Mannitol and osmotic diuretics
Mannitol is an osmotic diuretic: it raises the concentration of dissolved particles (osmolality), so more water is lost in the urine and water is drawn out of the brain.
Remember
Mannitol is freely filtered at the glomerulus (the kidney's filter) but is not reabsorbed (taken back into the blood), so it stays in the tubule (the long working tube of each nephron) and holds water there. It also raises the osmolality of the blood, so water moves out of swollen brain tissue.
Memory aid
mannitol is a sponge in the tubule, because it stays inside and keeps water with it
Picture mannitol as a sponge in the tubule that stays inside and keeps water with it.
Most diuretics work by blocking a specific transporter or receptor. An osmotic diuretic such as mannitol is different. Mannitol is a sugar that the body does not metabolise (break down), so it is freely filtered but is poorly reabsorbed. It therefore stays in the tubular fluid and raises its osmolality, which means the concentration of dissolved particles.
Water moves by osmosis, towards the side with more dissolved particles. The water is therefore held in the tubule instead of being reabsorbed, and more of it leaves as urine. This increase in urine volume, caused by particles left in the tubule, is an osmotic diuresis.
Because mannitol also raises the osmolality of the blood, it affects the brain too. Water moves out of brain tissue and cerebrospinal fluid (the fluid that surrounds the brain) towards the blood. That reduces cerebral oedema (swelling of the brain from excess water) and so lowers intracranial pressure, the pressure inside the skull. The same high osmolality therefore explains both the diuresis and the fall in pressure.
Mannitol does not usually cross the blood-brain barrier (the tight lining of the brain's capillaries) while the barrier is intact. It is given by intravenous infusion (a drip), and its side effects include dehydration and electrolyte disturbances.
Key facts
- Mechanism
- after mannitol is freely filtered, it is not reabsorbed, so its particles keep the tubular fluid high in osmolality and water stays in the tubule.
- Not a blocker
- it does not act on a sodium transporter, an enzyme or a hormone receptor.
- Brain effect
- raising the osmolality of the blood draws water out of brain tissue and cerebrospinal fluid, which lowers intracranial pressure.
- Uses
- raised intracranial pressure and cerebral oedema.
- Route
- it is given intravenously because it is poorly absorbed from the gut.
- Side effects
- dehydration and electrolyte disturbances.
Exam traps
- Constricting the afferent arteriole (the small vessel that carries blood into the glomerulus) lowers the amount of fluid filtered, so urine output falls. An osmotic diuretic does the opposite, because it works after filtration by holding water in the tubule.
- Blocking the receptor for aldosterone (a salt-retaining hormone) is how spironolactone works, not mannitol, because osmotic diuretics do not act on a hormone receptor.
- Furosemide, a loop diuretic, has a similar result, a lot of urine, but through a blocked transporter protein, not through particles left in the tubule.
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