Neuropathology Flashcards
Neuroectodermal tissue is _________
CNS tissue consisting of neurons and glia
Mesodermal tissue is _______
blood vessels and meninges
microglia
What are the two main types of neuronal damage?
Rapid necrosis > associated with acute failure of function
Slow atrophic changes > associated with gradual loss of function
There is no regeneration of _________
destroyed neurons
Describe what happens in acute neuronal injury?
Occurs in the context of hypoxia / ischaemia
Typically visible 12-24 hours after an irreversible “insult” to the cell
Results in neuronal cell death
Pattern:
Shrinking and angulation of nuclei
Loss of the nucleolus
Intensely red cytoplasm
Describe what happens in axonal injury?
Increased protein synthesis -> cell body swelling, enlarged nucleolus
Chromatolysis – margination and loss of Nissl granules
Degeneration of axon and myelin sheath distal to injury
Describe what happens in simple neuronal atrophy?
Shrunken, angulated and lost neurons, small dark nuclei, lipofuscin pigment, reactive gliosis
occurs in groups of functionally related nerones
Describe what sub cellular alterations / inclusions are?
inclusions shown in some neurones in some disease
e.g. neurofibrillary tangles in Alzheimer’s disease
Inclusions appear to accumulate with ageing
Also get inclusion in viral infections affecting the brain
What type of injury are oligodendrocytes sensitive to?
oxidative injury
What are the main cells involved in repair and scar formation in the CNS?
astrocytes
What is gliosis?
the scarring process undertaken by astrocytes
What is the most important histopathological indicator of CNS injury regardless of the cause?
gliosis
Describe the process of gliosis?
There is hyperplasia and hypertrophy of the astrocytes
There is an increase in fibril production
Later the cells atrophy leaving a dense meshwork of fibres
Microglial cell response to injury?
Microglia proliferate
Recruited through inflammatory mediators
Form aggregates around areas of necrotic and damaged tissues
Describe cerebral autoregulation to blood flow?
- If MABP rises, resistance vessels automatically constrict to limit blood flow
- If MABP falls, resistance vessels automatically dilate to maintain blood flow
This auto regulation works between a MAPB of 60-160mmHg
Neurons are very susceptible to ______
hypoxia
Describe excitotoxicity in hypoxia?
Toxicity of hypoxia is exacerbated by excitotoxicity as energy failure results in neuronal depolarisation which causes glutamate release , at same time astrocytes cant uptake glutamate so then get glutamate storm and excitation
Explain what cytotoxic oedema is?
Intracellular swelling in acute cerebral ischaemia due to hypoxia causing failure of the ATP-dependent ion channels (mainly sodium) so influx of ions and therefore influx of water (water and sodium follow each other!)
Explain what vasogenic oedema is?
There is extravasation and extracellular accumulation of fluid in the cerebral parenchyma. This is due to the infarction causing damage to the endothelium and disruption of the blood brain barrier so fluid can leak out. At this point the endothelium aren’t damaged enough to let out red blood cells.
Explain what haemorrhagic conversion is?
This is a sequelae to vasogenic oedema. Endothelial integrity completely lost and blood can enter the extracellular space.
Why are middle cerebral artery events more common?
it is in line with the internal carotid artery
Describe what happens in global hypoxic ischaemic damage?
Generalised reduction in cerebral perfusion
E.g. in cardiac arrests, shock/ severe hypotension trauma
Autoregulatory mechanism cannot compensate when the MAP falls below 50mmHg
What is a stroke?
Sudden disturbance of cerebral function of vascular origin that causes death or lasts over 24 hours (results in irreversible tissues loss)
Most strokes are caused by?
Thromboembolic event
thrombosis from atherosclerotic segment in middle cerebral artery
embolism from vessels surrounding the heart
Describe pathological findings in a brain between 0-12 hours after cerebral infarction?
little visible macro or microscopically
Describe pathological findings in a brain between 12-24 hours after cerebral infarction?
Macro
Pale soft and swollen with ill defined margin between injured and normal brain
Micro
early neuronal damage e.g. red neurons
Describe pathological findings in a brain few days after cerebral infarction?
Macro
Brain becomes gelatinous and friable. A reduction in the surrounding tissue oedema demarcates the lesion.
Micro
Microglia become predominant cell type; myelin breakdown. Reactive gliosis begins from as early as 1 week
Describe pathological findings in a brain between several weeks to months after cerebral infarction?
Macro
Increasing liquification apparent. Eventual formation of cavity lined by dark grey tissue.
Micro
Ongoing phagocytosis brings increasing cavitation and surrounding gliotic scar formation
What are the two types of stroke?
Ischaemic Haemorrhagic (spontaneous intracranial blaeding)
List 3 types of spontaneous intracranial bleeding that could cause stroke?
