Sodium and Potassium Balance Flashcards
What is osmolarity?
Measure of the solute (particle) concentration in a solution (osmoles/L)
Depends on the number of dissolved particles
So what is 1 Osmole?
1 Osmole = 1 mole of dissolved particles per litre (e.g. 1 mol of NaCl = 2 mol of particles in solution)
The greater the number of dissolved particles, the greater the osmolarity
How is osmolality different?
Osmolarity = number of particles of solute per liter of solution
Osmolality = number of particles of solute per kilogram of solvent
What is normal plasma osmolarity?
285-295 mosmol/L
What is the most prevalent solute in the plasma?
What else makes up plasma?
Sodium - 140 mmol/L (most important and dictates ECF volume)
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
What happens when you increase sodium dietary intake?
Increase total body sodium
Increased osmolarity (but this can’t happen due to semi-permeability of membranes)
So leads to increased water intake and retention
Increased ECF volume - until plateau reached
Increased blood volume and pressure
Then if you reduce sodium in your diet - you lose the water as you lose sodium from the system
What happens when you decrease sodium dietary intake?
Decrease total body sodium
Decreased osmolarity (but this can’t happen due to semi-permeability of membranes)
So leads to decreased water intake and retention
Decreased ECF volume - until plateau reached
Decreased blood volume and pressure
What happens under normal conditions of euvolemia?
Euvolemia has normal sodium levels = inhibition of Na+ intake
What controls sodium intake?
Lateral parabrachial nucleus - a set of cells that respond to serotonin and glutamate as transmitters to suppress basal sodium intake
What happens at the lateral parabrachial nucleus during Na+ deprivation VS euvolemia?
Na+ deprivation = increased appetite for Na+ driven by GABA and opioids
Euvolemia = inhibit Na+ intake
What is salt when present in low quantities in food?
What is salt when present in high quantities in food?
Appetitive = low sodium content in food
Aversive = high sodium content in food
Where is sodium reabsorbed in the nephron?
So how much sodium is actually excreted?
60-70% reabsorbed in PCT
As the tubular fluid travels down the descending limb of the loop of Henle, no sodium is reabsorbed
However, in the thick ascending limb a further 25% is reabsorbed
A further 5 % is reabsorbed in the DCT
A further 3% in the collecting duct
So less than 1% of the sodium that enters the tubular fluid is excreted
How would you increase the amount of sodium excreted?
Increase GFR (glomerular filtration rate) Increase sodium excretion
What affects GFR?
Is it desirable that changes in GFR are proportional to sodium lost?
Renal plasma flow
Mean arterial pressure
Proportional up to a threshold then plateaus
Not really
How does sodium affect GFR?
The DCT is in contact with cells around the glomerulus - so the DCT contains macula densa cells, which are in contact with the extraglomerular mesangial cells (found between the glomerulus and DCT), which are in contact with the juxtaglomerular cells (on the glomerulus)
High tubular sodium
Macula densa cells are found on the DCT and respond to high sodium levels by increasing sodium/chloride uptake via triple transporter
Causes Macula Densa cells to release adenosine
Detected by extraglomerular mesangial cells - which interacts with the juxtuglomerular cells to release renin
This causes smooth muscle cells of the glomerulus to contract = reduced blood flow
Reduces perfusion pressure and so GFR
Why is the macula densa production of renin in response to high sodium less important?
Over a short period of time = short term regulation system
So does not affect overall renin production long term
What is the best way to retain sodium and water?
Filter less
Reduction of pressure gradient at Bowman’s capsule
What factors allow for less filtration?
Sympathetic activity:
Contracts SMC of afferent arteriole
Stimulates sodium uptake of cells of PCT
Stimulates JGA (juxtaglomerular apparatus) to produce renin
Renin cleaves angiotensinogen to form angiotensin I, ACE cleaves angiotensin I to Angiotensin II
Angiotensin II promotes vasconstriction and reabsorption of sodium in PCT
Angiotensin II stimulates adrenal glands to produce aldosterone
Aldosterone promotes reabsorption in collecting duct
What factors allow for greater filtration?
ANP (atrial naturietic peptide) - acts as a vasodilator
Reduces reabsorption of sodium throughout nephron - PCT, DCT and CD
What is aldosterone and where is it synthesised?
When is it released and why?
