Sodium and Potassium Balance Flashcards
What is osmolarity?
Osmolarity is a measure of the solute (particle) concentration in a solution (osmoles/litre).
1 osmole = 1 mole of dissolved particles per litre (1 mole of NaCl = 2 moles of particles in solution).
Which ion is the most prevalent in plasma?
Sodium
What is the average osmolarity of sodium in plasma?
140mmol/L
What the normal plasma osmolarity?
285-295
What is the effect of an increase in dietary sodium?
The increase in the amount of sodium within the extracellular fluid will result in an increase in water retention –> Weight increase
There is a plateau in body weight gain
A reduction in dietary sodium causes a negative balance
What is the physiological response to an increase in total body sodium?
Increased water intake and retention in response to an increase in osmolarity (Must be maintained within a homeostatic end point)
This increases the ECF volume and subsequently blood pressure
Which nucleus within the brainstem regulates sodium intake?
Lateral parabrachial nucleus
What is the definition of euvolemia?
Inhibition of sodium intake (Activity of serotonin and glutamate)
Which hormones are involved with the inhibition of sodium intake?
Serotonin and glutamate
Which neurotransmitters are responsible for increasing the appetite for sodium?
GABA and opioids
Describe how dietary sodium intake is influenced at lower levels?
Enhances the taste of food
Describe the peripheral mechanism for regulating dietary intake?
Bimodal
At high concentrations of meal sodium, what is the impact?
Aversive
In euvolaemia, what is the response to sodium intake?
Inhibition of sodium intake
Where is the majority of sodium ions reabsorbed within the nephron?
Proximal convoluted tubule (67%)
What proportion of sodium ions are reabsorbed in the proximal convoluted tubule?
67%
What proportion of sodium is reabsorbed in the thick ascending limb of the loop of Henle?
25%
Which transporter is responsible for sodium reabsorption within the thick ascending limb?
Na-K-Cl triple transporter
How is sodium reabsorbed within the distal convoluted tubule (transporter)?
Na-Cl transporter
Which transporter is concerned with the reabsorption of sodium within the collecting ducts?
Sodium channel ENAC
If the GFR increases, what happens to the proportion of sodium that is filtered?
Remains the same (amount increases)
What approximate proportion of renal plasma enters the tubular system?
20%
What happens to renal perfusion flow with increasing blood pressure?
• 100mgHG RPF does not increase with increasing blood pressure –> There is a plateau effect to minimise electrolyte and water loss.
Where is the macula densa located?
Within the proximal part of the distal convoluted tubule separated from the glomerulus by extraglomerular mesangial cells and JG cells
Which two cells are concerned with the macula densa?
Extraglomerular mesangial cells
JG cells
Above a sodium tubular threshold, what happens in terms of the macula densa?
The macula densa releases adenosine and ATP, activating receptors in the extraglomerular mesangial cells
Above a tubular sodium threshold what is released by the macula densa?
Adenosine and ATP
What are the consequences in response to a high tubular sodium?
(Need to limit sodium loss, as more sodium is passing through DCT than normal)
Macula densa cells release adenosine, detected by extraglomerular mesangial cells
Stimulates the contraction of the smooth muscles of the afferent arteriole
This reduces renal plasma flow and perfusion pressure - this prevents the loss of sodium and fluid
Which cells secrete renin?
Juxtaglomerular cells (JG)
What effect does sympathetic stimulation have on tubular sodium regulation?
Increases uptake of sodium by the cells of the proximal convoluted tubule
Promotes the contraction of smooth muscle in the afferent arteriole to reduce GFR
Increased renin secretion
How is an increase in renin promoted by the sympathetic system?
Sympathetic stimulation increases the uptake of sodium by the cells in the proximal convoluted tubule.
• Activity of the sodium proton exchanger increases (relies on RAAS).
• Production of renin by the juxtaglomerular cells
• Reduce sodium reaching the distal tube (measured at the JGA). This reduces the production of adenosine from the Macula densa, thus there is reduced inhibition of renin release from the JG cells.
What effect does the sympathetic system have on extraglomerular cells?
: Sympathetic activity overrides the effect of extraglomerular cells SMC relaxation of the afferent arteriole – There is an overall contraction of smooth muscle and reduced GFR.
What is the effect of renin?
Converted into angiotensin-II by RAAS, angiotensin-II is a potent vasoconstrictor that increases vascular resistance and stimulates sodium uptake in the PCT
Where does angiontensin-II act within the nephron?
Promotes sodium reabsorption within the proximal convoluted tubule
What hormone is produced by the stimulation of angiontensin-II on the adrenal cortex?
Stimulates the synthesis of aldosterone
Where does aldosterone act on the nephron?
Stimulates sodium uptake in the DCT and collecting duct
Which peptide opposes increased sodium retention/reabsorption?
Atrial natruiretic peptide
What does ANP do to the nephron?
