sodium and potassium balance Flashcards
what is the normal plasma osmolarity?
285-295 mosmol/L
Sodium ~ 140 mmol/L chloride ~ 105 mmol/L bicarbonate ~ 24 mmol/L potassium ~ 4 mmol/L Glucose ~ 3-8 mmol/L Calcium ~ 2 mmol/L Protein ~ 1 mmol/L
Sodium most prevalent, and important, solute in the ECF.
what happens if you increase dietary sodium?
increased dietary sodium -> increased total body sodium -> increased plasma osmolarity (but this cant happen because of semipermeable membranes) -> increased water intake and retention -> increased ECF volume -> increased blood volume and pressure
the converse happens with decreased dietary sodium
how does the body regulate sodium intake?
central method:
in euvolaemia (normal conditions):
lateral parabracial nucleus tells the brain it doesnt want more salt, so there is less sodium dietary intake
moderated by cells that respond to serotonin and glutamate
in Na+ deprivation:
lateral parabrachial nucleus increases the bodys appetite for sodium intake
moderated by cells that respond to GABA and opioids
peripheral method:
taste buds
salt specific ones
if you have low body sodium it has a more appetitive effect
high body sodium it has a more aversive effect
where is sodium reabsorbed in the kidney?
67% in the PCT
25% in the thick ascending limb
5% in the DCT
3% in the collecting duct
less than 1% is excreted
bur these are proportions, so if you increase GFR, more will be excreted
what effects glomerular filtration rate?
as arterial blood pressure increases renal perfusion rate increases
so does glomerular filtration rate
but this relationship plateaus at blood pressure of about 100 mm Hg
this is useful in terms of eg. if you are exercising you dont want to lose sodium just because of that
how does sodium effect the macula densa?
the DCT is on close contact/association with the juxta glomerular apparatus
the JGA contains macula densa cells
when tubular sodium increases, there is increase uptake of sodium through the Na-Cl-K cotransporter
that causes the macula densa to release adenosine
adenosine triggers the extraglomerular mesangial cells to contract the smooth muscle cells of the glomerulus
this reduces the blood flow to the glomerulus, reducing the GFR
also triggers renin production (eventually increases blood pressure, but it doesnt have much of an effect on renin production over a long period of time)
to summarise:
High tubular sodium
Increased sodium/chloride uptake via triple transporter
Adenosine release from Macula Densa cells
Detected by extraglomerular mesangial cells
Reduces renin production
Promotes afferent SMC contraction
Reduces perfusion pressure and so GFR decreases
more sodium decreases GFR so less sodium is lost
what is the best way to retain sodium and water?
filter less
we do that by reducing the pressure gradient between the afferent arteriole and the efferent arteriole
reduce pressure in the efferent arteriole so it is more similar to that of the afferent
more blood will just go straight past and not be filtered
so better retention of sodium
what factors increase sodium reuptake in the kidneys?
beta 1 sympathetic activity:
directly contracts the afferent arteriole
it also increases uptake of sodium by the cells of the PCT
it stimulates the cells of the JGA to produce renin
this activates angiotensin II
ANGII also stimulates the cells of the PCT to take up sodium
ANG II also stimulates the production of aldosterone from the adrenals
aldosterone stimulates uptake of sodium in the DCT and the collecting duct
low tubular sodium also stimulates the production of renin which also stimulates ANG II production
what factors decrease sodium reuptake in the kidneys?
atrial naturietic peptide;
acts as a vasodilator in the afferent arteriole so higher GFR
reduces sodium reuptake in the PCT, DCT and collecting duct
it surpresses the production of Renin by the JGA
how does bloop pressure and volume affect GFR?
low blood pressure and volume = low GFR
high = high GFR
the lower the GFR the less sodium will be filtered
i think
what is aldosterone?
Steroid hormone
Synthesised and released from the adrenal cortex (zona glomerulosa)
Released in response to Angiotensin ll
stimulated by a Decrease in blood pressure (via baroreceptors)
angiotensin II promotes the synthesis of aldosterone synthetase
aldosterone synthase causes the last two steps of aldosterone synthesis from cholesterol
aldosterone is then released and has its function in the kidney
what is the function of aldosterone?
