Pathology Flashcards
List factors and substances that can damage cells of the CNS
Lack of oxygen (hypoxia) Trauma Toxins Metabolic disturbance Malnutrition Infection Ageing Genetic mutations
Which component of the CNS is most vulnerable to hypoxia? What key characteristic of this component would suggest acute hypoxic damage?
Neurones
Intensely red cytoplasm - ‘RED NEURONE’
Which cells are the “macrophage cells” of the CNS?
Microglia - involved in phagocytosis
Axonal injury involves a reaction in which part of the neurone?
Reaction within cell body
In which direction does the axon damage in response to injury?
Anterograde degeneration of axon distal to site of injury
Which process do astrocytes initiate in response to injury?
Reactive proliferation - gliosis - where cells undergo hyperplasia and hypertrophy
Which process if the most important histopathological indicator of CNS injury, regardless of cause?
Gliosis
Which cells line the ventricular system?
Ependymal cells
The brain receives how much of the cardiac output and how much oxygen, respectively?
15%
20%
What is the response of vasculature to the brain in hypotension and hypertension? What is this automatic response called?
Constricts in hypertension
Dilates in hypotension
Autoregulation
What are the two main sets of arteries supplying blood to the brain?
Branches of internal carotid + vertebral arteries (form anterior + posterior circulations)
Lack of blood supply in the anterior cerebral artery is associated with which dysfunctions?
Frontal lobe dysfunction
Contralateral sensory loss in foot + leg
Paresis of arm + foot
Lack of blood supply in the middle cerebral artery is associated with which dysfunctions?
Hemiparesis
Hemisensory loss
Aphasia/dysphasia
Apraxia
Lack of blood supply in the posterior cerebral artery (vertebrobasilar) is associated with which cerebellar dysfunctions?
Ataxia
Nystagmus
Intention tremor
Pendular reflexes
Lack of blood supply in the posterior cerebral artery (vertebrobasilar) is associated with which occipital lobe dysfunctions?
Homonymous hemianopia with macular sparing
When does gliosis occur following a cerebral infarct?
1-2 weeks
What is the most common cause of a subarachnoid haemorrhage?
Spontaneous rupture of a saccular aneurysm (Berry aneurysm)
List diseases that have increased incidence of Berry aneurysms
Polycystic kidney disease
Fibromuscular dysplasia
Coarctation of aorta
Most berry aneurysms occur where?
90% = arterial bifurcations near internal carotid artery 10% = vertebrobasilar circulation
At which diameter do berry aneurysms have greatest risk of rupture?
6-10mm
If over 25mm, risk of rupture decreases
Lacunar infarcts can be present in hypertensives. What are they?
Small cavities up to 10mm in diameter found in basal ganglia, thalami in pons
What is demyelination?
Destruction of myelin sheath surrounding an axon, either due to breakdown or abnormal production
What common disease comes under primary demyelination?
Multiple sclerosis
What is the female:male affected ratio for MS?
2:1
The external appearance of the brain and spinal cord in MS is usually normal. True/False?
True
MS is a grey matter disease. True/False?
False
MS is a white matter disease
Describe the morphology of MS
Well-demarcated plaques in white matter in a non-anatomical distribution
Describe the colour of MS plaques
Active lesions: soft pink
Non-active lesions: firm pearl-grey
What structures do MS plaques commonly affect?
Optic nerve Periventricular white matter Corpus callosum Brainstem Spinal cord
Where do chronic inactive MS plaques typically occupy?
Situated around lateral ventricles
Dementia is always pathological. True/False?
True
Neurodegenerative disorder, not just part of ageing!
List diseases classified as primary dementias
Alzheimer’s disease
Huntington’s disease
Pick’s disease
Lewy body dementia
What is the female:male ratio for Alzheimer’s disease?
2:1
List the genes the can be involved in Alzheimer’s disease
Amyloid precursor protein (c21)
Presenilin 1 (c14)
Presenilin 2 (c1)
ApoE (allele e4)
Describe the morphology of Alzheimer’s disease on the brain
Cortical atrophy
Widened sulci
Narrowed gyri
Dilated ventricles
Which lobes are particularly affected in Alzheimer’s disease?
Frontal
Temporal
Parietal
Which protein forms plaques in Alzheimer’s disease? How are the plaques formed?
Amyloid precursor protein forms central core of neuritic plaques
Oligomerisation of aB fibres
What colour does amyloid protein stain?
Congo red
Which protein in the brain can become tangled and defective in Alzheimer’s disease? What is it found in?
Tau protein
Neurofibrillary tangles
Which area of the brain is affected in Lewy body dementia leading to features of parkinsonism?
Substantia nigra
Which protein, when stained, can help detect Lewy bodies?
Ubiquitin
What happens to the caudate nucleus in Huntington’s disease?
Caudate atrophy with loss of neurons
What are the histopathological landmarks of Pick’s disease dementia?
