Week 2/3: pathology-response to CNS injury, vascular disease, congenital malformations Flashcards
Define four ways that neurons respond to injury
- ischemic cell change (red neuron)-8-24 hrs after insult, neuron shrinks, cytoplasms becomes eosinophilic. depletion of ATP, acidosis, buildup of intracell Ca2+, ROS
- Wallerian degeneration- when axon is transected. degeneration of axon and myeline sheath distal to transection. breakup into fragments that are phagocytosed and removed
- Central chromatolysis- swelling of neuronal cell body, dissolution of nissl granules, migration of nucleus to periphery (reversible)
- distal axonopathy - degeneration of axon and myelin sheath in distal parts of axon. “dies back”. due to exposure to toxins. damages ability of neuronal cell body to maintain metabolic needs of axon.
List 5 neuron inclusions and their associated disease.
- Neurofibillary tangle- Alzheimers
- Lewy body - Parkinsons
- Pick body - Pick disease
- Negri body - Rabies
- Cowdry type A - Herpes, CMV (nucleus)
- rest in cytoplasm
List three mechanisms by which myelin is reduced in amount in the central nervous system.
- multiple sclerosis- immune attack against myelin
- progressive multifocal leukoencephalopathy (PML)- small plaques of demyelination when oligodendroglial cells die and myelin they support degenerates
- leukodystrophies- myelin abnormally formed due to genetic abnormality, is unstable and breaks down
In which demyelinating disease are inclusions found in oligodendroglia?
PML - oligodendrogial cells susceptible to viral agents such as papova virus
Define astrogliosis and describe its appearance on histologic section.
In response to injury, astrocytes respond by gliosis –>proliferation and hypertrophy
-cytoplasm becomes apparent and is eosinophilic due to GFAP accumulation
Indicate the derivation of microglial cells in the CNS
- Derived from mesoderm, from bone marrow (not neuroectoderm as other glia are)
- enter brain during development and infiltrate along with blood vessels
Define the four ways in which microglial cells respond to injury.
- Reactive microglial cell: become activated, may up regulate expression of MHC molecules and cytokines
- Macrophage response: differentiate into macrophages, phagocytose tissue debris
- microglial nodule: may respond to single damaged neuron by encircling neuron and phagocytosing it. Neurophagia, results in formation of nodule.
- Multinucleated giant cell reaction: may accumulate in white matter in HIV encephalitis. Fuse to form multinucleate giant cells. Seen in AIDS dementia.
Describe the typical response of ependymal cells to disruption
-when ependyma disrupted and cells lost–>proliferation of adjacent subependymal astrocytes to form granulations. Disrupted ependymal cells may form small rosettes in adjacent brain tissue
List three ways in which vasogenic edema differs from cytotoxic edema
Vasogenic
1. fluid accumulates in extracellular space, predominately white matter
2. may result in increased intracranial pressure=mass effect
3. due to breakdown of BBB
Cytotoxic
1. intracellular accumulation of fluid
2. affect cells of gray matter predominately
3. usually no mass effect
4.due to toxic or metabolic events
List the 7 landmarks in the development of the nervous system and the gestational time during which they occur.
- neural tube closure: around 24-28 days anterior rostral and posterior caudal neuropore closes
- Outgrowth of the telencephalic vesicles: 5th week, vesicles arise, by 7-8 weeks, choroid plexus invaginated cavities
- Proliferation: cells of CNS generated from germinal tissue lining ventricular system or cerebrum and cerebellum, and pericanal region of cord
- cell migration: 7 weeks, neuroblasts move inside out
- gyration: 24 weeks, development of gyro
- myelination: begins at 20 weeks
- axonal, dendritic, synaptic development: synaptic remodeling occurs throughout life
Describe the gross morphologic features and known causes of spina bifida occulta.
- most mild form of spina bifida
- bony defect, usually in lumbosacral area that involves no nervous tissue
- believed to be defect of secondary neurulation
- Secondary neurulation: formation of non-epidermal tissues from a multipotential stem cell population in tail bud
- associated with tufts of hairy skin, lipomatous skin tags, tethered cord
Describe the gross morphologic features and known causes of meningocele.
- least common spina bifida
- the meninges are forced into the gaps between the vertebrae
Describe the gross morphologic features and known causes of myelomeningocele.
- most severe spina bifida
- the unfused portion of the spinal column allows the spinal cord to protrude through an opening. The meningeal membranes that cover the spinal cord form a sac enclosing the spinal elements
Describe the gross morphologic features and known causes of anencephaly.
-most severe type of neural tube closure defect, absent overlying skull
-Facies: ‘frog facies’,
Exposed brain:
Other anomalies: absent/hypoplastic skull vault, eyes protrude/shallow orbits, sellar abnormalities/hypoplastic pituitary gland, hypoplastic lungs, large thymus
-folic acid def. is risk factor
-incidence changed from 1/1000 to 1/5000
Describe the gross morphologic features and known causes of holoprosencephaly (HPE)
-common defect of forebrain and freq. mid face. incomplete dev. and septation of midline structures
-features: single nostril, one eye, cleft lip, hypotelorism
Causes:
Maternal DM, rubella, toxo, syphillis, fetal alcohol syndrome
Can be experimentally induced - mechanically and chemicaly
Several Chromosomal loci implicated (HPE1, …, HPE9)
Genes: SHH (sonic hedgehog)
-Incidence: 1/16,000 - 30,000 live births, 1:250 abortions/stillbirths
Distinguish between hydrocephalus types: obstructive, non obstructive, communicating and noncommunicating.
- obstruction of CSF pathway: tumors, aqueduct stenosis, chiari malformation, dandy walker malformation, inflammation
- if obstructive hydrocephalus occurs within brain=non-communicating
- communicating=obstruction in subarachnoid space or due to blockage of arachnoid granulation
- non-obstructive: due to excessive production of CSF by tumor of choroid plexus
Indicate which form of hydrocephalus are associated with each of the following:
- subarachnoid hemorrhage
- chronic meningitis
- choroid plexus papilloma
- edendymoma of 4th ventricle
- aqueduct stenosis
- dural sinus thrombosis
- arnold chiari malformation
- subarachnoid hemorrhage: Comm-Ob
- chronic meningitis: Comm-Ob
- choroid plexus papilloma: Non-ob
- edendymoma of 4th ventricle: NC-ob
- aqueduct stenosis: NC-Ob
- dural sinus thrombosis: Comm-ob
- arnold chiari malformation: NC-Ob
Define mental retardation and cerebral palsy and list the common causes of each.
- Mental retardation: IQ<70 with deficits in adaptive behavior and onset during developmental period
- causes: genetic abnormalities, environmental exposures, mostly unknown
- cerebral palsy: chronic disorders impairing control over movement that appear in first years of life. Faulty development of motor areas of brain
- possible causes: cerebral malformation, cerebral ischemia/hypoxia, cerebral hemorrhage, head injury, jaundice, infections
Of the different cell types in the CNS, which is most sensitive to global cerebral ischemia?
- Cortical Neurons
- also hippocampal pyramidal cells, esp CA1 and cerebellar Purkinje cells
Identify two common settings in which global hypoxia/ischemia may occur.
- cardiac arrest or shock
- when there is severe systemic hypotension