Neurapthology 1

Question 1

main cellular components of CNS?

Answer 1

nerve cells (neurons)
glial cells (astrocytes, oligodendrocytes, ependymal cells)
microglia (immune function)
supporting structures (connective tissue, meninges, blood vessels)

Question 2

damage to nerve cells and/or their processes can cause what?

Answer 2

rapid necrosis with sudden acute functional failure (stroke etc)
slow atrophy with gradually increasing dysfunction (age related cerebral atrophy, dementia etc)

Question 3

what is red neurone?

Answer 3

descriptive term for acute neuronal injury
occurs in context of hypoxia/ischaemia
visible 12-24 hrs after irreversible insult and results in neuronal cell death

Question 4

what is seen in red neurone?

Answer 4

shrinking and angulation of nuclei
loss of nucleus
intensely red cytoplasm

Question 5

how else may a neurone react to injury/disease?

Answer 5

axonal reactions
simple neuronal atrophy (chronic degeneration)
sub-cellular alteration - inclusions

Question 6

describe axonal reactions

Answer 6

increased protein synthesis > cell body swelling, enlarged nucleus
chromatolysis - margination and los of Nissl granules
degeneration of axon and myelin sheath distal to injry “wallertan degeneration)

Question 7

describe simple neuronal atrophy?

Answer 7

shrunken, angulated and lost neurons, small dark nuclei, lipofuscin pigment, reactive gliosis

Question 8

describe sub-cellular alterations

Answer 8

common in neurodegenerative conditions (e.g neurofibrillary tangles in alzheimers)
inclusions accumulate with ageing
also get inclusions in viral brain infections

Question 9

function of astrocytes?

Answer 9

start shaped cells in CNS with astrocytic processes which envelop synaptic plates and wrap around vessels and capillaries
involved in ionic, metabolic and nutritional homeostasis
work in conjunction with endothelial cells to maintain BBB
main cells involved with repair and scar formation

Question 10

what is gliosis?

Answer 10

astrocyte response to injury
most important histopathological indicator of CNS injury
shows astrocyte hypertrophy and hyperplasia
nucleus enlarges and becomes vesicular and the nucleolus is prominent
cytoplasmic expansion with extension of ramifying processes
in old lesions, nuclei are small and dark and lie in a dense net of processes (glial fibrils)

Question 11

function of oligodendrocytes?

Answer 11

wrap around axons forming myelin sheath in CNS

Question 12

how do oligodendrocytes respond to damage?

Answer 12

limited reaction
variable patterns and degree of demyelination
apoptosis
sensitive to oxidative damage
damage is a feature of demyelinating disorders

Question 13

function of ependymal cells and how do they react to damage?

Answer 13

line ventricular system
limited reaction to injury
- disruption associated with local proliferation of sub-ependymal astrocytes to produce small irregularities on ventricular surface called ependymal granulation

Question 14

function of microglia?

Answer 14

embryologically derived cells which function as a macrophage system (phagocytosis)
important mediators in acute nervous system injury
- M1 = pro-inflammatory, more chronic
- M2 = anti-inflammatory, phagocytic, more acute

Question 15

microglia response to injury?

Answer 15

microglia proliferate
recruited through inflammatory mediators
form aggregates around areas of necrotic and damaged tissues

Question 16

why is the brain so sensitive to hypoxia?

Answer 16

brain consumes 20% of all body resting oxygen consumption

cerebral blood flow can only increase twofold to maintain oxygen delivery, so cant cope well with hypoxia

Question 17

what happens in the rbain with hypoxia?

Answer 17

after onset of ischaemia, mitochondrial inhibition of ATP synthesis leads to ATP reserves being consumed within a few minutes

Question 18

describe the pathway of excitotoxicity?

Answer 18

energy failure (hypoxia) > neuronal depolarization and inhibition of astrocyte reuptake > release and inhibited reuptake of glutamate > glutamate storm and excitation > increased Ca2+ > oxidative stress, protease activation and mitochondrial dysfunction

Question 19

what are the 3 types of oedema?

Answer 19

cytotoxic (intoxication, reye’s, severe hypothermia)
ionic/osmotic (occurs in hyponatraemia and excess water intake/SIADH)
vasogenic (most important) - occurs in trauma/tumours/inflammation/infection/hypertensive encephalopathy

Question 20

haemorrhagic conversion?

Answer 20

complication of ischaemic stroke where bleeding occurs after reperfusion of the blocked artery

Question 21

cerebral arteries supply what general areas of the brain?

Answer 21

anterior = midline
middle = lateral aspects
posterior = posterior

Question 22

the brain uses how much of cardiac output?

Answer 22

15% of cardiac output and 20% of oxygen

Question 23

how is the brain supplied?

Answer 23

requires active aerobic metabolism of glucose
autoregulatory mechanisms help maintain blood flow over wide range of blood perfusion pressures at a constant rate by dilation and constriction of cerebral vessels

Question 24

what is cerebrovascular disease?

Answer 24

any abnormality of brain caused by a pathological process of blood vessels

Question 25

stroke essentially involves what 2 processes?

Answer 25

infarction/ischaemia/hypoxia etc haemorrhage/blood vessel damage/rupture etc - underlying link = hypertension

Question 26

global vs focal hypoxic ischaemic damage?

