pathology Flashcards
what does damage to nerve cells and their process lead to
-rapid necrosis with sudden acute functional failure
-slow atrophy with gradually increasing dysfunction
what does hypoxia cause to happen to a red neuron
acute neuronal injury
-shrinking and angulation of nuclei
-loss of nucleolus
-intensely red cytoplasm
axons response to injury/disease
-increased protein synthesis
-chromatolysis (margination and loss of Nissl granules)
-degeneration of axon and myelin sheath distal to injury
what are cellular inclusions and what causes them
various nutrients or pigments that can be found within the cell, but do not have activity like other organelles
-neurodegenerative disease
-accumulate with age
-viral infections
oligodendrocytes role
wrap around axons forming myelin sheath
oligodendrocytes reaction to injury
-variable patterns and degrees of demyelination
-apoptosis
-damage is a feature of demyelinating disease
what can damage to the myelin sheath result in
-conduction reduced
-axons exposed to injury
role of astrocytes
- Ionic, metabolic and nutritional homeostasis
- Work in conjunction with endothelial cells to maintain the BBB
- The main cell involved in repair and scar formation given the lack of fibroblasts within the CNS
what is gliosis
a nonspecific reactive change of glial cells in response to damage to the central nervous system (CNS
-most important histopathological indicator of CNS injury, regardless of the cause
what happens in gliosis
- Astrocyte hyperplasia and hypertrophy
- Nucleus enlarges, becomes vesicular and the nucleolus is prominent
- Cytoplasmic expansion with extension of ramifying processes
what produces changes in ependymal cells
infectious agents including viruses
microglia response to injury
- Microglia proliferate
- Recruited through inflammatory mediators
- Form aggregates around areas of necrotic and damaged tissues
M1 mediator in acute nervous system injury
pro-inflammatory, more chronic
M2 mediators in acute nervous system injury
anti-inflammatory. phagocytic, more acute
what can cause hypoxia in the nervous system
-cerebral ischaemia
-infarct
-haemorrhages
-trauma
-cardiac arrest
-cerebral palsy
what is excitotoxicity
energy failure leads to buildup of glutamate and excitation of post-synaptic NMDA receptors, which causes Ca2+ buildup → protease activation, mitochondrial dysfunction, oxidative stress
pathophysiology of oedema
- Cytotoxic oedema e.g. intoxication, Reye’s, severe hypothermia
- Ionic oedema e.g. hyponatraemia, excess water intake (e.g. in SIADH)
- Vasogenic oedema - most important, occurs in e.g. trauma, tumours, inflamamtion, infection, hypertensive encephalopathy
- Haemorrhagic conversion
how does raised ICP occur
-if the brain enlarges, some blood +/- CSF must escape from cranial vault to avoid rise in pressure
-once this process is exhausted, venous sinuses are flattened and there is little or no csf
-any further increase in brain volume results in rapid increase in ICP
causes of increased ICP
-increased CSF (hydrocephalus)
-focal lesion in brain (space occupying lesion)
-diffuse lesion in brain (e.g. oedema)
-increased venous volume
-physiological (hypoxia, hypercapnia, pain)
causes of hydrocephalus
-obstruction to flow of CSF
-decreased resorption of CSF (post SAH or meningitis)
-overproduction of CSF
non-communicating hydrocephalus
obstruction to flow of CSF occurs within ventricular system
communicating hydrocephalus
obstruction to flow of CSF outside of the ventricular system
-e.g. in the subarachnoid space or at the arachnoid granulations
what happens if hydrocephalus develops before closure of cranial sutures
then cranial enlargement occurs
what happens if hydrocephalus develops after closure of the cranial sutures
there is expansion of ventricles and increase in intracranial pressure
hydrocephalus ex vacuo
dilatation of the ventricular system and a compensatory increase in CSF volume secondary to a loss of brain parenchyma
effects of raised ICP
-intracranial shifts and herniations
-midline shift
-distortion and pressure on cranial nerves and vital neurological signs
-impaired blood flow
-reduced level of consciousness
clinical signs of increased ICP
-papilloedema
-headache
-nausea and vomiting
-neck stiffness
where are mets tumours commonly seen
at the boundaries between grey and white matter
what is the most common primary intracranial tumour
astrocytoma
what is the astrocytoma grading system
pilocytic - grade I
well differentiated - grade II
anaplastic - grade III
glioblastoma - grade IV
medulloblastoma
2nd most common tumour in children after pilocytic astrocytomas
-poorly differentiated/embryonal
