Pathology

Question 1

Central Chromatolysis

Answer 1

A reversible change that develops in the neuronal cell body after its axon has been transected; the RER disaggregates, the neuronal body balloons, and the nucleus is displaced toward the periphery of the cell

This is a reversible change that devel

Question 2

Neurofilaments

Answer 2

Intermediate fibers - 10nm in width; components of the neuronal cytoskeleton

Question 3

Neurotubules

Answer 3

Polymers of alpha and beta tubulin 20-26nm wide; components of the neuronal cytoskeleton

Question 4

Which proteins cross-link cytoskeletal proteins?

Answer 4

Tau protein
Microtubule associated protein (MAPs)

Link neurotubules to one another and anchor them to other cellular structures

Question 5

What do ischemic neurons look like on histology?

Answer 5

“Red dead” appearance - cells are shrunken, eosinophilic, and nuclei are pyknotic

Represents irreparable cell necrosis; visible on pathology 8-10 hours after cell death

Question 6

Wallerian Degeneration

Answer 6

Occurs following transection of an axon; the portion distal to the transection degenerates along with its myelin

The cell body undergoes central chromatolysis, by which it activates protein synthesis in order to regenerate the axon; Schwann cells distal to the transection proliferate and make new myelin

Question 7

How to astrocytes repair brain lesions?

Answer 7

Astrocytes respond to brain lesions by increasing the length and number of their intermediate filaments and processes to span destructive lesions; this repair process is less effective than collagenous repair elsewhere in the body and often leads to cyst formation

Question 8

Glial fibrillary acidic protein (GFAP)

Answer 8

Composes the intermediate fibers of astrocytes

Question 9

Rosenthal fibers

Answer 9

Inclusions of GFAP in astrocytic processes; seen in old brain scars and in some grade astrocytomas

Question 10

Alexander disease

Answer 10

Caused by mutations of GFAP in the astrocytic neurofilament; characterized by diffuse deposition of Rosenthal fibers resulting in white matter degeneration and neurological dysfunction

Question 11

Neuronophagia

Answer 11

The process by which microglial cells become activated to CNS damage via receptors that enable them to sense damaged tissue, and then encircle degenerating neurons to form clusters around small foci of necrotic brain tissue

Question 12

Microglial nodules

Answer 12

Small clusters of activated microglial cells around loci of necrotic brain tissue

Question 13

Sensory Ataxia

Answer 13

Axonal neuropathy involving the bipolar neurons of the DRG, causing degeneration of the central axon sof these neurons in the gracile and cuneate tracts of the spinal cord; associated with loss of position and vibration sense

Question 14

What is the role of microglia in CNS inflammation and repair?

Answer 14

Activated microglial cells produce trophic factors that are important for neuronal recovery and can recruit blood monocytes into the brain; they also make cytokines and neurotoxins (NO, glutamate) that mediate neuroinflammation and can kill neurons

Question 15

Endomysium

Answer 15

Extracellular space between individual muscle fibers; carries capillaries

Question 16

Perimysium

Answer 16

Fibrocollagenous sheath surrounding each muscular fascicle

Question 17

Dystroglycan

Answer 17

Transmembrane protein within the sarcolemma; binds dystrophin (bound to cytoskeletal actin) as well as merosin (bound to basement membrane laminin)

Question 18

Type 1 Muscle Fibers

Answer 18

Slow, red
Myofibers are rich in oxidative enzymes, mitochondria, myoglobin, and lipid; capable of protracted, slow action and clonic activity

Question 19

Type 2 muscle fibers

Answer 19

Fast, white

Rich in glycogen and glycolytic enzymes; capable of fast, powerful, tonic contraction

Question 20

Types of muscle disease - myopathy vs. denervation atrophy

Answer 20

Myopathy - primary disease of muscle characterized by proximal weakness, elevated CK, and characteristic EMG changes; includes muscular dystrophies and inflammatory myopathies

Denervation atrophy - characterized by distal weakness and atrophy with normal CK

Question 21

Epineurium

Answer 21

Connective tissue that surrounds the entire nerve trunk and gives off vascular connective tissue septa which separate fascicles from one another

Question 22

Perineurium

Answer 22

A sheath of cells that tie that axons of each fascicle together

Question 23

Endoneurium

Answer 23

Small amount of matrix present between individual axons running within a fascicle

Question 24

Myelin - CNS vs. PNS

Answer 24

CNS - Myelin is produced by oligodendroglial cells, each of which makes up multiple segments of myelin that can wrap around many axons

PNS - Myelin is produced by Schwann cells, each of which makes up only one segment of myelin

Question 25

Traumatic Neuroma

Answer 25

A proliferation of collagen, Schwann cell processes, and axonal sprouts caused by a failure of Wallerian degeneration

Question 26

Distal axonopathy

Answer 26

Caused by an inability of the neuronal body to keep up with the metabolic demands of the axon; degeneration of the axon and myelin develop first in the most distal parts of the axon, causing characteristic “stocking glove” sensory loss and weakness

Question 27

Classes of neuropathies (3) + examples

Answer 27

Wallerian degeneration - trauma, infarction of a peripheral nerve (diabetic neuropathy, vasculitis), neoplasm

Distal axonopathy - drugs, industrial poisons

Segmental demyelination - chronic inflammatory demyelinative neuropathy, Charcot-Marie-Tooth disease

Question 28

Segmental demyelination

Answer 28

Characterized by breakdown of myelin over a few segments, causing loss of saltatory conduction and decreased conduction velocity; axon remains intact and there are no changes to the neuronal body

Reversible, because Schwann cells make new myelin

Question 29

Hypertrophic neuropathy

Answer 29

Caused by repetitive segmental demyelination and regeneration of myelin in peripheral nerves; “onion bulb formations” form as concentric layers of Schwann cell processes and collagen around an axon, causing gross thickening of peripheral nerves

Hypertrophic neuropathy with onion bulb formation is characteristic of Charcot-Marie-Tooth disease

Question 30

Roles of astrocytes in the CNS

Answer 30

Metabolism/inactivation of neurotransmitters (GABA, glutamate)

Monitor ionic environment of the neuron

Structural support cells

Scar formation

Functional hyperemia

Question 31

How does axon regeneration occur following Wallerian degeneration?

Answer 31

Cell body undergoes central chromatolysis, producing new proteins which flow down the axon

Bands of Bugner form and ensheath proliferating Schwann cells

Growth cone elongates along the Schwann cell lined tube

Question 32

Bands of Bugner

Answer 32

Basal lamina-lined endoneurial tubes that ensheath the proliferating Schwann cells following Wallerian degeneration of an axon; the new axonal growth tube elongates along this Schwann cell-lined tube

Question 33

What is the order in which neurological function returns following axonal regeneration?

Answer 33

First: Autonomic (sweating)
Second: Sensation
Third: Motor

Question 34

How does EMG work? How can it help differentiate between myopathy and denervation atrophy?

Answer 34

Insert a needle into muscle and measure the sum of all of the electrical activity of the motor units that depolarize with voluntary contraction; this is the motor unit action potential (MUAP)

In myopathy, the MUAP is small; in peripheral nerve disease, the MUAP is small at first but grows as intact peripheral nerves sprout and re-connect to muscle fibers; these peripheral nerves “convert” the muscle via type grouping resulting in a more segregated MUAP pattern