Pathology if the CNS Flashcards
what two conditions can cause a significant loss of function to the CNS
- ischemia
- infection
why may a small injury from ischemia or infection to one cell cause loss of function to the whole CNS
because the cells in the CNS are connected
list the order of cells of the CNS which are susceptible to injury from most to least
- neurons
- oligodendrocytes
- astrocytes
what are the roles of astrocytes in the CNS
they maintain the homeostasis of ion channels and ions of the CNS and regulating ionic composition & neurotransmitters
how do astrocytes work in order to maintain homeostasis of components within the CNS
by picking up metabolites released in the CNS & picking up GABA & glutamate
what is the role of microglia in the CNS
act as macrophages in the CNS by removing infectious elements within the CNS
what is the role of oligodendrocytes in the CNS
involved in myelination around the nuclei
list the things which causes actions of neurons to injury in the CNS
- acute neural injury - ‘red neurons’
- sub-acute and chronic - ‘degenerations’
- ageing - inclusion bodies, lipofuscin
- neurodegeneration - alzheimer’s (neurofibrillary tangles)
what is acute damage in the CNS neurons caused by
ischemia
which areas of the brain tend to get infarcts and ischemia
areas between the main arteries e.g. the anterior cerbral artery - ACA & MCA or between the MCA & PCA
or
in the deeper structures e.g. basal ganglia & thalamus
why are the deeper structures such a basal ganglia & thalamus at risk to ischemia and stroke
as there is not any collateral supply to the deeper structures as around the brain you have the meninges surrounding it
what is the ACA, MCA & PCA areas known as
the watershed areas
what do the neurons appear as following an infarct with H and E staining
damaged cells are stained red (ischemic neurons under stress)
what do the neurons undergo following an infarct
necrosis & macrophages/microglia scavenge debris
which structure of the CNS is not as susceptible to ischemia compared to neurons
oligodendrocytes
what is the appearance of the nuclei of oligodendrocytes
small & round
what is the name of a tumour of the oligodendrocytes
oligodendoglioma
what happens as a result of a oligodendoglioma (tumour)
proliferation/increase in the number of oligodendrocytes compared to that of normal tissues
what is it called when there is an increase of the number of cells following a oligodendoglioma
hyperplasia
what is multiple sclerosis (MS)
a demyelinating disease (myelin loss - oligodendrocytes)
over which structure do oligodendrocytes have darker rounder nuclei
astrocytes (in H and E staining)
what are astrocytes
metabolic buffers and detoxifiers in the brain
what do astrocytes have a similar function to
fibroblasts (healing)
what do astrocytes form
part of the blood brain barrier
forms a protective structure within the choriocapillaris
why do astrocytes form part of the blood brain barrier
to protect the CNS from drugs (which is why it can be very hard to reach the brain)
why is it not useful to carry out chemotherapy if someone has a brain tumour, and what is a more effective alternative
astrocytes prevents the job of chemotherapy drugs to reach the CNS in the brain, brain surgery is more effective at removing the tumour
what is gliosis
the hypertrophy and hyperplasia of astrocytes in response to stress
what do you get an increase of in astrocyte hyperplasia
gliosis
what is the increase in astrocyte as response from
ischemic GFAP (glial fibrillary acidic protein)
what happens to the microglia in response to injury
proliferates, aggregates around foci of necrosis (as any other macrophage would, i.e. moves to the site of damage to initiate wound healing & repair), phagocytose apoptotic/necrotic neurons
what type of nuclei do microglia have
elongated rod like
what is a cerebrovascular disease e.g. stroke caused from
hypoxia, ischemia and infarct or haemorrhage
what is the cause of hypoxia, ischemia and infarct of cerebrovascular disease
impairment of blood supply and oxygenation of tissue (e.g. from heavy smoking reduces the amount of blood to the CNS)
what is the cause of a haemorrhage of cerebrovascular disease
resulting from rupture of CNS vessel e.g. blood vessel can cause aneurysm of the brain
what does the type of cerebrovascular disease injury depend on
- presence of collateral blood supply (e.g. if it was the watershed region or deeper within the structures or if its more peripheral)
- duration of ischemia
- magnitude and time-course of the reduction in flow (acute vs chronic) i.e. how long the amount of oxygen to the brain was restricted, determines how much damage was done to the brain
what is global cerebral ischemia
general reduction in cerebral perfusion (i.e. blood supply is cut off via):
- cardiac arrest - brain dead
- shock - loss of blood = fall in BP and volume (decreased capacity to get oxygen to brain)
- severe hypotension - watershed infarcts
what is focal cerebral ischemia caused by
- embolus (travel in the blood & get lodged in a BV)
- thrombosis of artery (thinning of artery)
- vasculititis (inflammation of the artery)
what is the appearance of an acute infarct in the brain under the microscope
pale region = blood supply is reduced there
what happens as a first sign in tissues 12-24 hours following an infarct under the microscope
appearance of ‘red nuclei’ due to necrosis
releasing glutamate, GABA and calcium as they lose the ability to maintain/regulate their own homeostasis, neurotransmitters, ions become toxic to surrounding tissues
