Applied Pathophysiology Lecture Notes PDF

Lecture Material is adapted from © 2022 Wolters Kluwer Health, Lippincott Williams & Wilkins Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease Chapter 10: Altered Neuronal Transmission Module 1: Alterations in Neuronal Impulse Conduction Module 2: Alterations in...

Lecture Material is adapted from © 2022 Wolters Kluwer Health, Lippincott Williams & Wilkins Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease Chapter 10: Altered Neuronal Transmission Module 1: Alterations in Neuronal Impulse Conduction Module 2: Alterations in CNS Function Module 3: Alterations in PNS Function Dr. Romeo Batacan Jr. MPAT12001 Medical Pathophysiology Lecture Series Copyright © 2017 Wolters Kluwer Health | Lippincott Williams &Wilkins  Processes of Neuronal Injury Mature neurons do not divide New neurons do not replace damaged neurons that lost function Loss of neurons leads to impaired neurologic transmission Impaired neurologic transmission leads neurologic disorders Cell damage Ageing Manifestations reflect Site of injury Functions that are controlled  Processes of Neuronal Injury Result of injury at the cellular level: Chromatolysis part of apoptosis swelling of a neuron and dissolution of chromophil substance in neurons Neuron with central chromatolysis at the left lower in certain pathological conditions or following an injury to the cell or axon corner. The RER disaggregates and the neuronal body balloons. Atrophy Three normal neurons are also seen. http://neuropathology‐ web.org/chapter1/chapter1aNeurons.html decrease of cell size Neuronophagia: phagocytosis and inflammatory responses caused by a dead neuron damaging neighboring cells Intraneuronal inclusions distinctive structures formed in the nucleus or cytoplasm Neuronophagia. Macrophages encircle degenerating neuron. http://neuropathology‐ web.org/chapter1/chapter1dMicroglia.html Substantia Nigra of a Parkinson’s disease patient https://www.nottingham.ac.uk/pathology/images/clbhe.jpg  Neuronal Injury Response to injury depends on the specific cell type involved Mirror the actual properties of the cell Injury responses of support cells: Astrogliosis Microglial nodules Ependymal damage: CSF alterations Injury responses of neuron Neuropathy Axonal degeneration Axonal regeneration (in Peripheral NS) Demyelination  Injury responses of supportcells Astrogliosis Astrocyte respond to local tissue injury by proliferation: Glial scar Common cause of tissue injury to elicit astrogliosis Contusion, wounds, tumors, abscesses, hemorrhage Unchecked proliferation can lead to neoplastic transformation Glioma (brain cancer) Inhibit axon regeneration http://www.cell.com/trends/neurosciences/fulltext/S0166‐2236(09)00153‐2  Injury responses of supportcells Microglia Immune response Reactive changes: nucleus extension: “rod cells” Joined with astrocytes to form: Microglial nodules Ependymal cell damage: Due to infection of ventricles Intraventricular hemorrhage CSF production and transfer altered Microglial nodule. Cluster of microglial cells and lymphocytes. http://neuropathology‐ web.org/chapter1/chapter1dMicroglia.html  Injury responses of neurons (CNS and PNS) Neuropathy Nerves damaged or destroyed disrupting neural communication Typically results in numbness, tingling, muscle weakness and pain Axonal Degeneration Breakdown of the distal parts of axons Caused by necrosis Inflammatory response stimulated leading to phagocytosis of cell debris Demyelination Myelin damage causing interruption in nerve conduction  Central and Peripheral Nervous System Neuronal Injury Mechanisms of injury Central NS Traumatic Central Nervous System Injury Traumatic Brain Injury Traumatic Spinal Cord Injury Ischemic Central Nervous System Injury Excitation Injury Central Nervous System Pressure Injury Peripheral NS Traumatic Peripheral Nerve Injury Peripheral Nervous System Pressure Injury Traumatic Central Nervous SystemInjury Impaired neurologic functioning Local Systemic Injury to site innervating a specific area: local effect Injury to site responsible for integrating transmission of impulses to multiple distant sites: systemic effect Traumatic Brain Injury Automobile accidents Falls sports‐related injuries “shaken baby syndrome” Two categories: 1. Closed head injury 2. Open traumatic injury Bullock S, Hales M. Principles of pathophysiology. 