Neurapthology 1 Flashcards
main cellular components of CNS?
nerve cells (neurons) glial cells (astrocytes, oligodendrocytes, ependymal cells) microglia (immune function) supporting structures (connective tissue, meninges, blood vessels)
damage to nerve cells and/or their processes can cause what?
rapid necrosis with sudden acute functional failure (stroke etc)
slow atrophy with gradually increasing dysfunction (age related cerebral atrophy, dementia etc)
what is red neurone?
descriptive term for acute neuronal injury
occurs in context of hypoxia/ischaemia
visible 12-24 hrs after irreversible insult and results in neuronal cell death
what is seen in red neurone?
shrinking and angulation of nuclei
loss of nucleus
intensely red cytoplasm
how else may a neurone react to injury/disease?
axonal reactions
simple neuronal atrophy (chronic degeneration)
sub-cellular alteration - inclusions
describe axonal reactions
increased protein synthesis > cell body swelling, enlarged nucleus
chromatolysis - margination and los of Nissl granules
degeneration of axon and myelin sheath distal to injry “wallertan degeneration)
describe simple neuronal atrophy?
shrunken, angulated and lost neurons, small dark nuclei, lipofuscin pigment, reactive gliosis
describe sub-cellular alterations
common in neurodegenerative conditions (e.g neurofibrillary tangles in alzheimers)
inclusions accumulate with ageing
also get inclusions in viral brain infections
function of astrocytes?
start shaped cells in CNS with astrocytic processes which envelop synaptic plates and wrap around vessels and capillaries
involved in ionic, metabolic and nutritional homeostasis
work in conjunction with endothelial cells to maintain BBB
main cells involved with repair and scar formation
what is gliosis?
astrocyte response to injury
most important histopathological indicator of CNS injury
shows astrocyte hypertrophy and hyperplasia
nucleus enlarges and becomes vesicular and the nucleolus is prominent
cytoplasmic expansion with extension of ramifying processes
in old lesions, nuclei are small and dark and lie in a dense net of processes (glial fibrils)
function of oligodendrocytes?
wrap around axons forming myelin sheath in CNS
how do oligodendrocytes respond to damage?
limited reaction
variable patterns and degree of demyelination
apoptosis
sensitive to oxidative damage
damage is a feature of demyelinating disorders
function of ependymal cells and how do they react to damage?
line ventricular system
limited reaction to injury
- disruption associated with local proliferation of sub-ependymal astrocytes to produce small irregularities on ventricular surface called ependymal granulation
function of microglia?
embryologically derived cells which function as a macrophage system (phagocytosis)
important mediators in acute nervous system injury
- M1 = pro-inflammatory, more chronic
- M2 = anti-inflammatory, phagocytic, more acute
microglia response to injury?
microglia proliferate
recruited through inflammatory mediators
form aggregates around areas of necrotic and damaged tissues
why is the brain so sensitive to hypoxia?
brain consumes 20% of all body resting oxygen consumption
cerebral blood flow can only increase twofold to maintain oxygen delivery, so cant cope well with hypoxia
what happens in the rbain with hypoxia?
after onset of ischaemia, mitochondrial inhibition of ATP synthesis leads to ATP reserves being consumed within a few minutes
describe the pathway of excitotoxicity?
energy failure (hypoxia) > neuronal depolarization and inhibition of astrocyte reuptake > release and inhibited reuptake of glutamate > glutamate storm and excitation > increased Ca2+ > oxidative stress, protease activation and mitochondrial dysfunction
what are the 3 types of oedema?
cytotoxic (intoxication, reye’s, severe hypothermia)
ionic/osmotic (occurs in hyponatraemia and excess water intake/SIADH)
vasogenic (most important) - occurs in trauma/tumours/inflammation/infection/hypertensive encephalopathy
haemorrhagic conversion?
complication of ischaemic stroke where bleeding occurs after reperfusion of the blocked artery
cerebral arteries supply what general areas of the brain?
anterior = midline middle = lateral aspects posterior = posterior
the brain uses how much of cardiac output?
