2.12B. Circulation of the brain. Cerebrospinal fluid. Blood-brain barrier.

Question 1

I. Circulation of brain
1. Characteristics of brain circulation

Answer 1

• Cerebral circulation is controlled almost entirely by local metabolites and exhibits autoregulation + functional/reactive hyperemia
• Most important local vasodilator is ↑CO2 (or ↑ H+) which is sensed by central chemoreceptors
• ↑ in cerebral pCO2 causes vasodilation of cerebral arteries, which results in ↑ in
  blood flow to assist removal of excess CO2
• Hyperventilating leads to ↓CO2-levels
  -> cerebral vasoconstriction -> unconsciousness

Question 2

I. Circulation of brain
2. What is the most important local vasodilator?

Answer 2

Most important local vasodilator is ↑CO2 (or ↑ H+) which is sensed by central chemoreceptors

Question 3

I. Circulation of brain
3. What are the consequences of increasing in cerebral pCO2?

Answer 3

↑ in cerebral pCO2 causes vasodilation of cerebral arteries, which results in ↑ in
blood flow to assist removal of excess CO2

Question 4

I. Circulation of brain
4. What are the consequences of hyperventilation?

Answer 4

Hyperventilating leads to ↓CO2-levels
-> cerebral vasoconstriction
-> unconsciousness

Question 5

II. important parameters of Cerebral circulation
1. What are the important parameters of Cerebral circulation?

Answer 5

QB = 750 – 800mL/min (15% of CO), regional differences (Qgray matter > Qwhite matter)

AVDO2 = 60mL/min (extracts less O2 from blood than heart)

If QB stops for:
- 5 seconds = loss of consciousness
- 5 minutes = irreversible brain damage

Question 6

II. important parameters of Cerebral circulation
2. What happen if QB stops for a specific time period?

Answer 6

• 5 seconds = loss of consciousness
• 5 minutes = irreversible brain damage

Question 7

III. Regulation of cerebral blood flow
1. What does cerebral blood flow depend on?

Answer 7

Cerebral blood flow depends on resistance and perfusion pressure

Question 8

III. Regulation of cerebral blood flow
2A. How can Resistance regulate cerebral blood flow?

Answer 8

By using these 5 mechanisms
1. Autoregulation
2. Metabolic changes
3. Effect of pCO2 on QB
4. Myogenic mechanism
5. Using astrocytes

Question 9

III. Regulation of cerebral blood flow - Resistance
2B. How can Autoregulation participate in Regulation of cerebral circulation

Answer 9

• Intrinsic ability of a body part to maintain a constant blood flow despite changes in perfusion pressure
• Processes that occur in the absence of neural and hormonal influences

Question 10

III. Regulation of cerebral blood flow - Resistance
2C. How can Myogenic mechanism participate in Regulation of cerebral circulation

Answer 10

• Tissue itself regulates the blood supply
• Ex: we run -> Pa↑ - but do not need QB↑
• Pa↑↑ (> 160mmHg) -> SYM activation -> vasoconstriction (alpha1-R) -> extended range of autoregulation -> keep QB constant

Question 11

III. Regulation of cerebral blood flow - Resistance
2D. How can metabolic changes participate in Regulation of cerebral blood flow

Answer 11

Neuronal activity↑
-> metabolism↑
-> pCO2↑ (pO2↓)
-> [H]↑, [K+]EC↑, adenosine↑
=> Vasodilation -> QB ↑
=> Most important regulators in cerebral circulation: pCO2, [K+]

Question 12

III. Regulation of cerebral blood flow - Resistance
2E. How can Effect of pCO2 on QB participate in Regulation of cerebral blood flow

Answer 12

• Blood vessels in brain have high pCO2-sensitivity, sensed by central chemoreceptors
• ↑ in pCO2 -> vasodilation (↑QB) for the removal of excess CO2
• If we hyperventilate -> pCO2↓ -> cerebral vasoconstriction -> loss of consciousness (collapse)

Question 13

III. Regulation of cerebral blood flow
2F. How can astrocytes participate in regulation of blood flow

Answer 13

• Are in close contact with synapses of neurons
• Take up K+ and other vasoactive metabolites
  -> Release them to the VSM -> vasodilation

Question 14

III. Regulation of cerebral blood flow
3. How can volume participate in Regulation of cerebral blood flow?

Answer 14

Vbrain tissue + Vblood + VCSF = constant
- Since skull is rigid = fluid is constant
- Any change only occurs if others change
- Increase will compress the brain tissue -> brain damage

Question 15

III. Regulation of cerebral blood flow
4. How can Intracranial pressure participate in Regulation of cerebral blood flow?

Answer 15

(Cushing reflex): Intracranial pressure (ICP↑) -> compression of cerebral arteries -> decreases cerebral perfusion and activates chemical chemoreceptors -> peripheral vasoconstriction + cerebral vasodilation
- ↑ arterial BP due to ↑ ICP -> arterial baroreceptors detect that  PARA activation -> HR↓
- In short: ↑ICP -> ↓HR + ↑BP

Question 16

IV. Blood-brain-barrier (BBB)
1. How is Blood-brain-barrier (BBB) formed?

Answer 16

• Formed by capillaries, which are connected by tight junctions

Question 17

IV. Blood-brain-barrier (BBB)
2. The role of Blood-brain-barrier (BBB)

Answer 17

Prevents the solutes in the lumen of the tight capillaries from having direct access to the brain ECF

Question 18

IV. Blood-brain-barrier (BBB)
3. How does transport occur in Blood-brain-barrier (BBB)?

Answer 18

Transport only possible through capillary endothelial cells
- O2, CO2 = lipid-permeable
- Glucose = GLUT1 transporter
- Amino acids = AA transporters
- H2O = aquaporins
- ABC transporter (require ATP)
=> Important to remove toxic substance from the brain

Question 19

V. Cerebrospinal fluid (CSF)
1. What is the volume of Cerebrospinal fluid (CSF)?

Answer 19

150 mL

Question 20

V. Cerebrospinal fluid (CSF)
2. What is the production rate of Cerebrospinal fluid (CSF)?

Answer 20

production rate = 550mL/day

Question 21

V. Cerebrospinal fluid (CSF)
3. What are the characteristics of Cerebrospinal fluid (CSF)?

Answer 21

• Mechanical protection (like a helmet)
• Brain floats in the CSF
• Acts like a ‘’sink’’ for the brain (helps to provide constant environment for neurons)
  => CSF is a clear fluid produced by ependymal cells in the choroid plexus of ventricles

Question 22

V. Cerebrospinal fluid (CSF)
4. What are the component of CSF?

Answer 22

Compared to blood:
- LowK+
- Low protein concentration (0,03g/dL)
- Lower pH

Question 23

V. Cerebrospinal fluid (CSF)
5. How does CSF secretion occur?

Answer 23

• Active removal of K+ from CSF = reduce [K+]EC

Question 24

2.17. Circulation of the brain. Cerebrospinal fluid. Blood-brain barrier.V. Cerebrospinal fluid (CSF)
6. How does Absorption of CSF occur?

Answer 24

• Passively through arachnoid villi (transcytotic manner)
  => Driven by pressure of CSF
• Goes through superior sagittal sinus
• CSF pressure = 100mmH2O
• If CSF pressure increases = absorption increases = brain damage in brain tissue