1st ed. Frenchs Forest, Pearson Australia; 2012.  Traumatic brain injuries: Closed headinjury Blunt force Coup: acceleration injury Contrecoup: deceleration injury Movement of the brain inside the skull causing the injury! Traumatic Brain Injury: Lacerations and contusions Traumatic Brain Injury: Open traumaticinjury Exposure of brain structures Meninges Brain tissue Risk of infection Risk of injury  Traumatic Brain Injury Strayer D, Rubin E. Rubin's Pathology: Clinicopathologic Foundations of Medicine. 7th ed. UK, Wolters Kluwer/Lippincott Williams & Wilkins; 2014 Increased seizure activity Concussion: temporary alteration in function Unconscious, dizzy Contusion: permanent damage Cortical contusion: may remain conscious Brain stem contusion: always cause coma / injury to RAS Hematoma Edema Skull fracture Increased ICP Respiratory depression Brain hernia Traumatic Brain Injury Diagnosis Brain imaging (CT, MRI) Brain activity: EEG Lumbar puncture (spinal tap): analysis of CSF and check presence of blood (intracranial haemorrhage) Treatment is targeted toward specific injury Surgery to evacuate hematoma or foreign fragments Reduce ICP Pain control Anticonvulsive medication Respiratory support Antibiotics to prevent infection Kumar, Robbins & Cotran: Pathophysiological basis of disease. 8th ed. Philadelphia: Saunders; 2010 Traumatic Spinal Cord Injury Bullock S, Hales M. Principles of pathophysiology. 1st ed. Frenchs Forest, Pearson Australia; 2012. Flexion‐Flexion/Extension Rotational Most SCI are among males May be the result of: Fractures Contusions Compression of the vertebral column Trauma to the head or neck Neurologic damage is the result of Pulling Twisting Severing Compression Hyperextension Compressing the neural tissue of the spinal cord Traumatic Spinal Cord Injury Traumatic Spinal Cord Injury Laceration: rip or tear from vertebral fracture, knife, bullet Transection: completely severed, penetrating trauma, fragments of vertebrae Contusion: falls, acceleration/deceleration accident Compression: crushing Distraction: pulling spinal cord apart (lap seatbelt and acceleration/deceleration accident: top moves while bottom fixed) Concussion: violent blow, no apparent damage to the cord, spinal shock may occur, deficits subside rapidly McCance KL, Huether S. Pathophysiology. 7th ed. N.S.W, Mosby; 2015 Traumatic Spinal Cord Injury Clinical manifestations of vertebrae fracture: pain maybe present Clinical manifestations of SCI: wide range From mild paresthesia (abnormal sensations) to quadriplegia (paralysis of all four extremities) Level of SCI and severity contributes to neurologic deficit Diagnosis: X‐ray (fracture) Neurologic examination Lumbar puncture CT, MRI Treatment Immediate immobilization to prevent further injury Corticosteroids to lessen inflammation Further treatment: traction, casting, surgery Ischemic Central Nervous SystemInjury Inadequate perfusion to neurologic tissue Impaired oxygenation (please review ischemic tissue injury) Tissue necrosis Cause of ischemia: 1. Local ischemia Occlusion of blood supply by thrombus or embolus 2. Global ischemia Inadequate blood supply to meet the needs of brain tissue Global ischemia leads to hypoxia Cardiac arrest or severe haemorrhage Spinal cord ischemia: occlusion of spinal blood vessels Ischemic Central Nervous SystemInjury Impaired blood flow lasting longer than a few minutes causes brain tissue infarction Cellular function ceases because of inability to use anaerobic processes or uptake glucose and glycogen Cell injury also causes local water, electrolyte imbalances and acidosis Free radical formation at injury site Increased release of excitatory neurotransmitter (glutamate) Infarction leads to inflammation Inflammatory response leads to edema development Edema leads to increased ICP  Ischemic Central Nervous System Injury Clinical manifestations are related to