic fibres release acetylcholine (Ach) ▪ Postganglionic fibres release norepinephrine also known as noradrenalin ▪ Recycled norepinephrine is repackaged into vesicles or broken down by monoamine oxidase (MAO)  Sympathetic Division ▪ Adrenergic receptors (G protein- coupled receptors; 2nd messenger activity): ▪ Alpha ▪ Alpha 1 (muscle contraction, most sympathetic target tissue) ▪ Activates phospholipase C ▪ creating inositol triphosphate (IP3) and diacylglycerol (DAG) ▪ Alpha 2 (smooth muscle relaxation, gastrointestinal tract and pancreas) ▪ Decrease in cAMP ▪ Beta ( differ in catecholamine affinity) ▪ B 1 (norepinephrine + epinephrine, heart muscle and kidney) Increase in cAMP ▪ B 2 (sensitive to epinephrine, blood vessels and smooth muscles) ▪ B 3 (sensitive to norepinephrine, adipose tissue) ▪ Table 11.2 in Silverthorn Text book  Autonomic nervous system (ANS) Sympathetic division ▪ There are preganglionic neurons whose axons terminate directly on the effector organ ▪ Adrenal gland ▪ Adrenal Medulla acts as a sympathetic ganglion ▪ Pre-ganglionic neuron synapses with chromaffin cells (in adrenal medulla) ▪ They in turn release neurotransmitter into blood vasculature ▪ Epinephrine or adrenalin ▪ Necessary during ▪ Exercise ▪ Stressful situations  Autonomic nervous system (ANS) Parasympathetic division ▪ Parasympathetic nervous system (prevail during rest) ▪ Leave CNS ▪ Cranial nerve ▪ III, VII, IX, X ▪ Spinal nerves ▪ Sacral nerves ▪ (S2-S4) ▪ Craniosacral outflow ▪ Vagus (X cranial nerve) ▪ Supplies thorax Autonomic nervous system (ANS) Cranial nerves  Autonomic nervous system (ANS) Parasympathetic division ▪ Preganglionic fibres synapse ▪ Autonomic ganglia ▪ Release Acetylcholine (Ach) ▪ Postganglionic fibres release ▪ Ach Autonomic nervous system (ANS) Neurotransmitters Autonomic nervous system (ANS)  Autonomic Agonists and Antagonists ▪ Direct agonists and antagonists ▪ Bind target receptor to either ▪ Block/mimic neurotransmitter action ▪ Indirect agonists and antagonists ▪ Alter secretion, reuptake and degradation of neurotransmitters ▪ Indirect agonist ▪ Cocaine ▪ Cholinesterase inhibitors ▪ Serotonin reuptake inhibitors ▪ Beta blockers 18  CNS Pathologies  Intracranial pressure (ICP)  Stroke Study Unit 8.1 FLG 332 Dr Y Hlophe Lecture 6 Reference: Raised Intracranial Pressure. Dunn LT. J Neurol Neurosurg Psychiatry 2002;73:i23-i27 Stroke. Hankey GJ. Lancet2017;389:641-54 2020  Intracranial pressure (ICP)  Intracranial pressure (ICP)  Pressure in the skull (brain tissue, intravascular blood & cerebrospinal fluid (CSF)  Raised ICP results in pressure gradients between compartments and a shift of brain structures  Cerebral perfusion pressure (CPP) gradient causing cerebral blood flow: Mean arterial pressure (MAP) subtracted from the ICP.  Cushing’s Triad  Due to increased ICP decreases the cerebral blood flow significantly.  A response is triggered that increases arterial pressure in order to overcome the increased ICP.  The signs of Cushing’s triad are:  Hypertension  Slow heart rate  Shallow breathing  If treatment does not occur to stabilise the ICP, herniation of the brain stem and occlusion of the cerebral blood flow can occur with dire consequences  Intracranial pressure (ICP)  Intracranial hypertension (ICH): elevated pressure in the cranium  Associated with:  Nausea  Vomiting  Extreme pain  Pressure headaches (throbbing exacerbated)  Progressive deterioration of conscious level  Subarachnoid haemorrhages  Pupillary dilation  Respiratory irregularities Reference:https://www.google.com/url?sa=i&url=https%3A%2F%2Fwww.ausmed.com%2Fcpd%2Farticles%2Fincreased-intracranial- pressure&psig=AOvVaw0kArNOVBQvxBzJZYDiI0vg&ust=1598602887407000&source=images&cd=vfe&ved=2ahUKEwi_kZn7- brrAhVRNRoKHWrDBDYQr4kDegUIARDPAQ  