Pathology Flashcards
what type of cells line the ventricular system
Ependyma cells (which are a type of Glial cell)
what cells act as the immune system in the brain
microglia
what cells act as a myelin sheath
oligodendrocytes
what are glial cells derived from
neuroectoderm
what are the 4 types of neuronal response to injury/disease
Acute neuronal injury
Simple neuronal atrophy
Sub-cellular alterations
Axonal reaction
what cells are most vulnerable to damage in the CNS when hypoxic and why
neurones
activation of glutamate receptors results in uncontrolled calcium entry into the cell
what is an axonal reaction
a reaction within the cell body that is associated with axonal injury
what is the cells response to axonal injury
increased RNA and protein synthesis swelling of cell body peripheral displacement of nucleus enlargement of nucleolus breakdown of myelin sheath
what is the most important histopathological indicator of CNS injury
Gliosis
what are features of gliosis
- astrocytes undergo hyperplasia and hypertrophy
- nucleus enlarges
- cytoplasmic expansion
what is the role of oligodendrocytes
warp around axons of neurones forming myelin sheath
what is injury to oligodendrocytes a feature of
demyelinating disorders
what is disruption of the ependymal cells associated with
ependymal granulations
local proliferation of sub-ependymal astrocytes
- produce small irregularities on the ventricular surfaces called ependymal granulations
what can cause changes in ependymal cells
infectious agents
viruses
how do microglia respond to injury
- proliferate
- develop elongated nuclei (rod cells)
- forming aggregates about small foci of tissue necrosis (microglial nodules)
- congregate around portions of dying neurones (neuronophagia)
how much CO does the brain receive
15% of CO
uses 20% of oxygen consumed by the body
what arteries branch off to provide blood supply to the brain
internal carotid artery
vertebral artery
what would a haemorrhage in the anterior cerebral artery cause
- frontal lobe dysfunction
- contralateral sensory loss in foot and leg
- paresis of arm and foot, relative sparing of thigh and face
what would a haemorrhage in the middle cerebral artery cause
- hemiparesis
- hemisensory loss
- aphasia/dysphasia
- apraxia
what is Vertebrobasilar insufficiency
temporary set of symptoms due to ischemia in the posterior circulation of the brain
what does the posterior circulation of the brain supply
brain stem
cerebellum
occipital lobe
what conditions would infection in the brain stem cause
midbrain - webers syndrome
pons - medial and lateral inferior pontine syndromes
medulla - lateral medullary syndrome
what is the classical presentation of occipital stroke to a posterior artery occlusion
Homonymous hemianopia with macular sparing
what would a lack of blood to the cerebellum cause
Ataxia
Nystagmous
Intention tremor
Pendular reflexes (abnormal response to stimulus)
what conditions come under the term cerebra-vascular disease
Brain ischaemia and infarction
Haemorrhages
Vascular malformations and developmental abnormalities
what pathology can brain ischaemia/infarct cause
Global hypoxic-ischaemic damage
Focal infarcts – due to local vascular obstruction
what happens in Hypoxic-ischaemic Damage
neurones affected more (as they are more vulnerable than glial cells)
what is meant by ‘watershed’ areas in reference to Hypoxic-ischaemic Damage
junctions of arterial territories (arterial border zones) – they are first to be deprived of blood supply during hypotensive episodes
what is the definition of a stroke
sudden disturbance of cerebral function of vascular origin that causes death or lasts over 24 hours
what are the 2 types of stroke
infarction
haemorrhage
what are the subtypes of stroke
infarction
- thrombotic
- embolic
haemorrhage
- intracerebral
- subarachnoid
- bleeding into infarct
what causes a cerebral infarction
local interruption of cerebral blood flow due to thrombosis or emboli
what is the risk factors of a cerebral infarction
Atheroma Hypertension Serum lipids, obesity, diet Diabetes mellitus Heart disease Diseases of neck arteries Drugs Smoking
what is the presentation of the brain between 4-12hrs, 15-20hrs and 24-36hrs after a cerebral infarction
4-12 = brain may appear normal
15-20 = ischaemic neuronal changes develop, defined margin between ischaemic and normal brain
24-36 = inflammatory reaction, extravasation of RBC. Activation of astrocytes and microglia
what is the presentation of the brain between 36-48hrs, day 3 and 1-2 weeks after a cerebral infarction
36-48 = necrotic area visible macroscopically, becomes swollen and softer than surrounding tissue
3 days = macrophages infiltrate into the area
1-2 weeks = stiffening of tissue and gliosis
what is the most common cause of a spontaneous SAH
rupture of a saccular aneurysm (i.e. Berry Aneurysm)
where do saccular aneurysm commonly occur
90% at arterial bifurcation of internal carotid artery
10% in vertebro-basilar circulation
what else can happen in a rupture of a Berry aneurysm apart from SAH
may also get intracerebral haematomas
infarcts of brain parenchyma
what are the symptoms of a SAH
abrupt onset severe headache vomiting LOC meningeal signs CSF grossly bloody no precipitating factor often
what are acute complications of SAH
cerebral infarcts (4-9 days), acute hydrocephalus, and herniation
what effect does hypertension have on the brain
increased amount of atheroma
hyaline arteriosclerosis
microaneurysms
what can complicate a case of severe hypertension
hypertensive encephalopathy
what is hypertensive encephalopathy
upper limit of autoregulation is exceeded by forced cerebral hyperperfusion, induced by eclampsia or malignant-phase hypertension.
