Sodium and Potassium Balance Flashcards
How does the body increase sodium retention?
What hormone decrease soudium reabsorption?
Increasing sodium retention
Aim is to reduce the amount going into the glomerulus. This is achieved by increasing sympathetic activity (causing greatest vasoconstriction in the afferent arteriole) which thus reduces the GFR.
o Increased sympathetic activity also stimulates Na channels in the PCT, thus increasing Na reabsorption in the PCT
o Increased sympathetic activity also stimulates the juxtaglomerular apparatus, which stimulates the mechanisms which drive Angiotensin II synthesis.
Angiotensin II also stimulates Na channels in the PCT, thus increasing Na reabsorption in the PCT
Angiotensin II also drives Aldosterone synthesis, which increases Na and water reabsorption in the DTC + collecting duc
t Because the uptake of Na in the PCT has been increased, the filtrate reaching the juxtaglomerular apparatus will have a lower salt concentration. This is detected, and further drives angiotensin II production.
ANP decreases soudium reabsorption
Decreasing sodium reabsorption??
Involves atrial natriuretic peptide (ANP), which acts as a vasodilator (predominantly on the afferent arteriole), stimulating increased GFR
o ANP also reduces the activity of Na uptake channels in the PCT, JGA + CT
What are the effects of Na+ in the distal nephron?
•
Stimulates Renin release from juxtaglomerular cells
By the time the filtrate reaches the JGA, its salt concentrated is monitored by the macula densa cells of the juxtaglomerular apparatus
A reduced filtrate Na concentration drives Renin synthesis, which converts angiotensinogen (angiotensinogen synthesised in the liver) to angiotensin I
o Renin synthesis is also stimulated by decreased blood pressure, fluid volume + increase beta1- sympathetic activity o R
enin synthesis is inhibited by an increase in blood pressure, fluid volume, decreased beta1- sympathetic activity + ANP
Angiotensin converting enzyme (present in the lungs) converts angiotensin I angiotensin II
Effects of AngII on proximal tibile and vascular system?
What type of hormone is aldosterone?
Where is it syntheisised and released?
What is it released in response to?
Aldosterone
- Steroid hormone
- Synthesised and released from the adrenal cortex
Released in response to Angiotensin ll,
- decrease in blood pressure (via baroreceptors)
- decreased osmolarity of ultrafiltrate
What type of cells does aldosterone stimulate and where are they found?
What effects does aldosterone have on these cells?
Aldosterone stimulates the principal cells of the distal convoluted tubule/cortical collecting duct
o Increased sodium reabsorption (+ thus water reabsorption)
o Increased potassium secretion
o Increased hydrogen secretion
What does aldosterone excess lead to?
Aldosterone excess leads to hypokalaemic alkalosis (reduced potassium concentration in the blood, in addition to reduced hydrogen concentration which increases the pH)
How does aldosterone carry out its affect inside cells and state what effects it has inside the cell?
Aldosterone binds to intracellular receptors, which causes a change in conformation which drives the receptor-aldosterone complex translocation into the nucleus.
o In the nucleus, the complex binds to specific regions of DNA, acting as a transcription factor:
Increase expression of the apical/luminal Na channel
Also promotion of activity via regulatory proteins (the proteins are converted from low to high affinity transporters)
Increased formation of the Na/K ATPase pumps
o Positive feedback also occurs, so that there is an increased effect of the aldosterone-receptor binding to the DNA
What happens if you have hypoaldosteronism?
What happens if you have hyperaldosteronism?
What is LIddle’s syndrome?
Response to baroreceptor activity
Name 4 effects of ANP and state what they are produced in response to?
Arial Natriuretic Peptide (ANP)
Small peptide made in the atria (also make BNP)
Released in response to atrial stretch (i.e. high blood pressure)
Actions:
- Vasodilatation of renal (and other systemic) blood vessels
- Inhibition of Sodium reabsorption in proximal tubule and in the collecting ducts
- Inhibits release of renin and aldosterone
- Reduces blood pressure
Where do Osmotic diuretics and carbonic anhydrase inhibitors , loop diuretucs, thiazides and K+ spacing diuretics act?
What do loop diuretics target?
What do thiazides target?
Name 2 pottasium sparring diuretics and what they target
HIGHER OSMOLARITY IN TUBULAR FLUID - LESS REABSORPTION
Diuretics
There are different types of diuretic drugs, all which act to increase the rate + volume of urine production.
The different diuretics have different sites of action along the nephron.
o Osmotic diuretics and carbonic anhydrase inhibitors - act on the proximal convoluted tubule
o Loop diuretics – act on the thick ascending limb of loop of Henle
o Thiazides – act on the proximal part of the distal convoluted tubule
o K+ spacing diuretics – act on the distal part of the DCT + cortical collecting duct
What drives tissue uptake of pottasium?
Potassium mainly comes from diet. By eating meat, you effectively are eating cells, thus eating IC space which contains lots of potassium. This leads to increased plasma potassium, which must be taken up into tissues
o This tissue uptake is driven by insulin (+ aldosterone and adrenaline)
Tissue uptake can be seen as the immediate response to dietary K+, which involves the Na/K pump transporting potassium out of the plasma into the cell.
o Potassium then leaks out of the cell via potassium channels, into the EC space surrounding cells
Potassium handling by the kidneys
~70% of potassium reabsorption occurs in the …………, with ~30% of the filtered load reaching to ……………………
Further reabsorption occurs in the loop of Henle, with ~10% remaining to reach the …………
Potassium secretion then occurs in the…………cells of cortical collecting duct, and this varies from 1-80% of the initial filtered load (prior to reabsorption).
Secretion is stimulated by:
List 4 things
On a cellular level, potassium secretion is driven by the basolateral Na/K pump, and the apical/luminal K+ channel
o The cell membrane potential also drives the secretion.
o ………… stimulates the action of both the basolateral Na/K pump, and the apical/luminal K+ channel
o An increase in tubular flow rate also increases K secretion. The rate increase is detected by ………… on ………… cells, linked to the ………… enzyme which activation increases the intracellular calcium.
This increasesstimulates the activity of the luminal K+ channel, causing more potassium to be excreted
Potassium handling by the kidneys
~70% of potassium reabsorption occurs in the PCT, with ~30% of the filtered load reaching to loop of Henle
Further reabsorption occurs in the loop of Henle, with ~10% remaining to reach the DCT
Potassium secretion then occurs in the principle cells of cortical collecting duct, and this varies from 1-80% of the initial filtered load (prior to reabsorption).
Secretion is stimulated by:
o Increased plasma [K+]
o Increased aldosterone
o Increased tubular flow rate
o Increased plasma pH
On a cellular level, potassium secretion is driven by the basolateral Na/K pump, and the apical/luminal K+ channel
o The cell membrane potential also drives the secretion.
o Aldosterone stimulates the action of both the basolateral Na/K pump, and the apical/luminal K+ channel
o An increase in tubular flow rate also increases K secretion. The rate increase is detected by cilia on principal cells, linked to the PDK1 enzyme which activation increases the intracellular calcium.
This increasesstimulates the activity of the luminal K+ channel, causing more potassium to be excreted
When do you see hypokalaemia?
•Diuretics (due to increase tubular flow rates)
•
•Surreptitious vomiting
•
•Diarrhoea
•
•Genetics (Gitelman’s syndrome; mutation in the Na/Cl transporter in the distal nephron)
When is hyperkalaemia seen?
•Seen in response to K+ sparing diuretics
•
•ACE inhibitors
•
•Elderly