Raised intracranial pressure (ICP)  Intracranial hypertension (ICH): sustained intracranial pressure above 15mmHg  Common causes:  Expanding tissue or fluid mass (Cerebral edema)  Water accumulation  Intra/extracellular spaces of the brain  Interference with normal CSF absorption (hydrocephalus)  Excess production in choroid plexus  Blockage of the ducts that connect the ventricles (lateral, third and fourth)  Inhibited absorption by arachnoid villi  Brain lesions: hematoma, neoplasm (glioma, meningioma)  Obstruction to major venous sinuses: (fracture overlaying venous sinus, venous thrombosis)  Infection: meningitis  Complications Associated to Increased Intracranial Pressure Reference: Adapted from: Pathology of the Nervous System. Pathology: A Modern Case Study, 2015 www.accessmedicine.com (HM Reisner; MacGraw-Hill Education )  Raised intracranial pressure (ICP) Effective Treatments  Cerebrospinal fluid (CSF) drainage  Ventriculostomy  risk infection and haemorrhage  Intraventricular catheter to monitor ICP, drain CSF  Head of bed elevation  Improves 30% venous jugular outflow and lowers ICP  Analgesia and sedation  Morphine  Neuromuscular blockade  Used if analgesia is ineffective  Diuretics  Osmotic agent to draw fluid from the brain  Stroke  Focal neurological deficit due to abnormality in cerebral circulation (infarction or hemorrhage) in the brain, retina or spinal cord  Focal symptoms correlate with the area of brain supplied by the affected blood vessel  Causes / Risk factors include:  Hypertension, Hypercholesterolemia, Diabetes  Smoking and heavy alcohol consumption  Oral contraceptive use  Carotid stenosis  Atrial fibrillation (irregular heartbeats)  Stroke Typical Symptoms  Unilateral weakness (one-side)  Numbness  Visual loss  Altered speech  Ataxia (stumbling, falling)  Vertigo (spinning or dizziness) Cerebral Circulation Disturbances  Stroke  Ischemic stroke  Thrombotic occlusion (major cerebral arteries, small vessels and venous occlusions)  Embolic (clot dislodge from artery to artery; cardio-embolism )  Haemorrhagic stroke (arterial aneurysm is the cause (weak arterial wall, bulges eventually ruptures)  Intracerebral haemorrhage:  Burst vessel  Brain tissue death  Swelling and pressure in the brain  Subarachnoid haemorrhage:  Bleeding in the subarachnoid space  Stroke Vascular injury that reduces cerebral blood flow (CBF)  Cerebrovascular disease encompasses pathology associated to vessels in the CNS  Pathologies are either ischaemic or haemorrhagic:  Ischaemic stroke  neurological dysfunction caused by cerebral, spinal or retinal infarction  Transient ischaemic attack (TIA)  Transient event (temporary) of neurological dysfunction caused by ischaemia of the brain, spinal cord, or retina without acute infarction.  Intracerebral haemorrhage (ICH)  Due to a collection of blood within the brain parenchyma or ventricular system  Subarachnoid haemorrhage  Bleeding originates in the subarachnoid space  Stroke Prevent recurrent stroke  Preventing recurrent ischaemic stroke of arterial origin  Aspirin use  Oral anticoagulants (warfarin commonly used)  Carotid stenting (symptomatic carotid stenosis)  Lower blood pressure  Lower LDL cholesterol  Manage diabetes Type 2  Hormone therapy for post-menopausal woman stopped  Nervous System Motor & Sensory Pathophysiology References: Study unit 8.3.3 Multiple Sclerosis: Immunology of Multiple Sclerosis. Pender et al. Current Allergy and FLG 332 Asthma Reports 2007,7:285-292. Dr Y Hlophe Multiple Sclerosis:. The cellular immunology of multiple sclerosis. Al-Omaishi et al. Lecture 3 Journal of Leukocyte Biology. 