Intracerebral haemorrhage
Sub-arachnoid haemorrhage
Haemorrhagic Infarct
Describe some risk factors for intracerebral haemorrhage?
Any causes of vascular injury ie: Hypertension Amyloid deposits (cerebral amyloid angiopathy) Diabetes Drugs: cocaine, alcoholism Vasculitis (infectious and inflammatory)
Aneurysms Vascular malformations Systemic coagulation disorders / iatrogenic anticoagulation Open heart surgery Neoplasms
Where does intracerebral haemorrhage most commonly occur?
most commonly in the basal ganglia
What type of vascular malformation is most commonly and most likely to result in a significant haemorrhage?
arteriovenous malformations
Describe what arteriovenous malformations are and how they predispose someone to intracerebral haemorrhage?
abnormal connection between arteries and veins, bypassing the capillary system resulting in torturous haphazardly arranged vessels containing arteries, veins and in between forms
Risk of bleeding is from shunting between arteries and veins which brings about hypertrophy of smooth muscle and loss of compliance and also formation of aneurysms in these areas which are also prone to rupture
Where do arteriovenous malformations most commonly occur?
In middle cerebral artery territory
What is the most common cause of a spontaneous subarachnoid haemorrhage?
rupture of a saccular aneurysm (Berry aneurysm)
CNS samples are normally ___________
acellular (occasionally with a small number of lymphocytes)
RBCs in a CSF sample would occur in ________
contamination of the sample
Increased lymphocytes in a CSF sample occurs in _______
autoimmune causes or underlying infection
Increased polymorphs/ neutrophils in a CSF sample will occur in ____________
bacterial infections e.g. bacterial meningitis
Increased protein levels in CSF sample will occur in ______________
bleeding, inflammation and tumour formation
Low glucose levels in a CSF sample will occur in _______________
bacterial, fungal or tuberculous meningitis
Define hydrocephalus
Increased volume of CSF within the cranial cavity
What is the most common cause of enlargement of the ventricles?
cerebral atrophy (loss of brain parenchyma as we get older so CSF fluid increases to accommodate)
Explain why hydrocephalus ex vacuo is?
Hydrocephalus ex-vacuo occurs when a stroke or injury damages the brain and brain matter actually shrinks. The brain may shrink in older patients or those with Alzheimer’s disease, and CSF volume increases to fill the extra space. In these instances, the ventricles are enlarged, but the pressure usually is normal
Acute hydrocephalus with increased ICP is most often due to ________
obstruction the free flow of CSF
Describe some things that could obstruct the flow of CSF and therefore cause hydrocephalus?
lesions adjacent to the inter ventricular foramen of Monro (inter ventricular foramina)
previous meningitis or subarachnoid haemorrhage resulting in partial obliteration of the CSF also blocks the flow
congenital malformations
Cranial sutures typically close between ___1____
If hydrocephalus occurs before this you get ____2____
If hydrocephalus occurs after this you get _____3_____
1) 2-3 yrs age
2) cranial enlargement with increase in occipital frontal circumference inappropriate for gestational age
3) expansion of the ventricles and increased intracranial pressure
What is normal range of intracranial pressure?
5-13 mmHg
If the brain enlarges some ____1_____ must escape from the cranial vault to avoid a rise in pressure
Once this process is exhausted ___2______
Any further increase in brain volume ______3_____
1) blood and or CSF must escape from the cranial vault
2) venous sinuses are flattened and there is little remaining CSF
3) will result in a rapid increase in ICP
Herniations occur through _______
The most common are ____________
routes of weakest resistance subfalcine tentorial tonsillar transcalvarial
Describe subfalcine herniation ?
asymmetrical expansion of the cerebral hemispheres displaces the cingulate gyrus underneath the falx cerebri (can result in associated compression of anterior cerebral artery branches – weakness in contralateral leg)
Describe tentorial herniation?
medial or inner most aspect of the temporal lobe herniates over the tentorium cerebelli (compression of ipsilateral 3rd cranial nerve and its parasympathetic fibres bringing about pupillary dilatation and a lack of responsiveness to light, also impairment of ipsilateral ocular movements)
Describe tonsillar herniation?
displacement of cerebellar tonsils through the foramen magnum (life threatening as compresses the brainstem so comprises vital respiratory centres in the medulla oblongata)
Describe transcalvarial herniation?
swollen brain herniates through any defect in the dura and skull
When do headaches caused by tumours tend to be worse and why?
tend to be worse in the morning as in the morning you are slightly hypercapnia which increases blood flow to the brain which increases volume which even more increases the pressure caused by the tumour
In children where do 70% of brain tumours arise? How does this differ from adults?
below the tentorium cerebelli
in adults the majority arise above the tentorium cerebelli
Describe characteristics of metastatic tumours?
