Neuropathology I Flashcards
What are the cellular components of the CNS?
Nerve cells, microglia, glial cells and supporting structures
What are some examples of glial cells?
Astrocytes, oligodendrocytes, ependymal cells
What are some supporting structures of the CNS?
Connective tissue, meninges, blood vessels
What are some causes of CNS injury?
Hypoxia, trauma, toxic insult, metabolic abnormalities, nutritional deficiencies, infections, genetic abnormalities, ageing
What can damage to nerve cells or their processes lead to?
Rapid necrosis with sudden acute functional failure
Slow atrophy with gradually increasing dysfunction
What causes acute neuronal injury?
Hypoxia or ischaemia = results in neuronal death
When does acute neuronal injury become visible?
Typically 12-24hrs after an irreversible insult to the cell
What are the features of acute neuronal injury?
Shrinking and angulation of nuclei
Loss of nucleus
Intensely red cytoplasm
What are some examples of axonal reactions?
Increased protein synthesis leading to cell body swelling and enlarged nucleolus
Chromatolysis
Inclusions
What is chromatolysis?
Margination and loss of Nissl granules
What are some features of axonal inclusions?
Common in neurodegenerative conditions
Accumulate with ageing
Can occur in viral infections
What is the appearance of astrocytes?
Star shaped with multipolar cytoplasmic processes = present throughout CNS
What are some features of astrocytic processes?
Envelop synaptic plates
Wrap around vessels and capillaries within the brain
What is the function of astrocytes?
Repair and scar formation
Work with endothelial cells to maintain BBB
What is the most important histopathological indicator of CNS injury?
Gliosis = astrocyte hyperplasia and hypertrophy, with cytoplasmic expansion and extension of ramifying processes
What happens to the nucleus of the astrocyte in gliosis?
Enlarges = becomes vesicular with prominent nucleolus
How do old gliotic lesions appear?
Nuclei become small and dark, and lie in a dense net of glial fibrils
What forms the myelin sheath?
Oligodendrocytes = wrap around axons
How do oligodendrocytes react to injury?
Limited reaction = demyelination and apoptosis
Sensitive to oxidative damage
Where are ependymal cells found?
Line the ventricular system = infectious agents produce changes in these cells
What is disruption of ependymal cells associated with?
Local proliferation of sub-ependymal astrocytes = produces ependymal granulations
What is the function of microglia?
Function as macrophages = embryologically derived
How do microglia respond to injury?
Microglia proliferate and are recruited through inflammatory mediators = form aggregates around areas of necrosis and tissue damage
How are microglia important mediators of acute nervous system injury?
M2 = anti-inflammatory, phagocytic, more acute M1 = pro-inflammatory, more chronic
What is the most important baseline cause of neuronal injury?
Hypoxia = cerebral ischaemia, infarct, haemorrhage, cerebral palsy, cardiac arrest
How much of the body’s resting oxygen does the brain consume?
20% = cerebral blood flow can only increase twofold to maintain oxygen delivery
What does onset of ischaemia cause the mitochondria to do?
Causes mitochondrial inhibition of ATP synthesis = leads to ATP reserves being consumed in minutes
What are the different kinds of oedema?
Cytotoxic, ionic, vasogenic and haemorrhagic conversion
What are some causes of cytotoxic oedema?
Intoxication, Reye’s and severe hypothermia
What causes ionic oedema?
Also called osmotic oedema = hyponatraemia and excess water intake
What is the most important kind of oedema?
Vasogenic = caused by trauma, tumours, inflammation, infection or hypertensive encephalopathy
What is the definition of cerebrovascular disease?
Any abnormality of the brain caused by a pathological process in blood vessels
What is the epidemiology of cerebrovascular disease?
3rd commonest cause of death
Commonest cause of adult disability
What are the different kinds of cerebrovascular disease?
Brain ischaemia and infarction, haemorrhages, vascular malformations, aneurysms
What are the two types of cerebral ischaemia?
Global or focal (vascular obstruction)
What is global hypoxic ischaemic damage?
Generalised reduction in cerebral perfusion = autoregulatory mechanisms cannot compensate
What are the causes of global hypoxic ischaemic damage?
Cardiac arrest, shock/severe hypotension, trauma
What areas are particularly sensitive to global hypoxic ischaemic damage?
Watershed areas = zone between two arterial territories
What cell types are most sensitive to global hypoxic ischaemic damage?
Neurons more sensitive than glial cells = neurons of neurocortex and hippocampus are most sensitive
What does severe ischaemia in global hypoxia ischaemic damage lead to?
