Sodium and Potassium Balance Flashcards
Define osmolarity and give its units
Measure of the solute concentration in a solution (osmoles/liter)
What does osmolarity depend on?
The number of dissolved particles
As the number of dissolved particles increases what happens to osmolarity?
It also increases
What is normal plasma osmolarity?
285-295 mosmol/L
What is the most prevalent solute in the ECF?
Sodium
What is the osmolarity of sodium in the ECF?
140 mmol/L
When sodium levels are normal what happens to desire to intake sodium?
Its supressed
What structure suppresses or stimulates sodium intake?
Lateral parabrachial nucleus in the brainstem
What receptors are involved in suppressing sodium intake?
Serotonin and glutamate
What receptors are involved in stimulating sodium intake?
GABA and opioids
What are the 2 mechanisms involved in sodium intake? Briefly describe them
Central mechanism- involves lateral parabrachial nucleus
Peripheral mechanism- involves taste
How does the peripheral mechanism for sodium intake work?
When we have low levels of salt in our body, foods with salt will taste more appetising
Where does most sodium reabsorption occur?
How much of sodium is reabsorbed around the rest of the nephron?
PCT (67%) Thick ascending limb (25%) DCT (5%) CCD (3%) Excretion (<1%)
What happens to GFR and renal blood flow as mean arterial pressure (MAP) increases
GFR and renal blood flow will increase proportionally to MAP until a certain point but then they will plateau (don’t need to excrete any more Na)
As the BP and amount of sodium entering the nephron increases, what happens in the DCT to reduce perfusion pressure and GFR?
DCT is in contact with JGA-
- High sodium levels in tubular fluid are detected by specialised macula densa cells in the JGA
- This increases sodium/chloride uptake via triple transporter
- Adenosine is released from macula densa cells
- Detected by extraglomerular mesangial cells
- This promotes afferent SMC contraction
- Reduces perfusion pressure and so GFR
- Adenosine also reduces renin production- this is short term however so won’t affect long term renin
What affect does increased sympathetic activity have on the nephron
INCREASES Na REABSORPTION
- Increased contraction of the afferent arteriole to decrease GFR
- Stimulates sodium uptake by PCT cells
- Stimulates cells of the juxtaglomerular apparatus to produce renin, renin leads to angiotensin II production, this stimulates cells of the PCT to take up sodium
- Angiotensin II stimulates adrenal glands to produce aldosterone -> aldosterone stimulates sodium uptake in the DCT and collecting duct
How does anti naturietic peptide affect sodium levels?
DECREASES Na REABSORPTION
Vasodilator so increases GFR
Reduces sodium movement into the PCT, DCT AND CT
Inhibits JGA production of renin
How is sympathetic activity affected when blood pressure and fluid volume falls?
Increases B1 sympathetic activity - vasoconstriction afferent arteriole (dec. GFR)
Increases Renin production
Renin converts angiotensinogen to angiotensin I
ACE converts this to angiotensin II
This stimulates production of aldosterone (zona glomerulosa) and vasoconstriction of afferent arteriole (decreases GFR)
All this increases Na/H2O reabsorption
How is sympathetic activity affected when blood pressure and fluid pressure rises?
Decreases beta 1 sympathetic activity
Increases ANP
Opposite of sympathetic activation
What type of hormone is aldosterone?
Steroid
Where and where is aldosterone synthesised and released?
From the adrenal cortex (zona glomerulosa)
Synthesized in response to dec. BP via baroreceptors
How does angiotensin II specifically increase aldosterone synthesis?
Promotes synthesis of aldosterone synthase which carries out the final 2 steps in aldosterone synthesis
What does aldosterone stimulate?
Sodium reabsorption
Potassium secretion
What does aldosterone excess lead to?
Hypokalaemic alkalosis- Aldosterone causes increased potassium excretion- this leads to negative charge in lumen, causing H+ to move in, leading to alkalosis
How does aldosterone work?
Aldosterone is water soluble so travels through membrane
Binds to mineralocorticoid receptor
Aldosterone then binds to HSP90, which causes HSP90 to be removed
The mineralocorticoid receptor now dimerises so it can translocate into the nucleus
It binds to DNA and stimulates production of mRNAs for genes under its control
What genes does aldosterone help upregulate?
The gene for the epithelium sodium channel in the collecting duct (ENaC)
The sodium potassium ATPase
What occurs physiologically in hypoaldosteronism?
