Neuropathology Flashcards
What cells of the nervous system are most sensitive to hypoxia?
Neurons
Neuroglia
Microglia cells
What are two responses neurones have to injury?
Hypoxia
Neuronophagia
Describe the neuronal response to hypoxia
Shrinking of the cell body, becoming eosinophilic and angular with loss of Nissl substance
Changes occur within 12 hours
Affected neuron surrounded by clear space (swelling of astrocyte processes)
Nucleus becomes dark and pyknotic (triangular) and loss of nucleolus
Describe the neuronal response of neuronophagia.
Irreversible damage
Phagocytosis of affected cell
When does neuronophagia often occur?
Rapid neuronal death in hypoxia or viral infection
Terminology: Polio- Leuko- Encephalo- Myelo- Malacia-
Polio = grey matter Leuko = white matters Encephalo = brain Myelo = spinal cord Malacia = necrosis
What is the term used to describe the reaction if the neuron cell body to axonal damage?
Central chromatolysis
Does central chromatolysis occur in the CNS, PNS or both?
Both
What occurs in the axonal reaction to damage?
central chromatolysis
Swelling, nucleus becomes peripheral, Nissl substance (rough endoplasmic reticulum) disperses
Pallor (pale colour to cell body)
What is the duration of the axonal reaction (central chromatolysis)?
Within a day, may persist for months
What is known as secondary demyelination?
Axonal (Wallerian) degeneration
What is the term used to describe the reaction that follows axon disruption?
Axonal (Wallerian) degeneration/secondary demyelination
Describe the axonal (Wallerian) degeneration process
24hr after injury: proximal and distal axonal stumps swell
Distal axon degenerates and fragments
1 month: axonal debris removed by phagocytosis
Myelin breaks down
Week(s): removal of myelin debris in PNS by macrophages (months/years in CNS)
PNS axon regrows (Schwann cell proliferation) 5-10mm/day - only occurs if connective tissue support remains suitably intact
What happens to the regeneration of axon sprouts in the PNS during axonal (Wallerian) degeneration process if there is loss of connective tissue integrity?
Fibres are unable to regenerate
Functional loss
When are viral inclusion bodies produced?
In viral infections e.g. Herpes simplex encephalitis and rabies
Where are viral inclusion bodies most likely found?
Neurons in specific locations: pyramidal cells of hippocampus/adjacent temporal cortex, Purkinje cells of cerebellum
What are interneuronal deposits?
Substances that accumulate within neurons
Permanent nature of cells make them prone to accumulating particular substances
Give an example of an intraneuronal deposit
Lewy bodies (Parkinson’s disease)
What disease are levy bodies present in?
Parkinson’s disease
What are Lewy bodies?
Abnormally phosphorylated neurofilaments in the substantia nigra/locus coerulus
What is a typical feature of spongiform encephalopathy?
Neuronal vacuolation
What is a vacuolated neuron?
Affected neuron with specific anatomic disruptions and vacuoles in the surrounding neuropil (due to swelling of astrocyte processes)
What causes vacuoles in the neuropil?
Swelling of astrocyte processes
What are the glial cells (neuroectodermal derivatives) of the nervous system?
Astrocytes
Oligodendrocytes
Ependyma
What are the functions of Astrocytes?
Formation of blood brain barrier Secretion of growth factors and chemokines (modulation of inflammation in CNS) Metabolic buffering Detoxification Nutrient supply Glucose transport Uptake of neurotransmitters Electrical insulation Antioxidant roles
What is the function of oligodendrocytes?
Formation of myelin sheaths in CNS
What is the function of expendyma cells?
Lines ventricles
What is gliosis?
Astrocytes response to injury (aka astrogliosis/astrocytosis)
Increased glial cell number and size
Fill small cavities/scars, wall off tumor/abscess
What is the result of oligodendrocyte damage?
Demylination - pale area
Poor proliferation/regeneration
What are the bone marrow derivatives of the nervous system?
Microglia
What are the functions of microglia?
Fixed macrophages in CNS (dead cells and lipids)
What are the main causes for increased intracranial pressure?
Focal space-occupying lesions (tumour, abscess, haematoma, encephalitis
Increase CSF volume (hydrocephalus)
Compression in spinal cord (disc herniation, unstable vertebral articulations)
What is a common response to increased intracranial pressure?
Herniation: movement of parts of the brain through natural openings into a different anatomical compartment
What are the various types of herniations of the brain that can occur due to increased ICP?
Subfalcine: medial portion of cerebral hemisphere (cingulate gyrus) moves laterally under falx cerebri
Transtentorial: medial temporal lobe moves under the tentorium cerebelli
Tonsillar/coning: protrusion of cerebellar tonsils causally through foramen magnum
What is the consequence of increased ICP in infants (neonates)?
Sutures and frontanelles allow expansion
What are the clinical presentations of increased intracranial pressure?
Headache, dullness, nausea, vomiting (papilledema)
Describe what a subfalcine herniation is.