Stimulates: Increased Sodium reabsorption (controls reabsorption of 35g Na/day) Increased Potassium secretion Increased hydrogen ion secretion
Aldosterone excess:
leads to hypokalaemic alkalosis
how does aldosterone work?
it is a steroid hormone, so lipid soluble
it can pass through the cell membrane
aldosterone binds to the mineralocorticoid receptor in the cytoplasm. this receptor is also bound to a protein called HSP 90. HSP 90 is removed once aldosterone binds
two molecules aldosterone-mineralocorticoid receptor complexes form a Dimer
this allows the complex to translocate into the nucleus, bind to DNA, stimulates the production of mRNA for genes that are under its control including:
the epithelial sodium channel (ENaC)
the sodium potassium ATPase
regulatory proteins that stimulate the activity of these two transporters
so not only more sodium channels but more active as well
what is hypoaldosteronism?
Reabsorption of sodium in the distal nephron is reduced
Increased urinary loss of sodium
ECF volume falls Increased renin, Ang II and ADH -> Dizziness Low blood pressure Salt craving palpitations
(addisons?)
what is 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 Increased ANP and BNP -> High blood pressure Muscle weakness Polyuria thirst
what is Liddle’s syndrome?
An inherited disease of high blood pressure.
mutation in the aldosterone activated sodium channel.
- channel is always ‘on’
- Results in sodium retention, leading to hypertension
looks like hyperaldosteronism
but people have normal or low aldosterone
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.
how do we measure blood pressure?
baroreceptors
atria (low BP) right ventricle (low BP)
pulmonary vasculature (low) carotid sinus (high) aortic arch (high) juxtaglomerular apparatus (high)
how does the low pressure side respond to blood pressure changes?
(atria, right ventricle, pulmonary vasculature)
low pressure: reduced baroreceptor firing -> Signal through Afferent fibres to the brainstem -> Sympathetic activity ADH release
high pressure:
atrial stretch
->
ANP, BNP released
how does the high pressure side respond to blood pressure changes?
low pressure:
Reduced baroreceptor firing
->
Signal through Afferent fibres to the brainstem
->
sympathetic activity
ADH release
AND
JGA cells
->
renin released
wha tis atrial naturietic peptide?
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
signalling pathway: guanylyl cyclase domian cGMP protein kinase G cellular responses
what happens in volume expansion?
decreased sympathetic activity
decreased renin
decreased ANG I
decreased ANG II
decreased aldosterone
increased ANP and BNP
decreased ADH
increased sodium (And water) excretion
what happens in volume contraction?
increased sympathetic activity
increased renin
increased ANG I
increased ANG II
increased aldosterone
decreased ANP and BNP
increased ADH
decreased sodium (And water) excretion
What would be the effect on water secretion of increased sodium levels reaching the collecting duct and why?
you would be able to reabsorb less water
as there is a sodium gradient in the collecting duct and the lumen
when osmolarity is higher in the interstitium due to sodium, water is reabsorbed
but if there is more sodium in the collecting duct there is less of a gradient so less water is reabsorbed
how do sodium levels affect ECF volume?
Na+ levels determine the ECF volume
Reducing ECF volume reduces BP
Reducing Na+ reabsorption reduces total Na+ levels, ECF volume and BP
what is a summary of the renin-angiotensin system?
renin is secreted from the JGA
renin activates angiotensinogen (from the liver) into angiotensin I
angiotensin converting enzyme (from lungs and kidneys) converts Ang I into Ang II
what are the effects of ACE inhibitors?
ACE Inhibitor
Reduced Angiotensin II
Vascular Effects:
vasodilation
increased vascular volume (not blood volume!)
decreased blood pressure
decreased water absorption (due to decreased GFR)
Direct Renal Effects:
decreased Na+ reuptake in the PCT
increased Na+ in the distal nephron
Adrenal Effects: Reduced aldosterone indirect renal effects: Na+ uptake in the CCT (Distal collecting duct) Na+ in the distal nephron
what are dome diuretics?
