The CNS Flashcards
types of cells of the NS
- the neuron
- neuroglia
types of neurglial cells
- astrocytes
- oligodendrocytes
- ependymal cells
neuron
- brains immune cells
- protect against injury and disease
astrocytes
- metabolic buffer, detoxifies
- modulate how neurons communicate
- surround blood vessels
oligodendrocytes
- produce myelin
- myelin wraps around axons as insulation
ependymal cells
- lines spinal cord and ventricles of brain
- produces CSF
where does sensory information go to in the brain
- medulla, pons, mesencephalon
- cerebellum
- thalamus
- cerebral cortex
- SC at all levels
what are effectors
- muscles or glands
- anatomical features that do the function the brain tells them to do
major levels of CNS function
- SC
- lower brain or subcortical level
- higher brain or cortical level
spinal cord level of CNS function
- upper levels send signals to SC
- SC performs functions necessary
lower brain function
- subconscious activity
- controlled by:
- medulla
- pons
- mesencephalon
- hypothalamus
- thalamus
- cerebellum
- basal ganglia
higher brain function
- done by cerebral cortex
- essential for thought processes
- cannot function by itself
cerebral cortex function
- thinking
- learning
- remembering
thalamus function
- interprets sensory messages like pain, temp, pressure
hypothalamus function
- controls homeostatic functions
- i.e. temp, respiration, HR
cerebellum function
- muscle tone
- posture
- balance
brain stem function
- HR and breathing
- plays role in consciousness
blood brain barrier
- selectively inhibits substances that reach the brain or CSF
components of the BBB
- capillaries
- astrocyte foot
- efflux transporters
role of capillaries in BBB
- have continuous tight junctions
- limit passage of most substances
astrocyte foot in BBB
- surrounds BV
- allows small and lipophilic molecules
- contributes to brain swelling
efflux transporters
- proteins
- help expel foreign substances that pass through capillaries
where does wallerian degeneration occur
in the distal axon of a severed axon
characteristics of wallerian degeneration
- swelling in distal axon
- neurofilament hypertrophy
- myelin sheath disintegrates
- axon degenerates and disappears
what happens at the proximal end of an injured axon?
- similar to wallerian degeneration but only to the next node of ranvier
what happens to the cell body of an injured nerve
- swells
- undergoes apoptosis
what happens 7-14 days after nerve injury
- new terminal sprouts project form proximal segment
- increase incidence of scar formation
astrocyte reaction to injury
- causes cellular swelling
- due to hypoxia, hypoglycemia, or toxic injuries
oligodendrocyte reaction to injury
- results in demyelinating disorders
where is CSF produced
choroid plexus of each ventricle
CSF function
- shock absorber for brain
- deliver nutrients and remove waste from brain
- regulate ICP
hydrocephalus
- increase in CSF within ventricles
- due to reduce flow or decreased resorption of CSF
what is the result of hydrocephalus in infancy?
enlargement of head due to unfused cranial sutures
what is the result of hydrocephalus after infancy?
expansion of ventricles and increased ICP
cerebral autoregulation
- BF maintained at constant levels
- range of 60- 150 mmHg
when is cerebral autoregulation lost?
at 180 mmHg
what is the result of lost cerebral autoregulation?
- cerebral vasodiation
- cerebral edema
what are the types of cerebral edema?
- vasogenic
- cytotoxic
vasogenic edema
- irreversible increase in extracellular fluid
- caused by BBB disruption and increased vascular permeability
cytotoxic edema
- reversible
- increase in fluid secondary to neuronal, glial, or endothelial damage
- caused by hypoxia or ischemia
intracranial components
- cerebral parenchyma
- CSF
- Blood
ICP
- pressure inside cranial cavity
- normally <15 mmHg
- pathologic HTN > 20 mmHg
intracranial compliance
- displacement of CSF into thecal sac
- decrease in volume of cerebral venous blood via venoconstriction and extracranial drainage
what happens if ICP increase?
blood supply to brain decreases and results in cerebral ischemia
herniation
- displacement of brain tissue past dural folds or through openings in skull
- due to increased ICP
when do you often see herniation?
