Cellular Pathology Flashcards
The principal functional unit of the central nervous system (CNS) is the ___________.
neuron
Of all the cells
in the body, neurons have a unique ability to _______, _________ and __________
receive, store, and transmit information.
Neurons
of different types and in different locations have __________properties, including functional roles,
distribution of their connections, neurotransmitters used, metabolic requirements, and levels of
electrical activity at a given moment.
** distinct **
A set of neurons, not necessarily clustered together in a
region of the brain, may thus show ______________ vulnerability to various insults because it shares
one or more of these properties.
selective
Since most mature neurons are incapable of cell division,
destruction of even a small number of neurons essential for a specific function may leave the
individual with a neurologic deficit.
Stem cell populations in the brain may represent a potential
mechanism for repair after injury. [1] The CNS is affected by a number of unique neurological
disorders, and also responds to common insults (e.g., ischemia, infection) in a manner that is
distinct from other tissues.
Reactions of Neurons to Injury.
Neurons vary considerably in structure and size throughout the nervous system and within a
given brain region.
Structural specializations associated with neuronal function include those
related to synaptic transmission as well as axonal and dendritic differentiation.
Neurons share
pathways for response to injury, including apoptotic mechanisms, with cells in other tissues.
During development,____________ has an important role in defining neuronal number; it
comes into play in a variety of disease states as well, including certain neurodegenerative
diseases.
neuronal apoptosis
The principal patterns of neuronal injury are the following
- Acute neuronal injury (“red neurons”)
- Subacute and chronic neuronal injury (“degeneration”)
- Axonal reaction
- Neuronal inclusions
- neuronal intracytoplasmic
inclusions,
________________ refers to a spectrum of changes that accompany
acute CNS hypoxia/ischemia or other acute insults and reflect cell death, either necrosis
or apoptosis(see Fig. 28-13B ).
Acute neuronal injury (“red neurons”)
“Red neurons” are evident with_____________ at about 12 to 24 hours after an irreversible hypoxic/ischemic insult.
hematoxylin and eosin
(H&E) preparations
The morphologic features of acute neuronal damage consist of __________________________
- shrinkage of the cell body,
- pyknosis of the nucleus,
- disappearance of the nucleolus,
- and loss of Nissl substance,
- with intense eosinophilia of the cytoplasm
______________ refers to neuronal death
occurring as a result of a progressive disease process of some duration, as is seen in
certain slowly evolving neurologic diseases such as amyotrophic lateral sclerosis (ALS).
Subacute and chronic neuronal injury (“degeneration”)
What is the histologic characteristic of subacute and chornic neuronal injury?
The characteristic histologic feature is
- cell loss, often selectively involving functionally related groups of neurons, and reactive gliosis.
In the early stage of neuronal damage in subacute and cic,hat i whrons the best indicator of pathologic process?
When the process is at an early stage, the cell loss is difficult to detect; the associated reactive glial changes are often the best
indicator of the pathologic process.
For many of these diseases, there is evidence that
cell loss is because of ___________
apoptosis.
Neuronal trans-synaptic degeneration is seen when
there is a destructive process that interrupts the majority of the _________________ input to a group
of neurons.
afferent input
_______________-refers to the reaction within the cell body that attends regeneration of
the axon;
Axonal reaction
Where is axonal reaction best seen?
it is best seen in anterior horn cells of the spinal cord when motor axons are
cut or seriously damaged.
In the axonal reaction there is increased protein synthesis associated with axonal
sprouting. This is reflected in__________________
- enlargement and rounding up of the cell body,
- peripheral displacement of the nucleus,
- enlargement of the nucleolus,
- and dispersion of Nissl substance from the center to the periphery of the cell (central chromatolysis).
Neuronal damage may be associated with a wide range of subcellular alterations in the
neuronal organelles and cytoskeleton.
Neuronal inclusions may occur as a** manifestation of aging,** when there are intracytoplasmic accumulations of__________, __________ and ______
complex lipids
(lipofuscin), proteins, or carbohydrates.
Abnormal cytoplasmic deposition of complex
lipids and other substances also occurs in genetically determined disorders of
metabolism in which substrates or intermediates accumulate ( Chapter 5 ).
In viral infection it
can lead to abnormal intranuclear inclusions, as seen in______________
herpetic infection
rabies
CMV
What inclusion is seen in herpetic and what is it called?
intranuclear: *Cowdry
body*
” Yatigidig STD”
What type of inclusion is seen in rabies and what is called?
cytoplasmic inclusion: Negri body
What type of inclusion is seen in CMV?
both nucleus and cytoplasm as in cytomegalovirus (CMV) infection.
What degenerative diseases of the CNS are associated with neuronal intracytoplasmic
inclusions, such as ___________, ______________ and _____________.
These aggregates are highly
resistant to degradation, contain proteins with altered conformation, and may result from
mutations that affect protein folding, ubiquitination, and intracellular trafficking (see
discussion of protein folding in Chapter 1 ).
The disorders may be referred to as
proteinopathies.
There is increasing evidence in many of these diseases that the visible
aggregates are not the basis of cellular injuries; rather, small multimers of the proteins
(oligomers) are the critical mediators of the damage.
- neurofibrillary tangles of Alzheimer disease
- and Lewy bodies of Parkinson disease;
- others cause abnormal vacuolization of the perikaryon and neuronal cell processes in the neuropil (Creutzfeldt-Jakob disease).
What is the intracytoplasmic inclusion of Parkinson disease?
