LM 2.8: Cellular Neuropathology Flashcards
which neurological cells are most susceptible to injury?
neurons
they are the most metabolically active and require the most oxygen so when there’s a cardiac problem, neurons are usually the first to go
in which diseases are oligodendrocytes selectively injured in?
- multiple sclerosis
- leucodystrophies
- autoimmune attacks like acute disseminated encephalomyelitis (ADEM)
- infections like progressive multifocal leucoencephalopathy (PML) which is often caused by JC virus
which neurological cells are most resistant to injury?
astrocytes
they’re the last things to go like if you have a stroke, what’s left is usually astrocytes that show reactive changes to survive the stroke that killed everything else
which region of the brain is selectively vulnerable in global ischemia?
excitotoxic injury to the hipopocampal neurons –> this is because all the other neurons that are dying send signals to the hippocampus and kill them from overstimulation = excitotoxic
there’s also selective injury to cerebellar Purkinje cells
which region of the brain is selectively vulnerable in Huntington?
caudate nucleus and putamen
which region of the brain is selectively vulnerable in Parkinsons?
substantia nigra of the basal ganglia
which region of the brain is selectively vulnerable in amyotrophic lateral sclerosis?
motor neurons
what is Nissl substance?
stacks of rough ER in the body of the neuron
they look like dark blue clumps in the body of the neuron (blue because they’re acidic)
how can you tell an astrocyte on an H&E stain?
doesn’t have a small nucleus like the oligodendrocyte
how do you know if a neuron is dead in an H&E stain?
if it’s red and you can’t see the nucleolus it’s dead!
also the nucleus will be small
what is central chromatolysis?
this is what happens to a neuron when you damage or cut off it’s axon; it’s unique to the brain
a neuron exists to send signals down the axon so without the axon it’ll try to repair the damage and you’ll see some histologic changes in the neuron:
- margination of nissl substance with central clearing of the cytoplasm = all the nissle substance is on the edges of the cell body and the middle off the cell is all clear cytoplasm = central chromatolysis
so the cytoplasm is being filled with smooth ER which is going to rebuild the axon and it’s shoving aside the rough ER which is usually there to make proteins and ship them down the axon for signaling
- peripheral displacement of the nucleus because the smooth ER is pushing it out of the way too!
what are axonal swellings?
if you damage or break an axon, there will still be stuff going down the axon and once it gets to the breaking point of the axon you’ll get a pile up that looks like a balloon
so this occurs at axonal breakage points but it doesn’t last for too long
it’s usually following closed-head trauma due to a stretching and snapping of long fibers (like with shaken baby syndrome)
there are also some diseases that can cause axonal swelling that’s not due to trauma; instead it’s because the transport doesn’t happen correctly and the stuff that’s supposed to be transported just piles up –> usually due to cerebellar degenerations
it can also be caused by vitamin E deficiency (rare)
what can cause axonal swellings?
- trauma
- neuronal degeneration; usually cerebellar
- vitamin E deficiency
what do you see in an H&E stain of an axonal swelling?
a little pink ball that’s a swollen damaged axon
what are neuronal inclusions?
something inside the neuron that shouldn’t be there!
what 3 conditions can cause neuronal inclusions?
- viral
ex. herpes, rabies, CMV, measles can form a virus wad in the axon = viral inclusion
remember the Guarnari bodies from pox virus?? this is them! they’re extranuclear inclusions!
- neurodegenerative diseases cause filaments to pile up in the neuron and cause filamentous inclusions
ex. neurofibrillary tangle, Lewy body, Pick body - neuronal storage diseases –> there’s an enzyme that’s supposed to be degrading something but it’s abnormal so the substance doesn’t get broken down and it piles up
which viruses specifically attack the meninges?
- coxacki
- echo
- mumps
which viruses specifically attack the temporal lobes?
herpes simplex
which viruses specifically attack the dorsal ganglia?
herpes zoster
lies dormant in the dorsal ganglia and reemerge to give you shingles
which viruses specifically attack the motor neurons?
- poliovirus
2. west nile
which virus specifically attacks the cholinergic neurons?
rabies
rabies starts out in a muscle peripherally and then it travels retrograde up the neuron to get to the brain and it does this by having this tropism for cholinergic neurons which are what are going down and innervating the muscles
which viruses specifically attack the oligodendrocytes?
JC virus –> leads to PML
which diseases can cause filamentous inclusions? what is the specific name for each filamentous inclusion associated with the specific disease?
- Alzheimers = neurofibrillary tangle (large, flame-shaped)
- Pick disease = Pick body (large)
- Frontotemporal dementia = TDP-43 inclusion (small)
- dementia with Lewy bodies = cortical Lewy body (small)
- Parkinson’s = classic brainstem Lewy body (large)
which diseases are neuronal metabolic storage diseases?
