Regulation of body water

This chapter is loosely associated with Section I1(i) of the 2017 CICM Primary Syllabus, which asks the candidates to "explain the distribution and movement of body fluids and their measurement". The specific question of how the total body water content is controlled seems fundamental but does not appear in the syllabus, contrary to the examiners referring to it as a "Level 1 topic" in their comments to Question 1 from the second paper of 2021.  It appeared again in Question 8 from the first paper of 2022. These were the only primary exam SAQs which mentioned asked the candidates to describe this essential feature of multicellular life.

To be sure, this question could be discussed from several different angles. One could talk about the movement of water between each different body fluid compartment (as this would fit into the distribution and movement part of the syllabus item), or one could discuss the mechanisms that maintain the tonicity and volume of each compartment (as they are all different), or one could focus on the actions of vasopressin (the dominant osmoregulatory hormone), or one could look pragmatically at the physiological responses to the loss or gain of water. Each would be a reasonable option for the discussion of body water behaviour, and being unable to choose between them, the author ultimately did all of the above:

• Movement of water between intracellular and extracellular body fluid compartments
• Mechanisms which maintain the intracellular fluid volume (and the related chapter on the control of intracellular volume and composition)
• Mechanisms which maintain the extracellular fluid volume (and the affiliated chapter on the humoral regulation of blood volume and flow)
• Mechanisms which maintain the extracellular fluid tonicity
• Vasopressin, and its various synthetic analogues
• Physiological response to oral water ingestion
• Physiological response to dehydration: the loss of 1L of body water
• Response to haemorrhage: the loss of 1L of blood (as contrasted with the completely separate response to isovolaemic anaemia)

However, from what the examiners wrote in response to Question 1 from the second paper of 2021, it would appear that the answer needed to be in a sensor-processor-effector format, similar to what was expected from the discussion of the humoral regulation of blood volume and flow. To satisfy this exam-centric requirement, this slightly expanded exam answer was fashioned from the rearranged bones of older chapters. 

Extracellular tonicity is the sensed variable.

• The normal value is about 285 mOsm/kg
• But: osmolality of the body fluids is not sensed directly
• Tonicity is the main determinant
• Determined mainly by serum sodium (which accounts for the vast majority of effective osmoles)

Hypothalamic osmoreceptors are the sensors

• Located in the organum vasculosum lamina terminalis (OVLT) and the subfornical organ
• These are circumventricular organs and lack a blood-brain barrier
• Fenestrated capillaries here expose the osmosensors to the tonicity of the blood
• These are mechanoreceptors which detect their own swelling and shrinking in response to changes in tonicity
• Increased  tonicity results in cell shrinkage and an increase in the rate of firing

Afferent signal is via 

• OVLT and subfornical organ nerves project fibres to the hypothalamus

Another mechanism of stimulating the same system is via hypotension

• The sensed variable is blood pressure, which is a surrogate for blood volume, which is in turn a surrogate for the volume of extracellular fluid and total body water
• It is sensed by the carotid baroreceptors
• Afferent signals are transmitted to the hypothalamus via the carotid sinus nerve, which is a branch of the glssopharyngeal nerve
• This is a much more potent stimulus for vasopressin release

Central controller/integrator is the hypothalamus

• Specifically, the hypothalamic supraoptic nucleus and periventricular nucleus
• There, the vasopressin-producing magnocellular neuron cell bodies reside

Efferent signal is vasopressin

• Vasopressin is released from nerve terminals in the posterior pituitary; these are the endings of axons descending from the hypothalamic supraoptic nucleus and periventricular nucleus
• Vasopressin secretion is minimal below an osmolality of 285 mOsm/kg,
• At normal euvolemia, usually the plasma level is 3 pmol/L
• It increases markedly (twentyfold) when extracellular tonicity increases
• It increases massively (a thousand fold) in the presence of hypotension

Effector organ is the renal collecting duct

• Vasopressin binds V2 receptors in the cortical collecting duct
• This increases the expression of apical aquaporin channels
• The increased permeability of the collecting duct cells results in the reabsorption of water
• Loss of vasopressin effect here produces diuresis

Effect is the reabsorption (or non-reabsorption) of urinary water

• Maximally concentrated urine is about 1200-1400 mOsm/kg
• Maximally dilute urine is about 40-50 mOsm/kg
• Maximal response occurs at a vasopressin concentration of about 5 pmol/L, corresponding to an extracellular fluid osmolality of around 290 mOsm/kg

Another effector mechanism is thirst

• Hypothalamic neurons project to the anterior cingulate gyrus and mediate thirst sensation as well as behavioural changes leading to a dopaminergic reward-driven pursuit of water
• This increases water intake

Indirectly, total body water is also affected through sodium regulation by:

• Renin-angiotensin system
• Aldosterone
• Natruretic peptides

Sure, there's plenty of peer-reviewed papers out there to act as references, but literally none of them seem to set things out in this exact way, so it seemed pointless to reference them.