1999,65:444-452. Acute Spinal cord injury: Epidemiology, Demographics and Pathophysiology of Acute Spinal Cord Injury. Sekhon et al.Spine 2001,26;24s:s2-s12. August 2020  Pathophysiology Study unit 8.3.3  Multiple sclerosis (MS)  Autoimmune disease of the central nervous system (CNS) results in :  Chronic inflammatory demyelination  Axonal damage  Progressive neurologic disability  MS affects  Brain, spinal cord, optic nerves,  MS does not affect Reference: https://www.mayoclinic.org/diseases- conditions/multiple-sclerosis/symptoms-causes/syc-20350269  Peripheral nervous system (PNS) 2  Multiple sclerosis (MS)  Inflammatory demyelinating lesions (plaques) in white matter of the CNS  Acute, chronic, active and silent  Inflammatory infiltrate consists of: T and B lymphocytes, macrophages and activated microglia and astrocytes 3 Reference:https://www.google.com/url?sa=i&url=https%3A%2F%2Fwww.frontiersin.org%2Farticles%2F10.3389%2Ffimmu.2018.00255%2Ff ull&psig=AOvVaw0CfQj3c- _fq2RDCthct8hi&ust=1597546161578000&source=images&cd=vfe&ved=2ahUKEwjpjYetmZzrAhUP_BoKHdvYAyoQr4kDegUIARCzAQ  Multiple sclerosis (MS)  Target of the disease  Oligodendrocytes myelinating cells of the CNS  Myelin: lipid bilayer with proteins anchored within it  Spaces between myelin and axon:  Nodes of Ranvier  Periaxonal space  Myelin associated protein (MAG) Reference:  Myelin basic protein (MBP) https://www.google.com/url?sa=i&url=https%3A%2F%2Fonlinelibrary.wiley.com%2F doi%2Ffull%2F10.1002%2Fglia.23665&psig=AOvVaw2tQzFLblCuXg9o4SwV28sr&ust= 1597545560947000&source=images&cd=vfe&ved=2ahUKEwiIutOOl5zrAhXa_IUKHcH  Proteolipid lipoprotein (PLP) 3D7AQr4kDegUIARDHAQ  Myelin oligodendrocyte glycoprotein (MOG)  All proteins can be targets for demyelination  During demyelination oligodendrocytes are damaged 4  Not clear if MS immune response main target is myelin or oligodendrocytes 5  Multiple sclerosis (MS)  In MS pathogenesis  Which cells cause oligodendrocyte damage?  Oligodendrocytes do not express MHC II  CD4 T cells cannot have a direct effect  The activated macrophage and microglia cells in the infiltrate  Secrete toxic molecules that damage myelin and the oligodendrocytes  Cytokines: IL1, IL12, IL-2,IFN, TNF, free radicals and complement proteins.  Mononuclear phagocytes (MP) engulf products of their own secretory destructive pathogenic events  MP (macrophages and microglia)  Lyse oligodendrocytes through antibody-dependent cell mediated cytotoxicity (ADCC)  In the presence of antibodies and complement proteins 6  Antibody-dependent cell mediated cytotoxicity (ADCC) Reference: Therapeutic Antibody Engineering , 2012https://www.sciencedirect.com/topics/medicine-and- 7 dentistry/antibody-dependent-cellular-cytotoxicity  Pathophysiology  Acute Spinal Cord Injury (SCI)  Primary mechanisms  Initial mechanical injury  results in local deformation Reference: https://ahlinyaasuhankeperawatan.blogspot.com/2014/06/acute- spinal-cord-injury-sci-jilid-2.html  Examples:  Fracture dislocation (loose bone stuck in dislocated bones)  Burst fracture (vertebral body compression)  Ruptured disc (protruding disc can pinch spinal nerve)  Ligamentous injuries (ligaments not aligned)  Spinal cord lacerations (tear within the spinal cord) 8  Acute Spinal Cord Injury  Secondary mechanisms  A cascade of biochemical and cellular processes  Initiated by the primary injury Examples:  Vascular changes  Ionic derangements  Neurotransmitter accumulation  Arachidonic acid release and free radical production  Programmed cell death 9  Acute Spinal Cord Injury  Free radical production  extra electron in the outer orbit  Free radicals form commonly from molecular oxygen  Incomplete electron transport in the mitochondria forms (O2) superoxide  Superoxide is converted to hydrogen peroxide H202 by superoxide dismutase  Catalase converts the H202 to H20 and O2.  