- glycogenoses (Pompe)
- sphingolipidoses (Tay-Sachs)
- sulfatidoses (Gauchers, Niemann-Pick)
- mucopolysaccharidoses (Herler)
what is the trans-synaptic degeneration of neurons?
it’s secondary degeneration of a neuron connected to a dying neuron that is totally unique to the CNS
so if there’s a neuron that doesn’t have other neurons to talk to, it’ll just give up and die – this can happen in an antegrate or retrograde fashion
this is pretty hard to do though unless you’re in a dedicated tract like the optic tract that synapses at exactly one neuron so they’re not connected to millions of cells and you could kill them easily like when you lose an eye
it’s potentially reversible if you can reconnect the neuron
what are the types of oligodendroglial inclusions?
- viral
2. filaments
which virus can cause a viral oligodendroglial inclusions?
PML caused by JC virus or papova virus
on an H&E stain, chromatin is pushed to the rim and the cytoplasm looks smudgy purple because it’s all virus!!
what can cause filamentus oligodendroglial inclusions?
glial cell inclusions can occur in some non-Alzheimer neurodegenerative diseases like corticobasal degeneration or multiple system atrophy, etc.
what do oligodendrocyte inclusions look like?
oligodendrocytes looks like there are whispy brown extensions attached to them
what can astrocytes do when everything else has been damaged?
- gliosis
- rosenthal fibers
- glial cytoplasmic inclusions
- make cytokines
what is gliosis?
hypertrophy and hyperplasia with synthesis of glial filaments
this is the brain equivalent of a scar
what are rosenthal fibers?
swellings of processes with heat-shock proteins
they look like cork screws in H&E stains and are bright pink – kind of hard to tell they have anything to do with astrocytes but they are swellings of astrocytes!
how can astrocytes make cytokines in response to injury?
so they interact with the immune system to some extent
they react to injury and have some paraimmune function
what are gemistiocytic astrocytes?
they’re enlarged astrocytes as a response to injury
they also have processes extending from them that look like stars; hence astrocytes
these are activated astrocytes after they’re responded to injury! eventually they can form a gliosis which is a brain scar
what do astrocytes do in Alzheimers?
they surround the alzheimers plaque to try and bock it off by forming filaments and engulfing it!
what is the function of microglia?
they are the innate immune system of the brain
they come from bone marrow in embryologic life so they’re immigrants to the brain after development and they stay there forever
they’re the CNS equivalent of macrophages and they form the brains first line of immune response
they respond to challenge with:
1. hypertrophy and hyperplasia
- production of cytokines = IL-1, TNF-alpha
- phagocytosis
they can also be seen inside Alzheimer’s plaques!
what do microglia do when they’re not responding as macrophages?
synaptic remodeling
what do microglia look like on an H&E stain?
irregular looking dark pink circles that you can only see in a specific immunohistochemistry stain that is specific for IL-1 that’s being released by the microglia
what are the 3 main metabolic brain disorders?
- hypoglycemia
- hyperglycemia
- hepatic encephalopathy
what is the effect of hypoglycemia on the brain?
low blood sugar that is honestly similar to the same effects hypoxia causes because neurons require both glucose and oxygen
so if you have an insulin overdose you can get neuron damage
what is hyperglycemia effect on the brain?
dehydration affects brain function because high sugar draws water out of the brain and dehydrates it
overly rapid rehydration can actually cause cerebral edema! brain swelling causes terrible problems because there’s nowhere for the swelling to go inside the skull
what is hepatic encephalopathy?
if you have liver failure, ammonia starts to break down in the blood = hyperammonemia
this leads to confusion and can progress to coma
what are the 2 main toxic disorders associated with the brain?
- ethanol
- methanol
- carbon monoxide
- radiation
- combined methotrexate and radiation injury
what is the toxic effect of ethanol on the brain?
massive, acute ethanol intoxication can cause cerebral swelling and death
unclear if ethanol alone has any chronic effects on the CNS
however fetal exposure to ethanol has severe neurologic deficits
associated nutritional deficiencies likely cause cerebellar dermal atrophy and WK syndrome
what is the toxic effect of methanol on the brain?
retinal degeneration that can lead to blindness
bilateral necrosis of the putamen (basal ganglia)
what is the toxic effect of carbon monoxide on the brain?
similar to hypoxic injury because CO2 kicks oxygen off of the RBCs since it has a higher affinity
bilateral necrosis of the globus pallidus can occur (basal ganglia)
delayed demyelination can also occur if you survive CO poisoning but this is rare
what is the toxic effect of radiation on the brain?
this can happen following radiotherapy for a malignant brain tumor
radionecrosis of the brain is due to endothelial injury with fibrinoid degeneration of vessel and thrombosis
radiation mainly effects the cells that are dividing so why does it effect the brain? it injures blood vessels because they’re mitotically active
the blood vessels on H&E look hot pink = fibrinoid necrosis
what is the toxic effect of combined methotrexate and radiation injury?
it’s white matter necrosis that can occur months after exposure to methotrexate/radiation
so methotrexate exacerbates the effects of normal radiation