ACE inhibitors
thiazide diuretics -DCT
osmotic diuretics - cant be reabsorbed in the PCT and thin descending loop, so the large chunk of water that should be reabsorbed here cant be
carbonic anhydrase inhibitors - blocks the enzyme in the PCT as it is most active here
loop diuretics - thick ascending loop
potassium sparing diuretics - collecting duct
how do carbonic anhydrase inhibitors work?
bicarbonate in the tubular fluid can no longer be converted into water and CO2
so that CO2 cant enter the cells
so in the cells it cant combine with H2O
so protons arent produced
so the sodium - proton exchange protein cant work, and sodium cant enter the cells to be reabsorbed
net reabsorbtion of sodium goes down
Carbonic anhydrase activity leads to Na+ re-absorption and increased urinary acidity
Carbonic anhydrase Inhibitors
reduced Na+ reuptake in the PCT
Increased Na+ in the distal nephron
Reduced water reabsorpt
how do loop diuretics work?
eg. furosemide
block the Na-CL-K triple transporter, reduces sodium upttake in the thick ascending loop of henle
Triple transporter Inhibitors
reduced Na+ reuptake in the LOH
Increased Na+ in the distal nephron
Reduced water reabsorption
how do thiazide diuretics work?
block the sodium-chloride cotransporter in the DCT
reduced Na+ reuptake in the DCT
Increased Na+ in the distal nephron
Reduced water reabsorption
Increased Calcium reabsorption - if you block sodium reuptake, but dont effect the sodium potassium ATPase on the blood side, you just depleat the cell of sodium. this increases the membrane gradient. but there are sodium-calcium antiporters (sodium going into the cell from the blood). so sodium enters the cell at the expense of calcium moving out.
how do potassium sparing diuretics work?
Inhibitors of aldosterone function (e.g. spironolactone)
aldosterone stimulates the production of a sodium channel
so less sodium leaves the tubular lumen
and more water is peed out
potassium sparing as the sodium potassium ATPase has less sodium to transport into the blood, so less potassium leaves into the lumen
what is the role of potassium in the body?
Potassium is the main intracellular ion (150 mmol/L), extracellular [K+] = 3-5 mmol/L.
Extracellular K+ has effects on excitable membranes (of nerve and muscle).
High K+ (extracellularly) : depolarises membranes - action potentials, heart arrhythmias.
Low K+ : heart arrhythmias (asystole).
what is the role of dietary potassium?
Potassium is the major intra-cellular ion but is low in the ECF
Potassium is present in most/all foods (especially unprocessed)
meal -> potassium absorbtion -> increases plasma potassium concentration -> insulin release (also aldosterone and adrenaline) -> uptake of potassium into tissues
how does insulin stimulate the uptake of potassium?
indirectly
insulin activates the sodium-proton exchanger
so sodium entering cells increases
the sodium entering the cell has to leave, it does this by the sodium potassium ATPase
so more potassium is brought into the cell
what happens to potassium in the kidney?
67% is reabsorbed in the PCT
20% is reabsorbed in the thick ascending loop
throught Na-K-Cl triple transporter
10-50% is secreted into the DCT
5-30% is secreted into the collecting duct
so between 50-80% leaves in the urine
(in potassium depletion, it is reabsorbed in the DCT (3%) and collecting duct (9%) instead)
what stimulates potassium secretion into the DCT and collecting duct?
increased plasma potassium concentration
increased aldosterone
increased tubular flow rate
increased plasma pH
how is potassium secretion into the tubular lumen done?
through principal cells
done through the Na-K ATPase
when plasma potassium concentration increases
there is more potassium to come into the cells (conc gradient)
so more potassium to enter the tubular lumen through potassium channels
this also has an effect on the membrane potential, which helps stimulate potassium secretion
what is the role of primary cillium and PDK1 in potassium secretion?
they respond to tubular flow
as flow increases
PDK1 is stimulated
this increases calcium concentrations in the cell
this stimulates the activity/openness of the potassium channels (on the tubular side)
what is hypokalaemia?
Hypokalemia one of the most common electrolyte imbalances (seen in up to 20% of hospitalised patients)
causes:
Inadequate dietary intake (too much processed food)
Diuretics (due to increase tubular flow rates)
Surreptitious vomiting (reduced intake)
Diarrhoea
Genetics (Gitelman’s syndrome; mutation in the Na/Cl transporter in the distal nephron)
what is hyperkalaemia?
Common electrolyte imbalance present in 1-10% of hospitalised patients
causes:
Seen in response to K+ sparing diuretics
ACE inhibitors
Elderly
Severe diabetes
Kidney disease
