Physiology for MRCEM Primary

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Renal physiology

Renal hormones

[box type=”download”]  Angiotensin II as the principal agent in sodium balance  Role of ACE in generating angiotensin II  Effects of angiotensin II on vessels, tubules, hypothalamus, adrenal cortex  Positive and negative feedback effects of angiotensin II  Effects of aldosterone and ANP in health [/box]

Renin, angiotensin and aldosterone

Renin cleaves plasma angiotensinogen into angiotensin I, which is converted by angiotensin-converting
enzyme (ACE) on endothelial cells (primarily in the lung) into angiotensin II.
Angiotensin II is the primary hormone for Na+ homeostasis, and has several important functions.
It is a potent vasoconstrictor throughout the vasculature, although in the kidney it preferentially constricts efferent arterioles, thereby increasing GFR.
It directly increases Na+ reabsorption in the proximal tubule by stimulating Na+–H+ antiporters.
It stimulates the hypothalamus to increase ADH secretion and also causes thirst.
It stimulates the production of aldosterone by the adrenal cortex.
Potentiate sympathetic activity (+ve feedback) and inhibit renin production by granular cells (-ve feedback).

ACE inhibitors are important for the treatment of heart failure, when the response to reduced blood pressure leads to detrimental fluid retention and oedema.
Aldosterone is required for normal Na+ reabsorption and K+ secretion.
It increases the synthesis of transport mechanisms in the distal nephron, including the Na+ pump, Na+–H+ symporter and K+ and Na+ channels in principal cells, and H+ ATPase in intercalated cells.
As aldosterone acts via protein synthesis, it takes hours to have any effect.
The production of aldosterone by the adrenal cortex is directly sensitive to small changes in plasma [K+], suggesting a primary role for K+ homeostasis.

Atrial natriuretic peptide (ANP; atrial natriuretic factor) is released from atrial muscle cells in response to stretch caused by increased blood volume. ANP inhibits ENaC in principal cells of the distal nephron, suppresses the production of renin, aldosterone and ADH, and causes renal vasodilatation.
The net result is increased excretion of water and Na+.


Osmotic diuretics (e.g. mannitol) cannot be reabsorbed effectively and, consequently, their concentration
in tubular fluid increases limiting water reabsorption.
Thus in uncontrolled diabetes mellitus, high plasma glucose results in copious amounts of urine containing glucose.

Diuretic drugs generally inhibit tubular transport mechanisms.
The most potent are loop diuretics (e.g. furosemide), which inhibit Na+–K+–2Cl− symporters in the thick ascending loop of Henle, thus preventing the development of high osmolality in the medulla and inhibiting water reabsorption.
The increased flow (and thus increased K+ secretion), coupled with reduced K+ reabsorption, enhances K+ excretion and can cause hypokalaemia.

Aldosterone antagonists (e.g. spironolactone) and Na+ channel blockers (e.g. amiloride) reduce Na+ entry in the distal nephron and inhibit K+ and H+ secretion; they are weak diuretics, but K+ sparing, and are often given with loop diuretics to reduce K+ loss.
Alcohol inhibits ADH release, and so promotes diuresis.