Pathology: Reactions of the nervous system to injury

Question 1

What are the 3 layers of the meninges?

Answer 1

Dura Mater
Arachnoid
Pia Mater

Question 2

In the brain, which of the white matter or grey matter is central and peripheral?

Answer 2

White matter = Central

Grey matter = Peripheral

Question 3

What cells predominate in the white matter of the brain?

Answer 3

• well-myelinated axons
• oligodendrocytes (support and insulation)
• astrocytes (maintain brain homeostasis and metabolism)

Question 4

What cells predominate in the grey matter of the brain?

Answer 4

• cell bodies of neurons
• dendrites
• glial cell processes (maintain homeostasis, support + protection)

to a lesser extent: oligodendrocytes, astrocytes and microglia

Question 5

What structures are in the dorsal funiculus of the spinal cord?

Answer 5

ascending sensory axons

Question 6

What structures are in the ventral funiculus of the spinal cord?

Answer 6

descending motor axons

Question 7

What structures are in the lateral funiculus of the spinal cord?

Answer 7

mix of both ascending and descending axons

Question 8

What are the major gross lesion patterns of the nervous system with examples?

Answer 8

• Deviation from normal anatomy: malformation, brain swelling, atrophy
• Space-occupying masses: tumour, abscess or granuloma
• Haemorrhage: Contusion/ Trauma, Circulation problem, Infection, Deficiency or Toxin
• Malacia (abnormal softening of tissue): Infarction, Deficiency or Toxin
• Selective white matter changes: dysmyelination, leukodystrophy, demyelination

Question 9

List the following cells in order of most susceptible to hypoxic/ anoxic injury to least

blood vessels, oligodendrocytes, neurons, astrocytes, microglia

Answer 9

neurons > oligodendrocytes > astrocytes > microglia > blood vessels

Question 10

Why are neurons the MOST susceptible to hypoxia/ anoxic injury?

Answer 10

Neurons have small energy stores which are entirely dependent on oxygen and glucose

Question 11

Can neurons regenerate in the CNS?

Answer 11

Neurons cannot regenerate in the CNS, nerve fibres may have small regeneration capability

Question 12

In the rest of the body the healing process is dependent on fibroblasts creating a fibrous mesh (scar), how does the CNS heal?

Answer 12

The CNS only has a few number of fibroblasts, which are located in the meninges. Healing of the CNS is mainly through proliferation of astrocyte processes, which have a very poor capsule and can break down easily

Question 13

What makes up the Blood Brain Barrier?

Answer 13

The BBB is formed by tight junctions of endothelial cells, aided by basement membrane and the end feet of astrocytes

Question 14

Which cells of the CNS are of Ectodermal origin?

Answer 14

Neurons
Astrocytes
Oligodendrocytes
Ependymal Cells

note: all of these cells are of ectedermal origin and are sensitive to hypoxia

Question 15

Which cells of the CNS are of Mesodermal origin?

Answer 15

Microglia (resident macrophages)
Vascular Endothelium

note: all of these cells are of mesodermal origin and are more resistant to hypoxia

Question 16

What is Excitotoxicity Injury?

Answer 16

Excitotoxicity Injury is when an excessive and sustained release of an excitatory neurotransmitter (commonly Glutamate), paired with the decreased removal of Glutamate by astrocytes due to ischemia, hypoxia or hypoglycemia causes Glutamate to bind to the neuronal membrane, causing an influx of Calcium into the neuron and the activation of proteolytic enzymes, and creation of Reactive Oxygen Species which leads to oxidative damage

Question 17

Describe ‘Chromatolysis’

Answer 17

Chromatolysis is the swelling of the cell body and the dissolution of Nissl granules with margination of the neuron nucleus

• It is a Degenerative but reversible change
• Non-specific causes: injury to axons, overstimulation/ deficiencies
• Is seen in Lower Motor Neuron Diseases: dysautonomia (grass sickness in horses) and copper deficiency in sheep

Question 18

Describe ‘Ischaemic Necrosis’/ ‘Acidophilia’

Answer 18

Ischaemic Necrosis is when cells are shrunken, angular and acidophilic due to ischemia, hypoxia, hypoglycemia, thiamine deficiency or seizures

• It is an acute degenerative and permanent change
• This particular change can only be detected on histopathology 6-8 hours following the triggering injury (important for PM)

Question 19

Describe ‘Vacuolar Degeneration’

Answer 19

Vacuolar Degeneration is the formation of nonlipid vacuoles in cytoplasm, most frequently due to edema or Storage diseases

• Some vacuoles can be found incidentally in certain brain regions
• Large neuronal vacuoles in high numbers within the Medulla and Midbrain are pathognomonic for Scrapie in Sheep and Goats, and BSE in Cattle

Question 20

What is suggestive of Inclusion bodies within the neurons of the CNS?