Aldosterone = steroid hormone
Synthesised and released from the adrenal cortex (zona glomerulosa)
Released in response to angiotensin II and a decrease in BP (detected via baroreceptors)
What does angiotensin II do to stimulate aldosterone production?
Promotes synthesis of aldosterone synthase (enzyme)
Aldosterone synthase causes the last 2 ezymatic steps in the production of aldosterone from cholesterol
What is the role of aldosterone in the kidney?
Stimulates: Increased Sodium reabsorption (controls reabsorption of 35g Na/day) Increased Potassium secretion Increased hydrogen ion secretion
What does aldosterone excess lead to?
Hypokalaemic alkalosis
How does aldosterone work?
Steroid hormone - lipid soluble so will pass through the cell membrane
Once inside the cell, binds to mineralocorticoid receptor inside cytoplasm bound to protein HSP 90
HSP 90 is consequently removed and the receptor is dimerised (no longer a monomer, instead is a dimer)
Allows it to translocate to the nucleus - i.e. moves into nucleus
It binds to DNA, where it stimulates transcription of mRNA genes that are under its control
What proteins are produced in response to aldosterone?
Na/K ATPase
Epithelial sodium channel
These travel to their respective membranes
Regulatory proteins that stimulate the activity of the 2 transporters (Na+/K+ ATPase and epithelial sodium channel) so the channels are active
What is hypoaldosteronism?
Reabsorption of sodium in the distal nephron is reduced
Increased urinary loss of sodium - leads to increased loss of water in the urine
ECF volume falls
Increased renin, Ang II and ADH
What are signs and symptoms of hypoaldosteronism?
Dizziness
Low blood pressure - responsible for the dizziness
Salt craving
palpitations
What is hyperaldosteronism?
Reabsorption of sodium in the distal nephron is increased
Reduced urinary loss of sodium = increase in total sodium
ECF volume increases (hypertension)
Reduced renin, Ang II and ADH
Increased ANP and BNP
What are symptoms of hyperaldosteronism?
High blood pressure
Muscle weakness
Thirst - we think we have insufficient water in our system and so drink more water (but this is because of the high total sodium in the body)
Polyuria - trying to get rid of all the water being drunk
What is Liddle’s syndrome?
Looks like hyperaldosteronism but with normal / low aldosterone levels
Inherited disease of high BP
Mutation in the aldosterone activated sodium channel
Channel is always in the ‘on’ state = sodium retention, leading to hypertension
How is feedback from increased of decreased ECF detected?
Via baroreceptors (pressure receptors)
Where are the low pressure baroreceptors found?
Atria
Right ventricle
Pulmonary vasculature
Where are the high pressure baroreceptors found?
Carotid sinus
Aortic arch
Juxtaglomerular apparatus
What happens in response to low pressure on the low pressure side of the baroreceptors?
Low BP
Reduced baroreceptor firing
Signal through afferent fibres to the brainstem
Leads to sympathetic activity
Leads to ADH release
What happens in response to high pressure on the low pressure side of the baroreceptors?
High BP
Leads to atrial stretch
ANP, BNP released
What happens in response to low pressure on the high pressure side of the baroreceptors?
Same as low pressure side (with reduced baroreceptor firing = sympathetic acitivy and ADH release) but also
Signals to JGA (juxtoglomerular apparatus) cells to suppress renin release
What is ANP?
Atrial Natriuretic Peptide
Small peptide made in the atria (also make BNP)
Released in response to atrial stretch (i.e. high blood pressure)
What are the actions of ANP?
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
How does ANP work?
Binds to a receptor that is guanylyn cyclase
Guanylyn cyclase causes conversion of GTP to cyclic GMP
Leads to activation of protein kinase G
Cellular responses in response to that - e.g. vasodilation of the renal and systemic blood vessels, inhibition of sodium in PCT and CD and inhibition of renin + aldosterone production
What happens in response to volume expansion of blood?
Reduced sympathetic activity leading to reduced sodium reuptake in the PCT, reduction in renin production (and so aldosterone)
Increase in ANP and BNP
Promotes sodium excretion
What happens when there is contraction of the blood volume?
Increased sympathetic activity leading to increased sodium reuptake in the PCT, increase in renin production (and so aldosterone)
Decrease in ANP and BNP, increase ADH production
Promotes sodium reabsorption
What would be the effect on water secretion of increased sodium levels reaching the collecting duct?
