Introduction to Neuropathology Flashcards

1
Q

What are the normal functions of neurons?

A

Neurons are the largest, most metabolically active cells in the brain and entire body. They are non-mitotically active, non-replicative cells. Stem cells in the brain do not serve to regenerate lost neurons, thus when they are lost they are gone.

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2
Q

What are four ways that a neuron responds to damage?

A

1) Total necrosis, loss and removal of neuron. 2) Chromatolysis, damage to axon causing death of neuron or regrowth of axon. 3) Acquisition of viral particles within nucleus or cytoplasm (viral infection) 4) Acquisition of abnormal material within cytoplasm (neurodegenerative processes or storage disorder.

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3
Q

What occurs when an axon is transected?

A

Necrosis of the axon distal to the site of injury, known as Wallerian degeneration. Swollen axonal processes visible with silver stain at site of injury. Chromatolysis process initiates in an attempt to regrow the axon.

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4
Q

What is the Nissl substance and how does it react to axotomy?

A

The Nissl substance is tightly packed Rough Endoplasmic Reticulum. After axotomy, the RER disaggregates and the neuronal body balloons. The nucleus is displaced towards the periphery. This is central chromatolysis, a reversible change that develops during repair of the neuron.

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5
Q

What are the basic components of the neuronal cytoskeleton?

A

Neuronal perikaryon and processes contain 10nm intermediate filaments (neurofilaments, distinct from other IF) and 20-26nm tubules (neurotubules, alpha and beta tubulin). Tau protein and microtubule associated proteins (MAPs) crosslink neurotubules and connect them to cell structures.

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6
Q

What alterations of the neuronal cytoskeleton components occur and what diseases are they associated with?

A

Phosphorylation of neurofilaments influences the structural stability of axons and the speed of transport. Abnormal filaments appear in Alzheimer’s disease, forming neurofibrillary tangles. Also, Pick bodies in Pick body disease, and Lewy bodies in idiopathic Parkinson’s disease.

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7
Q

Why are silver stains used and what type of silver is most common?

A

Silver stains are best for displaying axons and dendrites because they bind to cytoskeleton components. The most common stain is Beilschowsky stain, an ammoniacal silver that is reduced to black metallic silver. It shows these structures as well as Alzheimer’s lesions.

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8
Q

What are the normal functions of astrocytes?

A

Absorb NT, structural support covering the outer surface of the brain and blood vessels, become radial glia, major scar former in place of fibroblasts (but only by expanding its IF and processes, does not produce collagen, leads to cyst formation), maintain brain metabolic env, metabolize Glu and GABA, monitor ionic conc (esp K+), maintain BBB, and form abnormal appearances in many metabolic conditions.

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9
Q

What is GFAP and why is it important?

A

Glial Fibrillary Acidic Protein is a component of intermediate filaments in the astrocyte cytoplasm. GFAP was the first immunization developed, and antibodies against this protein are used to show reactive and neoplastic astrocytes.

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10
Q

What causes Alexander disease?

A

Mutations in GFAP cause diffuse deposition of Rosenthal fibers (eosinophilic fibers often seen in brain scars and astrocytomas) and leads to white matter degeneration and neurological dysfunction.

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11
Q

What are the normal functions of oligodendrocytes (oligodendroglia)?

A

Source of myelin in the white matter CNS, ensheathe unmyelinated axons, cluster around neurons in deeper layers.

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12
Q

What damages oligodendrocytes and what diseases result from their loss?

A

Very sensitive to irradiation, some viruses, or storage disorders. Lost from demyelinated plaques in MS. Viral infection of oligodendroglia may lead to subacute sclerosing panencephalitis or progressive multifocal leukoencephalopathy. Lysosomal enzyme deficiencies include metachromatic leukodystrophy.

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13
Q

What are the normal functions of ependymal cells?

A

Produce CSF, relatively inert, cilia may contribute to CSF movement, little proliferation or regeneration in response to pathological conditions. Close proximity to astrocytes. Usually irreparably damaged and lost in hydrocephalus, bacterial ventriculitis, or various viral infections.

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14
Q

What are the normal functions of microglia?

A

Microglia are the intrinsic, first line phagocytic system within the brain. Monocytes can also enter the brain, and distinguishing microglia and monocytes cannot be done morphologically. They are the target of viral infection in AIDS, express MHC class II, function as APCs, and help rebuild vasculature (via endothelial cell migration).

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15
Q

What is the response of microglia to brain injury?

A

The encircle degenerating neurons (neuronophagia) and form clusters around small foci of necrotic brain tissue (microglial nodules). Activated microglia produce trophic factors and also cytokines and neurotoxins, thus may help or hinder neuronal recovery. Persistent activation may contribute to alzheimer’s, parkinson’s, and HIV encephalopathy.

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16
Q

What are the key intracellular, transmembrane, and extracellular proteins associated with the sarcolemma?

A

Dystrophin, Dystrophin Associated Complex (2 dystroglycan, 5 sarcoglycan), and Merosin. Dystrophin is intracellular and is connected to cytoskeleton actin by its C-terminus. The N-terminus connects to B-dystroglycan, one of the two dystroglycans in the seven-member, transmembrane Dystrophin Associated Complex. Dystroglycan is bound to Merosin, the alpha2 chain of the basement membrane protein laminin 2.

17
Q

What diseases are defects in the trans-sarcolemma protein chain associated with?

A

Defects in this chain cause progressive muscle damage and muscular dystrophy. Dystrophin defects - Duchenne’s and Becker’s syndrome. Sarcoglycan defects - limb girdle dystrophies. Merosin defects - some congenital muscular dystrophies.

18
Q

What characterizes Type 1 muscle fibers?

A

Type 1, (slow-red) muscle fibers are rich in oxidative enzymes, mitochondria, myoglobin, and lipid. Capable of protracted slow action and clonic activity.

19
Q

What characterizes Type 2 muscle fibers?

A

Type 2, (fast-white) muscle fibers are rich in glycogen and glycolytic enzymes. Capable of fast, powerful, tonic contractions.

20
Q

How are Type 1 and 2 muscle fibers distributed in normal muscle?

A

Type 1 and 2 fibers are intermixed in all muscles. Type is determined by innervation. All muscle fibers innervated by the same neuron are of the same type.

21
Q

What muscle changes occur with denervation?

A

Denervation atrophy results in distal weakness and muscle atrophy. Serum CK is normal (no muscle damage). Characteristic EMG changes.

22
Q

What muscle changes occur with myopathies?

A

Myopathies are diseases that damage muscle fibers directly. Characterized by muscle weakness, elevated CK, and characteristic EMG changes.

23
Q

What is the process of Wallerian degeneration?

A

After the axon is transected, the distal region degenerates, the soma undergoes central chromatolysis, and schwann cells distal to the transection proliferate and begin remyelinating the new neuron.

24
Q

What is the process of segmental demyelination?

A

Segmental demyelination is the breakdown and loss of myelin over a few segments. The axon remains intact and no changes are made in the neuronal body. Loss of saltatory conduction results in a decrease of conduction velocity and conduction block. Deficits develop rapidly but are also reversible due to schwann cell regeneration.