Response to hyperosmolarity (ADH)
When a person consumes salty food, the plasma osmolarity increases. This increase (hyperosmolarity) acts as a powerful stimulus detected by hypothalamic osmoreceptors.
In response to excitation, the hypothalamus actively synthesizes antidiuretic hormone — vasopressin (ADH). It is important to understand that the hormone is not released directly into the blood: it is transported via axons to the posterior pituitary (neurohypophysis) and only secreted into the bloodstream from there.
Upon reaching the kidneys, vasopressin binds to V2 receptors on the membrane of collecting duct cells. An intracellular cascade is triggered:
- The enzyme adenylate cyclase is activated.
- The concentration of cAMP increases.
- Protein kinase A is activated and phosphorylates proteins.
- Water channels — aquaporins-2 — are incorporated into the apical membrane of the cells.
As a result, water reabsorption increases sharply: it returns to the bloodstream, plasma osmolarity is restored, and diuresis (urine volume) decreases. In addition, at very high concentrations, vasopressin can cause vasoconstriction of peripheral arteries.
Renin-angiotensin-aldosterone system (RAAS)
This system is activated by other trigger factors: blood loss, dehydration (leading to a decrease in circulating blood volume and blood pressure), or stenosis of the renal arteries (renal ischemia).
The RAAS cascade works in stages:
- In response to a drop in blood pressure, the juxtaglomerular apparatus of the kidneys secretes a proteolytic enzyme into the blood — renin.
- Renin acts on angiotensinogen (a protein synthesized in the liver), cleaving a fragment from it to form Angiotensin I.
- Under the action of ACE, it is converted into active Angiotensin II, which is the main effector of the system.
Angiotensin II acts comprehensively. It directly constricts blood vessels (vasoconstriction), stimulates the thirst center in the hypothalamus, and prompts the adrenal cortex to produce aldosterone. Aldosterone, in turn, travels to the distal renal tubules, where it enhances the reabsorption of sodium ions. Water is passively reabsorbed following sodium along the osmotic gradient. The end result of RAAS activity is the restoration of blood volume, an increase in blood pressure, and a return to homeostasis.
Sites of regulator synthesis
To understand water-electrolyte balance, one must clearly know where its main participants are synthesized. This information is frequently tested on exams.
| Substance | Site of synthesis | Additional |
|---|---|---|
| Vasopressin | Hypothalamus | Transported to the neurohypophysis |
| Oxytocin | Hypothalamus | Similar to the pathway of vasopressin |
| Aldosterone | Adrenal glands | Zona glomerulosa of the cortex |
| Renin | Kidneys | Juxtaglomerular apparatus |
| Angiotensinogen | Liver | Continuously circulates in the blood |
Clinical examples of disorders
During the removal of brain tumors, the pituitary stalk (infundibulum) is often damaged. This interrupts the transport of vasopressin from the hypothalamus to the neurohypophysis. Under conditions of ADH deficiency, water ceases to be reabsorbed in the collecting ducts. Central diabetes insipidus develops, the main symptom of which is polyuria — a sharp and uncontrolled increase in urine output.
Interestingly, polyuria also occurs in a completely opposite condition — primary hyperaldosteronism (excess aldosterone). Although the hormone is supposed to retain fluid, its overproduction leads to severe potassium loss. Hypokalemic nephropathy develops, causing the kidneys to lose their ability to concentrate urine, which paradoxically leads to excessive water excretion.
Briefly: answers to topical questions
By the action of which enzyme is angiotensin I converted into active angiotensin II, and where is it synthesized?
Angiotensin I is converted into active angiotensin II by angiotensin-converting enzyme (ACE). ACE is produced mainly in the lungs as well as in the vascular endothelium of other organs.
The synonym for ACE is carboxydipeptidyl peptidase. Mechanism of action: cleavage of two amino acids from the C-terminus of angiotensin I, a 10-amino acid peptide; resulting in the formation of active angiotensin II, an 8-amino acid peptide.
What types of aquaporins exist besides aquaporin-2, and in which nephron segments are they localized?
In addition to aquaporin-2, other types of water channels have been discovered in the nephron, providing passive water reabsorption.
- Aquaporin-1 — localized in the proximal tubules and thin limbs, where it provides constant (obligate) reabsorption.
- Aquaporin-3 — localized on the basolateral membrane of the collecting duct epithelial cells.
In total, eleven aquaporin homologs have been discovered in humans, a significant number of which are present in the renal tubules for water transport.
How do natriuretic peptides affect water-electrolyte metabolism, and where are they synthesized?
Atrial natriuretic peptide (ANP, natriuretic peptide) is synthesized in atrial cardiomyocytes. The stimulus for its release is atrial stretching due to increased circulating blood volume (CBV) and blood pressure.
Effect on water-electrolyte metabolism:
- increases renal excretion of Na+ and water;
- exerts diuretic and natriuretic effects;
- suppresses the renin-angiotensin-aldosterone system (RAAS);
- causes vasodilation and lowers blood pressure.
Class and exam questions
Why does polyuria develop in pituitary stalk injury?
Transection of the pituitary stalk interrupts the axonal transport of vasopressin from the hypothalamus. Without ADH, aquaporins are not inserted into the collecting ducts, water is not reabsorbed into the blood and is lost in the urine.
How does aldosterone affect circulating blood volume?
Aldosterone enhances the reabsorption of sodium ions in the distal renal tubules. According to the laws of osmosis, water is passively reabsorbed following sodium, which increases blood volume and raises blood pressure.
Which substance is the main effector of the RAAS?
Angiotensin II. It is the one that causes vasoconstriction, stimulates the thirst center, and triggers the synthesis of aldosterone in the adrenal glands.
What else to study on this topic
- Intracellular mechanism of action of vasopressin (adenylyl cyclase and cAMP pathway)
- Pathogenesis of hypokalemic nephropathy in hyperaldosteronism
- Structure and functions of the renal juxtaglomerular apparatus
- Differences between central and nephrogenic diabetes insipidus
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