Intro to Neuropath Flashcards
Neurons
1) main function
2) structure
3) replicative or non-replicative in brain?
1) transfer information in NS
2) large round, vesicular nucleus with inner nucleolus
dark Nissl substance (RER)
axons have neurofilaments = specialized intermediate fibers + tubules
3) non-replicative in brain
describe neurofilaments and neurotubules
what are they crosslinked by?
neurofilament = specialized cytoskeletal intermediate fibers (10 nm)
neurotubules = intermediate fibers that form tubules (20-26 nm) made of alpha/beta tubulin
crosslinked by tau protein and microtubule assoc proteins
what happens if axon of neuron damaged?
what is it called?
central chromatolysis
Nissl disappears
soma swells
nucleus displaced to side
neurons are particularly vulnerable to __ and ___ due to high metabolic rate
what changes are seen to reflect necrosis under these conditions?
name?
features?
anoxic injuries and low blood glucose
ischemic/red neuron
- cell shrink
- eosinophilic as lose basophilic Nissl substance
- mitochondria condense
- nuclei become pyknotic (DNA condenss)
Astrocytes
- functions
- clear NT from cleft
- structural support for blood vessels in BBB
- maintain ionic equilbirum
role of astrocytes in brain injury
effective or not?
1) scar formation
astrocyte hyperplasia and hyperplasia helps close gaps after neuron debris removed
2) incr synth of GFAP, filament elongation to allows astrocyte to extend processes across lesion
3) creates thick network but NOT effective b/c can’t fill gap
oligodendroglia
- function
- regeneration?
myelin cells of CNS
nutrition role for deep cortex + basal ganglia
little regeneration in injury
multiple sclerosis mechanism
death of oligodendroglia
ependymal cells
- function?
- regenerative?
ciliated cells lining ventricles for CSF movement
inert / limited regeneration from damage
what happens if ependymal cells are injured?
seen in what diseases
then are permanently damaged
seen in hydrocephalus, bacterial ventriculitis, viral infection
microglia
function?
difference in structure btwn surveillance and activated state?
sentinel cells activated by neuron damage, replicate, phag debris
surveillance = long nuclei + short processes activated = large nuclei + cytoplasm grows into highly branched patterns
microglia are replenished by…
activated microgllia secrete what? function of secretion?
replenished by blood monocytes and transform into brain macrophage
secrete neuronal trophic factors
assist in recovery
also secrete neurotoxins and cytokins for inflamm/kill neurons
significance of RER aka Nissl substance
what happens when axon transected (axotomy)
Nissl = stacks of RER and reflect active protein synth
when axon transected, Nissl subtance disaggregates
basic components of neuronal cytoskleeton
crosslinked by?
made of longitudinally arranged neurofilaments (10 nm long) and neurotubules (20-26 nm long)
crosslinked and fastened by tau protein + microtubule assoc proteins
function of tau and MAPs?
anchor cytoskeleton to membrane + organelles
mechanism of alzheimer’s diz at cell level?
abnormal paired helical filaments of hyperphosphorylated tau in perikaryon
perikaryon = cell body distinct from nucleus and form forms neurofibrillary tangles
how are silver stains used in histology of CNS
appears what color
visualizing axons and dendrites
- silver deposits on cytoskeletal elements dense in neuron
appears black
most common silver stain
used to stain what?
Bielschowsky stain = shows normal axons and dendrites + neurofibrillary tangles of Alzheimer’s
Where is GFAP found?
What are Rosenthal fibers?
Glial fibrillary acidic protein
- makes up intermediate filaments of astrocytes
- component of Rosenthal fibers in diseases
What are Rosenthal fibers?
Rosenthal fibers = homogenous, eosinophilic, elongated, or glob inclusion in astrocytes from longstanding gliosis, tumors or metabolic disease
mutations of GFAP cause what
describe disease
describe course of disease
Alexander disease
- widespread deposits of Rosenthal fibers
- causes white matter degeneration
slow progressing, fatal in children affecting myelin sheath
When and where is myelin first formed?
