Discuss the physiological significance of the blood-brain barrier
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.
- Organum Vasculosum Laminae Terminalis (OVLT) - Contains osmoreceptors directly in contact with peripheral circulation –> sends signal to release ADH in response to increased osmolality
- Subfornical Organ (SFO) contains osmoreceptors as well as glucose sensors –> Senses energy state of the body
- Posterior pituitary –> Releases ADH and oxytocin into the circulation
- 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:
- Protection
- BBB protects brain from endogenous and exogenous toxins in plasma - Immunological barrier
- Protects from pathogens in blood, protects body from own immune system (e.g. autoimmune reaction to exposed CNS tissue in CNS) - Maintain stable ionic, glucose and pH environment in CSF.
- 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.
Outline the role of the kidneys in the regulation of body water
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.