In the presence of free iron from haemoglobin, transferrin or ferritin  lowered pH 10  H202 forms highly reactive hydroxyl radicals (HO)  Acute Spinal Cord Injury Reference: https://www.intechopen.com/books/lipid-peroxidation/lipid-peroxidation-chemical-mechanism-biological-implications-and-analytical-determination 11  Acute Spinal Cord Injury  HO radicals cause lipid peroxidation (oxidative degradation of lipids)  Free radicals “inherit” electrons from lipids in the cell membrane, leading to cell damage  Resulting in:  Phospholipid-dependent enzyme impairment  Inhibit catalytic activity of the phospholipid enzymes  Na+/K+ ATPase inhibition  Ion and osmotic homeostasis inhibited  Ionic-gradient disruption  Charge across the plasma membrane gradient is disrupted 12  Acute Spinal Cord Injury  Membrane lysis  Degradation of the lipid bilayer that makes up the cell membrane  Decrease in tissue antioxidant levels  No protective mechanism against free radicals 13 14  Acute Spinal Cord Injury  Programmed cell death (apoptosis)  Oligodendrocytes most prevalent cells to undergo apoptosis in spinal cord injury (SCI).  Oligodendrocytes undergoing apoptosis are in areas of:  Wallerian degeneration ( chemical and molecular events that take place to clear axonal and myelin damage distal to the axonal injury )  Axonal demyelination (inflammatory response due to pathology)  Apoptosis induced in oligodendrocytes might be due to microglia activation  Microglia undergoing apoptosis in areas of neuronal 15 degeneration and demyelination  Acute Spinal Cord Injury  FAS and P75 (neurotrophin receptors) death receptors also mediate post- traumatic oligodendrocyte apoptosis  FAS binds FADD ligand  P75 binds a neurotrophin ligand (nerve growth factor (NGF), brain- derived neurotrophic factor (BDNF)  Facilitates axonal degeneration  Apoptosis occurs in ascending and descending white matter tracts around the lesion epicentre.  Targeting upstream events of caspase cascade can be used as therapeutic mechanisms to prevent neuronal and glial cell apoptosis in acute SCI. 16  Nervous System Motor function Study theme 8 Study unit 8.3.1 FLG 332 Dr Y Hlophe Reference: Human Physiology an integrated approach 6th ed D.U. Silverthorn 2012. Chapter 11 and 13  Nervous System Study Unit 8.3.1 2  Somatic Motor Division 3 4 5  Motor System  Single efferent neuron  Leaves CNS via ventral horn towards target tissue (Skeletal muscle)  Synapse of somatic motor neuron on muscle fibre =neuromuscular junction  Somatic efferent neuron vesicles release acetylcholine (Ach)  Ach taken up by nicotinic Ach receptors  Acetylcholine esterase inactivates Ach (by degrading it)  The esterase is in high concentration at cholinergic nerve ending  Inhibits contraction of skeletal muscles 6  Motor Cortical Homunculus 7 Reference: Evidence Based Medicine Consult. https://www.ebmconsult.com  Upper and Lower motor neurons 8 References: http://www.kenzanweb.com/upper-and-lower-motor-neurons Upper and Lower Motor Neurons  Upper motor neurons (UMN): are neurons in the higher centers of brain, which control LMN. 3 types:  Motor neurons in cerebral cortex  Neurons in basal ganglia and brainstem nuclei  Neurons in cerebellum  Lower motor neurons (LMN):  are the anterior gray horn cells in the spinal cord and the motor neurons of the cranial nuclei in brainstem, which innervates muscles directly.  