- cerebral edema
- increased CSF volume
- mass lesions
what is the most common type of herniation
- tonsillar herniation
- causes brainstem to compress
- compromises vital respiratory and cardiac centers in medulla
causes of hypoxia
- low partial pressure of oxygen
- impaired o2 carrying capacity
- toxins
- ischemia
broad classifications of ischemia
- global
- focal
global cerebral ischemia
- happens when BP is less than 50 mmHg
- usually due to cardiac arrest
- outcome depends on duration
- severe global ischemia -> brain dead pt
focal cerebral ischemia
- cerebral artery occlusion leading to focal ischemia then infarction
- causes are embolic infarction or thrombotic occlusions
clinical deficits due to ischemia depend on
- duration of ischemia
- magnitude and rapidity of reduction of flow
cerebrovascular disease classifications
- intrinsic issue of vessels
- process might originate elsewhere
- result of inadequate cerebral BF
- rupture of vessles
cerebrovascular disease classifications that can cause TIA or ischemic stroke
- when issue is intrinsic
- when process originates elsewhere
- when there is inadequate BF
cerebrovascular disease classifications that can cause hemorrhagic strokes
- when vessels rupture
TIA
- transient neurologic dysfunction due to ischemia
- no acute infarction
ischemic stroke
- infarction due to ischemia
- causes permanent damage
mechanisms of TIA
- large artery TIA due to atherosclerosis
- embolic TIA
- lacunar/ small artery due HTN
what is the penumbra
- area surrounding infarcted brain tissue that have the potential to recover
mechanism of ischemic cell injury
- inhibition of protein synthesis
- glucose utilization increases
- anaerobic glycolysis and tissue acidosis
- neuronal electrical failure
- membrane failure
- cell death
what happens if the brain structural integrity is lost
- breakdown of BBB
- cerebral edema
- hemorrhage into brain parenchyma
what is matrix metalloprotease (MMP)
protease that mediates loss of brain structural integrity
causes of intracranial hemorrhage
- HTN
- structural lesions
- tumors
types of intracranial hemorrhage
- intracerebral hemorrhage
- subarachnoid hemorrhage
causes of intracerebral hemorrahge
- HTN
- trauma
- vascular malformations
cause of subarachnoid hemorrhage
rupture of aneurysms
primary brain damage
- parenchymal blood accumulates
- tissue is disruputed
- mechanical damage due to mass effect
- increased ICP
- damaged BBB -> edema
secondary brain damage
- thrombin activation
- lysis of RBC -> release of Hb which is converted to heme and iron
- inflammatory reaction
what is another name for spina bifida
myelomeningocele
neural tube defect
- portion of neural tube doesnt close or reopens after closure
- can occur in brain, spine, spinal column
- present at birth
myelomeningocele
- cleft in vertebral column
- defect in skin so meningnes and SC exposed
- usually results in damage to SC and nerves
- can cause physical and intellectual disabilities
risk factor for myelomeningoceles
folate deficiency during first weeks of gestation
neurologic abnormalities of myelomeningoeceles
- SC problems -> issues with trunk, legs, bladder, bowel
- brain stem probelms -> chiari malformation
- hydrocephalus due to chairi II malformation
chairi malformation
structural defect when cerebellum pushes through foramen magnum
chairi II malformation
- brainstem and cerebellum pushed through foramen magnum
cerebral palsy
- permanent non-progressive motor dysfunction
- affects muscle tone, posture, and movement
cause of cerebral palsy
- most due to prenatal factors
- sometimes due to peri and postnatal factors
- prematurity/ low birth weight*
low birth weight and CP associations
- periventricular leukomalacla (PVL)
- intraventricular hemorrhage
- bronchopulmonary dysplasia
pathogenesis of CP
- necrosis of periventricular white matter
what is PVL
- necrosis of white matter near vetricles
- often occurs in premature infants
- due to decreased oxygen/ blood flow and damage to glial cells
diffuse brain injury (DBI)
- most common type of TBI
- due to impact, acceleration, and deceleration forces
- develops due to tissue seharing at interface of gray and white matter
what is the most severe form of DBI
diffuse traumatic axonal injury (DAI)
pathophys of diffuse axonal injury (DAI)
- axonal swelling
- release of excitatory neurotransmitters
- generation of free radicals causes secondary injury
