CNS Pathology 1 Flashcards
What are general causes of CNS pathologies?
Causes: acute (sudden) or Chronic (gradual):
- Cardiovascular disease (ischaemia)
- Infections (bacterial, viral)
- Chemical toxicity (drugs)
- Ageing/degenerative disorders
What are consequences of CNS pathologies?
Consequences: for CNS/brain function can be:
‘Global’ with generalized effects, including:
- Nausea, vomiting, seizures/convulsions
- Altered consciousness (lethargy, disorientation, coma)
‘Focal’ with effects more specifically related to:
•Injury site (plus selective dysfunctions in other CNS/brain areas that are directly connected to &/or depend on it)
How many types of glial cells are there in the CNS and what are they?
Three types of glial cells in the CNS and they are:
- Oligodendrocytes
- Microglial Cells
- Astrocytes
How many types of glial cells are in the CNS and what are they?
3 types of glial cells - these are Oligodendrocytes, Microglial cells and Astrocytes.
How do neurones respond to injury?
Essentially they don’t they just die really
How do Microglial cells and astrocytes respond to injury?
Microglial cells don’t die off as quickly as neurones.
Astrocytes proliferate (undergo hyperplasia)
When neurones encounter Ischaemia, Pathogens or toxicity what occurs?
Death by necrosis
How does death by necrosis occur for neurones when exposed to Ischaemia, Pathogens or toxicity?
First: ‘Pyknosis’:
- This is a Condensation of the nucleus & chromatin (DNA) with:
- Uncontrolled DNA fragmentation
- Breakdown of RER (rough endoplasmic recticulum which is referred to as Nissl bodies in neurones) & mRNA
- Loss of nucleic acids: leads to ‘red’ (eosinophillic) appearance [This can be seen under stain].
Then: cell swelling
- Breakdown of organelles (myelin figures) & membrane lysis which leads to…
- Discharge/leakage of contents (e.g., proteins, organelles)
- This results in a Pro-inflammatory reaction which attracts Neutrophils to ‘clean up’ the ‘debris’
What is the response of oligodendrocytes to injury?
Mixed - in the sense that they may either undergo death by necrosis or apoptosis.
How can we identify neurones undergoing necrosis from a section?
You stain the section with haemotoxylin and eosin - if the neurones are healthy we get a purple tinge all over, if the neurones are undergoing necrosis we find the appearance of red neurones as indicated by the arrows.
Despite whether they choose to undergo necrosis or apoptosis what do oligodendrocytes first do when encountering injury and what does this do?
They strip their myelin from their axons.
This results in the axons swelling and a failure of impulse conduction.
What would oligodendrocytes that have encountered injury look like on a section?
Compared to a normal healthy section , there would be lots of spaces ( where the myslin has been striped away) leading to the fomration of a vacuole.
What cells produce myslin sheaths in the CNS?
Oligodendrocytes
[Schwaan cells produce myelin sheaths in the PNS]
What is the function of microglial cells in the CNS?
They are basically macrophages of the CNS. They are permanently resident and involved in CNS surveillance (e.g. to detect damaged neurones or infectious agents).
How do microglial cells respond to injury?
In response to Injury they withdraw these branches & adopt an elongated (amoeboid) or ‘rod-shaped’ form (arrows, right) & move through the CNS tissue, to engulf necrotic/apoptotic neurons by Phagocytosis
What is the structure of microgial cells?
When ‘dormant’ they are ramified (i.e. they contain lots of branches).
What are the functions of astrocytes?
Astrocytes are Metabolic Buffers & Detoxifiers (i.e by mopping up any extra chemicals lying about) of the CNS & contribute to the Blood-Brain Barrier (e.g., via perivascular end-feet around capillaries)
They have similar reactions to FIBROBLASTS in scar tissue formation & wound healing.
How do astrocytes respond to injury?
Undergo hyperplasia (proliferation) in reacting to any CNS injury
(aka GLIOSIS)
How can we identify Astrocytes in a stain?
They are identified by staining for their specific cytoskeletal element = Glial Fibrillary Acidic Protein (GFAP)
How can you identify astrocytes responding to injury in a section?
What is a ‘typical’ sequence of events following acute CNS injury?
12-24 hours: ‘Red’ neurons & necrosis can be seen
Days 1-2: Neutrophils! Phagocytic, early-responding, white blood cells enter via damaged blood vessels & start indiscriminately ingesting neuronal & myelin debris
Day 7 onwards: Microglia are mobilized with more selective eating & healing (peak activity 3-4 weeks)
Finally: Astrocyte gliosis, with scar tissue formation (complete ~ 2 months)
What are the two types of stroke and what do they cause?
Heammorhagic stroke and Ischemic stroke.
Both: result in reduced partial pressure of oxygen (HYPOXIA) & regions of neuron cell death (INFARCT) via necrosis
In a CT scan how would an infarction look?
It would be a pale area (as there is no blood flow)
In pathology what is the appearance of a haemorrhagic stroke?
Red appearance - from the blood having gone everywhere.
How does meningitis affect by age?
What will be seen in pathology for bacterial meningitis?
Creamy purulent (pus) exudate which Settles (because of gravity) at base of the brain which can damage cranial nerves.
What is the problem with microglial cells?
When they get old they start acting up.
When old they become stiffer and end up perpetuating inflammatory responses (this basically means they end up continuing the inflammatory response).
(i.e. they have long projections (branches) that go to and from areas when they are injuried - this movement away from the area once its been sorted becomes slower (when older) and all the while they are still releasing cytokines thus they keep stimulating the inflammtory response beyond what it needs to be).
