Stroke

Front 1

What is a stroke?

Back 1

An interuption to the blood flow to the brain that results in ischaemia and hypoxia due to cerebrovascular disease. 3rd most common causes of death in the UK after heart disease and cancer.

Front 2

What are the 4 types of stroke?

Back 2

Ischaemic - thrombosis, embolism.

Haemorrhagic.

TIA

Front 3

Signs and Symptoms:

Back 3

FAST:

loss of facial tone and weakness.

cannot raise arms symmetrically

speech is slurred/changed

Front 4

What is cerebral thrombosis?

Back 4

Cerebral thrombosis is the development of a blood clot in a cerebral vessel caused by an atherosclerotic plaque in an artery. The plaque causes the vessel wall to degenerate and damages the endothelium. this damage attracts platelets and fibrin and the thrombus slowly grows.

Eventually during a period of reduced blood pressure the lumen closes and the distal circulation ceases. Decreased blood pressure may allow the vessel to narrow enough so that the lumen, comprised by the clot will close.

Front 5

What is an embolus?

Back 5

A foreign substance that occludes a blood vessel. Part of a blood clot that has broken off a thrombus and and lodged somewhere else in the vasculature away from the initial site of thrombus formation.Emboli can also be masses of bacteria.

Neurological signs develop rapidly with cerebral emboli and they usually don't progress. only rarely are they preceded by a TIA.

Usually occur during activity and conciousness is usually preserved.

Source of embolism is nearly always the L. side of the heart and leads to the production of emboli including AF, MI and defective/artificial heart valves.

Front 6

What is a TIA?

Back 6

Transient Ischaemic Attack = temporary. Ustable plaque.

small embolus that blocks and then rapidly dissociates from an artery or from a spasm in the artery.

temporary symptoms deficits occur within a few mins and resolves spontaneously within 24 hrs. often a precursor/ warning sign for a stroke = precede in 40% of cases.

Front 7

What is the problem with collateral cerebral vessels in the brain?

Back 7

They take time to open and establish blood supply to an area where there is a blockage. Brain dies before collaterals open and are functional.

Front 8

What percentage of stroke occur during sleep and why?

Back 8

60% of thrombotic strokes during sleep.

During sleep BP drops and therefore a vessel slowly constricts until an occlusion occurs due to thrombus in narrowing vessel.

Front 9

What percentage of strokes develop slow occlusions?

Back 9

20% of thrombotic strokes. due to the atherosclerotic plaque breaking off and re-lodging ==> slow occlusion.

Neurological symptoms followed by a period of normal functions then more symptoms.

Front 10

When does an embolism commonly lodge?

Back 10

During activity. breaks off from a blood clot somewhere else in the body. source is almost always an embolism in the L. side of the heart.

Neurological symptoms develop rapdily.

Front 11

What symptoms would be evident from a haemorrhagic stroke?

Back 11

Severe headache with progressive loss of mental function. = thunderclap headache.

Front 12

What are the risk factors for stroke?

Back 12

Diabetes, Hypertension, Smoking, Hyperlipidaemia, CAD, AF.

Front 13

What is the MOST IMPORTANT risk factor for stroke?

Back 13

HT

Front 14

What are the key causes of an embolism?

Back 14

AF
MI

Artificial Heart valves/defective heart valves.

Front 15

Compare and contrast a stable vs. an unstable clot:

Back 15

Stable: has a thick fibrous cap. lipid core is small.

THROMBOSIS

Unstable: has a thin fibrous cap and a rich lipid pool. TIA

Front 16

Describe a Haemorrhagic stroke:

Back 16

Intracerebral haemorrhage is assoicated with sudden onset (mins to hours) of neuro symptoms. It is frequently assoicated with a severe headache. possible due to the stretch of the vessels befor erupture. Unlike the occlusive stroke in which conciousness is presenvered, intracerebral haemorrhage may cause stupor or coma that may progress with time.

Usually HT present.

Front 17

What blood vessel/branches are the site of many strokes?

Back 17

Middle cerebral = continuation of the internal carotid. passes laterally between the superior surface of the ant. temp. and the inf. surface of the post. frontal.

Front 18

What are the branches from the MCA?

Back 18

Leticulo-striate arteries. Leaves the MCA at nearly 90 degrees and are very prone to blockage by an embolus.

Lenticulo-striate arteries supply the basal ganglia and the internal capsule.

The internal capsule supplies all the motor commands from the motor cortex to the brainstem and spinal cord.

Front 19

Where would a blockage produce ischaemia?

Back 19

Downstream of the MCA

Front 20

Describe the role of the Na+ pump in cells.

Back 20

Not just a role in AP transmission. In all cells it has a role to maintain membrane potential by maintian cell shape and structure.

In order to prevent a cell bursting from the osmotic pull of osmotic proteins inside the cell, an osmotically active particle must be pumped out to balance the osmotic forces generates by the internal proteins and DNA.

Na+ is excluded to balance the osmotic pull. The role of the pump is therefore to prevent cell swelling and bursting. In nerve cells Na+ pumps have to work at very high levels because the nerve cells have a very large surface area: volume ration meaning more sodium leakage and also Na+ is allowed in during an action potetnial which has to be then pumped out.

The brain has some of the highest energy uses in the entire body. Most of the ATP is used to fuel to the sodium pump.

Front 21

Outline the basic components/structure of the brain:

Back 21

Neurones and glia cells contained within a closed cavity = cranial cavity.

Normally there is an extracellular space filled with extracellular fluid of about 20% allowing diffusion of materials around and between cells.

Front 22

What happens to the Na+ pumps in the case of hypoxia?

