Sodium and Potassium Balance Flashcards
Define osmolarity
The measure of the solute (particle) concentration in a solution (osmoles/liter)
What is the normal range of plasma osmolarity?
285-295 mosmoles/L
What is the most prevalent solute and important in the ECF?
- sodium
- dictates the volume of the ECF
What is the relationship between dietary sodium and bodyweight?
- increased sodium intake will increase the total body sodium over time
- leads to increased water intake and increased water retention in order to maintain osmolarity
Why does a high salt diet lead to an increase in blood pressure?
- increased water intake and retention leads to increased ECF volume
- increased blood volume and pressure
What is the peripheral mechanism for controlling sodium intake and how does it work?
- taste
- salt is one of the major taste sensations
- appetitive when present at lower concetrations in food
- aversive at higher concentrations
Which part of the brain is central to alter appetite for salt?
Lateral Parabrachial nucleus.
How is sodium intake affected by euvolemia?
- serotonin and glutamate receptor cells suppress the desire for salt
- sodium intake is inhibited
How is sodium intake affected by sodium deprivation?
- GABA and opiod receptor cells increase the appetite for sodium
- sodium intake is increased
What proportion of filtered sodium load is reabsored by Distal convoluted tubule?
5%
What proportion of filtered sodium load is taken up by the Thick ascending limb of the loop of Henle?
25%
What proportion of filtered sodium load is taken up by Proximal convoluted tubule?
67%
What proportion of renal blood flow is filtered into the nephrons?
20%
How much sodium which enters the kidney tubule is excreted?
< 1%
What is the juxtoglomerular apparatus?
- anatomical unit at the hilus of the glomerulus
- 3 components: extraglomerular mesangial cells, juxtoglomerular cells and macula densa
- macula densa is the region where the DCT comes into contact with the glomerulus
What is the function of the juxtoglomerular apparatus?
Feedback control of renal blood flow and glomerular filtration rate
What is the effect of increased tubular sodium concentration on the macula densa?
- increased sodium uptake through the Na/K/Cl triple transporter
- leads to release of adenosine
What is the effect of adenosine release by macula densa cells?
- adenosine detected by extraglomerular mesangial cells
- detection causes smooth muscle cells on the arteriole wall to contract
- also reduces renin production by the juxtoglomerular cells
What is the effect of the contraction of smooth muscle cells on the arteriole wall?
- reduced renal blood flow into the glomerulus
- reduces the GFR
What is the effect of sympathetic activity on sodium excretion?
- contraction of smooth muscle cells on afferent arteriole which decreases GFR
- stimulates sodium uptake by proximal convoluted tubule
- stimulates release of renin by the JGA which in turn stimulates angiotensin II production
What else can increase renin release from the JGA?
Low tubular sodium
What is the action of renin?
Cleaves angiotensinogen into angiotensin I
What is angiotensin I converted to and how?
Cleaved by angiotensin converting enzyme to produce angiotensin II
What is the effect of angiotensin II?
- stimulates synthesis of aldosterone synthase in the zona glomerulosa
- aldosterone synthase increases aldosterone synthesis
What else stimulates aldosterone release?
Decreased blood pressure detected by baroreceptors
What are the functions of aldosterone?
- increased sodium reabsorption
- increased potassium secretion
- increased H+ secretion
What is the effect of excess aldosterone?
Hypokalaemic alkalosis
Where in the tubular system does aldosterone work?
Distal end of the DCT and CD
What acts to decrease sodium reabsorption?
Atrial natureitic peptide (ANP)
What are the actions of ANP?
- vasodilation of the afferent arteriole to increase GFR
- decreased sodium reabsorption at the PCT, DCT and CD
- suppresses renin production by the JGA which reduces angiotensis II and aldosterone
- reduces blood pressure
How does aldosterone work?
- binds to mineralocorticoid receptor inside cell bound to HSP90
- HSP90 is removed and to MR receptors bind to form a dimer
- MR dimer translocates to nucleus and binds to DNA
- transcribes genes for epithelial sodium channels and Na+/K+ ATPase as well as the regulatory proteins which activate them
What is the effect of hypoaldosteronism?
- reduced reabsorption of sodium in the distal nephron
- increased sodium excretion
- ECF volume falls
- renin, angiotensin II and ADH increase
What are the symptoms of hypoaldosteronism?
- dizziness
- low blood pressure
- salt cravings
- palpitations
What are the effects of hyperaldosteronism?
