Stroke Flashcards
Outline the timeline of changes in brain following a stroke
Acute phase 1d - 1wk
-Area is soft and edematous
-neutrophil infiltrate+ inflammatory response usually 24-72hr
-Pyknotic/eosinophilic nuclei (dense chromatin) (48 hr)
-loss of neuronal nuclei
-blurring of anatomical detail.
-neuronal cell necrosis
-macrophage
Subacute phase 1wk-1m
-Tumefaction
-Endothelial proliferation in response to anoxic cells releasing angioproliferative factors eg VEGF.
-Reactive astrocytosis
-Tissue destrcution
-Liquefactive necrosis
Chronic >1m
-Glial scar formation at site of stroke
-cavitation of tissue
-macrophages have phagocytosed necrotic debris.
Name the 3 types of ischemic stroke and causes of each
Thrombotic
-Clot/thrombus formation within a vessel supplying blood to brain.
-Can occlude blood flow
-Atherosclerosis
Embolic
-Embolism from another part of body travels to cerebral vasculature, occluding blood flow.
-Atrial fibrillation, Infective endocarditis, thromboembolism from ruptured atherosclerotic plaque, clot formation post-MI.
Hypoxic
-Severe hypoxemia
-asphyxiation during birth
-distributive shock e.g. anaphylaxis
What is the difference between a thrombus and an embolus
A thrombus is a fibrinous clot that forms in a living tissue, within a blood vessel, and obstructs blood flow at its point of origin.
An embolus is any undissolved material that originates from one part of the body, travels within the blood and can impact the cardiovascular system - fat embolus, air bubble, DVT, bacterial clumps
Define stroke/ CVA
A stroke/ CVA refers to the disruption of blood flow, oxygen and nutrients to neuronal tissue resulting in cell death + necrosis, with symptoms lasting longer than 24 hours. The disruption can occur due to artery occlusion of haemorrhage with effects ranging from mild impairment to death.
Management of ischaemic stroke
- Thrombolytics (if within 4 hours onset and no risk of haemorrhage) such as Alteplase, Reteplase, Streptokinase.
- Thrombectomy if large artery occluded/not suitable for thrombolysis.
- Reduce further risk with anti-platelets: aspirin/clopidogrel.
- Manage risk factors: smoking cessation, HTN, cholesterol, blood sugars.
Mechanism of action of thrombolytics
Thrombolytic drugs (tPA) binds to the fibrin component of clot/thrombus.
It activates plasminogen -> plasmin which then dissolves the clot through fibrin degradation.
inactivates fibrinogen, prothrombin and factors V + XII
-Therefore increases PT (Prothrombin time) and PTT (Partial thromboplastin time)
Name 2 common regions for haemorrhagic stroke and list 3 risk factors for a haemorrhagic stroke.
- Sub-arachnoid space i.e. SAH
- Basal ganglia i.e. hypertensive stroke involving the lenticulostriate arteries of MCA.
Risk factors include
- Hypertension
- Atherosclerosis
- Arteriovenous malformation (assoc with SAH)
What major artery supplies the thalamus? what are the names of the small arteries it supplies?
Posterior cerebral artery, central branch, via Thalamogeniculate branches.
Outline the response of neuronal tissue to oxygen deprivation
Oxygen deprivation leads to:
(i) Anaerobic metabolism leading to increase in lactic acid -> disruption of normal acid-base balance -> loss of normal neuronal function.
(ii) Reduction in ATP results in loss of Na+/K+ ATPase -> sodium + calcium accumulate in neuron resulting in glutamate release. -> Water follows by osmotic gradient -> cerebral oedema.
(iii) Accumulation of glutamate extracellularly results in increased activation of NMDA receptors, more calcium influx -> excitotoxicity -> ROS -> neuronal death.
(iV) inflammatory response due to microglial cells reacting to neuronal debris, release of pro-inflammatory cytokines (TNF-a, IFN-y, IL-1B) and neutrophil infiltrate (disrupted BBB).
Eventually leads to liquefactive necrosis.
Outline 4 reasons why a stroke might progress
- Progression to haemorrhagic stroke
-> can occur from weakening of blood vessels following the response to the initial ischemic stroke. - Uncontrolled hypertension
- Impaired blood clotting
-such as patients on anti-platelets/anti-coagulants.
-Those with severe liver disease. - Hyperglycemia
-> has been shown to be a risk factor for stroke progression as it is associated with increased Kallikrein which can affect normal platelet function. - Reduced baro-receptor sensitivity
-> due to autonomic dysfunction.
What is the normal intracranial pressure in an adult/child
7-15 mmHg adult
3-7mmHg child
Define cerebral perfusion pressure and how is it calculated. What is normal range
CPP is the net pressure gradient driving driving blood, oxygen + nutrients to the brain.
Calculated as
CPP = MAP - ICP or CVP whichever is highest.
Normally between 60-80 mmHg.
between what pressures can the cerebral vasculature function in an autoregulatory way to maintain constant CBF?
60-150mmHg.
If pressures fall below or above this, it can result in failure of the cerebral vasculature to counteract the changes, resulting in hypoperfusion or haemorrhagic stroke.
List 5 factors that can affect CBF
- Autoregulation
- PaCO2
- Metabolic demands of neuronal tissue
- Temperature
- PaO2.