Promotes dilation of the afferent arteriole, inhibits renin release and reduces sodium uptake in the PCT, DCT and CT
In response to low plasma sodium, what happens?
- Upregulation in sympathetic activity – contraction of afferent arteriole SMC.
- Reduced GFR Reduced delivery of sodium and water to the nephron
- Increased renin production Angiotensin-II and aldosterone synthesis
- Renal NaCl and water reabsorption to reduce volume loss
- Vasoconstriction Increase blood pressure
What type of hormone is aldosterone?
A steroid
Where within the adrenal cortex is aldosterone produced?
Zona glomerulosa
Which enzyme is activated by angiotensin-II, in order to synthesise aldosterone?
Aldosterone synthase
What is the function of aldsoterone?
• Increased sodium reabsorption (Control’s reabsorption of 35g Na/day)
• Increased potassium secretion (A consequence of sodium reabsorption).
The change in voltage promotes an indirect stimulation of proton secretion, there are additional direct effects of aldosterone on the secretion of proton via alterations in the expression of anion exchanges as H+-ATPase.
• Increased hydrogen ion secretion
in which cells does aldosterone have an impact on regarding sodium reabsorption?
Principal cells
In which cells does aldosterone have an impact on regarding proton secretion?
Intercalated cells
An excess of aldosterone can mediate as what?
Hypokalaemia alkalosis
Which types of receptors does aldosterone bind onto?
Intracellular mineralocorticoid receptors
Which protein dissociates from intracellular mineralocorticoid receptors upon aldosterone binding?
HSP90
Upon HSP90 dissociation what happens to the aldosterone-MR complex?
Dimerises
What function is performed by aldosterone-MR complexes?
Translocates to the nucleus, binding to promoter regions downstream to target genes, stimulating expression/transcription
How does aldosterone increase sodium reabsorption within the cortical collecting duct?
Increases the transcription and ultimate synthesis of ENaC (epithelial sodium channel)
• Coordinates increase in the number of sodium transporters, and their activity thereby increasing sodium reabsorption.
What pathologies or iatrogenic causes are linked with hypoaldosteronism?
NSAIDs, lead poisoning, diabetes and kidney disease
What are the impacts of hypoaldosteronism?
Reabsorption of sodium in the distal nephron is reduced manifesting as hyponatremia
Increased urinary loss of sodium
ECF volume falls - incresed renin, angiotensin-II and ADH
Hyperkalaemia and alkalosis
What are the symptoms associated with hypoaldosteronism?
Dizziness
Low blood pressure
Salt carving
Palpitations
What is hyperaldosteronism?
A disorder manifested by the hypersecretion of aldosterone from the adrenal gland
- adrenal tumours
What occurs due to hyperaldosteornism?
Hyperaldosteronism increases the reabsorption of sodium in the distal nephron. • Reduced urinary loss of sodium. • ECF volume increases (Hypertension) • Reduced renin, Angiotensin-II, ADH • Increased ANP and BNP
What the symptoms associated with hyperaldosteronism?
- High blood pressure
- Muscle weakness
- Polyuria –> Consequence of thirst and increased drinking.
- Thirst
What is Liddle’s syndrome?
An inherited disorder characterised by chronic hypertension and exhibits the same phenotype of hyperaldosteronism (despite normal to low levels of aldosterone).
• Mutation in the aldosterone activated sodium channel (Alters re-internalisation and degradation of the channel, or opening time of the channel Increasing likelihood of it being open).
• ENaC activity has overall increased (always ‘on’).
• Results in sodium retention Leading to hypertension
Which receptors detect pressure?
Baroreceptors
Which protein channel is always on in Liddle’s syndrome?
ENaC
What is the aldosterone level in Liddle’s syndrome?
Normal to low
Which brainstem centre regulates blood pressure?
Cardio-regulatory centre
What is the tonic frequency of baroreceptor firing rate?
baroreceptor firing of receptors which tonically suppress sympathetic activity
What happens due to reduced baroreceptor firing?
There is an upregulation in sympathetic activity and ADH release
What happens to the heart rate and stroke volume in response to reduced baroreceptor firing?
Increases (SAN and ventricular cardiomyocytes have sympathetic post-ganglionic neurones)
Which peptides are released in response to high pressure?
ANP and BNP, synthesised in response to atrial stretch
What is ANP?
A small peptide synthesised within the atria (In addition to BNP)
When his ANP released?
In response to atrial stretch due to high blood pressure, and circulates in blood where it binds to complementary receptors
Which enzyme is activated in response to ANP?
Protein kinase G
What effect occurs by ANP stimulation?
Vasodilation to reduce blood pressure (renal and systemic vessels)
Inhibition sodium reabsorption in the distal nephron
Inhibits renin and aldosterone release
What is the overall effect from ANP stimulation?
Reduces blood pressure
What is volume expansion?
