Nervous system pathology overview Flashcards
What are the 4 main types of tissue of the CNS?
Neurones
Glial cells
Migroglia
Supporting cells
What are the 4 glial cells?
- Astrocytes
- Oligodendrocytes
- Schwann cells (not CNS)
- Ependymal cells
What are the main supporting structures of the CNS?
- Connective tissue
- Meninges
- Blood vessels
What are the functions of astrocytes?
Structural support
Repair (In CNS injury)
Regulation of the BBB
What are the functions of oligodendrocytes?
Myelination of neurones within the CNS
Structural support of the CNS
Delivery of nutrients to neurone axons
What are the functions of the ependymal cells?
Line the brain ventricles and central canal
Produce and circulate CSF
What are microglia?
Macrophages of the CNS
What are the 2 main types of microglia?
- M1 - Pro-inflammatory
- M2 - Clean up of debris and pathogens
What main structures are found within the cell body of a neurone?
Nucleus
Nucleolus
Nissl substance
What is the Nissl substance?
A specialised form of RER found in neurones to produce the high amount of protein required for the neurone to function
What are some causes of acute irreversible neuronal injury?
Hypoxia
Ischaemia
What will histology show in acute irreversible neuronal injury?
- Red cytoplasm neurones
- Shrunken, angulated nuclei
- Loss of the nucleoli
Describe the histology of axonal damage
Increase protein synthesis so cell body swells, nucleus grows, Nissl substance breaks down (Chromatolysis) and the distal axon degenerated (Wallerian degeneration)
How does axonal damage differ between the CNS and PNS?
In the CNS, the myelin sheath degenerates due to oxidative stress on the oligodendrocytes
In the PNS, the myelin sheath is preserved, forming a neural tube to afford some generation
Describe the histopathology of neuronal atrophy
Shrunken and reduced number of neurones
Reactive gliosis/glial scar
Lipofuscin pigment
What is lipofuscin pigment?
This is the “wear and tear” pigment, acting as the cellular equivalent to rust
It is a granular yellow brown pigment occurring in proteins, lipids and highly oxidised metals in response to atrophy
What is reactive gliosis?
An early response to CNS injury in which astrocytes proliferate to contain and repair the damage
Describe the histopathology of reactive gliosis
- Hyperplasia and hypertrophy
- Nuclear enlargement and prominent nucleolus
- Cytoplasmic expansion
What is late gliosis?
This is the formation of a glial scar following CNS injury
What are the positives of glial scar formation?
It can shield the healthy tissue and isolate the injured area, preventing the spread of inflammation
What are the negatives of glial scar formation?
It can be a barrier to healing, blocking axonal regeneration and preventing injured neurones from reconnecting
What are the histological features of a glial scar?
- Small, dark nuclei
- Dense net of processes (glial fibrils)
What is excitotoxicity?
This is a major mechanism involved in acute neuronal injury
Glutamate acts as a fuel for uncontrolled Ca2+ entry, activating proteases and disrupting mitochondrial function
This causes oxidative stress, damaging cellular components
What is cytotoxic oedema?
Oedema occurring when dying cells begin to take up water as ions move in (There is no swelling as there is no increase in brain volume)
What diseases can cause cytotoxic oedema?
Hypothermia
Reye’s syndrome
Intoxication
What is vasogenic oedema?
A condition in which partial oedema of the BBB causes flooding a proteins and therefore water into the brain
What are some causes of demyelination?
- Autoimmune attacks (MS)
- Genetic factors
- Acquired (Trauma, infection, toxins)
What are some examples of primary demyelinating disorders?
Multiple sclerosis
Post-infections autoimmune disorders
What are some examples of post-infectious autoimmune disorder that can cause demyelination?
Acute disseminated encephalomyelitis
Acute haemorrhagic leukoencephalitis
What is acute disseminated encephalomyelitis?
A self-limiting post-infectious autoimmune disorder resulting in a mild “Power cut” like period, commonly affecting children
What is acute haemorrhagic leukoencephalitis?
A post-infectious autoimmune disorder, which can be rapidly fatal “Lightning strike”, commonly affecting adults
What are some types of secondary demyelinating disorders?
Viral
Metabolic
Toxic
What is a viral secondary demyelinating disorder?
JC virus, causing progressive multifocal leukoencephalopathy
What is a metabolic secondary demyelinating disorder?
Central pontine myelinosis
Describe the pathophysiology of central pontine myelinosis
- Sodium controls movement of water
- Rapid administration of IV NaCl in hyponatraemia can cause an increase in sodium in the blood, and therefore an increase in sodium in the brain
- Water is therefore drawn out of the cells to the Na+ in the brain causing demyelination
- This primarily affects the pons
What are some toxic causes of demyelination?
CO
Organic solvents
Cyanide
What are the 3 types of plaques found in MS?
Active plaques (Active battlefield)
Inactive plaques (Scorched battlefield)
Shadow plaques (Healing of landscape)
Describe the histopathology of active plaques in MS
Immune cells are active attacking white matter causing
ongoing demyelination
Describe the histopathology of inactive plaques in MS
- Immune cell attack ceased but gliosis takes over (scarring)
- Little myeline remaining and reduced oligodendrocyte
numbers
Describe the histopathology of shadow plaques in MS
- Areas of remyelination, lesions become less defined hence “shadow”
- Myeline sheath is thinner and more fragile