Define hydrocephalus. Name the 2 types of HC and differentiate between them.
Hydrocephalus is the abnormal enlargement of the cerebral ventricles as a results of hypersecretion or hypo-absorption of CSF.
(1) Communicating hydrocephalus
-caused by overproduction or under absorption without obstruction in flow.
(2) Non-communicating
- Obstructed passage of CSF as it passes between ventricles or into the subarachnoid space/ venous system.
What is the most common form of congenital hydrocephalus. List 4 causes.
Non-communicating hydrocephalus
Causes:
(i) Arnold chiari malformation - herniation of cerebellar tonsils through foramen magnum.
(ii) Dandy-walker malformation - failure of 4th ventricle to develop properly.
(iii) TORCH - congenital taxoplasmosis
(iv) Congenital stenosis of cerebral aqueduct of sylvius.
(v) Acquired HC - brain tumour - medullablastoma
list 4 signs of a raised ICP
- Nausea/vomiting
- Pupil dilation (early)
- Papillodema (late)
- Cushings triad
- Macrocephaly (in infants due to open fontanelles)
- Abducens nerve palsy - Loss of lateral rectus muscle function. Eye pulled medially due to unopposed medial rectus muscle.
What BP is classed as a hypertensive crisis?
Systolic >180mmhg
Diastolic >120 mmhg
Outline the cushings triad and the mechanisms behind each feature.
(1) Hypertension
(2) Bradycardia
(3) Irregular respirations
(i) Hypertension
-> Cerebral ischemia resulting from raised ICP activates the SNS.
-> Activation of alpha 1 adrenergic receptors of blood vessels causes vasoconstriction.
-> Systolic increase (wide pulse pressure)
(ii) Bradycardia
-> Hypertension stimulates the baroreceptor reflex causes increase PSNS action
-> Ach binding the M2 receptors of heart causes bradycardia.
(iii) Irregular respirations
-> due to compression of the respiratory centre in brain stem eventually leading to apnoea.
Where are the respiratory centres located?
Medulla oblongata
- Dorsal respiratory group -> Controls Rate and initiates inhalation by causing contraction of diaphragm and ext intercostals
- ventral respiratory group-> generates rhythm. Contain pre-botzinger cells that can modulate the DRG.
Pons
-Apneustic -> stimulates DRG by gradually increasing firing rate of inspiratory muscles. Overstimulation leads to long gasps and short exhales.
-Pneumotaxic- can increase rate and depth of breathing by shortening the inspiratory phase.
What pathway of fibres are assessed in the dolls eye reflex? Outline the pathway of this reflex.
Medial longitudinal fasciculus.
Turn head to right = eyes look left.
-Head turned to the right results in endolymph motion in vestibular apparatus.
- activation of the ipsilateral vestibulocochlear nerve which synapses on ipsilateral vestibular nucleus
-Activation of contralateral abducens nucleus -> lateral rectus of left eye
- Activation of ipsilateral occulomotor nucleus via MLF -> contraction of medial rectus of right eye
Eyes look left.
How does reperfusion result in ischemic to haemorrhagic progression of stroke?
“Reperfusion, or the reintroduction of oxygen to the brain tissue following ischemia, can lead to the production of reactive oxygen species (ROS) such as superoxide and hydrogen peroxide due to mitochondrial dysfunction caused by the ischemia.
This oxidative stress, along with elevated activity of matrix metalloproteinases (MMPs) released from microglia and astrocytes, can degrade extracellular matrix components. The inflammatory response that accompanies reperfusion further exacerbates the situation by increasing vascular permeability. Together, these factors disrupt the integrity of the blood-brain barrier (BBB), potentially leading to hemorrhagic transformation
outline the production of CSF and pH balance by the ependymal cells
“The CSF is an ultrafiltrate of plasma derived from fenestrated capillaries associated with the choroid plexus. The ependymal cells facilitate relevant ion exchange between blood and CSF, creating an osmotic gradient for water to pass through aquaporins on both the basolateral and apical surfaces of the ependymal cells.
Derivation of CSF:
The ependymal cells of the choroid plexus have various channels and pumps that mediate ion transport. On the basolateral surface, Cl-/HCO3- exchangers and Na+/H+ ATPase pumps play crucial roles. The Na+/H+ ATPase pump exchanges Na+ for H+, with Na+ entering the cell and H+ being pumped out. HCO3- can be exchanged with Cl-, which helps maintain the ionic balance and osmotic gradient necessary for water movement.
On the apical surface, NKCC channels (Na+/K+/2Cl- cotransporters) allow the co-transport of Na+, K+, and Cl-. Na+/K+ ATPase pumps maintain the concentration gradient needed for the passage of these ions. Water follows this osmotic gradient through aquaporins into the CSF.
Maintenance of pH:
The normal pH of CSF is maintained through the buffering action of HCO3-. HCO3- is actively transported into the CSF, where it neutralizes any excess H+. This process helps maintain a stable pH within the narrow physiological range. Additionally, the removal of H+ from the ependymal cells into the blood and the exchange of Cl- with HCO3- are critical in sustaining the CSF’s pH balance.”
What is average pH of CSF?
7.3-7.4
