Biology and Physiology

Question 1

What causes fluctuations in in solute concs in the ECF of the brain?

Answer 1

Changes in neuronal activity - this works both way though

Question 2

What process influences the composition of the ECF?

Answer 2

CSF synthesized by the choroid plexus

Question 3

What is the function of CSF? (cerebral spinal fluid)

Answer 3

• Fills ventricles (30mls) and forms thins layer around brain and spinal cord in the subarachnoid space (120mls)
• CSF is 150mls and turns over 3 times a day so total csf made daily is 500mls
• acts a cushions or shock-absorber to reduce acceleration of deceleration injuries
• provides appropriate local environment for neurones and glia
• medium of exchange between brain ECF and systemic blood
• Removal of waste products - metabolism, drugs, neurotransmitter metabolites
• Interface between brain and peripheral endocrine functions, i.e. releasing hormones from hypothalamus

Question 4

What are the two processes of CSF secretion?

Answer 4

1. Passive process: Ultra-filtration of plasma across fenestrated capillary wall into ECF beneath the basolateral membrane of the choroid epithelial
2. Active: choroid epithelial cells secrete fluid into the ventricles

Question 5

List the sequence of compartments through which the CSF moves

Answer 5

The third ventricle in the forebrain
The cerebral aqueduct or aqueduct of silvius in midbrain
Fourth ventricle in hindbrain
The central canal in the spinal cord

3 foramina projecting into the subarachnoid space permit CSF circulation around the brainstem, cerebellum, and cerebral cortex. Formina cerebral aqueduct potential sites of physical blockage => hydrocephalus

Question 6

What are the sites for CSF absorption?

Answer 6

Arachnoid villi within the subarachnoid space and vascular epithelium of the choroid plexus

Question 7

Mechanisms for the absorption of CSF

Answer 7

a) bulk flow via arachnoid villi 500mls/day
b) diffusion
c) active transport via choroid plexus - e.g. weak organic acids

Question 8

How can the CSF be used for diagnosis?

Answer 8

Spinal tap or lumbar puncture allows sampling of CSF
CSF sampling used for detection of pathogens e.g. MS, meningitis
Also used to measure CSF pressure for detection of hydrocephalus, sub-arachnoid haemorrhage
Routine procedure at L3-5

Question 9

What factors regulate the passage across BBB?

Answer 9

Lipid solubility: high lipid solubility = greater access
Degree of ionisation: drugs ionised at physiological pH (7.4) = less access
drug pKa value = pH at which 50% of drug molecules are ionised
Degree of plasma protein binding - in bound state tool large to cross BBB

Question 10

What compound being present in the CSF is a good indication of the amount of glucose being absorbed by the brain?

Answer 10

2-deoxyglucose

Question 11

How does L-DOPA precursor and peripheral DOPA decarboxylase inhibitor work?

Answer 11

Treatment for PD
Inhibitor prevents conversion of L-DOPA to dopamine outside of the brain and inhibitor doesn’t allow drug to enter CNS as it’s ionised at pH 7.4

Question 12

What can BB disorders lead to?

Answer 12

Tumours - leaky BBB leading to increased nutrients, increased growth)
Infiltration can lead to infection- increased antibiotic permeability
Ischaemia due to stroke - cellular damage - increased water, oedema

Question 13

Why do areas of the brain have no BBB?

Answer 13

• Brain areas lacking a BBB are called the circumventricular organs
• Posterior-pituitary: hormones released have direct access to general circulation
  -Median eminence: pick up releasing hormones via pituitary portal system to the anterior pituitary (oxytocin, vasopressin)
• Area postrema: chemoreceptor zone - vomitting
  Organum vasculosum of the lamina terminalis (OVLT) - important for actions of cytokines in the periphery (fever)