- increased sodium reabsorption in the distal nephon
- reduced sodium excretion
- increased ECF volume
- reduced renin, angiotensin II and ADH
- increased ANP and BNP
What are the symptoms of hyperaldosteronism?
- high blood pressure
- muscle weakness
- polyuria
- thirst
What happens to the filtered potassium load at the distal convoluted tubule?
- 3% is reabsorbed when potassium is depleted
- 10-50% is excreted potassium is normal or increased
What proportion of filtered potassium load is reabsorbed by Proximal convoluted tubule?
About 67%
What happens to the filtered potassium load at the collecting duct?
- 9% is reabsorbed when potassium is depleted
- 5-30% is excreted when potassium is normal or increased
What proportion of filtered potassium load is reabsorbed by Thick ascending limb of the loop of Henle?
About 20%
What is the relationship between osmolarity and the number of dissolved particles?
the greater the number of dissolved particles, the greater the osmolarity
How can the concentration of water be described as?
- the proportion of a solution that is water
- concentration of water is inversely proportional to the number of dissolved solutes
How is sodium reabsorbed in the collecting duct?
collecting ducts via the Na+ channel ENAC
What is the impact of GFR on sodium excretion?
- if GFR goes up, total amount of sodium excreted would go up
- increasing water loss and reduced blood volume
Where are the baroreceptors that detect low blood pressure?
- atria
- right ventricle
- pulmonary vasculature
Where are the baroreceptors that detect high blood pressure?
- carotid sinus
- aortic arch
- juxtaglomerular apparatus
What happens when low blood pressure is detected by both the low and high blood pressure mechanisms?
- reduced baroreceptor firing
- afferent signals sent to the brainstem
- sympathetic activity is increased
- ADH released
- high pressure mechanism suppresses renin release from JGA
What happens when high blood pressure is detected by the low blood pressure mechanisms?
- atrial stretch
- ANP and BNP is released
What is Arial Natriuretic Peptide (ANP)
- small peptides that are made in the atria (also make BNP)
- released in response to atrial stretch
What happens when there is an expansion in blood volume?
- reduced sympathetic activity
- decreased renin, angiotensin II and aldosterone
- afferent arteriolar dilation
- ANP release
- increased GFR (increased water and Na+ excretion)
- reduce Na+ uptake in the PCT, DCT and CT
- suppressed release of ADH
What happens when there is a contraction in blood volume?
- increased sympathetic activity
- increased renin/angiotensin/aldosterone production
- increased AVP expression which increase sodium reuptake, water retention and prevent further loss of volume.
How do you ensure water movement in a nephron?
generate a gradient of interstitial osmolarity through the renal medulla
What happens if the osmolarity of the fluid in the tubule is the same as the fluid in the interstitium?
no net water movement into the interstitium
What happens if the osmolarity of the fluid in the tubule is the higher than the fluid in the interstitium?
reduce water reabsorption
What happens if the osmolarity of the fluid in the tubule is the lower than the fluid in the interstitium?
increased water reabsorption
What is the major method used to reduce blood pressure?
diuretics by increasing sodium excretion
What is the mechanism of ACE inhibitors?
reduce the production of angiotensin II from angiotensin I
How do ACEi cause vasodilation?
- increases the vascular volume
- reduces blood pressure
- diuretic effects (reduced sodium reuptake in the PCT)
- reduced aldosterone reduces sodium intake in the CCT
- increased sodium in the distal nephron, reducing the osmotic difference between the tubular fluid and the interstitium to reduce water reabsorption
What are the effects of reduced angiotensin II?
- vasodilation
- reduced Na reuptake in the PCT
- increased Na+ in the distal nephron
- reduced aldosterone
- reduced Na+ uptake in the CCT
What is the basis of osmotic diuretics?
- adding something that can’t be reabsorbed as the water moves from the tubular fluid
- concentration of the non-reabsorbed substance increases
- osmolarity increases, reducing water reuptake
Where do carbonic anhydrase inhibitors act?
PCT
What is an example of an osmotic diuretic?
Mannitol
What is the action of carbonic anhydrase inhibitors?
- inhibits sodium uptake in the PCT
- increases levels of sodium in the distal nephron
- reduced difference between the tubular and interstitial osmolarity to reduce water reabsorption
What is the action of carbonic anhydrase?
- increase Na+ reabsorption
- increases proton excretion (increases urinary acidity)
Where do loop diuretics work?
Thick ascending loop of Henle
What is the mechanism of loop diuretics?