15% of cardiac output and 20% of oxygen
how is the brain supplied?
requires active aerobic metabolism of glucose
autoregulatory mechanisms help maintain blood flow over wide range of blood perfusion pressures at a constant rate by dilation and constriction of cerebral vessels
what is cerebrovascular disease?
any abnormality of brain caused by a pathological process of blood vessels
stroke essentially involves what 2 processes?
infarction/ischaemia/hypoxia etc
haemorrhage/blood vessel damage/rupture etc
- underlying link = hypertension
global vs focal hypoxic ischaemic damage?
global = generalised reduction in blood flow/oxygenation
(e.g cardiac arrest, severe hypotension)
focal (e.g vascular obstruction)
describe global hypoxic ischaemic damage/
generalised reduction in cerebral perfusion
autoregulatory mechanisms cant compensate
watershed areas are vulnerable
neurons more sensitive than glial cells
can lead to pan-necrosis if severe
definition of stroke?
sudden disturbance of cerebral function of vascular origin that causes death or lasts over 24 hrs
what causes cerebral infarction and who is it most common in?
interruption of cerebral blood flow due to thrombosis or embolization thrombosis - atherosclerosis - usually in middle cerebral artery embolic - from atheroma in internal carotid and aortic arch - travels from heart more common in men over 70
what can influence the end result of cerebral infarct?
arterial territory of affected artery
timescale of occlusion
extent of collateral circulatory relief
systemic perfusion pressure
when is damage first seen after cerebral infarct and what is seen?
12 hrs
12-24 hrs =
pale soft and swollen with ill defined margins
red neurones, oedema and swelling
what is seen 24-48 hrs after stroke?
increasing neutrophils, extravasation of red blood cells and activation of astrocytes and microglia
what is seen 2-14 days after stroke>
brain becomes gelatinous and friable reduction in surrounding tissue oedema demarcates the lesion microglia are predominant myelin breakdown reactive gliosis
what is seen several months after stroke?
increasing liquification
formation of cavity lined by dark grey tissue
ongoing phagocytosis increases cavitation and surrounding gliotic scar formation
what is haemorrhagic infarct?
where, in context of infarct, the blood brain barrier is damaged and deteriorates allowing blood to leak through after reperfusion following the infarct stroke
further disrupts damage of infarct
hypertension can cause what types of vessel remodelling?
accelerated atherosclerosis
arteriolosclerosis - thick, stiff and weak walls
fibrinoid necrosis of vessel walls if severe
formation of lacunes
microaneurysms
how can a vascular lesion be localised?
carotid artery disease = contralateral weakness/sensory loss, aphasia or apraxia if dominant hemisphere
middle cerebral artery = weakness in contralateral face and arm
anterior cerebral artery = weakness and sensory loss in contralateral leg
vertebrobasilar artery = vertigo, ataxia, dysarthria and dysphasia
4 consequences of hypertension?
lacunar infarcts
multi-infarct dementia
ruptured aneurysms and intra-cerebral haemorrhage
hypertensive encephalopathy
what are lacunar infarcts?
atheroma, embolism of small penetrating vessels leads to occlusion
vessels which supply basal ganglia etc
when multiple, contribute to multi-infarct dementia
hypertensive encephalopathy findings?
severe hypertension symptoms of raised ICP global cerebral oedema tentorial and tonsillar herniation arteriolar fibrinoid necrosis petechiae
2 types of intracranial haemorrhage, spontaneous includes what?
intracerebral haemorrhage
sub-arachnoid haemorrhage
haemorrhagic infarct
types of traumatic intracranial haemorrhage?
extra-dural haematoma sub-dural haematoma contusion (surface bruising) intracerebral haemorrhage sub-arachnoid
what can contribute to causing an intracranial haemorrhage?
hypertension aneurysms systemic coagulation disorders anticoagulation vascular malformations amyloid deposits open heart surgery neoplasms vasculitis
what morphology is seen in intracerebral haemorrhage?
asymmetry shifts/herniations are common intraparenchymal haematomas softening of adjacent tissue surrounding oedema
what is amyloid angiopathy and how can it cause haemorrhage?
accumulation of beta-beta sheets sticking together to form a plaque
causes vessels to become stiff and rigid so cant respond to changes in BP so likely to rupture
name 4 types of vascular malformations
arteriovenous malformations
cavernous angiomas
venous angiomas
capillary telangectases
what happens in an AVM?
abnormal torturous vessels - usually occurring in middle cerebral arteries in cerebrum
causes shunting from artery to vein which causes vein to undergo smooth muscle hypertrophy or aneurysms which can rupture
veins not made to cope with the pressure so can rupture easily
what commonly causes subarachnoid haemorrhage?
usually spontaneous
most common = rupture of saccular aneurysm
most are in internal carotid
arise in arterial bifurcations (circle of willis)
describe the morphology seen in subarachnoid haemorrhage?
presence of berry aneurysm blood in the subarachnoid space may see - intracerebral haematomas - infarcts of brain parenchyma - mass effect of haematoma and features of raised ICP - hydrocephalus
clinical features of subarachnoid haemorrhage?
severe headache
vomiting
loss of consciousness
usually no history of a precipitating factor
risk factors = smoking, hypertension, kidney disease