Swollen neurons (Pick's cells) Filamentous inclusions (Pick's bodies)
Which lobes does Pick’s disease usually affect?
Frontal
Temporal
What is the most common type of secondary dementia?
Vascular (multi-infarct) dementia
What is the main cell involved in repair ans scar formation in the CNS?
Astrocyte
Which cells in the CNS are most sensitive to oxidative damage?
Oligodendrocytes
Microglia are the main cells involved in the formation of _____ around necrotic and damaged tissue
Aggregates
Neurones are organised into aggregates. What is meant by the term ‘aggregate’?
Nuclei ganglia with columns/ layers and assigned functional domains
Subcellular alteration in neurones in response to injury would result in the accumulation of which component of the CNS?
Proteins
Hypoxia as a result of nervous system injury triggers what process in the cell?
Excitotoxicity
Energy failure in cell —> collapse of presynaptic MP —> release of glutamate into synapses —> alters calcium homeostasis —> APOPTOSIS
Outline the progress of oedema into haemorrhagic conversion
CYTOTOXIC OEDEMA: dying cells accumulate sodium and chloride ions, causing osmosis and the shift of water —> swollen cell
IONIC OEDEMA: BBB dysfunction; shift of sodium and chloride into cells creating an osmotic gradient (more water)
VASOGENIC OEDEMA: BBB becomes more dysfunct allowing larger molecules like albumin to cross (very osmotically active) —> profound oedema
HAEM CONVERSION: BBB lets in RBCs (noxious due to high iron content)
During osmosis in the brain tissue, there is an increased in fluid. True/ False?
False
Movement of fluid from extracellular to intracellular
Cerebral ischaemia and infarction can be classified into two categories. What are they? What are they caused by?
Global (generalised reduction in blood flow/ oxygenation) due to severe hypotension
Focal due to vascular obstruction
At what MAP are autoregulatory mechanisms unable to compensate, leading to reduced cerebral perfusion?
<50mmHg
Which area of the brain is particularly sensitive to reduced perfusion and is formed by the bridging of 2 arterial territories on peripheries?
Watershed areas
If cerebral ischaemia and infarction is severe enough, which pathological process will result?
Pan necrosis
List the processes of remodelling that occur in hypertension and cerebrovascular disease. Why are these processes significant in cerebral perfusion?
Increased atherosclerosis Arteriosclerosis Fibrinoid necrosis of BV walls Charcut-Bouchard (micro-aneurysms) INCREASED BP NEEDED TO PERFUSE BRAIN
List the long term consequences of prolonged hypertension
Lacunar infarcts Multi-infarct demetia (multiple lacunar infarcts) Aneurysm formation and rupture Intracerebral haemorrhage Hypertensive encephalopathy
What are the types of intracranial haemorrhage?
Spontaneous
Traumatic
What is the typical appearance of intracerebral haemorrhage?
Massive black spot on white matter of basal ganglia
List the causes of intracranial haemorrhage
Hypertension DM Vaculitis Coagulation disorders Amyloid angiopathy Amyloid deposits (ageing) Drugs Aneurysms/ vascular malformations Heart surgery SAH
What is the pathogenesis of amyloid angiopathy that can lead to ICH?
Lack of compliance of small blood vessels
What is the pathogenesis of AV malformation that can lead to ICH?
Shunting from an artery to a vein and the brain cannot cope with the high pressure in the artery
SAH can lead to what emergency clinical condition in affecting the brain?
Hydrocephalus (blood in subarachnoid space, creates haematomas, leading to increased ICP)
CSF should be clear and acellular. List the limited number of cells found in CSF.
Lymphocytes
Monocytes
Glucose
Protein
Which cells in particular should not be found in CSF?
RBCs
Neutrophils
What are the 3 mechanisms in which CSF can accumulate in the ventricular system? Give examples for each
Obstruction (e.g. inflam, pus, tumours) Reduced reabsorption (post SAH, meningitis) Overproduction (choroid plexus tumour)
What are the two types of hydrocephalus?
Non-communicating (obstruction of CSF flow in ventricular system)
Communicating (outside ventricular system)
Define ‘hydrocephalus ex vacuo’
Dilatation of ventricular system and compensatory increase in CSF secondary to loss of brain parenchyma
Brain herniation can result due to raised intracranial pressure. Describe a subfalcine herniation
Cingulate gyrus pushed under falx cerebri, resulting in limb weakness
Which structures are particularly at risk in a subfalcine herniation?
Anterior cerebral arteries
Paramedian cortex
Brain herniation can result due to raised intracranial pressure. Describe a transtentorial herniation
Medial temporal lobe squeezed under tentorium
Which structures are particularly at risk in a transtentorial herniation?
