1b Sodium and Potassium Balance Flashcards
What is the osmolarity?
measure of the amount of solute dissolved in a solution (osmoles/Litre)
What is meant by osmole?
1 mole of dissolved solute per litre
Describe how there is a constant osmolarity?
water and salt are inter-related
When there is increased salt, there will be increased water as water follows salt, resulting in an increased volume
- During water deprivation, how does the change in urine osmolarity compare to that of plasma osmolarity?
Urine concentrates = as the osmolality increases
Plasma = remains at the homeostatic set point
What allows the homeostatic set point of plasma osmolarity?
The semi permeable cell membrane allows the movement of water across the cell
What is the normal plasma osmolarity?
285-295 mosm/L
What is the most important and prevalent solute in the ECF?
Sodium - 140 mmol/L
What effect does increasing dietary sodium have on blood volume and pressure and how does it do this?
Increased dietary sodium → Increased total body sodium → Increased osmolarity (but this can’t happen - because of the semi permeable membrane, water will always follow) → Increased water intake and retention → Increased ECF volume → Increased blood volume and pressure
At euvolemia, what effect is had on Na+ intake and through what nucleus does this occur in?
Inhibition of sodium intake
Lateral parabrachial nucleus
Which neurotransmitters are working to inhibit sodium intake?
Seretonin and glutamate
Which neurotransmitters are working to increase a persons appetite for sodium?
GABA, Opiods
What is the peripheral control of sodium intake?
Taste, small amounts of Na+ is desirable, but as this increases it becomes aversive
How much sodium is absorbed into each part of the nephron?
Proximal - 67%
Thick ascending limb - 25%
Distal convoluted tubule - 5%
Collecting duct - 3%
What is GFR proportional to?
Renal Plasma Flow
Why do GFR and RPF eventually plateau?
We don’t want to excrete more sodium than is needed
What percent of renal plasma enters the tubular system and therefore how do you calculate GFR from renal plasma flow?
20%
GFR = RPF * 20
How is increased tubular sodium levels reacted to by the macula densa and how does this affect perfusion pressure and GFR?
- High tubular sodium
- Increased uptake of sodium from the macula dense (via the triple transporter)
- This triggers ADENOSINE release
- This is detected by the extraglomerular mesangial cells
- Renin production is reduced, which promotes AFFERENT smooth muscle cell contraction
- This reduced perfusion pressure so GFR decreases
MORE BLOOD FLOWS FROM AFFERENT TO EFFERENT rather than being filtered, leads to water being retained as water will follow salt
What is the best way to retain sodium?
Filter less sodium
How can you filter less sodium?
Reducing efferent arteriole pressure to increase pressure gradient and so more blood flow from afferent arteriole rather than being filtered out
So more retention of both sodium and water
-
What are 3 main physiological mechanisms that increase Na+ reabsorption and retention?
- Increased sympathetic activity
- Angiotensin II
- Aldosterone
How does increased sympathetic activity lead to more sodium retention?
- Causes SMC of afferent arteriole to contract so less is filtered
- Stimulates sodium uptake in the proximal convoluted tubule
- Stimulates juxtaglomerular apparatus to release Renin which forms angiotensin II (This further stimulates sodium reabsorption in the proximal convoluted tubule)
How does angiotensin effect sodium retention?
Stimulates sodium uptake from cells of PCT
how does aldosterone affect sodium reabsorption?
Stimulates sodium reabsorption in the DCT and collecting duct
How does the juxtaglomerular apparatus respond to low tubular sodium?
Causes the stimulation of renin production which makes angiotensin and aldosterone
What is the main protein involved in decreasing sodium reabsorption?
Atrial naturietic peptide
Describe the mechanism of action of ANP in order to decreased sodium reabsorption?
Vasodilator - reduces afferent arteriolar pressure so more is filtered to be excreted
ANP
Decreases uptake of Na+ from PCT, DCT, CT
Reduces renin secretion from Juxtaglomerular apparatus
What happens to blood pressure and volume when there is low sodium?
Decreases blood pressure and blood volume
This increases beta sympathetic activity
What does decreased Beta1 sympathetic activity cause when there is high sodium?
Atrial-Naturietic Protein production
Where is aldosterone synthesized and released?
The adrenal cortex - zona glomerulosa
When is aldosterone released?
released in response to angiotensin II
or a decrease in blood pressure which is detected by the baroreceptors
What effect does aldosterone have on blood pressure?
increases blood pressure
How is aldosterone release triggered by increased sympathetic activity?
Increased sympathetic activity stimulates the cells of the juxtaglomerular apparatus to release renin
Renin activity cleaves angiotensinogen to angiotensin I
Angiotensin I is cleaved by angiotensin converting enzyme to produce angiotensin II
Angiotensin II stimulates the synthesis of aldosterone synthase in the zona glomerulosa to increase the synthesis of aldosterone.
What effect does aldosterone have in the distal convoluted tubule and the collecting duct?
