Neuropathology 1 Flashcards
When might acute neuronal injury occur?
In any events which cause hypoxia / ischaemia
What is another term used for acute neuronal injury?
Red neuron
What microscopic changes will be seen in ‘red neuron’ death?
Shrinking and agglutination of the nuclei
Loss of nucleolus
Intensely red cytoplasm due to eosinophilia
What is an axonal reaction?
Neuronal cell body reaction associated with an axonal injury
List some examples of axonal injuries?
Swelling
Enlarged nucleolus from protein synthesis
Degeneration of axon and myelin
Define “Wallerian degeneration”:
This is when degeneration occurs distal to the site of the injury
When might simple neuronal atrophy occur
In chronic disease such as MS or Alzheimer’s
What are some of the features of simple neuronal atrophy?
Shrunken Neurons
Neuron loss
Lipofuscin pigmentation
Reactive gliosis
What cells are responsible for anaerobic glycolysis?
Astrocytes
What cells are astrocytes metabolically coupled to and why?
Neurons
Neurons don’t perform anaerobic glycolysis, so depend on astrocytes for ATP production
What CNS cells are extremely sensitive to oxidative stress?
Neurons
Give some examples of sub-cellular alterations that can occur to neuronal organelles and cytoskeleton?
Neurofibrillary tangles in Alzheimer’s
Lewy bodies
Neural inclusions in aging
Intranuclear and cytoplasmic inclusions of viral disease
What transmitter to astrocytes take up?
Glutamate
What is the purpose of the foot processes on astrocytes?
Regulate the blood brain barrier and cerebral blood flow by responding to neuronal signals
What sign is a prominent and important indicator of CNS injury?
Gliosis
What changes occur gliosis?
Hyperplasia & Hypertrophy of astrocytes
Astrocytes get prominent nuclei
Cytoplasmic expansion
What does gliotic tissue look like?
Translucent and firm
Seen to form a barrier to sites of tissue damage
What are oligodendrocytes?
They are the CNS version of Schwann cells
They form the myelin sheath on axons
Oligodendrocyte damage is a feature of what type of disorders?
Demyelinating disorders e.g. MS
What is the term for the process of membrane depolarisation ‘jumping’ from one node to the other in depolarisation?
Saltatory conduction
Axonal loss (oligodendrocyte damage) in the CNS is reversible / irreversible?
Irreversible
Oligodendrocytes do not have reparative abilities
Where are ependymal cells found?
Lining the ventricular system
What occurs from ependymal disruption?
Local proliferation of sub-endymal astrocytes causing small irregularities on the ventricular surfaces termed ependymal granulations
What can cause changes to the ependymal cells
Viruses
Tumours
How much of the bodies total O2 consumption is carried out in the brain?
20%
How much can cerebral blood flow increase if in need of increasing oxygen delivery?
Can increase 2fold
What occurs when after the onset of ischaemia in the brain at a cellular level?
Mitochondria inhibit the production of ATP, which leads to the ATP reserves being used up in a matter of minutes
Which neurons are most susceptible to hypoxic damage?
3rd 5th and 6th layers of the cortex
Hippocampus cells
Purkinje cells of the cerebellum
What is the term given for when dying cells accumulate water?
Cytotoxic oedema
What is ionic oedema?
This occurs after cytoxic oedema
Na+ ions cross the BBB creating an osmotic gradient for accumulation - leads to swelling
What is the term for when the blood brain barrier breaks down due to disruption of endothelial tight junctions allowing for water to pass through?
Vasogenic oedema
NOTE: this disruption is not enough to allow the passage of RBCs
When does haemorrhagic conversion occur?
When the endothelial integrity of the BBB is completely lost and blood begins to enter the extracellular space
What % of the cardiac output goes to the brain?
15%
What cells in the brain are responsible for the immune response and surveillance?
Microglial cells
Define Global Hypoxic ischaemic damage?
The system compromise to the circulation cannot be compensated for
There is a generalised reduction of cerebral perfusion
What are some causes of Global hypoxic ischaemic damage?
Cardiac arrest
Hypovolaemia shock
Define focal hypoxic ischaemic brain damage?
Restriction of blood flow to localised area of the brain
What is the main cause of focal hypoxic ischaemic damage?
Vascular obstructions e.g. clot
What are “watershed areas”?
These are neurons which are particularly sensitive to hypoxia
Where are watershed areas and why is their location significant?
They are in the periphery of the vasculature
Most distant from the heart and least well supplied
Define Stroke:
Sudden disturbance of cerebral function which is vascular in origin and lasts over 24 hours (or is fatal)
When is a stroke classified as completed?
When there is irreversible tissue loss due to local arrest OR due to severe reduction in blood flow
Which artery is most commonly affected by a thrombus/
The middle cerebral artery
When will neutrophil infiltration occur in a stroke?
Within the first 48 hours
Microglia will then become the dominant cells type
When will reactive gliosis begin following a stroke?
About a week later
What are some signs of vertebra-basilar artery disease
Vertigo
Ataxia
Dysarthria
Dysphasia
What disease is associated with the development of micro aneurysms in the brain?
Charcot-Bouchard
What pathological changes would be seen in a hypertensive encephalopathy?
Cerebral oedema
Herniations
Petechiae
Arterial wall necrosis
What is the morphology of a lacunar infarct (as seen on a cut surface)?
Asymmetrical distortion Various shifts and herniations Well demarcated intra-parenchymal haematomas Softening adjacent tissue Surrounding oedema
What is the most common congenital vascular abnormality of the CNS?
AV malformations commonly in the cerebral hemispheres (MCA territory)
What diseases increase your chance of berry aneurysms / subarachnoid haemorrhage
Polycystic kidneys Fibromuscular dysplasia Coartication of aorta AV malformations Collagen type 3 abnormality
When is amyloid angiopathy seen?
Alzheimer’s disease
also associated with age related changes
What are the three most common forms of herniation?
Subfalcine
Tentorium
tonsillar
What is a subfalcine herniation?
Unilateral or asymmetrical expansion of the cerebral hemisphere displaces the cingulate gyrus under the falx cerebri
What is tentorial herniation?
This is when the medial aspect of the temporal lobe herniates over the tentorium cerebri
What part of the temporal lobe is involved in a tentorium herniation?
Hippocampal uncus
Para-hippocampal gyrus
What cranial nerve can be compressed in a tentorium herniation and what might the clinical sign be?
CNIII
pupillary dilation and impairment of the ocular muscles
What is a tonsillar herniation?
Displacement of the cerebellar tonsils through the foramen magnum