Summary

• The body consists of an extracellular and intracellular compartment. Large changes in one compartment can be buffered by the other. But once a parameter in the body as a whole changes too much, it needs the help of the external environment.
• When the body senses a change in osmolality, it reacts by changing the amount of water (NOT amount of sodium). It does this by affecting ADH and thirst.
• When the body (primarily kidneys) senses a change in volume, it reacts by changing the amount of sodium (NOT amount of water). It does this by affecting the RAAS. The change in sodium then automatically triggers a corresponding change in volume by the osmolality feedback system.
• Hyponatraemia occurs whenever there is an excess of water compared to sodium. It should generally be viewed as a condition with too much water, rather than too little sodium.
• When the kidneys sense a relatively sudden and severe enough hypovolaemia, this above system is overridden, and ADH is released (even if osmolality is initially normal) to increase volume even more than the RAAS would on its own. As a side effect, there is now a lower sodium concentration and lower osmolality.
• This is the mechanism of hyponatraemia in both hypovolaemic and hypervolaemic states. Urine osmolality in these states is high, because ADH is (appropriately) high. Urine sodium is low, since volume is perceived to be low and the kidneys are conserving sodium by releasing as little as possible in the urine.
• ADH can also be inappropriately high. In such cases, urine osmolality is still high because ADH is high. However, the volume regulation system is working normally, so urine sodium is high. This also means the system stabilises at a normal volume by removing sodium and water in equal amounts, which is why SIADH is not hypervolaemic.
• In all 3 sets of cases above, it is ADH which is causing an excess of water compared to sodium, i.e. the hyponatraemia is being driven by ADH. The difference is that in the first two, the ADH is an appropriate response to the kidneys sensing a low perfusion. In the latter, the ADH is inappropriate. Thus it is not correct to diagnose SIADH simply based on a high urine osmolality.
• Excess water causing hyponatraemia may also occur completely independently to ADH. In these ADH-independent causes, there is either excess water intake or not enough water excretion. As there is nothing wrong with the kidneys, volume or osmolality feedback systems, ADH will be low in order to excrete as much pure water as possible, and the hyponatraemia is present despite maximal excretion of pure water via the kidneys. As ADH is low, urine water content is high, and so urine osmolality is low. Severe renal failure also comes into this category, but in this case urine osmolality will be very similar to serum osmolality (around 285mOsm) because the kidneys have lost the ability to concentrate or dilute urine, regardless of ADH levels.