Neuropathology 1: Cerebrovascular Disease Flashcards
Why are most disease processes in the brain not considered benign?
Brain is contained within the rigid cranium that does not allow for V increase; so, P increases as a consequences
What are bridging veins?
Vessels that course through the subarachnoid space and, adjacent to the sagittal-midline veins, perforate the arachnoid and dura
Cellular components of the CNS?
Neurones (nerve cells) - key communicating cells
Glial cells - derived from the neuroectoderm and provide support for neurones and their dendritic and axonal processes:
• Astrocytes - provide the brain with a fixed, 3D structure to support other CNS cells; these cells are closely coupled, functionally, with neurones
• Oligodendrocytes - wrap around axons, forming the myelin sheath
• Ependymal cells - line the ventricular system
Microglia (derived from the mesoderm) - originate in the bone marrow and serve as a macrophage system
Supporting structures:
• Connective tissue
• Meninges
• Blood vessels
Pathologies assoc. with all glial cells?
May all give rise to tumours within the brain
Causes of NS injury?
HYPOXIA - lack of oxygen or no oxygen (anoxia) of brain parenchyma; this is often a phenomenon that occurs secondary to other insults
Trauma - direct, avulsion / axotomy of neurones
Toxic insult, metabolic abnormalities, nutritional deficiencies
Infections
Genetic abnormalities
Ageing
How do cells respond to injury?
Damage to nerve cells and/or their processes can lead to:
• RAPID necrosis with sudden acute functional failure, e.g: this occurs in stroke
OR
• SLOW atrophy with gradually increasing dysfunction, e.g: this occurs in age-related cerebral atrophy
When does acute neuronal injury occur?
Represents a lethal injury to the neurone, typically caused by ischaemia or hypoxia, e.g: in the context of a stroke
Results in neuronal cell death
Changes are typically visible 12-24 hours after an irreversible insult to the cell
What are red neurones?
Describes what an acutely injured and dying neuronal cell body looks like; features include:
• Shrinking and angulation of nuclei
• Loss of the nucleolus
• Intensely red cytoplasm (eosinophilia)
If this can be seen, it indicates that that he underlying cause is of an acute hypoxic nature
What other neuronal responses occur to injury / disease?
Axonal reactions - a neuronal cell body reaction assoc. with axonal injury
Simple neuronal atrophy - occurs in diseases of long duration, e.g: MS or Alzheimer’s
Sub-cellular alterations - to neuronal organelles and cytoskeleton; it is common in neurodegenerative conditions
Pathology of axonal reactions?
Increased protein synthesis leads to:
• Cell body swelling
• An enlarged nucleus
Chromatolysis (margination and loss of Nissl granules)
Wallerian degeneration - degeneration of axon and myelin sheath distal to injury
Difference in axonal reactions that occur in the CNS and in the PNS?
In the PNS, there is often preservation of the myelin sheath to form a neural tube that can afford some regeneration
Pathology of simple neuronal atrophy?
Shunken neurones and neuronal loss; depending on the case, simple neuronal atrophy often affects functionally related neurones
Lipofuscin pigmentation
It is often assoc. with reactive gliosis
Situations where sub-cellular alterations to the neuronal organelles and cytoskeleton occur?
Includes:
• Neurofibrillary tangles in Alzheimer’s disease
• Lewy bodies in Lewy Body dementia and Parkinson’s disease
• Neural inclusions in ageing
• Intranuclear and cytoplasmic inclusions in viral diseases
Structure of astrocytes?
Star-shaped cells with multipolar cytoplasmic processes
Astrocytic processes:
and includes:
• Envelop synaptic plated
• Wrap around vessels and capillaries within the brain
Location of astrocytes?
Present throughout the CNS
Astrocytic processes envelop synaptic plates and wrap around vessels and capillaries within the brain
Function of astrocytes?
Ionic, metabolic and nutritional homeostasis
Work in conjunction with endothelial cells to maintain the BBB
Foot processes wrap around intracerebral small vessels and capillaries (regulate cerebral blood flow)
Main cell inv. in repair and scar formation, given the lack of fibroblasts
Why are astrocytes metabolically coupled to neurones?