Increase osmolarity of tubular fluid by increasing sodium
Reduce gradient across membrane into the medulla (loop of henle)
Reduce amount of water that can be reabsorbed
So reduced ECF volume
How are ACE inhibitors diuretics?
Reduces Angiotensin II production = vasodilation
Increases vascular volume = reduction in BP
Reduced Na+ reuptake in the PCT = reduced Na+ in the distal nephron
Reduces gradient across tubular fluid into interstitium at the loop of Henle = reduced water reabsorption
Reduced aldosterone = reduced uptake of sodium in the CD
Reduced ECF volume = reduced BP
What are some other diuretics and where do they act on the nephron?
Osmotic diuretics - PCT Carbonic anhydrase inhbitors - PCT Lymph diuretics - thin limb of loop of Henle Thiazide diuretics - DCT Potassium sparing - CD
How do carbonic anhydrase inhibitors work?
Reduced Na+ reuptake in the PCT
Increased Na+ in the distal nephron = reduced gradient across tubular fluid into interstitium at the loop of Henle = reduced water reabsorption
Reduced acidity of urine as CA no longer converted H2CO3 into H2O and CO2
How do loop diuretics work?
E.g. Furosemide
Block the triple transporter Inhibitors
Reduced Na+ reuptake in the loop of Henle
Increased Na+ in the distal nephron
Reduced water reabsorption
How do thiazide diuretics work?
Block Na/Cl transporter
Reduced Na+ reuptake in the DCT
Increased Na+ in the distal nephron
Reduced water reabsorption
Also increases calcium reabsorption (via sodium calcium antiporters)
How do potassium sparing diuretics work?
Inhibitors of aldosterone function (e.g. spironolactone)
Fewer sodium reuptake channels synthesised = reduced sodium reuptake in the distal nephron
What is potassium?
Potassium = main intracellular ion at 150 mmol/L, extracellularly = 3-5 mmol/L
What does extracellular postassium effect?
What does high extracellular K+ result in?
What does low extracellular K+ result in?
Excitable membranes
High K+ = depolarises membranes leading to more action potentials, heart arrhythmias
Low K+ = heart arrhythmias (asystole)
What happens to dietary potassium?
K+ present in almost all foods, esp. unprocessed foods
After a meal –> K+ is absorbed
Increases plasma K+ conc.
Tissue uptake of K+ is stimulated by insulin, aldosterone, and adrenaline
How does insulin stimulate uptake of K+ into tissues?
Stimulates Na+/H+ exchanger
Increases sodium entering cells
To reduce intracellular sodium Na+/K+ ATPase used
So Na+/K+ ATPase activity increases = brings in more K+
Where in the nephron is potassium reabsorbed and secreted?
So how much potassium is excreted via the urine overall?
67% (or 2/3) reabsorbed in the PCT
Further 20% reabsorbed in thick ascending limb of loop of Henle - via Na+/K+/Cl- triple transporter
Potassium secretion in DCT and CD
Up to 50% of K+ secreted in DCT
Up to 30% secreted in CD
15-80% of K+ in glomerular filtrate is excreted
Why can only 15% of the K+ in the filtrate be excreted?
Due to reabsorption in the DCT (3%) and CD (9%)
Why is there a range of what percentage of K+ is reabsorbed?
Depends on plasma concentration
What is K+ secretion stimulated by?
Increased plasma K+ concentration
Increased aldosterone
Increased tubular flow rate
Increased plasma pH
How is potassium secreted by the principal cells in the DCT and CD?
Increase in activity of Na+/K+ ATPase - affects membrane potential to stimulate K+ secretion
More potassium inside the cell = more potassium secreted into DCT / CD
How does K+ excretion respond to tubular flow?
Distal cells have primary cilia
Increase in flow detected by cilia = increase in PDK1
Increases Ca2+ conc in cell
Stimulates activity of opening K+ channels
K+ moves out of the cell as it is pumped by Na+/K+ ATPase
What is hypokalemia?
Low K+ levels (in blood)
Hypokalemia one of the most common electrolyte imbalances (seen in up to 20% of hospitalised patients)
What can cause hypokalemia?
Inadequate dietary intake (too much 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)
What is hyperkalemia?
High K+ levels (in blood)
Common electrolyte imbalance present in 1-10% of hospitalised patients
What causes hyperkalemia?
Seen in response to K+ sparing diuretics
ACE inhibitors
Elderly
Severe diabetes
Kidney disesase
