histology and pathology Flashcards
what are the types of glial cells? (macroglia)
- astrocytes
- oligodendrocytes
- schwann cells
- ependymal cells
- satellite cells of ganglia
what are microglia
the immune cells of the CNS
what is special about using the silver stain on neural tissue
can see the cell processes
explain the histology of the choroid plexus
an epithelial cell that line the ventricles
histology of epndymal cells
low columnar or cuboidal cells that line the central canal of the spinal cord and the ventricle within the brain - some have cilia to aid CSF flow
function of actin in neurons
allows for dynamic assembly/disassembly –> shape changes and movement
function of microtubules in neurons
axon transport
difference between dendrite and axon
dendrite - receives information from other neurons
axon - main conducting unit for carrying signals to other neurons
if you damage a neuron at random… why is it that the axon is often involved, not the cell body
because there is a high proportion of total cell volume in the axons and dendrites compared to the cell body
what is the difference between the electrical activity occurring down dendrites and axons
dendrites - passive electrotonic spread
axons - action potential propagated
what is a Nissl body
parts of the neuron that is involved in protein production
what are the passive support functions of astrocytes
- NT uptake and degradation (in particular GABA and glutamate)
- K+ homeostasis
- neuronal energy supply (take glucose from the blood and give to neurons)
- maintenance of the BBB
- injury response and recovery
what are the active functions of astrocytes
- modulation of neuronal function
- modulation of blood flow
how do astrocytes regulate NT uptake and degradation
express glutamate and GABA transporters
what happens when the glutamate and GABA transporters on the glial cells are inhibited and therefore their function removed
causes overexcitation of the neurons –> if this happens for a long period of time –> cell will die
excitation of glial cells leads to –>
modulations of intracellular Ca levels –> modifies activity of neighboring cells
do glial cells have synaptic vesicles?
yes!! - but very small number compared to neurons
what does the release of Ca from glial cells do to neurons?
inhibits neurons by hyperpolarising it through release of ATP
what is the mechanism for astrocytes regulating vascular tone
the calcium wave propagated by the glial cell causes vasoconstriction
what is the importance of astrocytes regulating blood flow
astrocyte can sense what is going on in the synapse and can therefore directly regulate the blood supply to meet the metabolic demand of the synapse
what type of glial cell is responsible for myelination in the CNS and the PNS
oligodendrocytes - CNS
Schwann cells - PNS
what is the difference in myelination by oligodendrocytes and Schwann cells other CNS vs PNS
oligodendrocytes - extend processes that wrap around parts of several axons
schwann cells wrap around a single axon
what are nodes of ranvier
small gaps in the myeination of an axon
function of microglia
constantly survey the CNS ensuring all the synapses are working properly and rapidly responding to inflammation or injury
where are perineurium, epineurium and endoneurium
perineurium - surrounds each fascicle of axons
epineurium - surrounds a bundle of fascicles
endoneurium - surrounds individual nerve fibres and schwann cells
what are autonomic ganglia
house the cell body of post-ganglionic neurons
What is a stroke
the development of a focal or global neurological deficit related to a vascular event
what are the 3 pathological processes involved in stroke and what are their prevalences
infarction - 75%
haemorrhage - 20%
subarachnoid haemorrhage - 5%
risk factors for cerebral infarction
age
hypertension
cardiac disease
hyperlipidaemia
DB
hypercoagulability states
smoking
obesity
definition of cerebral infarction
necrosis of cerebral tissue in a particular vascular distribution due to vessel occlusion or severe hypoperfusion
what are the mechanisms of cerebral infarction
- pump failure
- systemic hypotension
- narrowed vessel lumen
- occlusion by embolus
pathogenesis of large artery, small vessel and venous occlusion leading to cerebral infarction
large artery - embolic>thrombotic
small vessel - thrombotic>embolic
venous - thrombotic
common sites of atherosclerosis in the circle of willis
- internal carotid termination
- proximal middle cerebral artery
- vertebral arteries
- basilar artery
how does the Circle of Willis offer some protection from stroke
because of the anastomoses between anterior and posterior circulation - only works up to a point
what is an endarterectomy