Astrocytes do anaerobic glycolysis, while neurones do not; they produce lactate, which is transferred to the neurone for use as a metabolite for the production of ATP
What is gliosis?
It is an astrocytic response and is the MOST IMPORTANT histopathological indicator of CNS injury, regardless of cause
Histopathology of gliosis?
Astrocyte hyperplasia and hypertrophy (increased no. and size)
Nucleus enlarges and becomes vesicular; the nucleolus becomes prominent
There is cytoplasmic expansion with extension of ramifying processes
Histopathology of old lesions?
E.g: an area of gliosis in an old infarct
Nuclei become small and dark and lie in a dense net of processes (glial fibrils)
Oligodendrocyte response to injury?
Relatively limited reaction to injury:
• Variable patterns and degrees of demyelination
• Apoptosis
NOTE - oligodendrocyte damage is a feature of demyelinating disorders, leading to abnormalities in neuronal conduction
Oligodendrocytes are sensitive to which type of injury?
Oxidative damage; they die in respose to significant hypoxic injury
Conduction of membrane depolarisations?
Jump from one node of Ranvier to the next through saltatory conduction
What happens when there is axonal damage?
Wallerian degeneration - antegrade degeneration of the axon to the nearest node of Ranvier
Ependymal cell reaction to injury?
Limited reaction to injury; infectious agents, inc. viruses, produce changes in ependymal cells
Disruption of these cells is often assoc. with a local proliferation of sub-ependymal astrocytes; these produce small irregularities on the ventricular surfaces, referred to as EPENDYMAL GRANULATIONS
Microglia response to injury?
Microglia proliferate and are recruited via inflammatory mediators; they form aggregates around areas of necrotic and damages tissues
Types of microglia?
M2 - anti-inflammatory and phagocytic, mainly cleaning up at the centre of acute damage
M1 - pro-inflammatory and appear later after acute injury (more chronic); they can exacerbate aspects of acute brain injury and are important mediators of, e.g: Alzheimer’s disease and MS
What is the most important base-line cause of neuronal injury?
Hypoxia; causes include: • Cerebral ischaemia • Infarct • Haemorrhages • Trauma • Cardiac arrest • Cerebral palsy
What happens when ischaemia occurs in the brain?
After onset of ischaemia, mitochondrial inhibition of ATP synthesis leads to ATP reserves being consumed within a few minutes
Explain how excitotoxicity is responsible for acute neuronal injury?
NOTE - mainly caused by HYPOXIA and the secondary brain injury that follows trauma
In the above cases, there is energy failure and:
• Neural depolarisation leads to glutamate release
• Astrocyte reuptake is inhibited and this leads to a failure of glutamate reuptake
Above issues lead to a glutamate storm and excitation
There is uncontrolled Ca2+ entry into cells, leading to:
• Protease activation
• Mitochondrial dysfunction
• Oxidative stress
Apoptosis and necrosis occurs
Types of oedema and situations where they occur?
Cytotoxic oedema - a pre-morbid process that occurs in:
• Intoxication
• Reye’s
• Severe hypothermia
Ionic oedema (AKA osmotic oedema) occurs in: • Hyponatraemia and excess water intake (e.g: SIADH)
Vasogenic oedema:
• MAINLY occurs in trauma, tumours and inflammation
• Also in infection
• Hypertensive encephalopathy
Pathology of cytotoxic oedema?
Dying cells accumulate water (pre-morbid condition) as osmotically active EC ions, like Na+ and Cl-, move into cells and take water with them
In isolation, cytotoxicity of itself does not cause swelling; however, cytotoxic oedema can enhance ionic and vasogenic oedema
Pathology of ionic oedema?
1st dysfunction of the BBB
Occurs due to cytotoxic oedema, which results in the EC space being relatively devoid of Na+
Na+ ions cross the BBB and thus drive Cl- transport, creating an osmotic gradient for water accumulation
Gives rise to swelling
Pathology of vasogenic oedema?
Occurs along with deterioration and breakdown in the BBB
Due to disruption of endothelial tight junctions, plasma proteins (like albumin) cross into the EC space; these are potent osmotic factors, so water follows
NOTE - disruption of the BBB is not severe enough to allow passage of rbcs
