Physiology for MRCEM Primary

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Renal physiology

Plasma osmolality

[box type=”download”]  Overview of regulatory mechanism (hypothalamus, ADH, thirst, feedback loop)  Effects of ADH upon vascular tone systemically and renally  Sites of metabolism of ADH and appreciation of its rapid removal via feedback [/box]

The control of osmolality takes precedence over the control of body fluid volume.
Plasma osmolality is increased in water deficiency and decreased by the ingestion of water.
Osmoreceptors in the anterior hypothalamus regulate antidiuretic hormone (ADH), also known as vasopressin.
A rise in osmolality increases ADH release and stimulates thirst and water reabsorption.
ADH is synthesized in the hypothalamus and transported to the posterior pituitary (neurohypophysis) within nerve fibres (hypothalamohypophyseal tract), where it is stored in secretory granules.
Action potentials from osmoreceptors cause these to release ADH.
ADH binds to V2 receptors on renal principal cells and increases cyclic adenosine monophosphate (cAMP), causing the incorporation of water channels (aquaporins) into the apical membrane.
ADH also causes vasoconstriction (including renal) via V1 receptors.
The relationship between plasma osmolality and ADH release is steep, as is the relationship between plasma ADH and urine osmolality.
Normal urine production is ∼60 mL/h (urine osmolality, ∼300–800 mosmol/kg H2O).
Maximum ADH reduces the urine volume to a minimum of ∼400 mL per day (maximum urine osmolality, ∼1400 mosmol/kg H2O; this cannot be greater than that in the deep medulla).
In the absence of ADH, urine volume can reach ∼25 L per day / urine osmolality of ∼60 mosmol/kg H2O.
ADH is rapidly removed ( ∼50% in ∼10 min) via metabolism in the liver and kidneys.
Diabetes insipidus is the production of copious amounts of hypotonic (dilute) urine due to defective ADH-dependent water reabsorption.
This may be due to a congenital defect in ADH production (central diabetes insipidus, CDI), or to a failure to respond to ADH (nephrogenic diabetes insipidus, NDI) due to defective ADH receptors or aquaporins.

Control of body fluid volume

Plasma osmolality is strongly regulated by the osmoreceptors and ADH.
The control of body Na+ content by the kidney is the main regulator of body fluid volume.
Atrial and other low pressure (cardiopulmonary) stretch receptors detect a fall in central venous pressure (CVP), which reflects the blood volume and activates the baroreceptor reflex.
Increased sympathetic discharge causes peripheral vasoconstriction (increasing total peripheral resistance; TPR), including vasoconstriction of the renal afferent arterioles, stimulation of ADH release and water reabsorption, and release of renin from granular cells in the juxtaglomerular apparatus.
Decreased pressure in the renal afferent arterioles also stimulates renin release, as does reduced NaCl delivery to the macula densa in the juxtaglomerular apparatus and a reduced glomerular filtration rate (GFR).
In extremes, large falls in blood volume or pressure will promote ADH release and water retention at the expense of a decreased plasma osmolality.