Tend to be multiple and tend to arise in the boundary between white and grey matter
Explain why the terms benign and malignant do not readily apply to glial tumours?
No matter how differentiated or benign a glioma appears it almost invariably infiltrates into the adjacent brain, rendering complete surgical excision impossible and recurrence almost certain.
On the other hand no matter how rapidly growing and poorly differentiated the glioma appears, metastasis outside the CNS is very unlikely.
Describe macroscopic and microscopic appearance of an astrocytoma?
Macroscopically the tumour may be difficult to distinguish from the surrounding brain
Histologically the tumour is composed of cells resembling astrocytes
What type of variant of astrocytoma tends to occur in children and young adults?
pilocytic
What is by far the most common glial tumour and who does it usually arise in?
glioblastoma
patients aged over 50
Describe macroscopic and microscopic appearance of a glioblastoma?
Macroscopically it is firm white or yellow in colour with areas of haemorrhage and necrosis, it may appear well circumscribed but histologically there is infiltration of surrounding brain structures by tumour cells
mitoses, endothelial cell hyperplasia and tumour necrosis are present
Describe macroscopic and microscopic appearance of a oligodendroglioma?
relatively circumscribed and commonly calcified tumours
cells resemble oligodendroglial cells
Are oligodendrogliomas usually slow or fast growing?
slow
What type of tumours is a medulloblastoma?
primitive neuroectodemeral tumour of the cerebellum
Where does a medulloblastoma usually occur?
in the midline of the cerebellum
Medulloblastomas tend to spread ________ leading to _______
subarachnoid space
obstruction of CSF flow and hydrocephalus
Meningiomas are attached to the meninges and probably originate from ___________
arachnoid granulations
Where do meningiomas tend to arise?
adjacent to the major venous sinuses, commonly parasagittal or from the base of the skull, often in the region of the olfactory groove or the sphenoidal ridge
Single brain abscesses usually have a ________ e.g. ________
localised cause
chronic otitis media, sinusitis etc or direct implantation from skull fracture
Multiple brain abscess suggest _______ and tend to occur _______________ in conditions such as _________
haematogenous spread
grey and white matter boundaries
pneumonia, bacterial endocarditis, congenital heart disease, IV drug abuse
Symptoms of a brain abscess?
Symptoms of underlying infection PLUS symptoms of raided ICP
What are the two principal types of head injury?
missile/ penetrating
non-missile/ blunt
In blunt head injury what are the two main causes of damage to the brain?
acceleration/ deceleration
contact
Describe primary damage vs secondary damage in trauma?
Primary: injury to neurones that occurs at the time of the injury, it is irreversible, current interventions are preventive measures e.g. seatbelts and helmets
Secondary: this accumulates after the primary injury, potentially reversible, this includes haemorrhage, oedema
Describe some primary injuries after blunt trauma?
· Scalp lesions · Skull fractures · Surface contusions · Surface lacerations · Diffuse axonal injury · Diffuse vascular injury · Petechial haemorrhages
What do skull fractures indicate?
high degree of energy involved in the injury
Describe coup and contra coup injuries?
Coup injury occurs at site of impact
Contra coup occurs at site opposite impact
What is diffuse axonal injury?
Form of traumatic brain injury, it happens when the brain rapidly shifts inside the skull as an injury is occurring. The axons are sheared as the brain rapidly accelerates and decelerates inside the hard bone of the skull.
Where does diffuse axonal injury tend to occur?
Affects the central areas: brainstem corpus callous parasaggital areas inter ventricular septum hippocampal formation
Histologically what do you see with diffuse axonal injury?
axonal bulbing
What things contribute to secondary brain injury after trauma?
Due to intracranial haematoma, reduced cerebral blood flow, hypoxia, excitotoxicity, odema, raised ICP, infection
What do intracerebral haematomas tend to be associated with?
contusions and occur principally in the frontal or temporal lobe
What does the term burst lobe refer to?
the combination of an intracerebral haematoma in continuity with a subdural haematoma through surface contusions
What are extradural haematomas usually a complication of?
fracture in tempero-parietal region that involves middle meningeal artery
Where do subdural haematomas usually occur?
over cerebral convexities
Subdural haematomas have a high or low mortality?
high (so most people dot develop chronic ones)
Describe chronic subdural haematomas?
presents weeks or moths after an apparently trivial head injury (common in elderly)
haematoma is organised and becomes encapsulated in a fibrous membrane, see blood tinged yellow membranous fluid
can become quite large before symptoms appear
Define demyelination
Preferential damage to the myelin sheath
Relative preservation of the axons
What is the most common demyelinating disease?
Multiple sclerosis
Describe the macroscopic pathology of MS?