Answer 26

global = generalised reduction in blood flow/oxygenation (e.g cardiac arrest, severe hypotension) focal (e.g vascular obstruction)

Question 27

describe global hypoxic ischaemic damage/

Answer 27

generalised reduction in cerebral perfusion autoregulatory mechanisms cant compensate watershed areas are vulnerable neurons more sensitive than glial cells can lead to pan-necrosis if severe

Question 28

definition of stroke?

Answer 28

sudden disturbance of cerebral function of vascular origin that causes death or lasts over 24 hrs

Question 29

what causes cerebral infarction and who is it most common in?

Answer 29

``` interruption of cerebral blood flow due to thrombosis or embolization thrombosis - atherosclerosis - usually in middle cerebral artery embolic - from atheroma in internal carotid and aortic arch - travels from heart more common in men over 70 ```

Question 30

what can influence the end result of cerebral infarct?

Answer 30

arterial territory of affected artery timescale of occlusion extent of collateral circulatory relief systemic perfusion pressure

Question 31

when is damage first seen after cerebral infarct and what is seen?

Answer 31

12 hrs 12-24 hrs = pale soft and swollen with ill defined margins red neurones, oedema and swelling

Question 32

what is seen 24-48 hrs after stroke?

Answer 32

increasing neutrophils, extravasation of red blood cells and activation of astrocytes and microglia

Question 33

what is seen 2-14 days after stroke>

Answer 33

``` brain becomes gelatinous and friable reduction in surrounding tissue oedema demarcates the lesion microglia are predominant myelin breakdown reactive gliosis ```

Question 34

what is seen several months after stroke?

Answer 34

increasing liquification formation of cavity lined by dark grey tissue ongoing phagocytosis increases cavitation and surrounding gliotic scar formation

Question 35

what is haemorrhagic infarct?

Answer 35

where, in context of infarct, the blood brain barrier is damaged and deteriorates allowing blood to leak through after reperfusion following the infarct stroke further disrupts damage of infarct

Question 36

hypertension can cause what types of vessel remodelling?

Answer 36

accelerated atherosclerosis arteriolosclerosis - thick, stiff and weak walls fibrinoid necrosis of vessel walls if severe formation of lacunes microaneurysms

Question 37

how can a vascular lesion be localised?

Answer 37

carotid artery disease = contralateral weakness/sensory loss, aphasia or apraxia if dominant hemisphere middle cerebral artery = weakness in contralateral face and arm anterior cerebral artery = weakness and sensory loss in contralateral leg vertebrobasilar artery = vertigo, ataxia, dysarthria and dysphasia

Question 38

4 consequences of hypertension?

Answer 38

lacunar infarcts multi-infarct dementia ruptured aneurysms and intra-cerebral haemorrhage hypertensive encephalopathy

Question 39

what are lacunar infarcts?

Answer 39

atheroma, embolism of small penetrating vessels leads to occlusion vessels which supply basal ganglia etc when multiple, contribute to multi-infarct dementia

Question 40

hypertensive encephalopathy findings?

Answer 40

``` severe hypertension symptoms of raised ICP global cerebral oedema tentorial and tonsillar herniation arteriolar fibrinoid necrosis petechiae ```

Question 41

2 types of intracranial haemorrhage, spontaneous includes what?

Answer 41

intracerebral haemorrhage sub-arachnoid haemorrhage haemorrhagic infarct

Question 42

types of traumatic intracranial haemorrhage?

Answer 42

``` extra-dural haematoma sub-dural haematoma contusion (surface bruising) intracerebral haemorrhage sub-arachnoid ```

Question 43

what can contribute to causing an intracranial haemorrhage?

Answer 43

``` hypertension aneurysms systemic coagulation disorders anticoagulation vascular malformations amyloid deposits open heart surgery neoplasms vasculitis ```

Question 44

what morphology is seen in intracerebral haemorrhage?

Answer 44

``` asymmetry shifts/herniations are common intraparenchymal haematomas softening of adjacent tissue surrounding oedema ```

Question 45

what is amyloid angiopathy and how can it cause haemorrhage?

Answer 45

accumulation of beta-beta sheets sticking together to form a plaque causes vessels to become stiff and rigid so cant respond to changes in BP so likely to rupture

Question 46

name 4 types of vascular malformations

Answer 46

arteriovenous malformations cavernous angiomas venous angiomas capillary telangectases

Question 47

what happens in an AVM?

Answer 47

abnormal torturous vessels - usually occurring in middle cerebral arteries in cerebrum causes shunting from artery to vein which causes vein to undergo smooth muscle hypertrophy or aneurysms which can rupture veins not made to cope with the pressure so can rupture easily

Question 48

what commonly causes subarachnoid haemorrhage?

Answer 48

usually spontaneous most common = rupture of saccular aneurysm most are in internal carotid arise in arterial bifurcations (circle of willis)

Question 49

describe the morphology seen in subarachnoid haemorrhage?

Answer 49

``` presence of berry aneurysm blood in the subarachnoid space may see - intracerebral haematomas - infarcts of brain parenchyma - mass effect of haematoma and features of raised ICP - hydrocephalus ```

Question 50

clinical features of subarachnoid haemorrhage?

Answer 50

severe headache vomiting loss of consciousness usually no history of a precipitating factor risk factors = smoking, hypertension, kidney disease