Cerebral Blood Flow Regulation and The Blood Brain Barrier Flashcards
What are the proportions of blood flow to the brain
High 55ml/100g tissue/min 15% of CO 2% of body weight 20% oxygen consumption
What happens when blood flow to the brain is reduced by more than 50%
Insufficient oxygen delivery
Function becomes significantly impaired
What happens when CBF is interrupted
4 seconds - unconsciousness
minutes - irreversible brain damage
Define syncope
Fainting
Manifestation of reduced blood supply to the brain
What can cause syncope
Low blood pressure Postural changes Vaso-vagal attack Sudden pain Emotional shock
Why is the glucose supply to the brain vital
The brain cannot store, synthesise or utilise any other sources of energy (though in starvation ketones can be used)
What occurs in hypoglycaemia
Disorientation, slurred speech, impaired motor function
Dangerous below 2mM
What is CBF regulated by
Mechanisms affecting total cerebral blood flow
Mechanisms which relate activity to the requirement in specific brain regions by altered localised blood flow
What is the range of auto regulation for total CBF
between mean arterial blood pressures (MABP) of 60 and 160mmHg
What occurs when the CBF is above the auto regulatory pressure range
Swelling of the brain in the cranium causes an increase in intracranial pressure
What is the mechanism for changing total cerebral blood flow autoregulation
Arteries and arterioles dilate or contract to maintain blood flow
Stretch-sensitive cerebral vascular smooth muscle contracts at high BP and vice versa
What is local autoregulation
Local brain activity determines the local O2 and glucose demands
What are the 2 mechanisms of local regulation of CBF
Neural and chemical
Describe the pattern of vascularisation in the CNS tissues
Arteries enter the CNS tissue as branches of surface pial vessels (Pia mater)
These penetrate the brain parenchyma to form capillaries
These drain into venues and veins -> surface pial veins
What are neural factors that regulate CBF
Sympathetic nerve stimualtion (main cerebral arteries) - vasoconstriction
Parasympathetic (facial) stimulation - vasodilation
Central cortical neurones - vasoconstriction on catecholamine release (A/NA)
Dopaminergic neurones - vasoconstriction
What is the significance of dopaminergic neurones on CBF regulation
Innervate penetrating arterioles and pericytes around capillaries
Participate in the diversion of CB to high activity areas
Dopamine may cause contraction of pericytes via aminergic and serotoninergic receptors
What are the chemical factors that regulate CBF
CO2 pH NO K+ Adenosine Anoxia Kinins, prostaglandins, histamine, endothelins All vasodilate
What is the effect of CO2 on CBF
As CO2 increases CBF increases (sigmoid)
Explain how CO2 affects CBF
- CO2 from blood or local metabolic activity generates H+ using carbonic anhydrase, as it cannot cross the BBB from the blood
- low pH causes relaxation of the contractile smooth muscle
- Vessels dilate
- Increased blood flow
How are local changes to CBF measured
Equates to increased neuronal activity
Imaged via PET scanning and functional MRI
Where is CBF produced
Ependymal cells in the ventricles, aqueducts and canals that are modified to form the choroid plexus
Describe the circulation of CSF
- Lateral ventricles
Cereberal hemispheres - 3rd ventricle (via inter ventricular foramina)
Diencephalon - Cerebral aqueduct
Midbrain - 4th ventricle
Pons and medulla - Subarachnoid space (via medial and lateral apertures)
What volume of CSF flows at one time
80-150ml
What volume of CSF is produced each day and where
500ml
What are the functions of CSF
Shock absorbing – protection from trauma
Removes waste products from cellular metabolism
Supplies neurones with nutrients (secondary to blood)
Contains immune cells
What is the clinical relevance of CSF not having protein
If protein is presence may be damage or a bacterial infection
Describe the junctions of the blood brain barrier
Extensive tight junctions at the endothelial cell-cell contacts
Reduces solute and fluid leak across the capillary wall
Capillaries of the CNS parenchyma from the pial cells gain BBB properties the deeper they are
Describe inter endothelial junctions of peripheral capillaries and BBB capillaries
BBB has much fewer tight junctions
What are some difference between peripheral and BBB capillaries
Peripheral vessels have sparse pericyte coverage, BBB has a dense coverage
BBB are covered with end feet from astrocytes
Which substances are unable to cross the BBB but can cross the peripheral capillaries
Glucose, amino acids, many antibiotics, some toxins
How does the BBB control exchange of substances
Specific membrane transporters (influx and efflux transporters)
Where in the brain do blood-borne infectious agents mostly affect
The meninges as their vessels are not BBB, which reduces entry
Give examples of hydrophilic substances that enter the CSF and how they do so
Water - AQP1, AQP4
Glucose - GLUT1
Amino acids - 3 transporters
electrolytes - transporter systems
Give examples of lipophilic substances that enter the CSF and how they do so
Oxygen, CO2, alcohol, anaesthetics
diffuse passively across the barrier down concentration gradient
What are circumventricular organs
Capillaries that lack BBB properties
Found close to ventricles
Generally involved in secreting into the circulation
What are the features of circumventricular organs
Capillaries are fenestrated and leaky
Ventricular ependymal lining close to these areas are much tighter, limiting the exchange between them and CSF
Requires access to the blood
Give and example of how circumventircular organs use blood
Posterior pituitary and median eminence secrete hormones
The area postrema samples the plasma for toxins, inducing vomiting
Others are involved in sensing electrolytes and regulates water intake
What is the clinical importance of the BBB
Breaks down in many pathological states Inflammation Infection Trauma Stroke
Explain how antihistamines affect the brain
H1 blockers are hydrophobic and therefore can passively diffuse across the BBB
Histamine usually aids wakefulness and alertness so antihistamines make people drowsy
How does the BBB affect Parkinsons disease treatment
Key treatment involves increasing dopamine levels but dopamine cannot cross the BBB
L-DOPA crosses the BBB via amino acid transporter and is converted to dopamine in the brain
However, a lot of L-dopa is converted outside the brain and is therefore administrated with carpidopa to inhibit