Principally a white matter disease so the exterior surface of the brain typically appears normal
The cut surface of the brain shows plaques
Plaques are Well circumscribed, well demarcated, irregular shaped areas, glassy and almost translucent appearance, vary from very small to large lesions
Can occur at any site in CNS
Tend to distributed in a non symmetrical manner
What areas are MS plaques typically found?
periventricular areas, the corpus callosum, the optic nerves and chiasm, the brain stem, the ascending and descending fibre tracts, the cerebellum and the spinal cord
Describe inactive and active plaques in MS?
In acute active lesions there is evidence of ongoing myelin break down with abundant microglia which contain phagocytosed lipid debris. Inflammatory cells are present.
As active plaques age astrocytes undergo reactive changes (gliosis) and inflammatory cells reduce in number.
Define dementia
An acquired and persistent generalised disturbance of higher mental functions in an otherwise fully alert person
Name 4 primary dementias?
Alzheimers
Lewy Body Dementia
Pick’s disease (fronto temporal dementia)
Huntingtons Disease
What is the 1st, 2nd and 3rd most common dementias?
1st: Alzheimers
2nd: Vascular
3rd: Lewy body dementia
Alzheimers disease is more common in _____
women
more common after 60 yo (earlier may suggest a familial cause)
Describe macroscopic appearance of a brain with alzheimers disease?
Brain mass lost from cortical atrophy
location of atrophy is the frontal, temporal and parietal lobes (sparing of the occipital lobe)
there is widening of the sulk and narrowing of the gyri
Name 4 histological hallmarks of Alzheimers disease?
- extracellular senile plaques (amyloid a beta plaques)
- intracellular neurofibrillary tangles
- amyloid angiopathy
- loss of neurons and synapses
Almost all patients with Down’s syndrome who survive until they are 50 develop Alzheimers which suggests _______
chromosome 21 is important in the pathogenesis
Theories of pathogenesis of Alzheimers?
Mutations in amyloid precursor protein which causes pathological a beta amyloid to be produced which accumulates and triggers neuronal degeneration
Describe what sort of symptoms occur in Lewy body dementia?
Progressive dementia along with hallucinations and fluctuating levels of attention/ cognition
(some overlap with alzheimers but memory is affected later!)
Describe the relationship between parkinsons and lewy body dementia?
Only some people with parkinsons get lewy body dementia but almost everyone with lewy body dementia shows features of parkinsons
Macroscopic appearance of lewy body dementia?
similar to parkinsons, degeneration of substantia nigra, pallor in the substantia nigra where pigmented dopaminergic neurons run
Microscopic appearance of lewy body dementia?
loss of pigmented neurons, reactive gliosis, remaining neurons may show lewy bodies
Macroscopic appearance of brain in huntingtons disease?
Atrophy of the basal ganglia particularly the caudate nuculeus and to lesser extent the putamen, secondary atrophy of globus pallidus, compensatory expansion of the lateral and third ventricles. Later there is frontal, parietal and sometimes cortical atrophy.
Microscopic appearance of the brain in huntingtons disease?
simple neronal atrophy of striatal neurons the basal ganglia, pronounced astrocytic gliosis
Fronto temporal dementia is also known as ________
Picks Disease
Describe what sort of symptoms occur in Picks Disease?
A progressive dementia commencing in middle life (usually 50 and 60) characterised by progressive changes in character and social deterioration leading on to impairment of intellect, memory and language.
Describe macroscopic appearance of a brain with Picks disease?
Extreme atrophy of the cerebral cortex in the frontal and later in temporal lobes
Sparing the parietal and occipital lobes
Usually extent of atrophy is much more than alzheimers
Brain can be less than a kg
Describe microscopic appearance of a brain with Picks disease?
picks cells (swollen neurons), intracytoplasmic filamentous inclusions known as Pick’s bodies
Describe the pathogenesis of multi infarct dementia?
• Disorder involving a deterioration in mental functioning due to cumulative damage to the brain through hypoxia or anoxia (lack of oxygen) as a result of multiple blood clots within the blood vessels supplying the brain
• Successive multiple cerebral infarctions cause increasingly larger areas of cell death and damage
When a sufficient volume of the brain is damaged dementia results
What feature characterises multi infarct (vascular dementia)?
Insight
Sufferers are aware of their mental deficits and are prone to depression and anxiety
Describe pathological appearance of a brain with multi infarct (vascular) dementia?
Macroscopically see evidence of large vessel infarcts, larger infarcts are more common and scattered throughout the hemispheres, these are usually associated with atheroma of large cerebral arteries which provoke thromboembolism Small vessel (lacunar infarcts), rarer and occur in central subcortical distribution, particularly related to longstanding hypertension and atherosclerosis of small vessels
