SAQs 2013

Question 1

Discuss the physiological significance of the blood-brain barrier

Answer 1

BBB is the highly regulated interface that separates peripheral circulation from the CNS.

Anatomy:

• 3 layers (blood to CNS)
• • Endotheliam cells (interconnected through tight junctions - NO fenestrations
• Basal membrane (of both endothelial cells and astrocytes)
• Astrocyte pedicles (foot processes).

The layers contain enzymes which degrade neurotransmitters and prevent passage across BBB.

The layers contain transporters (e.g. GLUT-1) which allow controlled passage of specific electriclights, nutrients, and drugs.

5 CNS structures lie outside the BBB:
1. Area Postrema - the Chemoreceptor trigger zone - responsible for detection of noxious substances in peripheral circulation –> Trigger nausea/vomiting when detected.

2. Organum Vasculosum Laminae Terminalis (OVLT) - Contains osmoreceptors directly in contact with peripheral circulation –> sends signal to release ADH in response to increased osmolality
3. Subfornical Organ (SFO) contains osmoreceptors as well as glucose sensors –> Senses energy state of the body
4. Posterior pituitary –> Releases ADH and oxytocin into the circulation
5. Pineal glant –> responsible for regulating circadian rhythm via release of melatonin.

1, 2, 3 are circumventricular organs

Permeability of the BBB:

• Obeys Fick’s law of diffusion
• Therefore small, lipophilic substances are fine
• Impermeable to large, polar, negatively charged molecules

Some active/facilitated transport (e.g. GLUT-1 transpoter for glucose) exist, electriclights (Na, K, Ca, HCO3, Mg, Cl)

Physiological significance:

1. Protection
   - BBB protects brain from endogenous and exogenous toxins in plasma
2. Immunological barrier
   - Protects from pathogens in blood, protects body from own immune system (e.g. autoimmune reaction to exposed CNS tissue in CNS)
3. Maintain stable ionic, glucose and pH environment in CSF.
4. Barrier for neurotransmitters
   - Layers contain enzymes to degrade neurotransmitter from entering systemic circulation.

Anaesthetic drug examples:
- e.g. atropine, small, non-polar molecule can cross BBB, whereas glycopyrrolate is a polar quaternary amine, cannot cross BBB.

Question 2

Outline the role of the kidneys in the regulation of body water

Answer 2

Regulation is a balance between input and output of water –> Relative water deficiency or excess.

kidney’s roles:

• Volume of body water
• Osmolality of body water
• Distribution of body water (ICF vs ECF)

Achieves these by:

• Varying urine volume
• Varying urine osmolality

Renal factors effecting input of body water:

• Thirst
• Reduced intravascular volume –> decreased stimulation of renal baroreceptors –> Increased renin –> increased ATII (then increased ADH) –> Stimulate thirst –> Behavioural modification to seek water/fluid

Renal factors effecting output of body water:

• Regulate filtration and reabsorption/excretion of water
• The ability to produce hypo or hypertonic urine relative to plasma
• Determined by pressure and osmolarity via direct effects and hormone release.
• Tubuloglomerular feedback
• —> Increased GFR –> Macula densa detects increased [Na], increases adenosine, constricts afferent arteriole
• —> Decreased GFR –> Macula densa detects decreased [Na], releases NO –> dilate afferent arteriole.

Osmolarity
- Decreased osmolarity sensed by posterior pituitary –> Releases less ADH, therefore more diuresis (less dilute urine)

ADH works by the introduction of aquaporon II channels in the collecting ducts, therefore increasing the water which can be resorbed.