How long is myelin production
starts late in development in periphery
from birth –> many yrs
Describe how Schwann cells myelinate PNS axons
1) neurons induce Schwann proliferation and migration along axon length
2) Schwann cells elongate and ensheathe neuron
3) axons instruct Schwann to begin wrapping once basal lamina is formed
what induces Schwann myelination
induced by neurons thru cell-cell interactions and intrinsic gene expression program in Schwann
Role of microglia in CNS inflamm and repair
@ rest vs when find injury
secrete what?
microglia = first line phagocytic cells
1) @ rest, sample environment to sense foreign materials, toxins, and damage
2) when find injury/invasion –> activated –> nucleus larger and rod with ramified cyto
3) migrate to lesion, replicate, engulf damage
4) secrete cytokine and neurotoxin for neuroinflamm and can kill neurons; also secrete trophic factors for repair
what is encircling of degenerating neurons by microglia called
difference from microglial nodules
neurophagia
nodules = clustering of microglia aorund foci of necrotic brain tissue
what is sarcolemma?
structure?
function?
cell membrane of muscle cell
- invaginates deep into cytoplasm of cell –> T-tubules
T tubules allow depol of membrane to rapidly penetrate entire cell
what is connected to sarcolemma? how?
contractile myofibrils of muscle cells attach to sarcolemma nd ECM via dystrophin
dystrophin connects cytoskeleton to membrane and dystrophin assoc complex (DAC)
describe DAC and what it is mad eof
made of 5 sarcoglycan proteins ubunits + 2 dystroglycan protein subunits
bound to merosin (part of basement membrane)
mutations in dystrophin cause what?
what does it cause?
Duchenne and Becker muscular dystrophy
causes ongoing degneration/regen of muscle fibers
causes muscle damage d/t loss of mechanical force of contraction
long term changes in DMD and becker’s
degeneration faster than reegen so fibers undergo necrosis
muscle replaced by fat and connective tissue –> progressive weakness
mutations in gene for DAC can lead to ___
merosin mutations found in __
limb girdle dystrophies
some congenital dystrophies
describe how type 1 and type 2 fibers distrib in normal muscle and in denervation atrophy
appearance in staining
proportion varies based on muscle fxn
BUT ONLY 1 TYPE PER MOTOR UNIT (1 MOTOR NEURON + ALL FIBERS)
(neuron determines type of fiber)
appears as checkerboard under stain
what happens to type 1 and type 2 fiber distrib in denervation atrophy
what happens to appearance under stain
1) when motor neuron axon cut, muscle fibers lose innerv –> atrophy
2) nearby motor unit axons sprout new growth cones to re-innerv myocytes and incorporate –> new motor unit
3) change in fiber type to assume type of new motor unit (neighbors)
4) loss of checkerboard and creates grouping
what is myelin made of?
difference btwn central and peripherl myelin
myelin = 70% lipid + 30% proteins
lipid is same = galactocerebroside
proteins differ and usu glycosylated in PNS (not CNS)
proteins in myelin of PNS
P0
Peripheral myelin protein 22
schwann cell myelin protein
Myelin basic protein
proteins in myelin of CNS
myelin assoc glycoprotein
myelin oligodendrocyte protein
myelin basic protein
Describe Wallerian degeneration
what happens to soma
RER
nucleus
cytoplasm
due to?
when axon transected, everything distal degenerates
soma undergoes chromatolysis (swells)
RER disintegrates
nucleus displaces to periphery
cytoplasm –> smooth
due to activation of protein synth to regenerate
Wallerian degeneration
How do axons regenerate?
Schwann cells distal proliferate and provide growth substrate
regrows 1-3 mm per day
Describe segmental demyelination
causes what? effect on conduction velocity?
due to dysfunction of Schwann cell or damage to myelin sheath
(nothing wrong withaxon)
loss of myelin from breakdown in few segments –> causes loss of saltatory conduction, decr conduction velocity
schwann cells can make new myelin to repair but demyelin can cause loss of axons and perm damage
segmental demyelination
appearance of axon without myelin
thin regenerating myelin onion bulbs
presence of lewy body (eosinophilic body made of alpha synuclein means)
parkinson’s
rounded cytoplasmic neuronal inclusion seen in
pick’s disease
neurofibrillary
a
myopathy vs denervation
myopathy = prox weakness and atrophy
elevated CK
EMG changes
denervation = distal weakness and atrophy
normal CK
diff EMG changes
signs of acute denervation
randomly distrib small, angular fibers seen
usu type 2 selective
signs of chronic denervation
type 1 and type 2 proprotion equalizes
what are bands of bugner
in wallerian degeneration
basal lamina lined endoneurial tubes that ensheath prolif schwann cells
clinical signs of nerve regeneration
order
1) autonomic
2) sensation
3) motor
