Cerebral Blood Flow Regulation Flashcards by Rama Jha

When does unconsciousness occur and irreversible damage?

If CBF interrupted for 4secs = unconsciousness

Few minutes = irreversible damage

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Syncope?

Fainting

Common manifestation of reduced BS to the brain

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Main principle energy source for the brain?

Glucose

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[glucose] concentrations and impact?

Normal fasting levels = 4-6mM

If <2mM = unconsciousness, coma and death

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How is CBF regulated?

x mechanisms affecting TOTAL CBF

x mechanisms with alter LOCALISED BF depending on activity

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Auto-regulation range for CBF?

MABP 60-160mmHg

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How is the CBF autoregulated to maintain the MABP?

Stretch-sensitive cerebral vascular SM

High BP - contracts
Low BP - relax

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What can happen to the brain if the BP is too high?

Swelling of brain tissue as ‘closed’ cranium = intracranial pressure increases

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What is local regulation mediated by?

Neural control
AND
Chemical control

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How can local changes to CBF be measured?

Imaged on PET scans & fMRIs

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Explain the vascularisation of the CNS

Arteries from the pia mater penetrate into the brain parenchyma –> form capillaries

These brain into veins/venules –> into the surface pial vessels

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Relationship betw. neurone and capillary in the CNS

No neurone is >100um (micro) from a capillary

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4 neural factors affecting CBF regulation?

SN nerve stimulation
PSN (facial nerve) stimulation
Central cortical neurones
Dopaminergic neurones

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SN nerve stimulation (neural factor)?

To main cerebral arteries

VasoCONSTRICTION when MABP is high

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PSN facial nerve stimulation (neural factor)?

Produces sligh vasoDILATION

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Central cortical neurones (neural factor)?

Releases various vasoCONSTRICTOR NTs

e.g. catecholamines (A & NA)

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Dopaminergic neurones (neural factor)?

LOCALISED vasoCONSTRICTION

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Explain what dopaminergic neurones innervate

Innervate
x penetrating arterioles
x pericytes around capillaries

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Explain how dopaminergic neurones function

May participate in the diversion of CBS to areas of high activity

Dopamine may cause contraction of pericytes via. aminergic & serotoninergic receptors

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Pericytes?

Brain macrophages that wrap around capillaries - maintaining integrity & function

Diverse activity inc. immune function, transport property, contractile

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Chemical factors affecting CBF?

Generally localised

CO2 (indirect)
pH
NO
K+
Adenosine, anoxia, prostaglandins

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Effect of pCO2 on CBF?

An increase in pCO2 = BF increases

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Effect of CO2 on cerebral arteries?

Study These Flashcards

VasoDILATION

Increase in H+ = decreases pH inside VSMCs = cell relaxes = vessels dilate = INCREASED BF

Where can the H+ (in chemical factors) be derived from?

Study These Flashcards

Higher CO2 in blood (NOT directly from H+ in blood)

Increased neural metabolic activity

What produces CSF?

Choroid plexus (in the cerebral ventricles)

Choroid plexus?

Modifies ependymal cells that normally line the ventricles, aqueducts and canals of the brain

Capillaries of the choroid plexus vs. local ependymal cells?

Leaky vs. extensive tight junctions

Path of CSF?

1. Lateral ventricles 2. 3rd ventricle via. interventricular foramina 3. Central aqueduct 4. 4th ventricle 5. Subarachnoid space via. medial & lateral apertures LEAVES via. arachnoid granulations into superior saggital sinus

Volume of CSF?

80-150ml

Function of CSF?

Protection Nutrition Transport

What is similar in the composition of plasma & CSF?

pH (slightly more acidic in CSF) & osmolarity

What is different in the composition of plasma & CSF?

CSF - very LOW protein levels

At what level is the BBB present?

Level of CNS capillaries

Why is the BBB important?

CNS neurones sensitive to local envrionment - homeostasis is key for the brain

3 types of capillaries?

Continuous Fenestrated Sinusoid

From what are the CNS capillaris derived from?

Derived from surface pial vessels

What happens to the BBB capillaries the deeper it goes?

Extensive tight junctions at endothelial cell-cell contacts | remember capillary surrounded by endothelial and then pericytes

Importance of the change in property of BBB capillary the deeper it goes?

Reduces solute & fluid leakage across the capillary wall

BBB proper?

The deeper into the tissue, the less permeable BBB Little transcellular vesicular transport

Interendothelial junctions (IEJs)

More tightly knit - endothelial cells overlap on each other to give a tighter fit

Other than pericytes what else are BBB capillaries covered with?

Astrocytes - 'end-feet'

Which part of the CNS do blood-borne infections normally affect?

Meninges - as vessels are NOT BBB

Some evidence shows that loss of BBB can be good - why?

Can help with clearing some infections by allowing immune cells across

Example of lipophillic molecules that can cross the BBB?

O2 CO2 Alcohol

Examples of hydrophillic substances and specific transport mechanisms needed to cross BBB

Water - AQP1/4 channels Glucose - GLUT1 AA - 3 diff transporters Electrolytes - specific transporter systems

Area of the brain that lacks BBB? Where it is found?

Circumventricular organs (CVO) Found close to the ventricles

What are the capillaries of the CVOs like?

Fenestrates (therefore leaky)

Why do the CVOs capillaries have fenestrated type?

Need to sample blood OR secrete into the blood itself

Relationship between CSF and CVOs?

Ventricular ependymal lining close to the CVOs often MUCH TIGHTER than other areas To LIMIT exchange between them and the CSF

Area posterma?

Samples plasma for toxins - induces vomiting if found (example of CVO)

Antihistamines and BBB?

H1 blockers are hydrophobic so cross BBB by diffusion As histamine invovled in wakefullness can cause people to become drowsy

What have been changed about the antihistamines in regards to the BBB?

2nd-generation antihistamines Are POLAR (have a hydrophillic attachment) so do NOT readily cross the BBB so do NOT cause drowsiness

Issue with giving dopamine to treat Parkinson's Disease?

Need to raise dopamine levels in brain to treat PDs BUT Dopamine CANNOT cross the BBB

Issue with L-DOPA?

L-DOPA CAN cross the BBB via. aa transporter BUT Most of it is converted to dopamine peripherally so LESS AVAILABLE to access the brain

How to overcome the issue with L-DOPA?

Co-administer with DOPA decarboxylase inhibitor CANNOT cross BBB so does NOT interfere w conversion of L-DOPA in the brain

Example of DOPA decarboxylase inhibitor?

Carbidopa

Cerebral Blood Flow Regulation Flashcards

(56 cards)