Neuropathology 1 Flashcards
Name the 3 main cell categories of the CNS.
* Nerve * Glial * Microglial
Name the 3 types of glial cells.
* Astrocytes * Oligodendrocytes * Ependymal cells
What do ependymal cells do?
Line the ventricular system
Name the supporting structures of the CNS.
* Blood vessels * Connective tissue * Meninges
What can damage to nerve cells and/or their processes lead to?
* RAPID necrosis with sudden acute functional failure (e.g stroke)
* Slow atrophy with gradually increasing dysfunction
Give an example of slow atrophy.
Age- related cerebral atrophy
What is the red neurone known as?
A neuron with acute neuronal injury
What does the red neurone occur in response to?
Injury or Hypoxia
When is the red cell visible?
12-24 hours after irreversible insult to the cell
Red cells are reversible
FALSE - irreversible
What does acute neuronal cell injury cause?
Neuronal cell death
What is the sequence of events in neuronal cell injury?
* Shrinking and angulation of nuclei
* Loss of the nucleolus
* Intensely red cytoplasm
* Become eosinophilic
* Dying
Explain how damage occurs.
Distal degeneration of the axon and towards cell body in response to damage
Name 3 other responses to injury.
* Axonal reactions * Simple neuronal atrophy (chronic degeneration) * Sub-cellular alterations – inclusions
What is the typical pattern of axonal reactions?
* Increased protein synthesis - cell body swelling, enlarged nucleolus
* Chromatolysis – margination and loss of Nissl granules
* Degeneration of axon and myelin sheath distal to injury “Wallerian degeneration”
* Increased size of nucleolus due to increased protein synthesis
What is the typical pattern of simple neuronal atrophy?
Shrunken, angulated and lost neurons, small dark nuclei, lipofuscin pigment, reactive gliosis
What type of reaction is sub-cellular alterations common in?
Neurodegenerative conditions ie. neurofibrillary tangles in Alzheimer’s
What do incisions seem to accumulate with?
Ageing
What do you also get inclusions with?
Viral infections affecting the brain
Describe the appearance of astrocytes.
Star-shaped with multipolar cytoplasmic processes
Where are astrocytes found?
Throughout the CNS
What do astrocytic processes do?
* Envelop synaptic plates
* Wrap around vessels and capillaries within the brain tp regulate BBB and tone of capillaries
What are the roles of astrocytes?
* Ionic, metabolic and nutritional homeostasis
* Work in conjunction with endothelial cells to maintain the BBB
* Main cell involved in repair and scar formation, given the lack of fibroblasts
What is gliosis?
An astrocytic response to injury
What is gliosis the most important pathological indicator of?
CNS injury, regardless of cause
What happens in gliosis?
* Astrocyte hyperplasia and hypertrophy
* Nucleus enlarges, becomes vesicular and the nucleolus is prominent.
* Cytoplasmic expansion with extension of ramifying processes
Describe the appearance of old lesions that have undergone gliosis in the past.
Nuclei become small and dark, and lie in a dense net of processes (glial fibrils)
What happens to cells in early gliosis?
Hypertrophy and hyperplasia
What do oligodendrocytes do?
Wrap around axons, forming the myelin sheath
What are oligodendrocytes sensitive to?
Oxidative damage
What is oligodendrocyte damage a feature of?
Demyelinating disorders
Describe the reaction of oligodendrocytes to injury.
Reaction to injury is relatively limited: - variable patterns of demyelination - variable degrees of demyelination - apoptosis
The reaction of ependymal cells to injury is ______
LIMITED
What is disruption of ependymal cells often associated with?
A local proliferation of sub-ependymal astrocytes to produce small irregularities on the ventricular surface, termed ependymal granulations
What can produce changes in ependymal cells?
Infectious agents, including viruses
How are microglial derived?
Embryologically
Where are microglia made?
Bone marrow
What do microglia function as?
* A macrophage in phagocytosis
* Mopping up injured neuronal cells
* Anti-inflammatory
Outline the role of microglia in response to injury.
* Microglia proliferate.
* Recruited through inflammatory mediators.
* Form aggregates – around areas of necrotic and damaged tissues
Name the 2 important mediators in the acute response to injury in the NS.