functional areas involved Sensory and motor functions are often affected If injury in brain: manifestation reflect specific associated functions with motor deficits on contralateral side Loss of consciousness, weakness, difficulty speaking, impaired vision, paresthesia Diagnosis: CT, MRI, angiography to diagnose ischemic blockage PET scan: Altered metabolism in surrounding tissue Treatment Manage ICP Restore perfusion Thrombolytic therapy to dissolve clot Anticoagulation therapy to prevent future clot Excitation Injury Neurons that easily depolarized/hyperpolarized may cause altered transmission Excitation injury: pathologic consequences of increased impulse frequency, intensity, cascade of transmission Glutamate is the main excitatory neurotransmitter Glutamate binding to receptor leads to prolonged action potentials Prolonged action potentials stimulate protein breakdown, formation of free radicals, DNA damage, breakdown of nucleus Excitation Injury May result from cell inability to meet metabolic demand Tissue sensitive to hypoxia may suffer from permanent damage Hippocampus Cerebral cortex Manifestations Reduction in higher order functions Cognitive and memory abilities Excitation Injury During periods of deteriorating brain functions excitatory responses may predominate Severe brain injury: Difference is based on the injury site impacted or CNS involvement A: decorticate position (“mummy position”) Damage to cerebral hemispheres above midbrain B: decerebrate position Damage to brain stem (midbrain) Central Nervous System Pressure Injury Skull and vertebral column: rigid structure Restricted expansion Increase in pressure may result in injury: increased ICP Cause: 1. Excessive CSF volume 2. Cerebral edema 3. Space occupying lesion (tumor) Increased ICP Common response to pathologic events is increased intracranial pressure Leads to blood flow reduction (ischemia) Grade two papilledema http://webeye.ophth.uiowa.edu/eyeforum/cases/99‐ Pseudotumor‐Cerebri.htm Death of brain cells Damage to brain structure Functional loss Manifestations of increased ICP Headache Vomiting Papilledema (edema of optical disk) Mental deterioration Sclera Continuous with dura mater of brain posteriorly Treatment of increased ICP Excessive CSF: surgical shunting from intraventricular spaces Catheter >> left lateral ventricle >> internal jugular vein >> right atrium to right atrium: ventriculoatrial shunt to peritoneum: ventriculoperitoneal shunt Cerebral edema: Osmotic diuretics: mannitol Fluid removal and excretion Placement of a VP shunt. Reprinted from 'Principles of Neurosurgery,' 2nd edition, Edited by Setti S. Rengachary, Richard G. Ellenbogen, Copyright (2005), with permission from Elsevier McCance KL, Huether S. Pathophysiology. 7th ed. N.S.W, Mosby; 2015 Peripheral Nervous System Injury Peripheral nerves and their support cells/tissue are vulnerable Lack of protection: bone, membranes, BBB, CSF Frequent injury due to trauma or pressure Often anatomical location expose them Response is limited: Degeneration of axon Demyelination Main difference compared to CNS: Some regenerative capacity and reinnervation Mechanisms of Injury to the Peripheral NS Traumatic Peripheral Nerve Injury Crushing/cutting of neurons Severed area of nerve degenerates (Wallerian) Stimulate inflammatory processes Chromatolysis is induced in neuron Damage from traumatic injury manifests with sensory symptoms Numbness Paresthesia Pain Symptoms relates to the: Number of axons involved Ability of axons to regenerate Distance the fiber needs to regrow to restore communication Short has better prognosis Crushing injury has better prognosis  Peripheral Nervous System Pressure Injury Any nerve can be subject to compression Contributes to nerve injury and associated symptoms Edema in constricted space may cause this injury Carpal tunnel syndrome: pain and paraesthesia Trauma may lead to edema impinging nerve plexus Brachial plexus palsy: flaccid paralysis of the arm, neuroma may develop http://www.childbirthinjuries.com/erbs‐palsy/pictures/ http://www.childrenshospital.org/centers‐and‐services/brachial‐plexus‐program