Pan-necrosis
What is a stroke?
Sudden disturbance of cerebral function of vascular origin
What causes a cerebral infarction?
Interruption of cerebral blood flow due to thrombosis or emboli
What is the epidemiology of cerebral infarction?
Peak incidence age >70
More common in men
What are the two types of cerebral infarctions?
Thrombotic = usually middle cerebral artery territory Embolic = from atheroma in internal carotid or aortic arch
What are the risk factors for cerebral infarctions?
Atheroma, hypertension, obesity, diabetes, heart disease, disease of neck arteries, drugs, smoking
What changes can be seen up to 24hrs after a cerebral infarction?
0-12hrs = little change visible 12-24hrs = pale soft and swollen with ill defined margin between injured and normal brain, red neuron and oedema with generalised cell swelling
What changes can be seen 24-48hrs after a cerebral infarction?
Pale soft and swollen with ill defined margin between injured and normal brain, increasing neutrophils and extravasation of RBC, activation of astrocytes/microglia
What changes occur 2-14 days after a cerebral infarction?
Brain becomes gelatinous and friable, reduction in surrounding tissue oedema, microglia become predominant cell type, reactive gliosis begins from week 1
What changes occur several months after a cerebral infarction?
Increasing liquefication, cavity with dark grey tissue lining, ongoing phagocytosis brings increasing cavitation and surrounding gliotic scar formation
What occurs in haemorrhagic infarcts?
BBB disruption and haemorrhagic conversion
What is thrombolysis?
Occlusion of a vessel with reperfusion and leakage through a damaged capillary bed following lysis of the embolus
What symptoms occur if there is a lesion of the carotid artery?
Contralateral weakness or sensory loss, if dominant hemisphere there may be aphasia or apraxia
What symptoms occur if there is a lesion in the middle cerebral artery?
Weakness = predominantly contralateral face and arm
What symptoms occur if there is a lesion of the anterior cerebral artery?
Weakness and sensory loss in the contralateral leg
What symptoms occur if there is a lesion in the vertebro-basilar artery?
Vertigo, ataxia, dysarthria, dysphagia
What features occur in hypertension?
Accelerated atherosclerosis, lacunes, hyaline atherosclerosis, micro-aneurysms
What are the consequences of atherosclerosis?
Lacunar infarcts, multi-infarct dementia, hypertensive encephalopathy, ruptured aneurysms and intra-cerebral haemorrhage
What are the types of spontaneous intracranial haemorrhages?
Intracerebral, subarachnoid or due to haemorrhagic infarct
What are some causes of traumatic intracranial haemorrhage?
Extra/subdural haematoma, contusion, intracerebral or subarachnoid haemorrhage
What are the contributing factors to an intracerebral haemorrhage occurring?
Hypertension, aneurysms, coagulation disorders, vascular malformations, amyloid deposits, open heart surgery, neoplasms, vasculitis
What are the most common sites for intracerebral haemorrhages?
Basal ganglia, thalamus, cerebral white matter or cerebellum
What are the features of an intracerebral haemorrhage?
Asymmetrical distortion, herniations and shifts, well demarcated intraparenchymal haematomas, sofetning of adjacent tissue, surrounding oedema
What are some vascular malformations that can cause major bleeds?
Arteriovenous malformations and cavernous angiomas
What are some vascular malformations which rarely bleed?
Venous angiomas and capillary telangectases
What additional symptoms can vascular malformations cause?
Seizures, headaches and focal neurological deficits
What are some features of arteriovenous malformations?
Abnormal tortuous vessels shunting from artery to vein = undergo smooth muscle hypertrophy, non-compliant and rupture easily, form aneurysms
What are the two types of subarachnoid haemorrhage?
Spontaneous or traumatic
What is the most common cause of a subarachnoid haemorrhage?
Ruptured berry aneurysm = 90% in territory of ICA, other 10% in territory of vertebro-basilar circulation
Where do subarachnoid haemorrhages arise?
At arterial bifurcations = blood enters subarachnoid space
What are some features of subarachnoid haemorrhages?
Intracerebral haematomas adjacent to aneurysms
Infarcts of brain parenchyma
What are the risk factors for subarachnoid haematomas?
Smoking, hypertension and kidney disease
What are the clinical features of subarachnoid haemorrhages?
Abrupt onset and no history of precipitating factor
Severe headache and loss of consciousness
Vomiting
What is the prognosis of a subarachnoid haemorrhage?
50% die within several days of onset
Survivors are at risk of hydrocephalus