-occurs in midline of cerebellum
describe an abscess
central necrosis, oedema, fibrous capsule
symptoms of an abscess
-fever
-symptoms of raised ICP
-symptoms of underlying cause
diagnosis of abscess
CT or MRI
-aspiration for culture and treatment
what does missile or non-missile head trauma mean
penetrating or blunt
penetrating trauma
-focal damage
-lacerations in region of brain damage
-haemorrhage
-high vs low velocity
non-missile injury to brain
-sudden acceleration/deceleration of head
-smaller the contact time the larger the force
-brain moves within the cranial cavity and makes contact with the inner table of the cranium and bony protrusions
primary injury of head trauma
-scalp lesions
-skull fractures
-surface contusions
-surface lacerations
-diffuse axonal injury
-diffuse vascular injury
what are the three types of skull fracture
linear - straight, sharp fracture line
compound - associated with full thickness scalp lacerations
depressed
what is a coup injury
occurs to the brain on the side of the impact
what is a contracoup injury
diametrically opposite point of impact
what usually causes traumatic extradural haematomas
-usually a complication of fracture in tempero-parietal region that involves middle meningeal artery
-immediate brain damage often minimal
-but untreated leads to midline shift- compression and herniation
what is a subdural haemorrhage
-collections of blood between the internal surface of dura mater and arachnoid mater
-caused by disruption of bridging veins that extend from the surface of the brain into subdural space
acute subdural haemorrhage features
-clear history of trauma
-unilateral or bilateral
-gyral contours preserved - pressure evenly distributed
-swelling of cerebrum on side of haematoma
-non-treated, non fatal haematomas become liquefied and form a yellowish neomembrane
chronic subdural haematoma
-often associated with brain atrophy
-composed of liquefied blood/yellow-tinged fluid separated from inner surface of dura mater and underlying brain by neomembrane
what do oligodendrocytes do
insulate axons
-locally confining neuronal depolarisation
-protecting axons
-forming nodes of ranvier
what do nodes do
precipitate rapid saltatory conduction
what are some primary demyelinating diseases
-MS
-acute disseminated encephalomyelitis
-acute haemorrhagic leukoencephalitis
what are secondary demyelinating diseases
viral - progressive multifocal leukoencephalopathy
metabolic - central pontine myelinosis
toxic - CO, organic solvents, cyanide
definition of multiple sclerosis
auto-immune demyelinating disorder characterised by distinct episodes of neurological deficit, separated in time, and which correspond to spatially separated foci of neurological injury
what does the brain look like in MS
-principally a white matter disease
-extensor surface of brain seems normal
-cut surface of brain shows plaques
active plaques
-perivascular inflammatory cells
-microglia
-ongoing demyelination
inactive plaques
-gliosis
-little remaining myelinated axons
-oligodendrocytes and axons reduced in number
what degenerative diseases are in the cerebral cortex
-alzheimer’s
-pick disease
-CJD
what degenerative diseases are in the basal ganglia and brain stem
-parkinson’s disease
-progressive supranuclear palsy
-multiple system atrophy
-huntington disease
what degenerative diseases are in the spinocerebellar
spinocerebellar ataxias
what are neurodegenerative diseases characterised by
-progressive loss of neurons
-typically affecting functionally related neuronal groups
what are the primary dementias
-alzheimer’s
-lewy body dementia
-pick’s disease (fronto-temporal)
-huntingtons disease
pathology of the brain in Alzheimer’s
-decreased size and weight
-frontal, temporal and parietal lobe atrophy
-widening of sulci
-narrowing of gyri
-dilatation of ventricles
-brainstem and cerebellum normal
what mutations can cause familial alzheimers disease
the E4 allele of the apolipoprotein E gene, point mutations in the APP gene, and mutations in presenilin (PS)-1 and 2
what is amyloid angiopathy
a condition in which proteins called amyloid build up on the walls of the arteries in the brain
what is seen in amyloid angiopathy
-extracellular eosinophillic accumulation
-stains congo red
-disrupts blood brain barrier causing: serum leaking, oedema, local hypoxia
what type of condition is parkinsonism seen in
conditions which affect the nigro-striatal dopaminergic pathway
pathology of lewey body dementia
degeneration of substantia nigra
histological hallmarks of fronto-temporal dementia
-picks cells (swollen neurons)
-intracytoplasmic filamentous inclusions known as pick’s bodies