Reabsorption of sodium in the distal nephron is reduced
Increased urinary loss of sodium
ECF volume falls
Increased renin, Ang II and ADH
What are some symptoms of hypoaldosteronism?
Dizziness, low BP, salt craving, palpitation
What occurs physiologically in hyperaldosteronism?
Reabsorption of sodium in the distal nephron is increased
Reduced urinary loss of sodium
ECF volume increases (hypertension)
Reduced renin, ang II and ADH
What are some symptoms of hyperaldosteronism?
High blood pressure, muscle weakness, polyuria, thirst
What is Liddle’s syndrome?
Looks like hyperaldosteronism but normal or low aldosterone
An inherited disease of high blood pressure.
What occurs physiologically in Liddle’s syndrome?
Mutation in the aldosterone activated sodium channel.
Channel is always ‘on’- aldosterone suppression treatment will have no effect
Results in sodium retention, leading to hypertension
Where are baroreceptors that detect low BP located?
Atria
Right ventricle
Pulmonary vasculature
Where are baroreceptors that detect high BP located?
Carotid sinus
Aortic arch
Juxtaglomerular apparatus
What is the response of the low pressure side baroreceptors to high pressure?
Atrial strech
ANP and BNP are released
What is the response of the low pressure side baroreceptors to low pressure?
Reduced firing
Signals sent via afferent fibres to brainstem
Sympathetic activity increased and ADH released
What is the response of the high pressure side baroreceptors to low pressure?
Reduced firing
Signals sent via afferent fibres to brainstem
Sympathetic activity increased and ADH released
Reduced firing also detected by JGA cells so renin is released
How do ANP and BNP affect water loss?
They increase it
Where is ANP made?
Atria
What stimulates ANP release?
Atrial strech
What are the actions ANP?
Vasodilatation of renal (and other systemic) blood vessels
Inhibition of sodium reabsorption in proximal tubule and in the DCT and collecting ducts (by inhibiting ENaC)
Inhibits release of renin and aldosterone
Reduces blood pressure
What is the mechanism of action of ACE inhibitors?
Block the angiotensin converting enzyme which inhibits the conversion of angiotensin I to angiotensin II
Do ACE inhibitors cause vasodilation or vasoconstriction?
Where does this happen?
Vasodilation
Efferent arteriole
What effect do ACE inhibitors have in the kidney?
Reduced Na+ reuptake in the PCT
Increased Na+ in the distal nephron (inc. tubular osmolality so dec. gradient so dec. reabsorption)
What effect do ACE inhibitors have in the adrenals?
Reduced aldosterone (this results in reduced Na+ uptake in the CCT and increased Na+ in the distal nephron)
Where in the nephron do osmotic diuretics work?
PCT and descending limb of LOH
Where in the nephron do carbonic anhydrase inhibitors work?
PCT
Where in the nephron do loop diuretics work?
Thick ascending limb of the LOH
Where in the nephron do thiazides work?
DCT
Where in the nephron do K+ sparing diuretics work?
Collecting duct
Where in the nephron do aquaretics work?
Distal collecting duct
How does carbonic anhydrase activity affect Na+ levels?
Leads to more Na+ reabsorption
How does carbonic anhydrase activity affect urine pH?
How would a carbonic anhydrase inhibitor affect urine pH?
Make its more acidic
An inhibitor would make urine less acidic as increased bicarbonate presence
How do carbonic anhydrase inhibitors lead to less Na+ reabsoption?
Blocking carbonic anhydrase means less H2CO3 is produced
Less dissociation into H+ and HCO3-
Less H+ produced, less co transport of H+ out of the cell and less Na+ in (Na+/H+ co-transporter)
How do loop diuretics lead to reduced water reabsorption?
What do we also call loop diuretics?
Aka. Furosemide
They are triple transporter Inhibitors (Na+/2Cl-/K+)
Reduced Na+ reuptake in the LOH
Increased Na+ in the distal nephron so less water reabsorption
How do thiazide diuretics lead to reduced water reabsorption?
They block sodium chloride uptake transporter
Reduced Na+ reuptake in the DCT
Increased Na+ in the distal nephron so reduced water reabsorption
What other marked effect do thiazide diuretics have?
