5. Regulation of blood flow Flashcards
What happens when blood flow to the brain is reduced by more than 50%?
- More than 50% - function significantly impaired
* Total interruption - unconscious (irreversible damage >few minutes)
What is syncope and what are the causes?
• Fainting
- low BP
- postural changes
- vaso-vagal attack
- sudden pain
- emotional shock
(results in temporary interruption of blood flow to the brain)
What can be metabolised if there is a shortage of glucose to the brain?
Ketones
What are the symptoms of hypoglycaemia when brain function is affected?
- Disorientation
- Slurred speech
- Impaired motor function
What is the normal blood glucose range and what level does it have to fall to, to become dangerous?
- Normal: 4-6mM
* Below 2mM - unconsciousness, coma and death
What range of BP can autoregulation of cerebral blood flow occur in order to maintain constant flow?
- 60-160mmHg
* Arterioles dilate or contract
How is cerebral blood flow autoregulated?
Myogenic
• Increase in pressure on vessel wall
• Myogenic response - contraction of smooth muscle
• Decreased cerebral blood flow
What happens if blood flow is above the autoregulatory pressure range?
- Swelling of brain
* Increase in intracranial pressure
What are the 2 types of local regulation of cerebral blood flow?
Neural and Chemical
Describe the pattern of vascularisation in the CNS tissues
(pia matter contains arteries and veins)
• Arteries enter as branches of the surface pial vessels
• These penetrate into the brain parenchyma
• Branch into capillaries => venules => veins => pial veins
• Neurone always with 100μm from capillary
• Deeper down:
- arterioles surrounded by smooth muscle
- capillaries surrounded by pericytes
- innervation of these contractile cells is how dopaminergic neurones regulate blood flow at a capillary level
Describe local regulation of blood flow by neural control
- Sympathetic innervation of main cerebral arteries: high BP => vasoconstriction => less blood flow
- Facial nerves are innervated by parasympathetic fibres - vasodilation
- Central cortical neurones releasing neurotransmitters e.g. catecholamines adrenaline/NA - vasoconstriction
- Dopaminergic neurones - vasoconstriction
What are pericytes?
- Cells that surround capillaries in the brain
- Brain macrophage with immune function
- Transport properties
- Contractile
Describe how dopaminergic neurones cause vasoconstriction?
- Dopaminergic neurones innervate smooth muscle around arterioles and pericytes around capillaries
- When active => contraction
- Local action in certain areas allows for diversion of blood to more active areas of the brain
- Caused via aminergic and serotoninergic receptors
How is local cerebral blood flow chemically controlled?
- CO2, pH, nitric oxide, K+, adenosine, anoxia, histamines, prostaglandins etc. are all vasodilators
- Increase blood flow to particular tissues
- Active cells produce lactic acid => H+ causes drop in pH and vasodilation
- K+ released at one stage of action potential
- CO2 has indirect effect
How does H+ get to the brain?
- H+ does not cross the BBB - generated within the brain
- CO2 can cross BBB
- CO2 + H2O => bicarbonate + H+ [carbonic anhydrase]
How can local changes to cerebral blood flow be imaged?
- PET scan
- Functional MRI (fMRI)
- Increased blood flow => increased neuronal activity
How does NO affect blood vessels?
- NO stimulates guanylyl cyclase
- converts GTP => cGMP
- Vasodilation
What lines the ventricles, aqueducts and canals of the brain?
Ependymal cells
Where and how is CSF produced?
• Choroid plexus
- both lateral ventricles
- 3rd and 4th ventricles
• These comprise capillaries surrounded by ependymal cells - tight junctions/non-fenestrated - impermeable (even though capillaries are leaky)
• Ependymal cells secrete molecules into the ventricles to make the CSF
What is the path of CSF circulation?
- Lateral ventricles
- 3rd ventricle
- Cerebral aqueduct
- 4th ventricle
- Subarachnoid space
What is the volume of CSF and how much is formed per day?
- 80-150mL
* 450mL/day
What is the function of CSF?
- Chemical and physical protection
- Nutrition
- Transport
How is CSF different to plasma?
• Lower: K+, calcium, amino acids, bicarbonate
• Higher: magnesium, chloride
• More acidic
• Little protein - protein in CSF suggests brain injury or infection
(same osmolarity)
What is the function of the BBB?
- Protects brain from certain toxins and circulating transmitters e.g. catecholamines
- Protects from variations in ion concentrations
Describe BBB capillaries
- BBB has more dense pericyte coverage
- More extensive tight junctions
- Astroglial processes
What substances does BBB control and how?
- Tight junctions means that solutes than exchange across peripheral capillaries can’t cross the BBB
- Applies mainly to hydrophilic solutes - glucose, amino acids, many antibiotics etc.
- Specific membrane transporters can be used for control - water via aquaporins, glucose via GLUT1
- Lipophilic molecules can cross easily e.g. O2, anaesthetics, alcohol
How is reduced entry of blood-borne infectious agents into the CNS tissue significant?
- Infections of the meninges more common - vessels not BBB
* Evidence that loss of BBB can help clear some infections - immune cell access
What are circumventricular organs?
• Areas that lack BBB properties
• Found close to ventricles
• Fenestrated capillaries
• CVOs involved in secreting into circulation or sampling the plasma
• Include:
- median eminence region of hypothalamus and posterior pituitary
- area postrema samples plasma for toxins and induces vomiting
- subfornical organ
- organum vasculosum of the lamina terminalis
When can the BBB break down?
- Inflammation
- Infection
- Trauma
- Stroke
How do old antihistamines cross the BBB and how do second-generation antihistamines differ?
First-generation
• Hydrophobic - diffusion
• Histamine is important in wakefulness and alertness, so H1 antihistamines can induce drowsiness
Second-generation
• Polar
• Hydrophilic attachment
• Do not readily cross BBB - less drowsiness
Why is the BBB significant in the treatment of Parkinson’s disease?
- Dopamine can’t cross the BBB so peripheral administration doesn’t work
- L-DOPA can cross the BBB via an amino acid transporter - then converted into dopamine by DOPA decarboxylase
- However, most is converted outside the CNS - less available to access the brain
- Can’t increase dose due to peripheral affects of dopamine
- Can co-administer with DOPA decarboxylase inhibitor, Carbidopa - doesn’t cross BBB so only prevents peripheral conversion