M2 – anti-inflammatory, phagocytic, more acute
M1 – pro-inflammatory, more chronic
What is the most important base line of neuronal injury?
HYPOXIA
Give examples of pathologies that can lead to hypoxia of the brain.
* Cerebral ischaemia
* Infarct
* Hameorrhages
* Trauma
* Cardia arrest
* Cerebral palsy
What % of total body resting oxygen does the brain consume?
20%
To maintain oxygen delivery, by how much can cerebral blood flow increase?
2 fold
After the onset of ischaemia, what leads to the ATP reserves being consumed within a few minutes?
Mitochondrial inhibition of ATP synthesis
Outline the steps of hypoxia.
How can cytotoxic oedema occumulate?
Independantly or via pre-morbid processes
Suggest situatins in which cerebral cytotoxic oedmea may occur.
* Intoxication
* Reye’s
* Severe hypothermia
* Ischaemia
What happens to dying cells?
They accumulate more Na and Cl, thus there is a shift of water form the extracellular space into the cell causing the cells to swell
NOTE: the brain doesnt get bigger as there isnt more water, just the water is shifting location
What is another name for ionic oedema?
OSMOTIC oedema
What does ionic oedema occur in?
Hyponatraemia + excess water intake ie. in SIADH
When does vasogenic oedema occur?
* Trauma
* Tumours
* Inflammation
* Infection
* Hypertensive encephalopathy
When does haemorrhagic conversion occur?
Occurs when endothelial integrity is completely lost and blood can enter the extracellular space
In what condition does haemorrhagic conversion occur?
Ischaemic strokes
What arteries of the brain are most important?
Anterior, middle and posteror cerebral arteries
What problems may arise due to ischaemia of the anterior cerebral artery territory?
* trunk + legs – sensory and motor abnormalities
* Frontal lobe dysfunction
* Higher cognitive dysfunction
What areas may be damaged in ischaemia of the area supplied by middle cerebral artery territory?
Major bulk of the sensory and motor cortex
What may ischaemia of the posterior cerebral artery terriroty result in?
Problem in occipital lobes, leading to homonymous hemianopia with visual field defect in both eyes on the same side as the lesion
What % of the cardiac output does the brain recieve?
15%
What % of oxygen consumed from the body does the brain use?
20%
To function, what does the brain require?
Active metabolism of glucose
The brain maintains blood flow over a wide range of ______ pressures?
PERFUSION
What do ‘autoregulatory’ mechanisms do?
Help to maintain blood flow at a ‘constant’ rate by dilatation and constriction of cerebral vessels
What is ‘cerebrovascular disease’?
Any abnormality of brain caused by a pathological process of blood vessels
Cerebrovascular disease is the _rd most common cause of death
3rd
What is cerebrovascular disese the commonest cause of?
Adult disability
Cerebrovascular disease is a medical emergency with a high mortality that is also treatable
TRUE
Give examples of different types of cerebrovascular disease.
* Brain ischaemia and infarction.
* Haemorrhages i.e strokes.
* Vascular malformations.
* Aneurysms
Cerebrovascular disease involved 2 processes. What are they?
1 – hypoxia, ischaemia and infarction, resulting from impairment of blood supply and oxygenation of tissue
2 – haemorrhage, resulting from rupture of CNS vessels
What is the overlapping process (both hypoxia and haemorrhage) that causes cerebrovascular disease?
HYPERTENSION
Infarction that is a few days old
SAH
What is GLOBAL hypoxic ischaemic damage?
Generalised reduction in blood flow/oxygenation - when there is systemic compromise to circulation which cannot be compensated for by CNS autoregulatory mechanisms
Give examples of global hypoxic ischaemic damage.
* Cardiac arrest
* Severe hypotension
What is the main cause of severe hypotension?
Trauma with hypovolaemic shock
What is focal ischaemia typically due to?
Vascular obstruction
Describe simply what global ischaemia entails.
A generalised reduction of cerebral perfusion
When does global ischaemia occur?
MAP <50 mmHg
What happens when MAP <50 mmHg?
Autoregulatory mechanisms can no longer compensate
Suggest situations in which MAP <50 mmHg.
