Case 5 - blood supply to the brain and ischaemia Flashcards
stroke is what number in the leading cause of death tables
2nd leading cause of deaths worldwide
how much of body weight is the brain
2-3%
how much of the cardiac output does the brain receive
15%
How much of the body’s glucose and oxygen does the brain receive
20% of the oxygen and 25% of glucose
what is the furthest distance from a blood supply capillary is a neurone
20-30 micrometres
what are the two pairs of arteries that supply the brain
the internal carotid arteries (anterior) and the vertebral arteries (posterior)
the anterior cerebral artery is a branch of which artery
the internal carotid artery
what does occulsion of the anterior cerebral artery cause
paralysis and sensory loss in contralateral leg and perineum
what is the largest branch of the internal carotid artery
the middle cerebral artery
where does the middle cerebral artery pass though
the lateral sulcus and travels along the lateral surface of the frontal and parietal lobes
what is the most common site for a stroke
the middle cerebral artery
what would occlusion of the middle cerebral artery cause
contralateral paralysis - mostky in lower face and in the arm
general somatosensory deficits
speech deficits (aphasia) if dominant hemisphere is affected
where does the basilar artery run
forward in midline on ventral surface of the pons
what are the branches of the basilar artery
anterior inferior cerebellar, pontine and superior cerebellar
where does the basilar artery divide nd what does it divide into
at rostral end of the midbrain and the posterior cerebral arteries
what happens if there is occlusion of the basilar artery
coma - followed by death due to respiratory failure
where does the posterior cerebral artery run
curves around. the midbrain and reaches medial surface of the cerebral hemisphere
what are the important branches of the posterior cerebral artery
cortical branches supply the visual cortex, posterior chroiodal and posterior communicating
what does occlusion of the posterior cerebral artery lead to
blindness
what does the circle of willis form
an anastomoses
why are anastomoses not sufficient
due to narrowing of large vessels and communicating arteries because of vascular disease
functional consequences of stroke diagram
what are the series of events in an ischaemic stroke
- 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
progression of an intracerebral haemorrhage
- 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
what is the primary region of damage to the brain referred to as
the core
what is the main characteristic of the core
this is where blood supply is reduced to dramatically low levels which is less than 20% of normal flow
what is the penumbral region
an area with reduced blood flow, but not as severe as the core.
how much of normal blood flow is there in the penumbral region
20-50% normal flow
how do neurones behave in the penumbral region
they are still functionally active
what does the core have that the penumbra does not
dead tissue
penumbra characteristics
- 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
what does a CT show
only the core and dead tissue
what is the key, major excitatory transmitter in the brain
glutamate
what does glutamate produce
downstream signals
what happens if you have glucose in excess
it overwhelms the synapse, and glucose is taken back up unto the presynaptic terminals or by glial cells
what happens to the process of glucose reuptake in stroke
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
what happens when there is a collapse of membrane patents
release of degenerative oxidative stress
what is degenerative oxidative stress driven by
changes in the mitochondria
what happens in oxidative stress
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
what drives inflammation
oxidative stress
what is the term used to describe the relationship between coagulation cascades and inflammation processes
thrombi-inflammation
what happens when the tight junctions in the brain are broken down
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
what are released by dying neurones
damage associated molecular patterns
what happens to these DAMPs
these are recognised by the microglia, innate lymphocytes and infiltrated myeloid cells
what does this cause s
stero-inflammation
what does stero-inflammation lead to
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
characteristics of IL-1
- 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
what is anakinra
an IL-1 receptor antagonist that blocks the biologic activity of IL1. it is naturally occurring
what are the two processes in recovery of stroke in the brain
neurogenesis and angiogenesis
what is brain plasticity
when other areas adopt or take over the function that wasn’t done before
why is inflammation important
stem cells release inflammatory substances
what are the three brain/nerve stimulations
- directly
- transcranial
- vagus nerve stimulation
what are the problems with tPA
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
percentage of stroke patients treated in the UK
12%
what is the initial event in a stroke
excitotoxic insult resulting in a necrotic core infarct
followed by inflammatory and oxidative events leading to delayed, penumbral cell death
what are the 3 regenerative processes
plasticity, angiogenesis, neurogenesis
