LEC-3 Neuropathology Flashcards
The principal functional unit of the CNS is…?
Neuron
Describe acute neuronal injury.
- “Red neurons”
- Acute CNS hypoxia/ischemia cause cell death by either necrosis or apoptosis. “Red neurons” are evident with H&E 12-24 hrs after irreversible hypoxic insult.
- The morphologic features consist of cell body shrinkage, pyknosis of nucleus, disappearance of nucleolus, loss of Nissl, intense eosinophilia of cytoplasm.
Describe subacute and chronic neuronal injury.
- “Degeneration” - Neuronal death occurs due to a progressive disease process (e.g. ALS).
- Characteristic histologic feature: cell loss (often of functionally related groups of neurons) and reactive gliosis.
- Early on, cell loss is not evident, but associated reactive glial changes are the best indicator of pathology.
- Cell loss mainly due to apoptosis.
In the context of subacute and chronic neuronal injury what is neuronal trans-synaptic degeneration?
Seen when there is a destructive process that interrupts the majority of the afferent input to a group of neurons.
What is the axonal reaction?
The reaction within the cell body that attends regeneration of the axon; best seen in anterior horn cells of the spinal cord when motor axons are cut or seriously damaged.
What are the features of the axonal reaction?
Increased protein synthesis associated with axonal sprouting; enlargement and rounding up of cell body, peripheral displacement of nucleus, enlargement of nucleolus, dispersion of Nissl from center to periphery of cell (central chromatolysis).
Neuronal inclusions may occur as a manifestation of aging, when there are intracytoplasmic accumulations of complex lipids (___________).
Lipofuscin
Abnormal cytoplasmic deposition of complex lipids and other substances also occurs in ___________________________ in which substrates or intermediates accumulate.
genetically determined disorders of metabolism
Viral infection can lead to abnormal intranuclear inclusions, as seen in __________.
Herpetic infection
Viral infection can lead to abnormal cytoplasmic inclusions, as seen in _______.
Rabies. (Negri body)
Viral infection can lead to abnormal nuclear AND cytoplasmic inclusions, as seen in _______.
Cytomegalovirus (CMV) infection
Some degenerative diseases of the CNS are associated with neuronal intracytoplasmic inclusions, such as neurofibrillary tangles of _______ and Lewy bodies of _______.
- Alzheimer disease
- Parkinson disease
Other degenerative diseases of the CNS are associated with abnormal vacuolization of the perikaryon and neuronal cell processes in the neuropil (seen in _______).
Creutzfeldt-Jakob disease
Why are these disorders referred to as proteinopathies?
- Because the aggregates are highly resistant to degradation, contain proteins with altered conformation, and may result from mutations that affect protein folding, ubiquitination, and intracellular trafficking.
- In many of these diseases, the visibile aggregates are not the basis of cellular injuries; rather, small multimers of the proteins (oligomers) are the critical mediatiors of the damage.
What cell type derives its name from its star-shaped appearance?
Astrocyte
Astrocytes have multipolar, branching cytoplasmic processes that emanate from the cell body and contain ___, a cell type-specific intermediate filament.
Glial fibrillary acidic protein (GFAP)
What is the function of astrocytes?
Astrocytes act as metabolic buffers and detoxifiers within the brain.
Besides the metabolic buffer and detoxifier function of astrocytes, what other function do astrocytes serve (through their foot processes)?
The foot processes surround capillaries or extend into the subpial and sub ependymal zones, where they contribute to BARRIER functions controlling the flow of macromolecules between blood, CSF, and brain.
What is the most important indicator of CNS injury?
Gliosis (or astrogliosis) is the most important histopathologic indicator of CNS injury, regardless of etiology, and is characterized by both hypertrophy and hyperplasia.
Describe what happens to astrocytes in the astrogliosis reaction.
- The nuclei of astrocytes, which are typically round to oval (10 um wide) with evenly dispersed, pale chromatin become enlarged, vesicular, and develop prominent nuclei.
- The previously scant cytoplasm expands to a bright pink, irregular swath around an eccentric nucleus, from which emerge numerous stout, ramifying processes.
Astrocytes that have undergone the astrogliosis reaction are called…?
Gemistocytic astrocytes
When directly injured, astrocytes can react with…?
Cytoplasmic swelling
What direct astrocyte injuries can lead to cytoplasmic swelling?
Acute insults that cause the cell’s ATP-dependent ion channels to fail, as in hypoxia, hypoglycemia, and toxic injuries.
Describe the Alzheimer type II astrocyte.
A gray-matter cell with a large (two to three times normal) nucleus, pale-staining central chromatin, an intranuclear glycogen droplet, and a prominent nuclear membrane and nucleolus.
Why is the name Alzheimer type II astrocyte a misnomer?
It is mainly not seen in Alzheimer disease but in individuals with long-standing hyperammonemia due to chronic liver disease, Wilson disease, or hereditary metabolic disorders of the urea cycle.
Astrocytes are not spared from processes that cause the formation of cytoplasmic inclusion bodies. What are Rosenthal fibers?
Thick, elongated, brightly eosinophilic, somewhat irregular structures that occur within astrocyte processes, and contain two heat-shock proteins (alphabeta-crystallin and hsp27) as well as ubiquitin.
In what conditions are Rosenthal fibers observed?
Rosenthal fibers are typically found in regions of long-standing gliosis; they are also characteristic of one type of glial tumor, pilocytic astrocytoma.
In Alexander disease, a leukodystrophy associated with a mutation in the gene encoding GFAP, abundant Rosenthal fibers are found in periventricular, perivascular, and subpial locations. More commonly seen are…?
Corpora amylacea (or polyglucosan bodies)