where are surgeon goes in a removes the thickened intima and some of the media of an atherosclerotic vessel to try and prevent the formation of thrombus/embolus –> stroke
what happens macroscopically a few hours after a stroke
the brain can start to swell due to cytotoxic oedema and adjacent vasogenic oedema –> herniation –> death
what happens microscopically to the neurons of the brain after stroke
- initially swell up
- then become hypereosinophilic
- shrink
- nucleus become pyknotic and then eventually disappears
what happens macroscopically a few days-weeks after stroke
the infarcted tissue becomes necrotic (liquefactive)
what happens macroscopically a few months-years after stroke
eventually a cystic space becomes of what was the tissue
what causes haemorrhagic stroke
when the vessel becomes occluded and then becomes reperfused very quickly with blood –> haemorrhagic infarction
how can hypertension lead to stroke
hypertension –> hyaline arteriolosclerosis of the small vessels of the brain (particularly deep vessels) –> narrowing and ballooning
what are lacunar infarcts
small infarct due to hypertension
what is the main reason for people to die after stroke
due to the consequences of their incapacitation after their stroke
- pneumonia
- CVD
- pulmonary thromboembolism
(can also die from cerebral swelling and the stroke involving vital centres)
causes of intracerebral haemorrhage
hypertensives small vessel disease
amyloid angiopathy blood disorders
coagulopathy
tumour
vasculitits
vascular malformation
drugs
what is the difference in effect on the type of stroke, between hypertensive small vessel disease and amyloid angiopathy small vessel disease
hypertensive - tends to involve deep cerebral structures like the basal ganglia and brainstem
amyloid angiopathy - tends to involve superficial cortical areas
what is amyloid angiopathy
deposition of Abeta amyloid in the walls of the superficial supratentorial blood vessels
causes of non-traumatic subarachnoid haemorrhage
- rupture of saccular aneurysm in the COW
- rupture of other types of aneurysm
- extension of intracerebral hemorrhage
risk factors for developing saccular aneurysm
- female
- PCKD
- coarctation of the aorta
- type 3 collagen deficiency
- HT
- smoking
- alcohol
where are the favoured sites for berry/saccular aneurysm of the COW
- bi/trifurcation of the MCA
- junction of the ICA and posterior communicating artery
- anterior communicating artery (tend to be more anterior circulation)
why does a surgeon want to go in and clip a berry aneurysm
because the blood from the rupture is spasmogenic of the cerebral vessels –> can lead to further infarction
how do you get concussion
follows sudden change in the momentum of the head
what is concussion
instantaneous loss of consciousness, temporary respiratory arrest and loss of reflexes
what is a “closed” brain injury
when movement (change in momentum) or compression (tumour/haemorrhage) of neural and vascular structures with the skull
what are the secondary effects of traumatic brain and spinal cord injury
ischaemia and hypoxia - tend to be acute
cerebral swelling –> raised ICP
infection and epilepsy - usually delayed
what is the term describing a skull fracture with splintering of the bone?
comminuted
what does blood/CSF from the nose/ears suggest
that there may be a basal fracture
how do you get extradural and subdural haematomas?
extradural - rupture of MMA
subdural - rupture of subdural veins
why are older people less likely to get extradural haemorrhages and more likely to get subdural haemorrhages?
because with aging - the dura becomes more tightly attached to the skull (less potential to accumulate blood here), and also because the brain starts to atrophy with aging and therefore there is more stretch placed on the subdural veins - more easily ruptured
what is a contrecoup
a contusion that has occurred on the opposite side of the brain to that of the site of impact
what is the typical clinical sign of a basal contusion?
ansomnia or loss of smell
what does the brain look like macroscopically when recovered from a contusion?
the crests of the gyri collapse down and become yellowish (due to the action of macrophages)
what part of the brain is particularly vulnerable to axonal injury
corpus callosum
what macroscopic feature suggests that there is axonal injury
small spotty haemorrhages (due to small BVs being ruptured along with the axonal injury)
what is the histological feature of axonal injury
axonal spheroids/swellings
what are the macroscopic features of the longterm effects of diffuse axonal injury
- corpus callosum atrophy
- thin white matter
- large lateral ventricles
why is a spinal cord injury not localised to just the site of impact?
