Regulation of sodium and potassium balance Flashcards
State the relative amounts of sodium reabsorbed in different parts of the nephron.
65% - PCT
25% - loop of Henle
8% - DCT
Up to 2% - collecting duct
Describe the relationship between GFR and sodium reabsorption.
The greater the GFR the greater the sodium reabsorption
what is the most important solute.
Sodium most prevalent, and important, solute in the ECF.
What are the effects of
changing sodium levels
Increased dietary sodium Increased osmolarity (but the body can’t let this happen) Increased ECF volume Increased blood volume and pressure
Decreased dietary sodium Decreased osmolarity (but the body can’t let this happen) Decreased ECF volume Decreased blood volume and pressure
How can you alter GFR to preserve sodium? What components are involved in the preservation of sodium?
Reduce the amount of blood going through the kidneys
Aldosterone - stimulates reabsorption of sodium from the DCT and collecting duct
Angiotensin II - stimulates reabsorption of sodium from the PCT (and stimulates release of aldosterone)
Increased sympathetic activity causes vasoconstriction of the afferent arteriole so less blood reaches the nephron. It also stimulates the JGA and PCT to reabsorb more Na+.
JGA is also stimulated by low tubular Na+ concentration
What triggers the juxtaglomerular apparatus to produce renin?
Low tubular Na+ concentration
Low renal perfusion pressure
What hormone is involved in decreasing sodium reabsorption?
Atrial Natriuretic Peptide (ANP)
Where do you find a lot of ACE?
Lung Endothelium
What effect does angiotensin II have on sodium reabsorption? Which parts of the nephron does it affect?
Increase sodium reabsorption in the PCT
Describe the effects of aldosterone on absorption and secretion.
Increase Na+ reabsorption
Increases H+ secretion
Increases K+ secretion
What is the result of aldosterone excess?
Hypokalemic Alkalosis
How does aldosterone work? How does it cause an increase in sodium reabsorption?
Aldosterone is a steroid so it has a genomic effect and binds to type 1 intracellular receptors.
It relocalises the vesicles containing sodium transporters to the apical membrane
It also increases transcription and production of more sodium channels and Na+/K+ channels
What are the consequences of hypoaldosteronism?
Reabsorption of sodium in the distal nephron is reduced
Increased urinary loss of sodium
ECF volume falls
Increased Angiotensin II and Vasopressin secretion , renin
Low blood pressure, dizziness, palpitations, salt craving
What are the consequences of hyperaldosteronism?
Increased sodium reabsorption in the distal nephron
Reduced urinary loss of sodium
ECF volume increases - HYPERTENSION
Reduced angiotensin and vasopressin secretion , renin
Increased ANP and BNP
Leads to high blood pressure, muscle weakness, polyuria and thirst
What is Liddle’s Syndrome?
Inherited disease of high blood [ressure
Mutation in the aldosterone dependent Na+ channel - the channel is permanently switched on resulting in sodium retention and HYPERTENSION
How does aldosterone work? How does it cause an increase in sodium reabsorption?
Aldosterone is a steroid so it has a genomic effect and binds to type 1 intracellular receptors.
It relocalises the vesicles containing sodium transporters to the apical membrane
It also increases transcription and production of more sodium channels and Na+/K+ channels
Synthesised and released from the adrenal cortex
Released in response to Angiotensin ll,
decrease in blood pressure (via baroreceptors)
decreased osmolarity of ultrafiltrate
How can GFR be affected to help lose sodium?
Increase GFR = more sodium removed
what are the drugs that can affect the tubular system where they act in the nephron.
ACE inhibitors: lower blood pressure . Doesn’t only affect kidneys but also other places around the body.
Diuretics:
Osmotic diuretics (glucose in diabetes and mannitol): increase osmolarity in the tubular system and so allow less water and sodium to exit via the para-cellular routes.
Carbonic Anhydrase Inhibitors : prevent the production of protons and block pumps in the PCT
Loop Diuretics : usually block triple transporter in the ascending loop
Thiazide Diuretics: DCT
Potassium Sparing Diuretics: block K+/Cl- co-transporters which leads to a change in calcium uptake because less sodium is taken in.
What is the basis behind diuretics with regards to tubular osmolarity?
They increase the tubular osmolarity so there is less of a gradient between the collecting duct and the interstitial compartment so less water is reabsorbed.
What do loop diuretics do? Name a loop diuretic.
Furosemide - they block the Na+/K+/Cl- triple transporter
What do thiazide diuretics do?
Inhibit Na+/Cl- cotransporter
What do K+ sparing diuretics do? Name two.
Amiloride - Na+ channel blocker - prevents entry of Na+ from the tubule lumen
Spironolactone - aldosterone antagonist
Why do you get a smaller natriuresis with K+ sparing diuretics?
Because they act on the collecting duct, which is only responsible for 2% of the reabsorption of Na+
Why are they called K+ sparing diuretics?
They don’t cause increased excretion of K+
What is a serious consequence of high extracellular K+?
It can cause depolarisation of membranes (e.g. resulting in arrhythmia)
What stimulates the uptake of K+ into tissues?
INSULIN
Aldosterone and Adrenaline
How does tubular flow affect K+secretion?
Principal cells have cilia that move with the flow. The movement of the cilium stimulates a protein called PDK1, which stimulates an increase in intracellular Ca2+ concentration
This stimulates the activity of the K+ channels
Flow is increased by diuretics, which is one of the problems with non-potassium sparing diuretics because they cause an increase in K+ secretion
State some causes of hypokalaemia.
Diuretics
Diarrhoea
Surreptitious Vomiting
Genetics (Gitelman’s syndrome; mutation in the Na/Cl transporter in the distal nephron)
State some causes of hyperkalaemia.
Ageing
Potassium-sparing diuretics
ACE inhibitors
what is the immediate response to dietary potassium
is for it to be pumped into cells via Na+K+ATPase, over time it equilibrates and the output at the collecting duct ranges between 1%-80% of what goes into the tubular system.
what is the variation stimulated by?
Increase in plasma K+ concentration
Aldosterone (increase in)
Increase in tubular flow rate
Increase in pH
what are the mechanisms by which potassium secretion is regulated?
-secreted by principal cells
- Na+K+ATPase activity
- Permeability of potassium channel (aldosterone)
- tubular flow (flow sensors primary cilium are linked to potassium
what do bararecptors measure and where?
Measure on the low pressure and high pressure sides, measure stretch of vessels/
Low pressure: atria, right ventricle, pulmonary vasculature
High pressure: carotid sinus, aortic arch and JGA
