Next Lesson - Control of Potassium
- Plasma Osmolarity and Plasma Osmolality
- Neurohormonal Mechanisms to Control Plasma Osmolarity
- The Medullary Counter Current Mechanism
- The Big Picture
- Osmoreceptors in the hypothalamus are responsible for detecting changes in plasma osmolarity.
- Changes in plasma osmolarity can be corrected through the release of ADH from the posterior pituitary gland, or through the feeling of thirst.
- The release of ADH and its actions on the kidney can only correct for small changes in plasma osmolarity. Large changes are compensated for through thirst or the need to consume salt.
- The medullary counter current mechanism is the mechanism which is responsible for allowing the kidney to selectively reabsorb water.
Osmolality and osmolarity are different measurements of this electrolyte-water balance. They are functionally the same in practice, even though they are technically different.
Before working out the difference, one first has to understand the ‘osmole’ – an osmole is a unit of osmotic concentration, measuring the number of moles of solute that are in the solution that are contributing to the concentration of the solution. For example, one mole of NaCl in solution would produce two osmoles (Na+ and Cl-).
Osmolarity (with an ‘R’) is defined as the number of osmoles per litre of solution.
Osmolality (with an ‘L’) is defined as the number of osmoles per kilogram of solvent.
Basically, a larger number when measuring osmolarity or osmolality means a higher concentration.
Changes in plasma osmolarity indicate that there is a disorder of overall water balance in the body. There are two neurohormonal mechanisms by which the body controls plasma osmolarity: antidiuretic hormone (ADH) and thirst.
Osmoreceptors are located in the hypothalamus. These detect changes in plasma osmolarity, and then stimulate secondary responses which ultimately lead to two outcomes: increased reabsorption of water from the urine (leaving small amounts of very concentrated urine), and thirst.
ADH is released with an approximately 1% change in plasma osmolarity, and thirst is stimulated with an approximately 10% change in plasma osmolarity.
Under conditions of increased plasma osmolarity, osmoreceptors stimulate the increase of antidiuretic hormone release from the posterior pituitary gland, leading to decreased renal water excretion (remember: anti-diuresis = conserving water). Conversely, when plasma osmolarity decreases, ADH secretion is inhibited. The two mechanisms together for a feedback loop which stabilises osmolarity.
ADH increases the permeability of the collecting duct to water and urea; an increase in ADH means more water is reabsorbed by the kidney and plasma osmolarity will decrease. ADH increases the insertion of aquaporin (AQP) channels into the apical membrane of the cells of the collecting duct.
Whilst this control of plasma osmolarity is important, in situations where intravascular volume is depleted, the kidneys will conserve water in an attempt to maintain blood pressure – even if this means the osmolarity of body fluids changes.
Diabetes insipidus is a condition in which water is inadequately reabsorbed from the collecting ducts, so a large quantity of urine is produced. There are two types of diabetes insipidus: central and nephrogenic.
Central diabetes insipidus occurs when plasma levels of ADH are too low, this can be due to many causes like:
- Damage to the hypothalamus or pituitary gland, for example; due to a skull fracture, a tumour, or an aneurysm.
- Sarcoidosis or tuberculosis.
- Some forms of encephalitis or meningitis.
- Langerhans cell histiocytosis – although this is rare.
Nephrogenic diabetes insipidus is caused by an acquired insensitivity of the kidney to ADH.
Both types of diabetes insipidus are managed by ADH injections or ADH nasal sprays.
Syndrome of Inappropriate ADH Secretion
Syndrome of inappropriate ADH secretion (SIADH) is another condition in which ADH secretion is abnormal. In SIADH there is excessive release of ADH from the posterior pituitary gland (or from another source like a neuroendocrine tumour). This results in abnormal retention of water from the urine, causing a dilutional hyponatraemia where there is low plasma sodium but an increase in overall total body fluid.
Large changes in plasma osmolarity can only be partially compensated for by the kidney through the action of ADH. In these situations, ingestion of water (when plasma osmolarity is high) or salt (when plasma osmolarity is low) is needed.
