Control of Renal Function
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Causes retention of…
Activation of angiotensin II is the end result of activation of the renin-angiotensin system. Causes massive vasoconstriction. Also causes the release of ADH and aldosterone. Also has its own direct effect on the kidneys activated when there is low BP.
The production of angiotensin II is reduced with ACE inhibitors, and its effects can be prohibited by angiotensin-II receptor blockers (ARBs). Clinically these drugs have very similar effects.
When the JG apparatus experiences a low BP it release Renin. This activates angiotensinogen to AG-I, which is then activated by ACE to AG-II
Vasopressin (ADH)
Acts on the DCT and causes increased synthesis of water channels, thus increasing water re-absorption. Released by the pituitary in response to low BP
Doesn’t have a direct effect on Na and K. may cause secondary retention of ions via osmosis, to a small degree. if there is excess ADH, then there will be a dilutional hyponatraemia.
Acts on the PCT where the majority of sodium is reabsorbed, causing synthesis of more sodium channels.
Produced by the adrenal glands in response to angiotensin-II and high potassium levels.
Excess of aldosterone can cause excessive sodium reabsoprtion, excessive potassium excretion. also, lack of aldosterone has the opposite effect
Also – excess sodium retention can cause alkylosis! This because sodium is retained in exchange for H+ at some channels – thus excess H+ will be excreted
e.g. Frusemide
Acts on the thick descending loop of Henle. It prevents the sodium / potassium / chloride channel from functioning, thus these ions remain in the filtrate.
25% of potassium reabsoprtion is prevented. Highly effective at reducing BP and increasing sodium and water excretion. when the drug is stopped there is rebound sodium retention. Excreted by the kidney. Can cause; renal failure (as a result of massive drop in BP), hyponatraemia, hypokalaemia, chochlear damage, hypocalcaemia, hypomagnesaemia
e.g. bendroflumethazide
Acts on the sodium / chloride transported and prevents it from functioning properly. Thus sodium is not retained. Over time will cause vasodilation as well. Longer acting than loop diuretics, but not as effective
6-8% of potassium reabsoprtion is prevented Can cause; hypokalaemia, salt and water retention, hypercalcaemia – note this is the opposite of loop diuretics!, hypokalaemia – which in turn can cause glucose intolerance – as glucose is taken up into cells with potassium!
e.g. spironolactone
These block aldosterone’s receptors. Thus they only work in the presence of aldosterone. sodium is lost, and potassium is spared (potassium sparing diuretics).
2-3% of potassium reabsoprtion is prevented These are the least effective of the diuretics.
Note that nothing (to any great extent) increases potassium retention.
Normal renal physiology and mechanism of action of diuretics
Normal renal physiology and mechanism of action of diuretics. Image by Haisook at English Wikipedia

The renin-angiotensin system (RAAS)

The renin-angiotensin system (sometimes called the renin-angiotension-aldosterone system, or RAAS) is really important. It is the main mechanism by which the kidneys control blood pressure.

  • There are 3 ways BP is regulated – renin-angiotensin, autonomic nervous system, and autoregulation (where afferent and efferent arterioles will constrict and relax)
  • About 25% of ALL cardiac output goes to the kidneys, via the renal arteries
  • When the kidneys sense a drop in blood pressure (hypotension) the RAAS is activated

The RAAS is controlled by the JG (juxtaglomerular) apparatus.
Renin is synthesised by the JG cells of the kidneys. It is stored in its inactive form – prorenin. A drop in BP, sympathetic stimulation or decreased delivery of sodium and chloride ions to the macula densa will cause the release of renin. Often a combination of all these factors is involved.

  • Renin is an enzyme!

Angiotensin is a vasoconstrictor. The liver synthesises and releases angiotensinogen (the inactive precursor of angiotensin) in the general circulation. When angiotensinogen comes into contact with renin, it is turned into Angiotensin-I . Angiotensin-I’s main function is as a precursor to Angiotensin-II, however, it has some extremely weak vasoconstricting properties of its own, but these aren’t significant enough to have any noticeable effect.
Angiotensin-I will continue in the general circulation until it reaches the lungs, where converting enzyme (ACE) will convert it to Angiotensin-II. Converting enzyme is found in the endothelial cells of the lungs.

  • Angiotensin-II is a very powerful vasoconstrictor, but it is only present in the blood for 1-2 minutes, before it is removed by angiotensinases.
  • Whilst active, angiotensin will cause vasoconstriction of arteries, and to a lesser extent, veins. The purpose of venoconstriction is to increase venous return to the heart, and thus help the heart pump against the increased arterial pressure.
  • Angiotensin-II also has a longer term effect on the kidneys – causing more reabsoprtion of sodium and water, and thus increasing extracellular fluid volume. This effects continues to last for hours and even days.
  •  It also stimulates aldosterone release by the adrenal glands, which acts on the DCT and collecting system to increase sodium (and thus water) reabsoprtion.
    • The direct effect of angiotensin is about 4x as great as the effect of aldosterone on raising blood pressure
  • It also acts on the CNS, causing:
    • Increased sensation of thirst
    • Increased section of ADH by the pituitary gland, causing reabsoprtion of water in the DCT and collecting system.
    • Increased sympathetic activity to cause vasoconstriction

The renin-angiotensin system acts when there is a fall in BP. Thus, it keeps GFR normal, but decreases total urine output (perhaps to 1/5 of the average value). When there is a rise in BP, the system becomes less active, and the naturally increased BP causes an increase in GFR – thus keeping the GFR relatively stable.

The production of angiotensin II is reduced with ACE inhibitors, and its effects can be prohibited by angiotensin-II receptor blockers (ARBs). Clinically these drugs have very similar effects.

Renin-angiotension-aldosterone system
Renin-angiotension-aldosterone system

Natriuretic peptides

  • These are released when there is a sever rise in BP. They are released in response to stretching of the heart muscles. There are two types:
    • ANP – atrial natriuretic peptide – released by the atria in response to stretching
    • BNP – brain natriuretic peptide – released by the ventricles (despite what the name says!) in response to stretching.
  • They will cause dilation of the afferent, and constriction of the efferent arteriole, and thus reduce the GFR when BP is raised. They will cause decreased reabsoprtion of sodium ions, and thus result in increased urine output
  • They are also markers for heart failure.
  • Also, constriction of the afferent arteriole by sympathetic stimulation will also decrease GFR.
Aldosterone this is a mineralocorticoid. Causes the retention of sodium. Acts on the DCT to synthesise and transport more sodium channels to the surface. An excess is associated with potassium loss
ADH (vasopressin)produced by the hypothalamus, secreted by the posterior pituitary. Acts on the medullary collecting ducts and makes them more permeable water.
It does this by increasing the synthesis of water channels – aquaporins. This results in a more concentrated urine, and reduces fluid loss.

Synthetic Mechanisms
See Diuretics,ACE inhibitors and angiotensin II receptor blockers

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Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) FRACGP currently works as a GP and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University, and is studying for a Masters of Sports Medicine at the University of Queensland. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

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