* Cardiac arrest
* Shock/severe hypotension
* Trauma
What areas of the brain are particulary sensitive to hypoxic damage?
Watershed areas -
* these are 2 areas between arterial territories (i.e parieto-occipital)
* these are areas at the periphery of vascular territories and contain neurones particularly sensitive to hypoxia as they are the most distant from the heart, and least well supplied
What cells are more sensitive - neurones or glial cells?
Neurones
What type of neurones are the most sensitive?
NEOCORTEX + HIPPOCAMPUS
What does severe ischaemia lead to?
Pan-necrosis
What is a stroke?
A sudden disturbance of cerebral function of vascular origin that causes death, or lasts over 24 hours
What type of stroke is most common?
Infarction - thrombotic
What is cerebral infarction caused by?
Interruption of cerebral blood flow, due to thrombosis or emboli
What is the peak age of incidence of a cerebral infarct?
70 yo
In what geneder is cerebral infarct most common?
MEN
What is thrombosis?
An atherosclerotic segment
Where does thrombosis most often occur?
The middle cerebral artery
What does an embolic infarct arise due to?
Atheroma in the internal carotid artery, and aortic arch.
or
From heart
Outline the main risk factors for a cerebral infarction.
Atheroma
- Intracranial vessels
- Extracranial vessels
Hypertension
Risk factors for atheroma anywhere in intra and extracranial vessels
- Also causes changes in cerebral vessel walls
Serum lipids, obesity, diet
Diabetes mellitus – changes to small vessels that makes them less compliant and more likely to form atheroma
Heart disease
Diseases of neck arterie
Smoking
LOOK AT THE TABLE FOR MICROSCOPIC AND MACROSCOPIC APPEARANCE OF CEREBRAL INFARCTION
What happens after 48 hours of cerebral infarction?
Phagocytosis by macrophages
What happens after 1 week of cerebral infarction?
Reactive gliosis begins
Astrocyte hypertrophy and hyperplasia
What happens after a few weeks of a cerebral infarct?
Gliotic scar
Describe an OLD, cerebral infarct.
Eventually, a cystic gapremains as a permanent marker of the site of an old infarction.
(below shows where there has been a middle cerebral artery infarct)
What does the image show?
What is it a sign of?
Cystic gap
A sign that there has been a middle cerebral artery infarct
What does this show?
Gliotic scar
What does this show?
An infarct after 48 hours
When is this post infact?
What does it show?
1 week
Reactive gliosis
What is disrupted in a haemorrhagic infarct?
BBB
What may occur in a haemorrhagic infarct?
Haemorrhagic conversion
Explain how thrombolysis can be implicated in a haemorrhagic infarct
An occluded vessel may be reperfused by thrombolysis.
This, however, may lead to leakage through a damaged capillary bed following lysis of the embolus.
What process does this show?
Haemorrhagic infarct
How may a stoke, due to carotid artery disease present?
* Contralateral weakness or sensory loss.
* If dominant hemisphere – there may be aphasia or apraxia
How may a stroke, due to a problem in the middle cerebral artery present?
With weakness predominantly in the contralateral face and arm
How may a stroke, due to a problem in the middle cerebral artery present?
With weakness and sensory loss in the contralateral leg
What are the features of vertebra-basilar artery disease?
Vertigo, ataxia, dysarthria and dysphasia.
àcomplex ‘brain stem syndromes.’
What is the other name given to microaneurysms?
Charcot - Bouchard
What does hyaline atherosclerosis result in?
Thinning and weakening of small vessel walls, making them more prone to occlusion and to rupture
What is associated with the development of micro-aneurysms?
Chronic hypertension
Where do microaneurysms particulary occur?
In small MCA branches, most commonly within the basal ganglia
What does rupture of small branches of MCA result in?
Intracerebral haemorrhage
What is the consequence of hypertension in the brain?
Lacunar infarcts
Who gets hypertensive encephalopathy?
Severely hypertensive patients
Outline the process that leads to the development of hypertensive encephalopathy.
Upper limit of autoregulatory mechanism is saturated, and the BBB becomes incapable of resisting movement of plasma proteins like albumin and water àvasogenic oedema
List the symptoms of hypertensive encephalopathy.