Increases sodium reabsorption
Increases potassium secretion
Increases H+ secretion
What does aldosterone excess lead to?
Hypokalaemic alkalosis
Can aldosterone pass through the lipid membrane?
Yes - it is lipid soluble
Describe the mechanism by which aldosterone works?
Passes through cell membrane - steroid hormone
Binds mineralocorticoid receptor
Binds another and becomes a dimer
Translocates into the nucleus
Binds and enables transcription of genes and mRNA of proteins which help it carry out its function
Transcription of what proteins are increased by Aldosterone?
ENaC
Na+ K+ ATPase
regulatory proteins needed for the channels
Resulting in more sodium and more active sodium channels
What are the symptoms of hypoaldosteronism?
Dizziness, low blood pressure, salt craving and palpitations
Describe the pathophysiology of hypoaldosteronism?
- Less aldosterone
- Less reabsorption of sodium in the distal convoluted tubule
- More sodium is lost in the urine, and more loss of water
- ECF falls
Increases Renin, Angiotensin II and ADH to try and compensate
Describe the pathophysiology of hyperaldosteronism?
- Too much Aldosterone
- Reabsorption of sodium in the distal nephron is increased
- Less urinary loss of sodium, more water retention, ECF increases
reduced renin, Ang II and ADH
In states of hyperaldosteronism which two proteins are raised?
ANP and BNP
ANP - tries to decreases sodium reabsorption to compensate for the increase which the hyperaldosterone is causing
what are the symptoms of hyperaldosteronism?
high blood pressure
Muscle weakness
Polyuria
Thirst
What is Liddle’s syndrome?
An inherited disease of high blood pressure = where there is a mutation in the aldosterone activated sodium channel meaning it is always on, resulting in constant sodium retention = hypertension
Describe the pathway involving the kidney though which increased sympathetic stimulation increases aldosterone levels
Increased sympathetic activity stimulates the cells of the juxtaglomerular apparatus (0.5 mark) to release renin (0.5 mark). Renin activity cleaves angiotensinogen to angiotensin I (0.5 mark). Angiotensin I is cleaved by angiotensin converting enzyme (0.5 mark) to produce angiotensin II (0.5 mark). Angiotensin II stimulates the synthesis of aldosterone synthase (0.5 mark) in the zona glomerulosa (0.5 mark) to increase the synthesis (0.5 mark) of aldosterone.
What would be the expected effect of spironolactone treatment on the blood pressure of a person with Liddle’s Syndrome?
No effect (1 mark). The mutation in Liddle’s syndrome is in the aldosterone sensitive ENaC sodium channel. This mutation means that the channel is always on so that there will be minimal effect on sodium reuptake (1 mark).
When hypertension is resistant to diuretics, what is then used?
Diuretics = spironolactone
In the heart where are the baroreceptors that respond to low pressure?
Atria
Right ventricle
In the heart, where are the baroreceptors which respond to high pressure?
Carotid sinus
Aortic Arch
In the low pressure side, how is low pressure dealt with?
Low pressure → Reduced baroreceptor firing → Signal through Afferent fibres to brainstem → Sympathetic activity & ADH Release which promotes Water retention to try and increase pressure again
In the low pressure side, how is high pressure dealt with?
High pressure → Atrial stretch → ANP, BNP released
Stop sodium retention, therefore more sodium excreted
On the high pressure side, how is low pressure dealt with? (2 ways)
Low pressure → Reduced baroreceptor firing → Signal through Afferent fibres to brainstem → Sympathetic activity and ADH Release
Low pressure → Reduced baroreceptor firing → JGA cells → Renin released
When is ANP released?
In response to atrial stretch
What are the four actions of ANP?
- Vasodilation of renal blood vessels
- Inhibition of sodium reabsorption in th PCT and CD
- Inhibits renin and aldosterone
- Reduces blood pressure
Which protein kinase does ANP stimulate?
Protein Kinase G
Describe the physiology which occurs in response to volume expansion?
Volume expansion = decreased sympathetic activity ===
- Reduces renin → reduced Angiotensin I → reduced angiotensin II → reduced aldosterone
- Increases ANP & BNP → Reduces GFR and Na+ uptake in the DCT and CT and also DECREASES AVP from the brain, reduces renin, Reduces aldosterone production from adrenal gland, Reduces AVP → Decreased aquaporins into the epithelial wall in the CT
Describe the physiology which occurs in response to volume contraction?
Volume contraction = increased sympathetic activity
- Increases renin -> increases angiotensin 1 -> increases angiotensin II -> increases aldosterone so increased sodium reabsorption
- Decreases ANP and BNP
- Increased AVP from brain = increased sodium reabsorption in collecting duct
Where does angiotensin II cause increased sodium reabsorption?
Distal convoluted tubule
What would be the effect on water reabsorption of increased sodium levels reaching the collecting duct and why?