what happens 1-2 days following an infarct to the CNS under the microscope
neutrophils marginate/emigrate from blood vessels in the surrounding areas and perfuse the area to deal with the acute inflammation (clearing it up)
once neutrophils have approached the area of infarction in the CNS, what do they recruit
macrophages
10-14 days following an infarction to the CNS, what occurs
macrophages & microglia will come into the area & initiate wound healing
how do macrophages and microglia initiate wound healing following an infarct to the CNS
by laying down collagen fibres and phagocytosing necrotic tissues
which cell of the CNS deals with scarring and repairing the wound from an infarct to the CNS and how
astrocytes, by laying down collagen granulation tissue & trying to reorganise the damaged area
what is the result of scarring of the damaged area of the brain following infarction
the scarred part of the brain won’t function too well
what causes a haemorrhagic infarct ‘red’ in the CNS
- an embolus
either a cardiac or thrombus set free from the artery (from the heart) to create an embolism which causes an infarct - fat or bone marrow embolism secondary to fracture
- blood leaks from collateral vessels or through necrotic capillaries
what causes a non haemorrhagic infarct ‘pale/bland/anaemic’
- a thrombosis (thinning of the arteries)
arterial block
thrombosis of atherosclerotic plaque
which therapy is warranted < 3 hours following a non haemorrhagic infarct to the CNS and why
thrombolytic therapy (drug can be given to break down the thrombosis & restore function to the area) to preserve the penumbra
what is the penumbra region and why is it at risk following a non haemorrhagic infarct to the CNS
region on border of infarct that is as risk of necrosis (due to release of neurotransmitters & microglia & astrocytes to the area)
which type of infarct can be given treatment and which one cannot
a white non haemorrhagic infarct caused by a thrombosis can be given treatment
but a haemorrhagic infarct caused by an embolis cannot
what are the two classes of infarct to the CNS
- haemorrhagic ‘red’
- non haemorrhagic ‘white’
what are retinal microglia
surveyors of the environment of the retina and check for any diseases or pathology by dynamic movements of their processes, allowing the neural parenchyma to be completely sampled every few hours with very little movement of the microglial somata
what do microglial cells of the retina react to
injury
what appearance do the RPE cells have in a young retina
hexagonal shape cells
in a younger retina, where is the microglia located
limited to the outer plexiform layer and above in the inner plexiform layer & ganglion cell layer, maybe one odd microglia cell found in the RPE
in an older/aged retina, where is the microglia located
more microglia found at the RPE as it breaks through the OPL, as also found at the sub retinal space as well as in the outer segments of the retina
what do microglia secrete
neuroprotective substances (implicated in alzheimer’s & ARMD through reduced surveillance & protection)
what are neuroprotective substances which the microglia secretes important for
the maintenance of the health of the neural retina
as well as microglia not remaining in the OPL and migrating to the RPE, what does an old retina lack in compared to a young retina and what does this result in
ramification (is reduced)
therefore not able to protect the retina as well as there are less branches of the microglia and therefore less able to search & touch surrounding neural tissues
in order to carry our surveillance, what has to occur in the microglia structure over time
growth and extension of the microglia axons which occurs in young and old microglia
although both young and old microglia axons can grow and extend the same over time, what difference is there with the axons which has an advantage in surveillance in younger microglia
younger microglia axons have larger movements which are also more frequent and older microglia axons have slower movements so are slower at detecting movements
at what rate does a laser burn in a young compared to an old microglia accumulate
both accumulate at the same rate
as the young and old microglia can accumulate at a laser burn at the same rate, what difference to they have following the accumulation
dispersal and healing in a younger microglia is quicker, and slower in an aged microglia i.e. slower to phagocytose & repair the damaged tissue
what does a crush of the optic nerve cause
glaucoma
what does a crush of the ONH cause a loss of
RGCs
what is identified as the ending of the disc of the ONH
limit of bruch’s membrane found my modern imaging
what can finding the limit of bruch’s membrane help with
finding the cup disc ratio much better as it promotes the disc margins
what does the ophthalmic artery branch down to
central retinal artery
where does the ONH get their supply from
central retinal artery
whittles branched off the ophthalmic artery
short & long posterior ciliary arteries
where does the long posterior ciliary artery go to and why
to the front of the eye, to supply that region
what is the lamina cribrosa
holes in the sclera through which axons of the RGCs pass in sheaths
what type of fit do the sheaths of RGCs that go through the lamina cribrosa have
tight fit
how does IOP cause damage to the sheaths of the RGCs in the lamina cribrosa
by creating more pressure
which theory does the damage of the sheaths of the RGCs in the lamina cribrosa created by IOP =