An increase in plasma sodium, increasing blood pressure and ECF volume
What effect does reduced sympathetic activity have on GFR?
Afferent arteriole dilation increasing GFR (to increase sodium and water delivery)
- Reduces sodium uptake in the PCT and reduce renin-angiotensin and aldosterone levels to reducing sodium reuptake in the distal nephron.
- Reduced sodium reabsorption –> Reduced water reabsorption (excretion of both).
What effect does ANP have on ADH?
Suppresses the release of ADH
Which ion determines ECF volume?
Sodium
What is the mechanism of action of ACE-inhibitors?
Reduce the conversion of angiotensin-I to angiotensin-II
What are the vascular effects of ACEi?
Vasodilation - increasing the vascular volume to accommodate and reduce blood pressure
What are the diuretic effects of ACEi?
Reduces sodium uptake in the PCT
What effect does ACEi have on aldosterone?
Reduced aldosterone - reduced sodium reabsorption
How does mannitol work?
• Add substrate that cannot be reabsorbed + increase tubular osmolarity to promote water retention in the filtrate.
What is a carbonic anhydrase inhibitor?
Carbonic anhydrase activity leads to sodium uptake and proton export in the PCT (urinary acidity)
• Inhibitors –> Inhibits sodium uptake into PCT cells, leading to a greater concentration of sodium in the distal nephron.
• Reduced difference between the tubular and interstitial osmolarity Reduces water reabsorption.
What is the mechanism of action of loop diuretics?
Loop diuretics target the triple transporter in the ascending limb of the loop of Henle.
• Inhibit sodium uptake – leading to higher levels of sodium in the distal nephron
• Reduction in the osmolarity of the interstitial fluid.
• Reduce the difference between the tubular and interstitial osmolarity – reduce water reabsorption.
What type of diuretic is furosemide?
Loop diuretic
What is the target and location of thiazides?
Sodium chloride transporter
Distal convoluted tubule
What is the effect of thiazides?
Reduces sodium uptake and increases tubular sodium concentration
What is the side effect concerned with thiazides?
increase in calcium reabsorption
Why is there an increase in calcium reabsorption with using thiazides?
Calcium is reabsorbed across the lumen membrane down its concentration gradient that is generated by the activity of the sodium calcium exchanger
Blocking the entyr of sodium into the cell through the Na-Ca exchanger , whilst the Na-K still works means that the return of sodium into the cell via the Na-Ca is increased
This reduces sodium calcium concentration in the cell and therefore increases the potential for calcium to be removed from the tubular fluid
How do potassium sparing diuretics work?
Inhibitors of aldosterone function (Spironolactone as a MR antagonist)
Decreases sodium reabsorption and subsequently water retention is impaired
What risk is associated with Spironolactone?
Hyperkalaemic acidosis
Which is the main ion intracellularly?
Potassium
How is a high intracellular potassium ion maintained?
By the sodium potassium ATPase
What effect does high K+ have?
Depolarises membrane, action potentials, heart arrhythmias (Tented T waves).
What effect does a low K+ have?
Heart arrhythmias (asystole)
What effect does insulin have on potassium?
Plasma insulin mediates the tissue uptake of potassium
How does insulin mediate increased potassium uptake?
Stimulates the activity of the sodium proton exchanger which increases intracellular sodium
The increase in intracellular sodium activates sodium potassium ATPase, increasing potassium uptake
What % of filtrate potassium is reabsorbed in the proximal convoluted tubule?
67%
Which factors influence plasma secretion?
Plasma potassium, aldosterone, tubular flow rate , and plasma pH
Which cells are responsible for plasma potassium?
Principal cells
How do principal cells increase potassium excretion?
Increased activity of the sodium potassium ATPase, and reduce return of potassium into the plasma so increased potassium excretion
What type of flow regulates potassium excretion?
Tubular flow
How does tubular flow regulate potassium excretion ?
Activates cilia, activates PDK1
This increases calcium ions within the cell, stimulating the opening of potassium channels on the apical membrane
What are the causes of hypokalaemia?
Common electrolyte imbalances (20% of hospitalised patients).
• Inadequate dietary intake (Processed food).
• Diuretics (Due to increase tubular flow rates)
• Surreptitious vomiting
• Diarrhoea
• Genetics (Gitelman’s syndrome: Mutation in the Na/Cl transporter in the distal nephron).
Increases aldosterone synthesis in response to low sodium – thus hypokalaemia.
What is Gitelman’s syndrome?
• Genetics (Gitelman’s syndrome: Mutation in the Na/Cl transporter in the distal nephron).
Increases aldosterone synthesis in response to low sodium – thus hypokalaemia.
What are the common causes of hyperkalaemia?
- Common electrolyte imbalance present in 1-10% of hospitalised patients.
- Response to K+ sparing diuretics (spironolactone)
- ACE-inhibitors
- Elderly
- Severe diabetes
- Kidney disease