Increased Na+ in the collecting duct means there is increased osmolarity and so it is more difficult to reabsorb water since water will migrate via osmosis into the collecting duct since there is a higher osmolarity here
How does sodium excretion relate to ECF volume?
reducing sodium reabsorption reduces total Na+ levels, ECF volume and therefore blood pressure
What are the vascular effects of ACE Inhibitors?
Vasodilation -> Increased vascular volume -> Lower blood pressure
What are the renal effects of ACEi?
decreased sodium reuptake in the proximal PCT-> increased Na+ in distal nephron → decreased water reabsorption → decreased blood pressure
What are the adrenal effects of ACEi?
Reduced aldosterone resulting in the following indirect renal effects:
- Lower Na+ reabsorption in the collecting duct
- Therefore more sodium in the distal nephron, therefore more water retention, so blood volume is higher, blood pressure higher
Which part of the nephron do osmotic diuretics and carbonic anhydrase inhibitors work on?
PCT
Which part of the nephron do Loop Diuretics work on?
Thick Ascending Limb
Which part of the nephron do Thiazides work on?
Distal CT
Which part of the nephron do K+ sparring diuretics work on?
CCD
How do carbonic anhydrase inhibitors work?
- Less bicarbonate produced
- Therefore less H+, so less H+ Na+ exchange, so less Na+ to exchange with K+ into the blood, therefore less sodium reuptake
Therefore LESS Na+ reabsorption in the PCT and reduced water reabsorption
what is an example of a loop diuretic?
Furosemide
How do loop diuretics work?
They are triple transporter inhibitors
Therefore less Na+ Reuptake in the LOH
Increased Na+ in the distal nephron
How do thiazides work?
Inhibit the Na+ Cl- transporter on the apical side of the distal collecting duct
- Therefore reduced reuptake of Na+ in the DCT, and reduced water reabsorption
Why does calcium reabsorption increase when on thiazides?
The basolateral Na+ K+ ATPase is unaffected
Therefore since more sodium is leaving the cell, the gradient is going to increase
Therefore the 3Na+ Ca2+ transporter is going to becomes more active so more Ca2+ pumped back into the blood, and more Na+ into the cell to balance
How do potassium sparing diuretics work?
They bind to the MR receptor and cause an inhibition of aldosterone function
What is the main intracellular ion?
Potassium
How does high extracellular potassium effect the membrane?
Depolarises the membrane = action potentials leading to heart arrhythmias
What condition does low potassium lead to?
Abnormal heart rhythms
Describe how dietary potassium is absorbed?
Meal = increased potassium absorption = increased plasma K+ = increased tissue uptake
What stimulates an increased tissue uptake of potassium?
Insulin, aldosterone and adrenaline
How does insulin stimulate K+ uptake after dietary intake?
Indirectly
Insulin stimulates basolateral sodium proton exchanger
This increases intracellular Na+ so to decrease this, the Na+K+ ATPase is stimulated to increase uptake of K+
Where is most of the K+ reabsorbed from in the nephron?
PCT
What 4 factors stimulate K+ secretion from CCD and DCT?
Increased Plasma [K+]
Increased aldosterone
Increased tubular flow rate
Increased plasma pH
Which cells in the kidney are involved in potassium secretion?
Principal cells
In K+ depletion, how does the reabsorption of K+ change?
Instead of being secreted, in the DCT and CCD, it is reabsorbed from the tubular fluid
This leads to less K+ being excreted
How does potassium secretion (back into urine) by principal cells in the DCT and CCD occur, in response to increased plasma [K+]?
Activity of basolateral Na+/K+ATPase increases intracellular K+ which is then removed into the tubular fluid by K+ channels on the apical side
Therefore more K+ excreted in the urine to counteract the increased K+ the blood
How does potassium secretion occur in the DCT and CCD as a result of increased tubular flow?
Increased tubular flow stimulates the primary cilium present on the distal cells in the nephron
This activates PDK1 which increases calcium concentrations in the cell
This stimulates the ‘openness’ of the K+ channels on the apical side of the cell so K+ can leave the cell & enter tubule since there is a higher K+ intracellularly due to the Na+/K+ATPase
What are some causes of hypokalemia?
Inadequate dietary intake
Diuretics - increased tubular flow rate
Surreptitious vomiting - reduced intake
Diarrhoea - reduced intake
Genetics
Gitelman’s syndrome - Mutation in the Na+/Cl- transporter in the distal nephron
What are some causes of hyperkalaemia?
Seen in resonse to K+ sparing diuretics - Blocks aldosterone
ACE inhibitors
Seen in elderly
Severe diabetes
Chronic Kidney disease
Describe how Potassium Sparing Diuretics are potassium Sparing?
They are inhibitors of Aldosterone
This means, there is less Sodium reabsorption in the DCT, so the basolateral 3 Na+ 2 K+ Channels are not needing to work as much, therefore less potassium is taken from the blood into the principal cells and therefore the lumen