types of focal brain injury
- brain contusion
- intraparenchymal brain hemorrhage
- subdural hematoma
- epidural hematoma
brain contusion
- bruising of brain tissue
- blunt trauma between brain and skull
- can be in location of impact (coup) on opposite side of brain (countercoup)
intraparenchymal brain hemorrhage
- develops from tears in brain tissue and/or vasculature
subdural hematoma
- dura is still intact
- bridging blood vessels cross subdural space
- cerebral cortical hemorrhage caused by direct brain trauma
epidural hematoma
- after blunt trauma
- may be result from disruption of middle meningeal artery and vein
TBI
- heterogenous disease
- rated based on glasgow coma scale
pathophys of primary brain injury
- shearing mechanisms leads to DAI
- focal cerebral contusions
- extra axial hematomas
pathophys of secondary TBI
- neurotransmitter mediated excitotoxity
- electrolyte imbalances
- mitochondrial dysfunction
- inflammatory responses
- apoptosis
- secondary ischemia
concussion
- acute mild TBI
- based on glasgow scale rating measured 30 min after injury
pathophys of concussion
- result of direct external contact forces
- can also be from brain being slapped against intracranial surfaces
- may result in neurological changes
- acute clinical sx related to function
traumatic vascular injury
- near universal feature of severe TBI
- direct trauma or disruption of vessel wall
pathophys of traumatic vascular injury
- injured cerebral microvasculature -> microthrombi and neuronal death
- BBB disruption, edema, focal ischemia
- in elderly stretched bridging veins -> subdural hematoma
chronic traumatic encephalopathy (CTE)
- dementing illness that develops after repeated head trauma
- leads to build up of tau proteins in superficial cortical layers
etiology of CTE
- repreated concussions cause cumulative neuropsych deficits
- parkinsonism
- speech and gain abnormalities
how can infections cause damage to CNS?
- directly injuring glia or neurons
- indirectly through microbial toxins
- inflammatory response
- immune-mediated mechanisms
how can microbes access the CNS?
- hematogenous spread- most common
- direct implantation
- local extension
- peripheral nerves
meningitis
- inflammation of leptomeningies in subarachnoid space
- mainly due streptococcus pneumoniae or neisseria meningitidis
how is meningitis classified
- acute pyogenic
- aseptic
- chronic
what is the difference between meningitis and meningoencephalitis?
- meningitis- only meninges are infected
- meningoencephalitis- meninges AND brain parenchyma infected
pathogenesis of meningitis
- cytokines produced
- increased BBB permeability
- altered cerebral BF
- increased ROS
- all lead to neuronal damage and increased ICP/ edema
bacterial meningitis
- infection of arachnoid mater and CSF in subarachnoid space and ventricles
triad of bacterial meningitis
- pathogen penetration
- NF-kB activation
- leukocyte transmigration at BBB
what is the role if NF-kB
- transcription factor
- activated when bacteria invade BBB
- causes cascade of events in meningitis infection
viral meningitis
- most common type of meningitis
- less severe- self limiting
- fever, no neurologic dysfunction
main cause of viral meningitis
- enteroviruses
clinical features of meningitis
- fever
- HA
- stiff neck
- altered mental status
- N/V
- sx are the same for viral and bacterial
early onset dementia (EOD)
- significant acquired cognitive impairment
- interferes with independence in daily activities
- affects learning, memory, language
- onset: 18-65 y/o
causes of EOD
- Alzheimers disease
- parkinsons disease
- prion disease
- MS
what is the most common cause of dementia in older adults
Alzheimer disease
neuropathologic changes seen in AD
- neuritic plaques
- extracellular deposits of amyloid beta peptides
- neurofibrillary degeneration by tau proteins
how are neuropathologic changes ranked in AD?
- amyloid beta plaque distribution score
- tau protein distribution stage
- neuritic plaque density score
what are the two types of AD
- early onset= familial
- sporadic, occurs in people over 65 y/o
- 95% of cases are sporadic
pathogenesis of early onset AD
- APP mutation
- PSEN1 mutation (most common)
- PSEN2 mutation
- also due to role of inflammation
- basis of cognitive impairment due to presence of plaques and tangles
what are the three enzymes that normally cleave amyloid precursor proteins?