Back 22

Reduced oxygen delivery reduces ATP supply and os the nerve pumps stop working resulting in Na+ leakage into the cells. Cells swell. The brain is contained in an enclosed box = cranial cavity thus the swelling cells exert a pressure on each other and the amount of extracellular space decreases. This causes a riser in ICP. This is an important sign of respiratory stress.

A rise in ICP will compress the cerebral veins leading to a loss of blood flow and thus a worsening of hypoxia.

In severe cases the rise in ICP may cause the brain to herniate out of the foramen magnum leading to compression of the brainstem, coma and death. Hypoxic brain EC space = 5%

Front 23

How does a stroke cause brain damage?

Back 23

Hypoxia results in brain damage due to compression of the brain from hypoxia swelling due to reduced activity of the ATP-dependant Na+ pumps that normally maintain osmotic pressure.

Front 24

What is an immediate action that can reduce the metabolic demands of cells?

Back 24

Cool down the brain

Front 25

In a healthy brain, the active neurones release K+ which is take up into glial cells which act to maintian the homeostasis of the brain environment. In a hypoxic brain what happens to the K+?

Back 25

Not removed and the increased ECM K+ depolarised the adjascent cells leading to NT release. Therefore stroke causes the release of excess NT.

Front 26

What happen to the NT normally in nerve cells, and what happens in hypoxia?

Back 26

Normally they are uptaken into nerve cells by uptake pumps or transporters and these use ATP..

When ATP is low, during hypoxia the NTs are not taken up and instead remain the in synaptic cleft of EC space.

Front 27

What is the resilt of the excessive leaves of NT due to smaller EC space and reduced NT uptake?

Back 27

Cell damage = excitotoxicity i.e. the effects of excitatory NTs.

Front 28

Summarise the actions of stroke on the brain:

Back 28

1. Osmotic swelling the neurones reduced the EC space from 20% to 5% due to low ATP to supply the Na+ pumps that normally pump out Na+ to maintain an osmotic gradient.

2. K+ ions are not uptaken by the neurones due to hypoxia reducing ATP to fuel the uptake pumps in glial cells and neuroness therefore remain in the EC space causing depolarisation of neurones and release of more NTs- glutamate.

3. The excess release of NT in the reduced EC space results in excitotoxicity and cell damage.

Front 29

What is the main excitatory NT in the brain and what receptors (2) does it act on?

Back 29

Glutamate

NMDA - excess stimulation of this receptor after 3-5 minutes anoxia leads to excess influx of Ca2+ into the cell and this is the cause of early/fast excitotoxicity.

AMPA - excess stimulation over several hours leads to slow/delated excitotoxicity.

Front 30

What is the excitotoxic loop and what is the effect on increased Ca2+ influx on the metabolic demand of the cell?

Back 30

Hypoxia - decreased Na+ pump activity => swelling and reduced EC space + decreased uptake of K+, remains in EC space and depolarises adjascent neurones and glia => increased glutamate release overstimulating/ activating NMDA receptors leading to influx of Ca2+ which increases further the metabolic demands of the cell...further reducing ATP and oxygen supply and the Na+ pump activity etc...progressive worsening.

Front 31

What is the consequence of influx of Ca2+ into the cell?

Back 31

Increased metabolic demand on the cell and use of more oxygen.

High metabolic demand in the absence of oxygen leads to the formation of free radicals which triggers cell death = apoptosis.

Front 32

Describe the 3 areas of the brain around a stroke focus

Back 32

Inevitable death zone at point of stroke focus.

Penumbra region - to die or not to die?

Almost certain survival = outermost zone.

Front 33

What are the 3 current treatment aims post stroke?

Back 33

AIM: maintain the survival of neurones in the penumbra.

3 strategies:

Restore blood flow

Combat excitotoxicity.

Combat free rad damage.

Front 34

How can blood flow be restored?

Back 34

Use of tissue plasminogen activators (clot busters) improves after stroke.

Cleaves plasminogen to plasmin.

Plasmin degrades fibrin so promotes reperfusion.

(type 1 tissue plasmingoen activator inhibitor = PAI-1 and alpha2- antiplasmin by contract block this cascade)

Front 35

How can excitotoxicity be combatted?

Back 35

NMDA antagonists e.g. cerestat

block NDMA recetpros and fast excitotoxicity. however not successful in practice perhaps administered too late after onset. + serious SEs.

AMP antagonists e.g. NBQX: reduce excitotoxicity (hold out more hope as AMPA effects are delayed and drug treatment after 1 hr may be beneficial)

Newer drugs prevent delayed triggering of apoptotic pathways ' programmed cell death' e.g. Lithium.

Front 36

How is free radical damage reduced?

Back 36

Antioxidants: Vit C and E boost the brains antioxidant defences.

dietary supplements to those at risk has been shown to reduce the risk of stoke in vulnerable populations.

Free radical scavenging enzymes e.g. superoxide dismutase = low in stroke patients.

Cool down the brain

Front 37

What are the most modifiable risk factors?

Back 37

High BP and AF.

Hypertensiona accounts for 35-50% of stroke risk.

Blood pressure reduction of 10mmHg systolic of 5mmHg diastolic reduces the risk of stroke by 40%.

Those with AF have a yearly 5% stroke risk and this risk is higher in those with valvular AF. Anticoagulant medications like warfarin or aspirin are useful for prevention.

High cholesterol levels have been inconsistently associated with ischaemic stroke. statins reduce the risk by 15%.

DM 1 and 11. Increases the risk of stroke by 2/3 times. Intensive control of blood sugar has been shown to reduce the microvascular complications such as nephropathy and retinopathy but doesn't reduce the macrovascular complications such as stroke.