- target the triple transporter in the ascending loop of Henle
- inhibit sodium reuptake
- higher levels of sodium in the distal nephron
- reduced osmolarity of the interstitial fluid
- reduced difference between the tubular and interstitial osmolarity to reduce water reabsorption
What is an example of a Loop diuretic?
Furosemide
Where fo Thiazides act?
DCT
What is the mechanism of Thiazides?
- target the sodium chloride transporters
- reduces Na+ uptake in the DCT
- increases tubular Na+ in the distal nephron
What is a side effect of Thiazides?
Increased calcium reabsorption
What causes the unwanted increased calcium reabsorption in Thiazides?
- Blocks the Na+/Cl- transporter on apical membrane whilst the Na+/K+ ATPase on basolateral membrane still functions
- intracellular sodium is reduced
- Na+ into the cell via the Na+/Ca+ antiporter on basolateral membrane is increased
- this reduces the Ca+ concentration in the cell and therefore increases the potential for calcium to be removed from the tubular fluid.
Where do potassium sparing diuretics work?
Collecting duct
What is the mechanism of potassium sparing diuretics?
- Inhibitors of aldosterone function by binding to mineralocorticoid receptor
- reduces sodium reabsorption
- reduced potassium excretion
What is the relationship between GFR and Renal Plasma Flow Rate?
proportional
What is the main intracellular ion?
potassium (150mmol/L)
What is the extracellular concentration of potassium?
3-5mmol/L
What maintains the strict intracellular potassium concentration?
sodium potassium ATPase
What does extracellular potassium have an affect on?
excitable membranes (of nerves and muscles)
What is the impact of high extracellular potassium?
- membrane depolarisation
- action potentials
- heart arrhythmias
What is the impact of low extracellular potassium?
Heart arrhythmias (asystole)
What is the impact of dietary potassium?
- in most foods, especially unprocessed foods
- plasma potassium will increase after a meal
- needs to be taken up into tissues
- uptake of potassium is mainly stimulated by insulin but also aldosterone and adrenaline
How does insulin cause potassium uptake?
- indirectly
- stimulates Na+/H+ exchanger
- increases intracellular Na+ which needs to be reduced
- therefore Na+/K+ ATPase activity is increased and more K+ is absorbed into the cells
Where in the nephron can potassium be both reabsorbed and excreted?
Distal convoluted tubule and collecting duct
What is the impact of normal/high potassium levels on potassium reabsorption?
Potassium is secreted
What stimulates K+ excretion?
- high plasma K+
- high aldosterone
- high tubular flow rate
- high plasma pH
What is the impact of high plasma K+?
- increased Na+/K+ ATPase activity in principal cells
- reduced K+ plasma reabsorption
- increased K+ excretion
How does tubular flow regulate potassium excretion?
- activates primary cilia that activate PDK1
- increases Ca+ in the cell
- stimulates the opening of potassium channels on the apical membrane
- increases K+ excretion
What can cause hypokalaemia?
- inadequate dietary intake (too much processed food)
- increased tubular flow rate (due to diuretics)
- non-renal excretion (vomiting, diarrhoea)
- genetics (Gitelman’s syndrome)
What is Gitelman’s syndrome?
- mutation in the Na+/Cl- transporter in the distal nephron
How common is hypokalaemia?
Common electrolyte imbalance present in 20% of hospitalised patients
How common is hyperkalaemia?
Common electrolyte imbalance present in 1-10% of hospitalised patients
What can cause hyperkalaemia?
- K+ sparing diuretics
- ACEi
- Elderly
- Severe diabetes
- kidney disease
What is Liddle’s syndrome?
inherited genetic high blood pressure
- mutations in the aldosterone activated sodium channel
- increases ENaC activity causing increased sodium retention and hypertension
- looks like hyperaldosteronism but aldosterone levels are normal
What part of the nephron is impermeable to Na?
the descending LOH
What part of the nephron is permeable to Na?
the ascending LOH
What part of the nephron is permeable to Na in the presence of aldosterone?
Collecting Duct
What happens when blood volume falls or sodium levels are low?
- Increased sympathetic activity leads to a reduced GFR, reduced delivery of sodium and water to the nephron
- Increased renin production (converts angiotensinogen into angiotensin I which is then converted into angiotensin II in circulation)
- Angiotensin II promotes NaCl reabsorption and water reabsorption to reduce volume loss and causes vasoconstriction to increase blood pressure.
- causes the release of aldosterone, causing Na+ reabsorption and water reabsorption.
What is the best way to retain sodium?
reduce glomerular filtration
When is spironolactone used in hypertension?
used in hypertension which is resistant to other diuretic