Direct (pyramidal/corticospinal) pathway 10 Corticospinal pathway  Corticospinal pathway  Voluntary movement  From the cerebral cortex, descending to the thalamus, brain stem and finally spinal cord  Fibres that end in the brain stem (corticobulbar tracts)  Innervates muscles of the head (larynx, tongue, of eye movement ) 11  Controls movement of axial muscles (of the trunk), oblique and rectus muscles 12 13  Cerebellum  Vestibulocerebellum:  Concerned with equilibrium and eye movement  Spinocerebellum:  Receives proprioceptive input from the body  Cerebrocerebellum:  Interacts with the motor cortex in planning and programming movements Reference: Functional divisions of the cerebellum. Principles of Neural Science 4th ed.McGraw-Hill,2000. 14  Basal Ganglia  Five divisions of the Basal Ganglia:  Caudate nucleus Striatum  Putamen Lenticular nucleus  Globus Pallidus  Subthalamic nucleus  Substantia nigra  Neurons in the Basal Ganglia discharge before movements begin.  Dopaminergic, cholinergic and GABAergic system: from the striatum to the substantia nigra.  Involved in planning and programming of movement 15 16 Indirect (extrapyramidal/extracorticospinal) pathway  Includes motor pathways not part of the pyramidal pathway  Upper motor neuron (UMN) originate in deep nuclei in the cerebrum not the cerebral cortex  UMN do not pass through the pyramids  The system includes:  Rubrospinal  Vestibulospinal  Reticulospinal  Tectospinal tracts  Regulate:  Axial muscles that maintain balance and posture  Muscles controlling course movement of the proximal portions of limbs  Head, neck and eye movement  Involuntary movement 17 18 19 Voluntary Movement  Control of posture and movement depends upon activity of skeletal muscles.  Due to balance of different muscle groups.  same side of a joint (agonist)  opposite side of a joint (antagonist)  The action is accomplished efficiently because of special nervous system connections, called reciprocal innervation. Reciprocal Innervation  Reflex 22 23  PAIN Study Unit 8.4 FLG 332 Dr Y Hlophe Lecture 5 Reference: Review of Medical Physiology 23rd ed W.F. Ganong 2010 Chapter 10+11 2020  Pain  Pain is an:  unpleasant sensory and emotional experience  Nociception is:  Unconscious activity induced by harmful stimulus applied to a sense receptor  A sensation, warning that something is wrong  advantage  Prolonged pain, results in tissue damage  disadvantage  Nociceptor pathways are activated 19th August 2019  Pain  Sensory neurons that respond to pain  comprise of two fibre types:  Thinly myelinated Aδ fibres (fast pain)  Unmyelinated C fibres (slow pain)  There are several nociceptor receptors that activate these sensory neurons  Mechanical nociceptors  Thermal nociceptors  Chemically sensitive nociceptors  Polymodal nociceptors (respond to a combination of stimuli) 19th August 2019  Pain  Thermal nociceptors  Cold menthol-sensitive receptor 1 (CMR1)  Respond to cold  Two vanilloid receptors (VR1 and VRL-1)  Respond to heat 19th August 2019  Pain  Fast pain  sharp, localised sensation  associated with Aδ fibres  Slow pain  dull, intense and unpleasant  associated with C fibres 19th August 2019  Pain  Acute pain (physiologic)  Has a sudden onset  Recedes during healing  Considered “good pain”  Important protective mechanism  Example : withdrawal reflex  Chronic pain (pathologic)  Neuropathic pain caused by chronic progressive nerve disease  Result of injury or infection  Considered “bad pain” 19th August 2019  Pain  Chronic pain (pathologic) Can be caused by: nerve injury (diabetic neuropathy) toxin induced nerve damage ischaemia Accompanied by: hyperalgesia and allodynia  Hyperalgesia  Exaggerated response to noxious (harmful) stimulus  Allodynia  Pain sensation in response to innocuous (weak) stimulus  Eg: sensation from warm shower, when skin is sunburned  Hyperalgesia/allodynia  Increased sensitivity to nociceptive afferent fibres 19th August 2019  Pain Nociceptors sensitization from inflammatory response 19th August 2019  Pain Nociceptors sensitization