Answer 20

Viral Infection:

• Rabies – Negri bodies (eosinophilic cytoplasmic)
• Herpes virus (intranuclear inclusions)
• Canine distemper virus (intranuclear, intracytoplasmic)
• Borna disease (Joest-Degen inclusion bodies)

Non-Viral Inclusions:

• Pigments associated with aging (incidental finding)
• Storage Diseases

Question 21

Describe ‘Neuronophagia’

Answer 21

Neuronophagia is Neuronal necrosis with neurophagia, suggestive of many viral infections
- the death of a neuron provokes the gathering of phagocytes around the cell body and the removal of the debris

Question 22

The Myelin Sheath is made by what cells in the CNS and in the PNS?

Answer 22

CNS: Oligodendrocytes (regenerates poorly)
PNS: Schwann Cells (better regeneration)

Question 23

What is Anterograde Axoplasmic Flow?

Answer 23

A directional flow from cell body to synapse within a neuron

• Slow (1mm/day): for growth and maintenance
• Fast (1000mm/day) for synaptic function

note: same direction used by the Herpes Simplex Virus

Question 24

What is Retrodrage Axoplasmic Flow?

Answer 24

A directional flow from axon termini to cell body within a neuron
- directional flow used by returning synaptic vesicles and other materials

note: used by infectious agents (listeria + rabies)
used by toxins (tetanus)

Question 25

Describe Demyelination, and the difference between primary vs secondary

Answer 25

Demyelination is when the myelin sheath has been removed from the axon

Primary Demyelination: axon remains intact (e.g. damage to oligodendrocytes from a viral infection like distemper or ischaemia)

Secondary Demyelination: follows axon damage (e.g. proximal or distal axonopathy, ischemia or trauma)

Question 26

Where in the Nervous system (CNS or PNS) is Remyelination more likely and has a greater chance?

Answer 26

PNS

Question 27

Define a ‘Dysmyelinating Disease’

Answer 27

A disease where there is a qualitative defect in the myelin produced

Question 28

Define ‘Wallerian Degeneration’

Answer 28

Wallerian Degeneration is a series of degenerative and reparative events which can be seen histologically, distal to the axon injury
Common causes include: trauma, compression, severed axon, toxins and lead poisoning

Question 29

What are the 4 types of Neuroglial cells?

Answer 29

Astrocytes
Oligodendrocytes
Microglia
Ependymal Cells

note: they are all supporting cells within the brain

Question 30

What is the function of Astrocytes?

Answer 30

Maintain intercellular homeostasis of ions, glutamine, and neurotransmitters, transport nutrients
Detoxification of e.g. oxidants and ammonia
Insulate and isolate white matter tracts
Involved in inflammatory and immune response, expressing cytokines, growth factors and adhesion molecules, antigen presentation
Form the glia limitans with perivascular foot processes an integral part of the blood brain barrier

Question 31

How do Astrocytes react to injury?

Answer 31

• They can swell (edema): e.g. after ischemia
• Proliferate
• Limited ability to wall off damaged areas/ scarring

note: a reactive astrocyte is called a gemistocyte

Question 32

How do Oligodendrocytes react to injury?

Answer 32

• Dont exhibit a wide range of reactions, generally just undergo a rapid lysis when injured

Question 33

What are Ependymal Cells?

Answer 33

Cuboidal cells with cilia that line the central canal, ventricles and the choroid plexus
- They function in the formation of the cerebrospinal fluid and the bidirectional flow and circulation of CSF

Question 34

How do Ependymal cells react to injury?

Answer 34

• Undergo necrosis in viral, inflammatory or traumatic injuries
• Undergo atrophy during hydrocephalus
• Unable to regenerate

Question 35

Where can the choroid plexus be found in the brain?

Answer 35

Lateral ventricle
Third ventricle
Fourth ventricle