what is ‘auto regulation’ and what happens when this fails
mechanisms help to maintain blood flow at a “constant” rate
hypoxic brain damage likely
what pathology is seen in hypertension and the brain
- Lacunar infarcts
- Intracerebral haemorrhage and haematoma formation – ruptured aneurysms
- Multi-infarct dementia
- Hypertensive encephalopathy
what is demyelination
Preferential destruction of myelin sheath around axon
Relative preservation of axons themselves
what causes demyelination
Diseases of myelin or oligodendrocyte/Schwann cell
what does myelin allow for
rapid conduction of electrical impulses along cell membranes.
disruption of myelin sheath leads to disruption of electrical conductivity within the CNS
what is a primary demyelinating disorder
MS
what are examples of secondary demyelinating disorder
- central pontine myelinosis
- sub-acute sclerosing panencephalitis
- AIDS
- axonal degeneration
what are other causes of demyelinating disorders
Metabolic
Toxic - cyanide, CO, solvents
what is the morphological appearance of MS
External appearance of brain and spinal cord usually normal
Cut surface - multiple areas of demyelination, termed “plaques”
Well-demarcated plaques in white matter
May act as SOL
what matter does MS affect
white matter
how might plaques differ in appearance
acute lesions tend to be soft/pink
older lesions are firmer/pearly grey
what areas can MS affect
occur at any site in the CNS
commonly seen in CN II, periventricular white matter, corpus callosum, brain stem and spinal cord
what are the types of MS plaques
Acute active plaques
Chronic (inactive) plaques
Chronic active plaques
Shadow plaques
what is the appearance of acute active plaques
demyelinated plaques that are yellow/brown, with an ill-defined edge which blends into surrounding white matter
what is the appearance of inactive plaques
centre of an inactive plaque contains little or no myelin.
Astrocytic proliferation and gliosis are prominent.
how do shadow plaques appear
Border between normal and affected white matter is not clearly defined.
Abnormally thinned out myelin-sheaths can be identified, especially at the outer edges.
what is the appearance of chronic plaques
well-demarcated grey/brown lesions in white matter, classically situated around lateral ventricles
to summarise what are the main histological features of MS
Demyelination
Inflammation
Gliosis (astrocytic gliosis particularly)
dementia is subdivided into primary and secondary - what are examples of both
primary/organic dementia
- Alzheimer’s. diffuse levy body disease, huntington’s disease, Pick’s disease
secondary - vascular, metabolic, infection, trauma
what is the most common cause of dementia in the elderly
Alzheimer’s disease (AD)
what genetic condition has increased incidence of AD
Down’s Syndrome - Trisomy 21
what are genetic links for familial AD
amyloid precursor protein (APP) gene found on chromosome 21,
presenilin 1 gene on chromosome 14
presenilin 2 gene on chromosome 1
what is the macroscopic pathology of AD
- decreased size and weight of brain (cortical atrophy)
- widening of sulci
- narrowing of gyri
- compensatory dilatation ventricles, 2° hydrocephalus
what lobes are affected in AD
frontal, temporal and parietal
what is the microscopic pathology of AD
neurofibrillary tangles
Aß amyloid plaques (senile plaques)
amyloid angiopathy
extensive neuronal loss with astrocytosis
what stain is used to look for amyloid collections
congo red
it goes Apple-green birefringence in the presence of amyloid
what are the neurofibrillary tangles seen in AD mainly composed of
TAU protein
what is the hallmark features of dementia with lewy bodies (DLB)
progressive dementia with hallucinations and fluctuating levels of attention
what type of features can develop in DLB
features of Parkinson’s disease
what are the pathological features of DLB
Degeneration of the substantia nigra
Remaining nerve cells contain abnormal structures called Lewy bodies
Degeneration of the cortical areas of the brain
how can degeneration of the cortical areas of the brain with formation of lewy bodies be detected
immunochemical staining for the protein ubiquitin.
