Case 5 - blood supply to the brain and ischaemia

Question 1

stroke is what number in the leading cause of death tables

Answer 1

2nd leading cause of deaths worldwide

Question 2

how much of body weight is the brain

Answer 2

2-3%

Question 3

how much of the cardiac output does the brain receive

Answer 3

15%

Question 4

How much of the body’s glucose and oxygen does the brain receive

Answer 4

20% of the oxygen and 25% of glucose

Question 5

what is the furthest distance from a blood supply capillary is a neurone

Answer 5

20-30 micrometres

Question 6

what are the two pairs of arteries that supply the brain

Answer 6

the internal carotid arteries (anterior) and the vertebral arteries (posterior)

Question 7

the anterior cerebral artery is a branch of which artery

Answer 7

the internal carotid artery

Question 8

what does occulsion of the anterior cerebral artery cause

Answer 8

paralysis and sensory loss in contralateral leg and perineum

Question 9

what is the largest branch of the internal carotid artery

Answer 9

the middle cerebral artery

Question 10

where does the middle cerebral artery pass though

Answer 10

the lateral sulcus and travels along the lateral surface of the frontal and parietal lobes

Question 11

what is the most common site for a stroke

Answer 11

the middle cerebral artery

Question 12

what would occlusion of the middle cerebral artery cause

Answer 12

contralateral paralysis - mostky in lower face and in the arm
general somatosensory deficits
speech deficits (aphasia) if dominant hemisphere is affected

Question 13

where does the basilar artery run

Answer 13

forward in midline on ventral surface of the pons

Question 14

what are the branches of the basilar artery

Answer 14

anterior inferior cerebellar, pontine and superior cerebellar

Question 15

where does the basilar artery divide nd what does it divide into

Answer 15

at rostral end of the midbrain and the posterior cerebral arteries

Question 16

what happens if there is occlusion of the basilar artery

Answer 16

coma - followed by death due to respiratory failure

Question 17

where does the posterior cerebral artery run

Answer 17

curves around. the midbrain and reaches medial surface of the cerebral hemisphere

Question 18

what are the important branches of the posterior cerebral artery

Answer 18

cortical branches supply the visual cortex, posterior chroiodal and posterior communicating

Question 19

what does occlusion of the posterior cerebral artery lead to

Answer 19

blindness

Question 20

what does the circle of willis form

Answer 20

an anastomoses

Question 21

why are anastomoses not sufficient

Answer 21

due to narrowing of large vessels and communicating arteries because of vascular disease

Question 22

functional consequences of stroke diagram

Answer 22

Question 23

what are the series of events in an ischaemic stroke

Answer 23

• lack of blood supply
• energy failure - no ATP made
• anoxic depolarisation of cell membranes, excitotoxicity, oxisdative stress, necrosis
• peri-infarct depolarisation, calcium overload, mitochondrial damage
• inflammation and programmed cell death

Question 24

progression of an intracerebral haemorrhage

Answer 24

• rupture of a blood vessel
• blood leaking into the brain causes disruption to the tissue, physically will displace tissue in the Brin
• increase in inter cranial pressure
• reduce blood flow - secondary ischaemia
• midline shift in extreme causes

Question 25

what is the primary region of damage to the brain referred to as

Answer 25

the core

Question 26

what is the main characteristic of the core

Answer 26

this is where blood supply is reduced to dramatically low levels which is less than 20% of normal flow

Question 27

what is the penumbral region

Answer 27

an area with reduced blood flow, but not as severe as the core.

Question 28

how much of normal blood flow is there in the penumbral region

Answer 28

20-50% normal flow

Question 29

how do neurones behave in the penumbral region

Answer 29

they are still functionally active

Question 30

what does the core have that the penumbra does not

Answer 30

dead tissue

Question 31

penumbra characteristics

Answer 31

- vulnerable tissue - surrounding regions - blood supply compromised but not cut off - cells under threat but not dead - potential for rescue - must start treatment early - can become core when the core expands and kills this as the core releases toxins

Question 32

what does a CT show

Answer 32

only the core and dead tissue

Question 33

what is the key, major excitatory transmitter in the brain

Answer 33

glutamate

Question 34

what does glutamate produce

Answer 34

downstream signals

Question 35

what happens if you have glucose in excess

Answer 35

it overwhelms the synapse, and glucose is taken back up unto the presynaptic terminals or by glial cells

Question 36

what happens to the process of glucose reuptake in stroke

Answer 36

this process is overwhelmed because of the loss of energy and the glutamate builds up and it spills over and begins to activate other types of glutamate subtype receptors which lead to cell death though downstream mechanisms

Question 37

what happens when there is a collapse of membrane patents

Answer 37

release of degenerative oxidative stress

Question 38

what is degenerative oxidative stress driven by

Answer 38

changes in the mitochondria

Question 39

what happens in oxidative stress

Answer 39

the mitochondria membranes will collapse this will release free radicals and reactive oxygen species e.g hydrogen peroxide this is then acted upon by free radicals such as superoxide these free radicals which are extremely toxic, will lead to changes within the cell which leads to oxidation of proteins, perioxidation of lipids and cell death

Question 40

what drives inflammation

Answer 40

oxidative stress

Question 41

what is the term used to describe the relationship between coagulation cascades and inflammation processes

Answer 41

thrombi-inflammation

Question 42

what happens when the tight junctions in the brain are broken down

Answer 42

there will be exposure of the underlying basement membrane. this leads to the release of Von Willibrand factor which will bind platelets, these platelets will then bind fibrin and neutrophils and will form a clot in the vessel itself

Question 43

what are released by dying neurones

Answer 43

damage associated molecular patterns

Question 44

what happens to these DAMPs

Answer 44

these are recognised by the microglia, innate lymphocytes and infiltrated myeloid cells

Question 45

what does this cause s

Answer 45

stero-inflammation

Question 46

what does stero-inflammation lead to

Answer 46

leads to the up regulation and productions of chemokine and cytokines e.g IL-1B pro-inflammatory lymphocytes and anti inflammatory lymphocytes are thought to both contrubre to dementia

Question 47

characteristics of IL-1

Answer 47

- pro inflammatory cytokine - neonatal onset- multisystem inflammatory disease - rheumatoid arthertiiss - released by brain cells in response to injury - 2 ligands - alpha and beta - both released as precursor molecules

Question 48

what is anakinra

Answer 48

an IL-1 receptor antagonist that blocks the biologic activity of IL1. it is naturally occurring

Question 49

what are the two processes in recovery of stroke in the brain

Answer 49

neurogenesis and angiogenesis

Question 50

what is brain plasticity

Answer 50

when other areas adopt or take over the function that wasn't done before

Question 51

why is inflammation important

Answer 51

stem cells release inflammatory substances

Question 52

what are the three brain/nerve stimulations

Answer 52

- directly - transcranial - vagus nerve stimulation

Question 53

what are the problems with tPA

Answer 53

currently only a small proportion of patients treated as need to be given early and stroke services need to be optimal for this to happen there is an increased risk of haemorrhage incomplete re-canalisation and high (27%) re occlusion rate repercussion itself can be detrimental as results in infammatio and oxidative stress

Question 54

percentage of stroke patients treated in the UK

Answer 54

12%

Question 55

what is the initial event in a stroke

Answer 55

excitotoxic insult resulting in a necrotic core infarct followed by inflammatory and oxidative events leading to delayed, penumbral cell death

Question 56

what are the 3 regenerative processes

Answer 56

plasticity, angiogenesis, neurogenesis