* Headache
* Vomitng
* Fits
* Confusion
* Coma
What are the symptoms of hypertensive encephalopathy due do?
RAISED ICP
What does the pathology of hypertensive encephalopathy reveal?
Global cerebral oedema.
Tentorial and tonsillar herniation.
Petechiae.
Arteriolar fibrinoid necrosis.
What can increasing numbers of lacunar infarcts contribute to?
Multi-infarct dementia
What can a small lacunar infarct of the internal capsule result in?
Extensive motor weakness, including effecting the face, arm and leg
What can intracranial haemorrhage be due to?
Spontaneous or trauma
Give the 3 sub-types of spontaneous intracranial haemorrhage.
Intracerebral haemorrhage.
Sub-arachnoid haemorrhage.
Haemorrhagic infarct
Give the 5 sub-types of traumatic intracranial haemorrhage.
Extra-dural haematoma.
Sub-dural haematoma.
Contusion – surface bruising.
Intracerebral haemorrhage.
Sub-arachnoid.
List the contributing factors to intracerebral haemorrhage.
* Hypertension – small vessel disease, stiff and lack of compliance
*Aneurysms
*Systemic coagulation disorders
* Anticoagulation
* Vascular malformations
* Amyloid deposits (cerebral amyloid angiopathy)
* Open heart surgery
* Neoplasms
* Vasculitis (infectious and non-infectious)
Where is the most common site for intracerebral haemorrhage to occur?
Basal ganglia
Where do intracerebal haemorrhages also occur?
Thalamus.
Cerebral white matter.
Cerebellum.
Describe the morphology of an intracerebral haemorrhage on the cut surface.
* Asymmetrical distortion.
* Various shifts and herniations are common.
* Well-demarcated in intra-parenchymal haematomas.
* Softening of adjacent tissue.
* Surrounding oedema.
What does amyloid angiopathy occur in?
Alzheimer’s disease.
Age-related change
Describe the process of amyloid angioapthy.
Beta amyloid forms tightly packed beta pleated sheets which are deposited within cerebral and meningeal vessels.
As a result, these vessels become less compliant and less able to deal with localised increased pressure, and can ruptureas a result àforming a lobar intracerebral haemorrhage
Name the 4 major types of vascular malformation.
* Arteriovenous
* Cavernous
* Venous
* Capillary telangactes
As well as bleeding, what else can vascular malformations cause clinically?
Headaches, seizures and focal neurological deficits
Technically, what are AVM’s?
SOL’s
Where do AVM’s most commonly arise?
In cerebral hemispheres in MCA territory
Describe the vessels in AVM’s.
Large
Abnormal
Tortuous
Shunting can occur from an artery to a vein. What are the effects of this?
Vein undergoes smooth muscle hypertrophy.
àtherefore not compliant, and ruptures easily.
Also forms aneurysms which rupture
What is the most common cause of SAH?
Rupture of a saccular aneurysm (Berry aneurysm)
Where do 90% of SAH’s occur?
In the territory of the ICA
Where do 10% of SAH’s arise?
In vertebra-basilar circulation
Where do SAH’s arise?
Arterial bifurcations
Where is blood in an SAH?
In the subarachnoid space
What may be seen pathologically in an SAH?
* Intracerebral haematomas, adjacent to aneurysms.
* Infarcts of brain parenchyma may also develop due to arterial spasm (40%) of cases.
* Mass effect of haematoma and features of raised ICP
What are the 3 main risk factors to SAH?
* Smoking
* Hypertension
* Kindey disease
The onset of an SAH is?
ABRUPT
What are the symptoms of SAH?
Severe headache.
Vomiting.
Loss of consciousness.
Meningeal signs, including neck rigidity
What are people with SAH at risk of?
Hydrocephalus
SAH is very severe. What percentage of people die within 1 week?
50%
Who gets SAH?
Women > men
Usually over 50 years old
What is Reye’s syndrome?
* Swelling in the liver and brain
* Affects children and teenagers recovering from a viral infection, most commonly the flu or chickenpox
* Causes cytotoxic cerebral oedema