what is the inheritance pattern of Huntington’s disease (HD)
Autosomal dominant
huntingtin gene of chromosome 4
what is the pathological appearance of HD
loss of neurons in caudate nucleus and cerebral cortex accompanied by reactive fibrillary gliosis
what is Pick’s disease
progressive dementia commencing in middle life (usually between 50 and 60 years) characterised by slowly progressing changes in character and social deterioration leading to impairment of intellect, memory and language
pathology of Picks disease
Extreme atrophy of cerebral cortex in frontal and temporal lobes
Neuronal loss and astrocytosis
Pick’s cells (swollen neurons) Pick’s bodies (intracytoplasmic filamentous inclusions)
what are symptoms in Pick’s disease related to
damage to frontal and temporal lobe
what is multi-infarct dementia
deterioration in mental functioning due to changes or damage to the brain tissue from hypoxia or anoxia (lack of oxygen) as a result of multiple blood clots within the blood vessels supplying the brain.
what causes multi-infarct dementia
successive, multiple cerebral infarctions cause increasingly larger areas of cell death and damage
what are people with multi-infarct dementia prone to
anxiety and depression as they are aware of their mental deficits
multi-infarct dementia can be difficult to distinguish from AD, what is more suggestive of multi-infarct dementia
Abrupt onset
Stepwise progression
History of hypertension or stroke
Evidence of stroke will be seen on CT or MRI
what are the 2 types of causes of head injury
missile
non-missile
what happens in a non-missile injury
Sudden acceleration/deceleration of head
Brain moves within cranial cavity and makes contact with bony protrusions.
what are causes of a non-missile brain injury
RTAs
Falls
Assaults
what are the different types of fractures seen in the skull
fissure fracture
depressed fracture
compound fracture
base of skull fractures
what occurs at the moment of injury and what can it cause if severe
diffuse axonal injury
coma/vegetative state
what are causes of diffuse axonal injury
trauma raised ICP progression of inflammatory disease progression od dementia hypoxia
what is the pathological time scale of axonal injuries
2-4 hrs - focal axonal accumulation of APP
12-24 - axonal swelling
24hrs - 2weeks - axonal swelling
2weeks - 5months - glial reaction
5months - years - degeneration and loss of myelinated fibres
when is a traumatic extradural haematoma often a complication
fracture in temparoparietal region that involves middle meningeal artery
what can happen is a extradural haematoma is left untreated
midline shift – compression and herniation
associated brain damage often minimal
what are causes of raised ICP
SOL Oedema Increased CSF (hydrocephalus) Increased venous volume physiological - hypoxia, hypercapnia, pain
what are the effects of raised ICP
Intracranial shifts and herniations
Distortion and pressure on cranial nerves and vital neurological centres
Reduced level of consciousness
Impaired blood flow
where are the common sites for herniations
falcine/cingulate
uncal
tonsillar
transcalvarium
clinical signs of Raised ICP
papilloedema
nausea and vomiting
headache
neck stiffness
what are examples of SOL
tumours (primary or mets)
abscess (single/multiple)
haematoma
localised swelling
what are causes of a single abscess
- otitis media
- sinusitis
- nasal/facial/dental infections
- skull fractures
- penetrating injury
- neurosurgical procedures
what are causes of multiple abscess
- septicaemia
- acute bacterial endocarditis
- bronchiectasis
- lung abscess
- cyanotic heart disease
- IV drug use
what causes focal oedema
present as a result of other pathological lesions, such as infarcts, can also lead to an increase in intracranial pressure.
what is generalised cerebral oedema
Increased water content of the brain (either intracellular or extracellular)
what commonly causes extradural haemorrhages
rupture of meningeal arteries
skull fractures
what happens in an extradural haemorrhage
compress the subjacent dura and flatten gyral crest of underlying brain
what can be complications of an extradural haemorrhage
uncal gyral/cerebellar tonsillar herniation
death.
what causes subdural haemorrhages
disruption of bridging veins that extend from the surface of the brain into subdural space
what is a subdural haemorrhage
Collections of blood between the internal surface of dura mater and arachnoid mater
what are features of an acute subdural haemorrhage
clear history of trauma
unilateral or bilateral
associated with other traumatic lesions
gyral contours preserved
swelling of cerebrum on side of haematoma
what are features of a chronic subdural haemorrhage
associated with brain atrophy
composed of liquefied blood/yellow-tinged fluid
what are Sx of a chronic subdural haemorrhage
altered mental status
focal neurological deficits
what are astrocytes
star shaped glial cells
what are the functions of astrocytes
provide support to blood brain barrier
role in repair and scarring
provision of nutrients
maintenance of ion balance