CN III
Posterior cerebral artery
Cerebral peduncle
Upper brainstem (later)
Brain herniation can result due to raised intracranial pressure. Describe a cerebellar tonsillar herniation
Cerebellar tonsils forced through foramen magnum
Which structures are particularly at risk in a tonsillar herniation?
Brainstem
CSF outflow
Brain herniation can result due to raised intracranial pressure. Describe a transcalvarial herniation
Outside skull forced through fracture
List types of space occupying lesions that can increase ICP. Which is most common?
Primary tumour
Metastatic tumour (most common)
Abscess
Haematoma
How do patients with SOLs typically present?
Headaches (worse in morning)
Vomiting
Seizures
Visual defects inc. papilloedema
Why do patients with SOLs have headaches worse in the morning?
Hypercapnia develops overnight
CNS tumours can occur in all age groups. In which age group are CNS tumours the most common solid malignancy?
Childhood
The most common malignant primary tumour in adults is…
Astrocytoma
The most common malignant primary tumour in children is…
Medullablastoma
The most common benign primary tumour is…
Meningioma
Abscesses will present with symptoms of SOL and which other clinical sign?
Fever
How are abscesses diagnosed and managed?
CT/MRI
Aspiration for culture
Antibiotics
List the two main types of skull fracture
Linear (diastatic fracture)
Compound (full thickness scalp laceration (depressed))
What is a surface contusion?
Bruise to brain
What are the two types of surface contusions?
Coup: impact on brain
Contra-coup: Opposite side that the brain hits off
What are the two theories explaining why contra-coup injuries are worse than coup?
Dense CSF moves to impact coup first
Low pressure cavitation bubbles gravitate to contra-coup side
Intracranial haematoma can be divided into two sub-categories. What are they?
Extradural (80%)
Intradural (20%) - subdural, intracerebral
Intracranial haematomas typically arise due to a fracture to what area of the skull? What artery is affected?
Squamous portion of temporal bone
Middle meningeal artery
What are the two subdivisons of subdural haematoma? What is their aetiology?
ACUTE: History of trauma, usually head injury in elderly
CHRONIC: Associated brain atrophy
Which T cell factors influence the pathogenesis of MS?
TH1: IFNg macrophages
TH17: recruit and activate damaging leukocytes
What humeral factor influences the pathogenesis of MS?
Oligoclonal IgG bands on CSF
Define ‘dementia’
Acquired and persistent generalised disturbance of higher mental functions in otherwise fully alert person
Outline the pathogenesis of dementia
Progressive loss of neurones, typically affecting functionally related neuronal groups
List diseases classified as secondary dementias
Multi-infarct (vascular) dementia
Infection (HIV, syphillus)
Trauma
Metabolic
Which form of dementia is the most common cause of dementia in the elderly?
Alzheimer’s
Define ‘Alzheimer’s dementia’
Insidious impairment of higher intellectual function, with alterations in mood and behaviour
Outline the pathogenesis of amyloid angiopathy
Extracellular eosinophillic accumulation forms B pleated sheets from aB fibres that disrupt the BBB (leads to oedema and hypoxia)
Define ‘Lewy Body dementia’
Progressive dementia with hallucinations and fluctuation of attention/ cognition
What clinical sign distinguishes Lewy Body dementia from Alzheimer’s?
Memory is affected later in Lewy Body dementia
Idiopathic parkinsonism is otherwise defined as…
Parkinson’s Disease
Define ‘Hintingdon’s disease’
Relentlessly progressive neuropsychiatric disorder, occuring between the ages of 30-50yo
List the clinical symptoms of Huntingdon’s disease. Highlight the classical feature.
CHOREA Myoclonus Clumsiness Slurred speech Depression Irritability Apathy
Outline the inheritance pattern of Huntingdon’s Disease
Gene on chromosome 4p
Increase in CAG repeats corresponds to severity of diasease
Define ‘Picks Disease’
Progressive dementia, typically occuring in 50s-60s characterised by change in character and social deterioration leading to impairment of intellect, memory and language
List the clinical symptoms of Picks Disease, corresponding to damage to the frontal and temporal lobes
Personality and behavioural change
Speech and communication problems
Changes in eating habits
Reduced attention span
Define ‘multi-infarct dementia’
Disorder involving deterioration in mental function due to cumulative damage to the brain via hypoxia from multiple blood clots in BVs of the brain
Multi-infarct dementia is more common in males than females. True/ False?
True
What clinical sign distinguishes multi-infarct dementia from Alzheimer’s?
Abrupt onset
Stepwise progression
History of hypertension or stroke
Evidence of stroke on CT/ MRI
Morphologically, multi-infarct dementia can be classified into two types depending on the size of the infarcts. What is the aetiology of these types of infarcts?
LARGE: atheroma of large cerebral arteries causing thromboembolism
SMALL (LACUNAR): Longstanding hypertension
What is the primary location where Alzheimer’s disease starts within the brain?
Nucleus of Meynert