trauma/mechanical theory of glaucoma
what strengthens the lamina cribrosa
collagen
what is the type of collagen fibres we have in our lamina cribrosa important for
mechanical strength & how flexible the lamina cribrosa is
in relation to the collagen fibres of the lamina cribrosa, how can a rigid lamina cribrosa cause more trauma to RGCs which pass through
eye movements around the rigid lamina cribrosa
what factor determines the type of collagen we have in our lamina cribrosa which can determine susceptibility to glaucoma
genetic factor
how can the ONH be more vulnerable to hypoxia, inflammation & glaucoma
if a smoker or diabetic
list the potential things which can cause glaucoma
- pathogenesis
- age
- hypoxia
- trauma
- genetics (afro Caribbean/diabetes)
what does early signs of glaucoma show in visual fields
small isolated/localised scotomas
as glaucoma progresses, what do the small localised scotomas become
merge and become an arcuate scotoma
what does the arcuate scotoma in more advanced glaucoma respect
the horizontal line
what type of visual field defect can a tumour if it is in the retina cause
visual field defect can be anywhere in the retina as it does NOT respect the horizontal or the vertical midline
if the tumour is post chiasmatic, what will it respect in terms of visual fields
the horizontal midline
if the tumour is pre chiasmatic, what will it respect in terms of visual fields
the vertical midline
which visual field areas are lost, when theres a loss of RGCs
areas above and below the horizontal midline (i.e. glaucoma)
what do RGCs undergo with high IOP
apoptosis
what does TGD-beta stand for
transforming growth factor beta
what two things increase with increased IOP with signs of microglia & macrophages from damage to the ONH
TGF-beta & collagen-1
what type of eyes is transforming growth factor beta highly expressed in
glaucomatous compared to non glaucomatous eyes (showing pinkish blobs/hue in glaucoma ONH)
what is TGF beta secreted by and what does this mean
macrophages so immune reaction against ONH (which is damaged from elevation in IOP)
list the things that can cause infections of the CNS
- haematogenous spread - artery/veins
- traumatic - infection secondary to trauma (e.g. brain injury from orbital cellulitis) or congenital malformation or meninges
- local - sinuses, teeth, osteomyelitis
- peripheral nervous system to CNS (zoster, rabies) feed back into CNS
when can infections spread to the body/CNS especially
when in a coma as can’t speak if they are getting symptoms
what is acute meningitis
inflammation of CSF + pia mater & arachnoid mater, known as the leptomeninges
what can be the three types of causes of acute meningitis and give examples
- acute pyrogenic: bacterial = E. Coli (young), N. meningitidis (adult) stereptococci (old) - aseptic: viral - chronic: tuberculosis
what are the neurological symptoms and systemic signs of an acute pyrogenic ‘bacterial’ CNS infection
shown via spinal tap:
- CSF cloudy
- high neutrophils number
- increase protein concentration
- decreased glucose
- bacterial culture positive
why is there decreased glucose in an acute pyrogenic ‘bacterial’ CNS infection
as the bacteria eats the glucose up
what are the fever & neurological symptoms of an acute aseptic ‘viral’ CNS infection
shown via spinal tap:
- lymphocytes in CSF (CSF = non cloudy)
- protein elevation mild high
- glucose normal
- usually self-limiting
what causes the infection of the brain called viral meningoencephalitis
brain + meninges
- many ‘arboviruses’ = arthropod borne virus
- mosquito vectors
leads to seizures, ocular palsies, coma, death
what does viral meningoencephalitis lead to
seizures, ocular palsies, coma, death
what is HSV-1
herpes simplex virus, retrograde infection through trigeminal to temporal lobes
which herpes virus is NOT sexually transmitted
herpes simplex virus -1 (HSV-1)
what are the symptoms of herpes simplex virus -1
- cold sores
- change in mood, memory and behaviour (as frontal lobe impaired)
- temporal & frontal lobes (infection can get into CNS and effect)
what type of population is herpes simplex virus -1 most common in
children
what do 10% of herpes simplex virus -1 sufferers have
previous exposure
what type of herpes is herpes simplex virus -2
genital herpes (sexually transmitted)
how many % of children acquire herpes simplex virus -2 and how
50% during birth if mother is infected
what do herpes simplex virus -2 sufferers develop
encephalitis (viral meningitis)
what two things does viral encephalitis show in HSV-2
- perivascular cuffs of leukocytes
- microglial nodules - clusters of reactive astrocytes + microglia & rod nuclei
what are microglial nodules common in
viral infections
what is a motor neuron disease the degeneration of which neurons
upper and lower neurons
what is a motor neuron disease mutations in
super-oxide dismutase
which part of the spinal chord does a motor neuron disease thin
anterior/motor (ventral) roots
what does a motor neuron disease cause atrophy in
- precentral gyrus (motor cortex)
- anterior horn neurons
- motor ventral column of spine (in motor neuron disease)
what can be associated in the late stages of a motor neuron disease
ocular palsies
what does a motor neuron disease cause the atrophy of
ventral motor column of CNS/spine
what does alcoholism cause in the CNS/brain
cerebellar degeneration (wiped out)
what symptoms and why, does cerebellum degeneration due to alcoholism cause
staggering, as it is involved in fine movement