- alpha secretase
- beta secretase
- gamma secretase
result of APP mutation
- increased activity of beta secretase
- results in amyloid beta protein accumulation
result of PSEN1 or 2 mutations
- increased activity of gamma secretase
- results in accumulation of amyloid beta proteins
why do tau proteins aggregate in AD
they become hyperphosphorylated
what is the gene mutation associated with sporadic AD
- ApoE
- inhibits clearance of amyloid beta proteins
what are the cardinal clinical sx of AD
- memory impairment
- executive function and judgement/ problem solving issues
- behavioral and psychological sx
parkinson disease
- progressive neurodegenerative disease
- due to basal ganglia death leading to less DA production
- multifactorial disease
basal ganglia circuits in parkinson disease
- basal ganglia produce DA
- have increased inhibition of thalamus
- also have reduced excitatory input to the motor cortex
compensatory mechanisms in PD
- increased synthesis of DA in surviving neurons
- proliferation of DA receptors
- gap junctions allow rapid communication between neurons
three stages of compensation during presymptomatic period of PD
- early period where compensation can mask disease
- increased basal ganglia activity
- increased intensity in motor cortex
clinical features of PD
- resting tremor
- bradykinesia
- rigidity
- postural instability
amyotropic lateral sclerosis (ALS)
- progressive neurodegenerative disease
- leads to muscle weakness, disability, death
- 90-95% sporadic
risk factors for ALS
- age
- family history
- smoking*
- environmental toxin exposure
- military servce
possible etiology of ALS
- largely unknown
- abnormalities in RNA metabolism
- excitotoxicity
- viral infections- polio and enterovirus
- inflammatory responses
pathology of ALS
- intracellular inclusions in degenerating neurons and glia
- motor neuron degeneration and death with gliosis
- SC becomes atrophic
- affected muscles show denervation atrophy
hallmark sx of ALS
- combo of upper and lower motor neuron signs and sx
- weakness
- slowness
- hyperreflexia
- spasticity
- atrophy
- fasciculations
multiple sclerosis
- autoimmune inflammation due to auto-reactive lymphocytes (T cells)
major pathologic mechanisms of MS
- inflammation
- demyelination
- axonal degeneration
pathogenesis of MS
- immune mediated
- microglia form complex with activated T cells -> destruction of myelin and oligodendrocytes
- see lesions or plaques in brain
classifications of MS
- clinically isolated syndromes
- relapsing- remitting
- secondary progressive
- primary progressive
clinicaly isolated syndromes of MS
- first attack of a disease
- shows characteristics of inflammatory demyelination
- doesn’t fulfill MS dx criteria
relapsing- remitting MS
- clearly defined relapse with full recovery
- sequeelae and residual deficit upon recovery
secondary progressive MS
- initial RR disease that gradually worsens
primary progressive MS
- progressive accumulation of disability
- from disease onset with occasional plateaus, temporary minor improvements, or acute relapses
types of glial cell tumors
- astrocytoma
- oligodendrogliomas
- ependymomas
- mixed gliomas
classifications of primary brain tumors
- Grade I
- Grade II
- Grade III or IV- malignatn or high grade gliomas
generalized sx of brain tumors
- HA
- seizures
- N/V
- depressed level of consciousness
- neurocognitive dysfunction
focal sx of brain tumors
- seizures
- weakness
- sensory loss
- aphagia
- visual spatial dysfunction
glioma
- primary brain tumor
- histological features of glial cells
- diffuse gliomas are most common
- generally affect cerebral hemispheres of adults
classifications of diffuse gliomas
- histologic characteristics
- molecular characteristics like IDH mutant astrocytomas
astrocytoma formation
- inactivation of p53 tumor suppressor gene
- point mutations in IDH 1
- mutations in chromatin regulator gene
why are IDH mutations associated with astrocytomas
- leads to accumulation of 2-HG
- causes global changes in DNA and histone methylation
- impairment of cellular differentiation
- tumorigenesis
glioblastoma multiforme (GBM)
most malingnat form of astrocytoma
transition from low-grade to malignant glioma associated with
- cell cycle checkpoint inactivation
- tumor suppressor gene inactivation
- angiogenesis
pathophys of GBM
- complex
- multiple genetic mutations
- upregulation of vascular endothelial GF (VEGF)
result of VEGF
- increases vascular permeability
- increases endothelial gaps
- increases fenestrations
- allows for rapid growth of tumor
meningioma
- mainly benign tumor of adults
- arise from meninges
- main risk factor is radiation therapy to head and neck
what is the most common cytogenic cause of meningiomas
abnormal chromosome 22 mutations
clinical features of meningioma
- usually slow growing tumors
- HA and weakness in arm or leg are most common sx
- express progesterone receptors so may grow more rapidly during pregnancy
primary sites of origin of metastatic brain tumors
- lung
- breast
- skin (melanoma)
- kidney
- GI tract
- most common brain tumor in adults
clinical features of metastatic brain tumors
- HA that has changing pattern, worsens with change in position
- seizures