Movement of the cingulate gurus (medial part of cerebral hemisphere) underneath falx cerebri - can compress on anterior cerebral artery
Describe what a transrentorial herniation is.
Movement of the incus of the hippocampus and medial parts of temporal lobe beneath the tentorium
Can produce a grossly visible groove
What are the possible consequences of a transrentorial herniation?
Movement mid brain compression - coma
Oculomotor nerve compression - ipsilateral pupil dilation
Aqueduct compression - further ICP increase
Posterior cerebral artery compression - occipital infarction - blindness
Arterial and venous tears in brain stem - haemorrhage
(Mass effect in one or both cerebral hemispheres)
What are the consequences of cerebral oedema?
Herniation due to raised CSF, fixed volume of CNS compartment and lack of effective lymphatic drainage
What are the possible causes of cerebral oedema?
Vascogenic
Cytoxic
Interstitial hypo-osmotic
What is the most common form of oedema?
Vascogenic oedema
What causes Vascogenic oedema?
Increased vascular permeability from trauma/vascular necrosis within infarcts/tumours
Second impact syndrome
What causes cytoxic oedema?
Intracellular fluid accumulation due to toxins or ischemia and water overload
What causes interstitial oedema?
Build up of fluid due to obstructive hydrocephalus (peri ventricular regions)
What is hypo-osmotic oedema?
Oedema caused by water intoxication
Which form of oedema can be treated by reducing brain swelling using diuretic agents?
Vascogenic
What is hydrocephalus?
Increased CSF volume within cranial cavity
How often is CSF renewed?
3-5 times per day
What are the various types of hydrocephalus?
Internal (ventricular)
External (subarachnoid)
Communicating (ventricles and subarachnoid space)
Active
Arrested
Compensatory (increased CSF secondary it reduced volume of brain substance)
What is the cause of hydrocephalus?
Obstruction of CSF flow
What is the result of an obstruction at the foramen of Munro?
Unilateral ventricular hydrocephalus
What is the result of an obstruction at the third ventricle or mesencephalic aqueduct?
Hydrocephalus of lateral ventricles
What is the result of an obstruction at the foramina of Luschka (lateral apertures of fourth ventricle)?
Affects whole ventricular system
What is the result of an obstruction of the subarachnoid?
While ventricular system and communicating
Where do the obstructive materail causing hydrocephalus arise from?
Masses: neoplasms
Congenital malformations: non-patent mesencephalic aqueduct
Iflammation
Hernias
What are causes of hydrocephalus by destroying arachnoid villi?
Vitamin A deficiency
Severe meningitis
What are some of the ceerebral signs of hydrocephalus?
Headache Nausea Blurred vision Dullness Confusion Memory loss Irritability Poor intellectual performance Urinary incontinence
Are neurons more tolerable of hypoxia or ischemia?
Hypoxia
Define the term malacia.
Necrosis in CNS (breakdown of Blood Brain Barrier)
Due to cardiac arrest, anesthetic accidents, atherosclerosis
What is a “stroke”
Clinical term used for the syndrome resulting from infarction and haemorrhage in the CNS
What are some of the causes of stroke
Aphasia, hemiplegia, blindness
Dependant on site affected
What are some of the causes of arterial obstruction in CNS?
In situ thrombosis (atherosclerosis) Embolism of cardiac thrombi Tumor Air/fat Arterial compression from herniation/masses
What is excitocity?
Imbalance in stimulatory neurotransmitters seen in CNS disease, hypoxia/ischemia (glucose deprivation) resulting in penumbral death
Increased release of glutamate and aspartate
Reversible acute swelling of depolarised neuron (influx of sodium ions, chloride ions and water)
NDMAR opened by glutamate - Ca influx - generation of reactive oxygen and nitrogen species
How can Astrocytes moderate the damage of exocitoxicity?
Convert glutamate to glutamine (neutralising free radicals)
What aids in protecting the CNS from infections.
Bone, dura, blood brain barrier, microglia
What are the possible routes for infectious agents to reach the CNS?
Haematogenous (bacteria)
Local extension (osteitis, sinusitis, tooth roots, vertebral abscesses, middle ear infections)
Direct implantation (skull fracture, penetrating injuries, grafts, surgical exposure)
Neural (rabies, tetanus toxin, prions)
What happens if an infectious agent does gain access to the CNS?
Rapid dissemination via the ventricular system (CSF), aided by poor fibrous response and low degree of immuno-surveillance
What are the two key bacterial infections?
Meningitis
Abscessation
What are the key features of meningitis?
Subarachnoid purulent exudate (neutrophils)
More apparent in basal cisterns and sulci
CSF obstruction and hydrocephalus (oedema)
Superficial cortical necrosis and encephalitis
Some diffuse brain swelling
What are the key features of abscessation?
Clinically appears to be SOL - surrounding oedema
Only thin capsule (collagen and astrocytosis
