Week 2/3: pathology-response to CNS injury, vascular disease, congenital malformations Flashcards Preview

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Flashcards in Week 2/3: pathology-response to CNS injury, vascular disease, congenital malformations Deck (52)
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Define four ways that neurons respond to injury

1. ischemic cell change (red neuron)-8-24 hrs after insult, neuron shrinks, cytoplasms becomes eosinophilic. depletion of ATP, acidosis, buildup of intracell Ca2+, ROS
2. Wallerian degeneration- when axon is transected. degeneration of axon and myeline sheath distal to transection. breakup into fragments that are phagocytosed and removed
3. Central chromatolysis- swelling of neuronal cell body, dissolution of nissl granules, migration of nucleus to periphery (reversible)
4. 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.

1. Neurofibillary tangle- Alzheimers
2. Lewy body - Parkinsons
3. Pick body - Pick disease
4. Negri body - Rabies
5. Cowdry type A - Herpes, CMV (nucleus)
-rest in cytoplasm


List three mechanisms by which myelin is reduced in amount in the central nervous system.

1. multiple sclerosis- immune attack against myelin
2. progressive multifocal leukoencephalopathy (PML)- small plaques of demyelination when oligodendroglial cells die and myelin they support degenerates
3. 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.

1. Reactive microglial cell: become activated, may up regulate expression of MHC molecules and cytokines
2. Macrophage response: differentiate into macrophages, phagocytose tissue debris
3. microglial nodule: may respond to single damaged neuron by encircling neuron and phagocytosing it. Neurophagia, results in formation of nodule.
4. 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

1. fluid accumulates in extracellular space, predominately white matter
2. may result in increased intracranial pressure=mass effect
3. due to breakdown of BBB
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.

1. neural tube closure: around 24-28 days anterior rostral and posterior caudal neuropore closes
2. Outgrowth of the telencephalic vesicles: 5th week, vesicles arise, by 7-8 weeks, choroid plexus invaginated cavities
3. Proliferation: cells of CNS generated from germinal tissue lining ventricular system or cerebrum and cerebellum, and pericanal region of cord
4. cell migration: 7 weeks, neuroblasts move inside out
5. gyration: 24 weeks, development of gyro
6. myelination: begins at 20 weeks
7. 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
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:
1. subarachnoid hemorrhage
2. chronic meningitis
3. choroid plexus papilloma
4. edendymoma of 4th ventricle
5. aqueduct stenosis
6. dural sinus thrombosis
7. arnold chiari malformation

1. subarachnoid hemorrhage: Comm-Ob
2. chronic meningitis: Comm-Ob
3. choroid plexus papilloma: Non-ob
4. edendymoma of 4th ventricle: NC-ob
5. aqueduct stenosis: NC-Ob
6. dural sinus thrombosis: Comm-ob
7. 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


Identify the brain regions and specific neuronal subtypes most susceptible to global ischemia.

-watershed areas are first to become ischemic-the most distal portions of the territories of cerebral arteries. Between distributions of ACA and MCA and MCA and PCA.


Identify the vessels supplying the brain that are pst susceptible to the development of atherosclerosis.

-Larger vessels such as common carotid, especially at the bifurcation, also the origin of the MCA and the basilar artery


Define cerebral infarction.

-ischemia of the brain due to occlusion of the arteries supplying the brain


What are two common causes of vascular occlusion leading to infarction due to external compression by tumor or another type of mass?



Describe the differences between embolic and thrombotic strokes.

-thrombi form more slowly, emboli usually results in immediate occlusion of affected vessel
-artery to artery emboli more common than thrombotic
-emboli may be multiple infarcts
-emboli more likely to be hemorrhagic


List 3 sources of emboli to the brain

-heart: cardiac thrombi
-distal: emboli from distal sites
-from venous circulation if there are atrial septal defects
-from fat or bone marrow


Identify the vascular territory most commonly involved with infarction.

-most large infarcts in the brain caused by thromboembolic occlusion in the territory of the MCA


Describe the gross and microscopic appearance of recent and old infarcts

-recent: 12-24 hrs post infarct-pallor, edema, eosinophilic ischemic necrosis becomes small pyknotic nuclei, nothing much left
-older: hypercellular, influx of macrophages, gliosis an capillary prominence
-recent: discolored, hemorrhagic, darkened, softened
-old: congestion, swelling, progressive softening and discoloration culminating in cavitation


define hydrocephalus ex vacuo

-enlargement of a ventricle due to to loss of tissue and compensatory hydrocephalus


Define lacunar infarct and identify the predisposing factors for this event

-small infarcts due to small vessel arteriosclerosis with chronic hypertension and diabetes as major risk factors
-often affecting basal ganglia and pons

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