Lewy bodies
what are the intacytoplasmic inclusion in Creutzfeldt-Jakob disease?
others cause abnormal vacuolization of the perikaryon and neuronal
cell processes in the neuropil
The astrocyte derives its name from its_________________.
star-shaped appearance
These cells have multipolar,
branching cytoplasmic processes that emanate from the cell body and contain the glial fibrillary
acidic protein (GFAP), a cell type–specific intermediate filament ( Fig. 28-1 ).
Astrocytes
What is the function of Astrocytes?
- act as metabolic buffers and detoxifiers within the brain.
- Additionally, through the foot processes, which surround capillaries or extend to the subpial and subependymal zones, they contribute to **barrier functionscontrolling the flow of macromolecules between the blood, the cerebrospinal fluid (CSF), and the brain. **
________________ is the most important histopathologic indicator of CNS injury, regardless of etiology, and is **characterized by both hypertrophy and
hyperplasia. **
Gliosis (or astrogliosis)
What is the appearance of Gliosis?
In this reaction, the nuclei of astrocytes, which are typically round to oval (10 μm
wide) with evenly dispersed, pale chromatin, enlarge, _become vesicular, and develop prominent
nucleoli._The previously scant cytoplasm _expands to a bright pink, somewhat irregular swath
around an eccentric nucleus_, from which emerge numerous stout, ramifying processes; these
cells are called gemistocytic astrocytes
What is gemistocytic astrocytes
The previously scant cytoplasm expands to a bright pink, somewhat irregular swath
around an eccentric nucleus, from which emerge numerous stout, ramifying processes;
When directly injured, astrocytes can react with_____________. This is seen in acute
insultsthat cause thecell’s ATP-dependent ion channels to fail, as occurs in hypoxia,
hypoglycemia, and toxic injuries.
cytoplasmic swelling
The Alzheimer type II astrocyte is 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.
The Alzheimer type II astrocyte is its name is a misnomer,
as it is mainly seen not in Alzheimer disease but in what?
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
. Rosenthal fibers are thick, elongated, brightly eosinophilic, somewhat irregular
structures that occur within astrocytic processes, and contain two heat-shock proteins__________, __________ and ________.
- αBcrystallin and hsp27)
- as well as ubiquitin
Rosenthal fibers are typically found in regions of______________
- longstanding gliosis;
- they are also characteristic of one type of glial tumor, pilocytic astrocytoma.
In Alexander disease, a leukodystrophy associated with a mutations in the gene encoding__________,
abundant Rosenthal fibers are found in periventricular, perivascular, and subpial locations.
GFAP
What are Rosenthal fibers?
thick, elongated, brightly eosinophilic, somewhat irregular
structures that occur within astrocytic processes, and contain two heat-shock proteins (αBcrystallin
and hsp27) as well as ubiquitin
What are commonly seen in astrocyte cytoplasmic inclusion?
More commonly seen are corpora amylacea, or polyglucosan bodies
What are corpora amylacea, or polyglucosan bodies
These are round, faintly
basophilic, periodic acid–Schiff (PAS)–positive, concentricallylamellated structures of 5 to 50
μm in diameter that are located wherever there are astrocytic end processes, especially in the
subpial and perivascular zones.
What are the contents of copora amylacea?
- primarily of glycosaminoglycan polymers,
- they also contain **heat-shock proteins and ubiquitin. **
Corpora amylacea occur in______________
increasing numbers with advancing age and are thought to represent a degenerative change in the astrocyte.
The _____________ that are seen in the cytoplasm of neurons (as well as hepatocytes, myocytes,
and other cells)inmyoclonic epilepsy(Lafora body myoclonus with epilepsy) have a similar
structure and biochemical composition.
Lafora bodies
Reactions of Other Glial Cells to Injury.
In contrast to astrocytes, oligodendrocytes and ependyma_________________
do not participate in the active
response to CNS injury and show a more limited repertoire of reactions.
Oligodendroglial
cytoplasmic processes _____________
** wrap around exons and form myelin. **
Each oligodendrocyte function to ______________________
myelinates
numerous internodes on multiple axons.
Injury or apoptosis of oligodendroglial cells is a feature
of_______________ and _____________.
** acquired demyelinating disorders** and** leukodystrophies. **
Oligodendroglial nuclei may harbor
viral inclusions in progressive multifocal leukoencephalopathy. Glial cytoplasmic inclusions,
primarily composed of______________are found in oligodendrocytes in multiple system atrophy
(MSA).
** α-synuclein, **
_____________ the ciliated columnar epithelial cells lining the ventricles, do not have specific
patterns of reaction.
Ependymal cells,
When there is inflammation or marked dilation of the ventricular system,
disruption of the ependymal lining is paired with__________________
proliferation of subependymal astrocytes to
produce small irregularities on the ventricular surfaces (ependymal granulations).
Certain
infectious agents, particularly ____________, may produce extensive ependymal injury, with viral
inclusions in ependymal cells.
CMV
Microglia are derived from what germ layer?
mesoderm-derived
What is the primary function of microglia?
cells whose primary function is to serve as a fixed macrophage
system in the CNS.
Microglia share many surface markers with peripheral monocytes/macrophages
(such as _______ and ____.
CR3 and CD68)
Microglia response to injury by?
(1) proliferating;
(2) developing elongated
nuclei (rod cells), as in neurosyphilis;
(3) forming aggregates about small foci of tissue necrosis
(microglial nodules); or
(4) congregating around cell bodies of dying neurons (neuronophagia).
In addition to resident microglia,_____________ are the principal phagocytic cells
present in inflammatory foci.
blood-derived macrophages