from inflammatory response  Injured cells release bradykinin and prostaglandins  This activates the nociceptors and releases  Substance P and calcitonin gene-related peptide (CGRP)  Substance P acts on mast cells causes degranulation and histamine is released also activating nociceptors  CGRP dilates blood vessels  Substance P causes plasma extravasation  Serotonin is released from platelets activates nociceptors  Resulting in edema and causing additional release of bradykinin 19th August 2019  Pain Deep pain  Experienced in deep and not superficial structures  Is usually slow, because of deficiency of Aδ fibres in deep structures  Poorly localized, associated with nausea, sweating and blood pressure changes  Experienced in joints and ligaments  Pain initiates reflex contraction of nearby skeletal muscles  Contraction persists and muscles become ischaemic  The ischaemia stimulates pain receptors in the muscles  The pain in turn initiates more spasms 19th August 2019  Pain Visceral pain  Poorly localized and unpleasant  Associated with nausea and autonomic symptoms (dizziness, sweating)  Nociceptors are sparsely distributed in comparison to somatic structures  Visceral pain radiates and is referred to other areas,  Visceral pain can be severe  Receptors in the walls of hollow viscera are sensitive to distension of these organs  Example:  Colic, intestinal obstruction  Above the obstruction dilated intestine contracts  Visceral organ becomes inflamed  Cause severe pain (hyperalgesia) 19th August 2019  Pain Referred pain  Referred to structure that developed from the same embryonic segment or dermatome as the structure from where the pain originates  Know as the dermatomal rule  Example: heart and arm have the same segmental origin 19th August 2019 19th August 2019  Pain Referred Pain: Convergence-Projection Theory Visceral organ irritation frequently produces pain felt not at the site but in some somatic structure Pain is also referred when somatic and visceral pain fibres converge onto the same second-order neuron in the dorsal horn and project to the thalamus and further to the somatosensory cortex. Known as the convergence-projection theory 19th August 2019  Pain Referred Pain: Convergence-Projection Theory Somatic and visceral neurons converge (lamina I-VI of ipsilateral dorsal horn) Neurons in lamina VII receive afferents from both sides of the body (explains referral to the side opposite that of the source of pain). Somatic nociceptive fibres do not normally activate second order neurons When visceral stimulus is prolonged This facilitates the stimulation of the somatic fibre ending This results in second order neuron stimulation And the brain cannot determine whether the stimulus came from viscera or from the referral area (somatic fibres) 19th August 2019  Pain Phantom pain Associated with the removal of a limb or the absence of a body part. The cortical region of the neighbouring digit for example, takes the place of the amputated digit. The change in somatosensory representation in the cortex Indicates the cortical plasticity Example: Someone with an amputated arm, stroking different parts of the face leads to feeling of being touched in the area of the missing limb 19th August 2019  Pain Anteriorlateral or Spinothalamic tract Aδ fibres terminate on laminae I and V in the dorsal horn Synaptic transmitter released is glutamate C fibres terminate on neurons in laminae I and II Synaptic transmitter released is substance P 19th August 2019  Pain Endogenous analgesic system in relation to pain transmission  The analgesic opioids act as neurotransmitters and neuromodulators  Opioid receptors in the brain are activated by a family of endogenous peptides released by