because the spinal cord gets squished both proximally and distally so that it further damages itself
what are 4 long term sequelae of brain trauma
infections
hydrocephalus
epilepsey
chronc traumatic encephalopathy
what happens in chronic traumatic encephalopathy
- brain atrpohy due to neuronal loss
- abnormal deposition of Tau protein
- diffuse deposition of A-beta plaques in cortex
what is the mechanism leading from increased CSF to brain death
- expulsion of as much CSF and venous blood as possible
- IC pressure starts to rise
- herniations of brain tissue occur through dural openings
- as ICP approaches arterial pressure, brain perfusion ceases
what are potential causes for increased intracranial pressure
trauma
tumour
infarction
haemorrhage
infection
cerebral oedema
overproduction/obstruction to flow/absorption of CSF
2 main subtypes of cerebral oedema
vasogenic
cytotoxic
what is vasogenic cerebral oedema due to
BBB disruption with increased vascular permeability
what is cytotoxic cerebral odema due to
increased intracellular fluid secondary to neuronal, glial or endothelial cell membrane injury
which type of cerebral oedema is responsive to steroid treatment
vasogenic
what are the 5 potential sites of obstruction of CSF
- foramen of monro (interventricular foramen)
- 3rd ventricle
- aqueduct of Sylvius (cerebral aqueduct)
- foramina of Luschka and Magendie
- basal cisterns/subarachnoid space
what are the 3 major sites of herniation of the brain due to raised IC pressure from subdural haematoma
- subfalcine herniation of cingulate gyrus
- transtentorial herniation of medial temporal lobe
- transforaminal herniation of cerebellar tonsil
what is Duret?
brainstem haemorrhages due to brainstem herniation
what are the outcomes of a CNS neuron that has been injured
- neuron dies
- adjacent neuron retracts its processes
- adjacent neuron can “sprout” and make new local connections
- little/no regeneration
what happens up to 2 weeks post-injury of a PNS neuron
- the nucleus in the cell body becomes peripheral
- loss of Nissl substance
- Wallerian degeneration
- (muscle fibre atrophy - if motor neuron)
what is the fancy name for loss of Nissl substance
chromolysis/chromatolysis
what is Wallerian degeneration
- degeneration of axon and myelin sheath below the site of injury
- debris phagocytosed by macrophages
what happens at 3 weeks post injury of a PNS neuron
- Schwann cells proliferate –> forming a compact cord - Growing axons penetrate the Schwann cell cord and grow at a rate of 0.5-3mm/day
what happens at 3 months post injury to a PNS nerve
successful regeneration with the electrical activity restored and (muscle fibre regeneration if a motor neuron)
how does a neuroma form
from unsuccessful regeneration of a PNS neuron - axon misses its target and keeps growing and growing due to the GF and therefore bundles up at the end = neuroma
what makes a crush injury to a neuron better than a cut injury
the alignment is still intact and the Schwann cells and ECM are continuous in a crush injury
what is the difference between Schwann cells and oligodendrocytes in nerve injury
oligodendrocytes - inhibitory to nerve regrowth
Schwann cells - stimulatory of nerve regrowth
what is the thought behind giving tPA for stroke
minimizes the extent of the primary damage to the neurons (as while the blood clot is there the primary damage is still occurring)
what is primary injury to a neuron
physical damage causing cell loss
what causes secondary injury to neurons
- ischaemia
- Ca influx
- lipid peroxidation and free radical production
- glutamate excitotoxicity
- BBB breakdown
- immune cell infiltration/microglia activation
- cytokines, chemokines, metalloproteases
what happens due to Secondary injury of neurons
- axonal degeneration
- demyelination
- apoptosis
- astrocytic gliosis and glial scar
- also syrinx (cavity) formation, meningeal fibroblast migration
general things you can research and work on to promote CNS repair
- neuroprotection of surviving cells
- axonal regeneration and functional integration
- regrowth of surviving neurons and remyelination
- modulate astrocytic gliosis - neural stem cells
what stops axonal regeneration in the CNS
- lack of trophic support to encourage axons to regrow
- inhibited by the injury environment (astrocytic gliosis, glial scar, myelin inhibitors, developmental guidance molecules)
what happens during astrocytic gliosis (7)
- upregulate astrocyte cytoskeletal proteins
- hypertrophy
- proliferate
- secrete cytokines and GFs
- secrete ECM
- upregulate expression of developmental axon guidance molecules
what does a glial scar do
forms a barrier between undamaged tissue and injury site - prevents regrowth of axons through injury site
what is the importance of Rho kinase in CNS neuron regeneration
it is a common mediator of inhibition of the growth of axons
- therefore if you can inhibit Rho kinase - may be beneficial
how do neurons die in the CNS
by apoptosis and necrosis
where are the two main places in the adult brain with neural stem cells
the subventricular zone of the lateral ventricle the subgranular zone of the dentate gyrus in the hippocampus
what is the importance of Epo trials for neural regeneration
helps promote the neural stem cells in the lateral ventricle to survive
what are the things that inhibit CNS neural regeneration
- astrocyte gliosis
- myelin inhibitors
- upregulation of developmental axon guidance molecules
what are the things that may help promote neural regeneration
- neuroprotection
- modulate gliosis
- promote axonal regeneration by blocking inhibitory molecules
- activation or transplantation of stem cells