The urge to drink water is induced by an increase in plasma osmolarity. This increases the amount of free water which in turn lowers plasma osmolarity. When sufficient fluid has been consumed, this urge stops, although the exact mechanism by which this happens is unknown.
The medullary counter current mechanism refers to the functional organisation of the kidney which allows the kidney to concentrate urine. This is achieved largely by the creation of a vertical osmotic gradient – a term which means that the osmolarity of the renal medulla is greater (more concentrated) than that of the renal cortex. There are many parts that make up this mechanism:
- Juxtamedullary Nephrons – these account for around 20% of all nephrons (the other 80% being cortical nephrons). They have a particularly long loop of Henle which ‘dips’ into the renal medulla, allowing the creation of the vertical osmotic gradient.
- Vasa Recta – long, straight capillaries that surround juxtamedullary nephrons and help to maintain the vertical osmotic gradient.
- Collecting Ducts of All Nephrons – all collecting ducts pass through the renal medulla so use the vertical osmotic gradient, along with ADH to produce urine of varying concentrations.
- Urea – plays a small role in the concentration of urine.
The descending limb of the loop of Henle is highly permeable to water due to the presence of AQP-1 channels in the membrane which are always open. The descending limb is not permeable to sodium, so sodium remains in the descending limb and the filtrate concentration (osmolarity) increases as water moves into the interstitium. The maximum concentration of the filtrate is at the tip of the loop of Henle.
The ascending limb actively transports sodium chloride (NaCl) out into the interstitium and is impermeable to water. As NaCl leaves and water remains, the osmolarity of the filtrate decreases so fluid entering the distal convoluted tubule (DCT) has a low osmolarity.
The combination of both of these factors means that a large vertical osmotic gradient is established in the interstitial fluid of the renal medulla – the interstitial fluid of the medulla increases in osmolarity progressing deeper into the medulla.
This process is called counter-current multiplication and the loop of Henle is referred to as a counter-current multiplier.
As previously mentioned, the vertical osmotic gradient is initially set-up by the loop of Henle, but it is maintained by the vasa recta. The vasa recta act as a counter-current exchanger.
Without the vasa recta, the solutes in the interstitium would simply be washed out, as water from the descending loop of Henle would diffuse out and ruin the vertical osmotic gradient. The blood in the vasa recta flows in the opposite direction to the filtrate in the tubules, which allows it to maintain the vertical osmotic gradient.
In the descending limb of the vasa recta blood is isosmotic. As the vasa recta enters into the renal medulla, the high concentration of sodium, chloride, and urea in the extracellular fluid encourages these solutes to diffuse into the vasa recta. This increases the osmolarity of the blood in the vasa recta as it reaches the tip of the loop.
In the ascending limb of the vasa recta, blood moves towards the renal cortex and has a higher osmolarity than the interstitium of the cortex. This causes water to move into the vasa recta from the descending limb of the loop of Henle. This prevents the water from staying in the interstitium and ruining the vertical osmotic gradient – thus the gradient is maintained.
Urea plays a small role in the creation of the vertical osmotic gradient. Urea is reabsorbed from the medullary portion of the collecting ducts, and it then moves into the interstitium before diffusing back into the loop of Henle.
While urea is in the interstitium, it increases it's osmolarity, further increasing the vertical osmotic gradient. Due to this, it is referred to as an “effective osmole”.
The release of ADH promotes more urea moving into the interstitium, allowing it to draw more water into the interstitium.
As mentioned before, the medullary counter current mechanism allows the collecting ducts to concentrate urine, and the above points show how this is created and maintained.
Due to these multiple factors, the collecting ducts pass through the hyperosmotic renal medulla and the increased osmolarity of the interstitium draws water out of the collecting ducts. This removal of water concentrates the urine, and the amount can be modulated by ADH.
When changes in plasma osmolarity are too big to be compensated for by the kidney, the feelings of thirst and salt craving are used to decrease or increase plasma osmolarity respectively.
Edited by: Dr. Maddie Swannack
Reviewed by: Dr. Thomas Burnell