neurons  enkephalins, dynorphins, endorphin  Opioids decrease calcium influx, results in decrease of nociceptor action potentials  Opioids hyperpolarise the membrane and decrease the amplitude of the excitatory post synaptic potential (EPSP)  Nervous System Sensory function Study theme 8 Study unit 8.3.2 FLG 332 Dr Y Hlophe Reference: Human Physiology an integrated approach 6th ed D.U. Silverthorn 2012. Chapter 10 Review of Medical Physiology 23rd ed W.F. Ganong 2010 Chapter 11+16 2  Somatic Sensation  Sensation occurs in response to stimuli  external or internal environment  via sensory receptors  receptors (transducers) convert  stimuli into receptor potential which triggers an  action potentials in neurons (afferent)  activates the central nervous system (CNS) 3  Classification of Sensations  General senses  Cutaneous (skin)  Touch, temp, pain  Deep (muscle, tendon,joints)  Pain, pressure, movement, proprioception  Visceral (internal organs)  Homeostasis , respiration  Special senses  Visual; hearing; equilibrium; smell ;taste 4  Sensory Receptors  Mechanoreceptors  Touch  Pressure  Nociceptors  Pain  Extreme heat/cold  Thermoreceptors  Temperature changes  Chemoreceptor  Change in chemical composition  Photoreceptors  Rods and cones in retina  Proprioceptors 5  Position of body in space at given time  Sensory (afferent) Fibres  Three types of primary afferent fibres  With cell bodies in the dorsal root ganglia  Mediate cutaneous sensation  Myelinated (L) A fibres (α and β)  Impulses from mechanical stimuli  Myelinated (S) A fibres (δ)  Impulses from cold receptors, nociceptors, mechanoreceptors  Unmyelinated (S) C fibres  Pain, temperature and mechanoreceptors 6  Sensory Pathways (tracts) 7  Sensory Pathways (tracts)  Ventrolateral / anterior lateral or spinothalamic tract  Mediates pain and Temperature  Second order neurons cross the midline  Ascend in ventrolateral quadrant of spinal cord  Synapse at the ventral posterior lateral (VPL) nucleus in the thalamus  Other dorsal horn neurons that receive nociceptive input synapse in the reticular formation of the brain stem (spinoreticular pathway) then project to the thalamus. Responsible for autonomic responses to pain.  Lateral to the spinothalamic tract 8 Dorsal column pathway/ spinocortical or posterior tract  Fibres ascend ipsilaterally to the medulla.  They synapse in the Fasciculus gracilus and cuneate nuclei in the medulla.  Second order neurons cross the midline.  Ascend in the medial lemniscus synapse in the thalamus.  Third order neurons synapse in the primary somatic sensory region, in the parietal lobe. 9  Somatotopically organised  Within the dorsal column, fibres from different sections of the spinal cord are somatotopically organised  Sacral cord fibres  Medially positioned  Neurons from the foot  Cervical cord  Laterally positioned  Neurons from the finger  Arrangement continues in the brain stem and thalamus. 10  Trigeminal Tract  Consist of sensory part of the trigeminal nerve  Cranial nerve V, 3 sub divisions:  Ophthalmic (V1, sensory)  Maxillary (V2, sensory)  Mandibular (V3, motor sensory)  Enters brain stem at the pons  Crosses over contralateral side  and forms trigeminal pathway  Join fibres of the dorsal column/spinocortical pathway 11  Sensory Pathways  Third order thalamic neurons project to  Primary somatic sensory areas of the cortex in the  Postcentral gyrus of the parietal lobe  Parts of the body are represented in order along the postcentral gyrus 12  Sensory Cortical Homunculus  The size of the cortical area receiving the impulse from a body part is proportionate to the use of that body part  Sensory homunculus  Indicating the different body parts represented across the postcentral gyrus 13