They increase calcium reabsorption- if you block Na+/Cl- transporter theres dec. Na in tubular cell so inc. gradient, therefor Na+ moves from blood into cell via 3Na+/Ca2+ transporter- Ca2+ moves into blood
How do potassium sparing diuretics lead to reduced water reabsorption?
They are inhibitors of aldosterone function (e.g. spironolactone)
They bind to the mineralocorticoid receptor and block its function
This will reduce sodium reuptake in the distal nephron (therefore less K+ excreted)
What is the main intracellular ion?
K+
What does extracellular K+ affect?
Excitable membranes of nerve and muscle
What does high K+ cause?
Membrane depolarisation, can lead to heart arrhythmias
What does low K+ cause?
Heart arrhythmias (asystole)
What are potassium levels in the ECF compared to intracellular levels?
Low in ECF
High intracellular conc.
Why does the body usually have to reduce potassium levels?
There is potassium in almost all food so levels are usually high
How are potassium levels reduced?
Potassium is taken into tissues, this is promoted by insulin (and a bit by aldosterone and adrenaline)
What hormone promotes uptake of K+ into tissues?
Insulin mainly, aldosterone and adrenaline a bit
What is the mechanism of potassium uptake into tissues?
Insulin stimulates the sodium proton (H+) exchanger
This leads to more sodium in the tissue cells
Sodium conc is reduced via sodium potassium ATPase bringing more potassium into the cell
Where is potassium reabsorbed in the nephron?
Mainly the PCT and TAL and a bitin DT and CD
What happens to potassium in the DCT and CD when levels are normal and when they are depleted?
When levels are normal it is secreted into the tubular fluid
When levels are low it is reabsorbed
How much potassium is usually excreted in the urine?
15-80% of what entered the filtrate
What stimulates potassium secretion in the DCT and CD?
Increased plasma [K+]
Increased aldosterone
Increased tubular flow rate
Increased plasma pH
How is potassium secreted in principal cells?
Via Na+/K+ ATPase
How does tubular flow affect K+ secretion?
As tubular flow increases, cilia are more stimulated
Cilia stimulate PDK1
PDK1 increases calcium conc in the cell via uptake
This opens potassium channels and allows more secretion
How common is hypokalaemia?
One of the most common electrolyte imbalances (seen in up to 20% of hospitalised patients)
What are some causes of hypokalaemia?
Inadequate dietary intake (too much processed food)
Diuretics (due to increase tubular flow rates)
Surreptitious vomiting
Diarrhoea
Genetics (Gitelman’s syndrome)
What is Gitelman’s syndrome?
Mutation in the Na/Cl transporter in the distal nephron
How common is hyperkalaemia?
Common electrolyte imbalance present in 1-10% of hospitalised patients
What drug can commonly cause hyperkalaemia?
K+ sparing diuretics
What can cause hyperkalaemia?
ACE inhibitors
Who is hyperkalaemia often seen in?
Elderly
Severe diabetics
Those with kidney disease
How would I calculate volume of ECF?
No. of moles in ECF/ Conc
How does total body sodium affect blood pressure?
Inc dietary Na -> Increased total body Na -> Increased osmolality (this can’t acc happen in entire body due to semi-permeable membrane- only in kidneys) -> Increased water intake and retention -> Increased ECF volume -> Increased BP
How much of renal plasma flow enter the tubular system and how would i use this to calculate GFR?
20%
GFR = RPF x 0.2
What is the best way to retain sodium?
Filter less
Do this by reducing pressure in afferent arteriole and efferent arteriole (vasodilation) -> less filtration pressure -> better Na and H2O retention
What is the mechanism of ANP?
Binds to guanylyl cyclase domains
Leads to production cGMP
cGMP activates PKG and PDE which cause cellular responses
What does volume expansion lead to?
Action on Heart? Brain? GFR? Lung?
Decreased sympathetic activity Increases GFR (need to get rid of Na and water) Heart: Inc. ANP and BNP Brain: Dec. AVP Lung: Dec. ang II production
What does volume contraction lead to?
Action on Heart? Brain? GFR? Lung?
Increased sympathetic activity Decreased GFR (need to retain Na) Heart: Dec ANP and BNP Brain: Inc. AVP Lung: Inc. ang II production
What is the relationship between Vascular volume and blood pressure?
In increase in vascular volume is going to lead to a decrease in blood pressure (to dec. volume)
As well as insulin, what else stimulates increased plasma potassium?
Aldosterone
Adrenaline
