Sodium potassium balance Flashcards
What is the effect of a high sodium diet on body weight?
weight goes up as more water uptake
What is the effect of high sodium in diet?
high osmolarity -> increased ECF volume -> high blood volume and blood pressure
What is the effect of low sodium in diet?
low osmolarity -> decreased ECF volume -> low blood volume and blood pressure
Where is sodium reabsorbed?
PCT - 65%
Descending LoH - 25%
DCT - 8%
CD - UP TO 2%
What does increasing increasing glomerular filtration do to sodium reabsorption?
more sodium filtered out of blood and 65% of a larger amount reabsorbed so more reabsorption
What is done to increases sodium reabsorption?
- Increase SNS:
- Vasoconstrict AA -> reduce GFR and pressure gradient
- Stimulates reabsorption at PCT
- Stimulates JGA to release renin - Low tubular sodium at the JGA -> releases renin -> converts angiotensinogen to angiotensin I -> ACE mediates AT-1 to angiotensin II
- Angiotensin 2 stimulates release of aldosterone which stimulates reabsorption at CT and DCT and PCT.
What leads to decreased sodium reabsorption?
ANP/Atrial Naturietic Peptide:
Dilates the AA -> increase GFR
Reduces sodium uptake in PCT and CT
Reduces stimulation to JGA
How does juxta glomerular apparatus stimulate renin production and where is it?
Reduced sodium detected by macula densa cells
Leads to production of prostaglandin 2, stimulating juxtaglomerular cells to produce renin
AFFERENT ARTERIOLE AND DCT
What are the 3 main effects of angiotensin 2?
Stimulate vasoconstriction in the vascular system -> raise BP
Act on PCT to increase sodium reabsorption -> raise BP
Stimulate adrenal cortex to create aldosterone
What stimulates and inhibits renin production?
stimulates
- low blood pressure
- low fluid bolume
- sympathetic system
inhibits
- high blood pressure
- high fluid volume
- ANP
What is aldosterone?
Steroid hormone synthesised and secreted from the adrenal cortex in response to angiotensin 2, decrease in BP or decrease in osmolarity of ultrafiltrate
What does aldosterone stimulate?
- more sodium reabsorption
- more potassium and hydrogen ion secretion
What is the effect of too much aldosterone?
hypokalemic alkalosis
Aldosterone mechanism of action
Aldosterone binds to type 1 intracellular receptors: aldosterone enters -> binds to cytosolic receptors -> HSP dissociate -> receptors form homo-dimer -> homodimer translocates to nucleus -> modifies transcription
What are the effects of aldosterone inside of the cell?
Upregulate production of apical sodium transporters and activity
Upregulate production of basolateral Na+/K+-ATPase
Upregulate regulatory proteins
Diseases of aldosterone
Hypoaldosteronism:
- less sodium reabsorption so ECF volume falls (hypotension)
- increased renin, Ang-II and ADH
- dizziness, hypotension, salt craving and palpitations
Hyperaldosteronism
- more sodium reabsorption so ECF volume rises (hypertension)
- increased ANP and BNP
- decreased renin, Ang-II and ADH
- hypertension, muscle weakness, polyuria and thirst
What is Liddle’s syndrome?
Inherited disease of high blood pressure
Mutation in aldosterone activated sodium channel so it is always open
Results in sodium retention and hypertension
Where are baroreceptors found and what pressures do they work under?
Heart:
Atria – low pressure
Right ventricle – low pressure
Vascular system: Pulmonary vasculature – low pressure Carotid sinus – high pressure Aortic arch – high pressure JGA – high pressure
What is ANP and its actions?
A small peptide made in the atria (they also make BNP)
Released in response to atrial stretch
Actions to reduce BP:
- Vasodilation of renal blood vessels
- Inhibition of sodium reabsorption in PCT and CD
- Inhibits release of renin (and aldosterone therefore)
What do baroreceptors on the low pressure and high pressure side do to counteract pressure changes?
The low pressure side responds to both a decrease in pressure and and increase in pressure involving SNS + ADH in decreased and ANP + BNP in increased
The high pressure side only responds to reduced pressure using SNS, ADH and renin release
What do diuretic drugs do?
They reduce BP
What does ACE inhibitors do?
ACE Inhibitors reduce BP by reducing Ang-II production -> less aldosterone, less vasoconstriction and less reabsorption directly at PCT.
Give examples of diuretic drugs and where they work
Osmotic Diuretics – PCT/descending LoH
Carbonic anhydrase inhibitors – PCT
Loop Diuretics – Ascending LoH – E.G furosemide
Thiazides – DCT
K+ sparing diuretics – DCT – E.G. amiloride
E.G. spironolactone
How do osmotic diuretics work?
Glucose or mannitol in the tubular fluid decreases the osmotic gradient by raising the osmolarity in the CD tube and so less water is reabsorbed
How do carbonic anhydrase inhibitors work?
Less carbonic anhydrase -> less protons -> indirect inhibition of proton pump -> thus less sodium reabsorption via transporter -> less water reabsorption
How do loop diuretics work?
Directly blocks the triple Symporter (soidum, chloride and potassium) -> less sodium reabsorption -> less water reabsorption
How do thiazides work?
Directly blocks Na+/Cl- co-transporter -> less sodium reabsorption -> less water reabsorption.
What is the main intracellular ion?
What are its effects extracellularly when too high/low?
Potassium is main intracellular ion (150mmol/L), extracellular (3-5 mmol/L)
Extracellular K+ effects:
High – depolarises membranes -> Action potentials and heart arrhythmias
Low – heart arrhythmias (asystole)
What happens after a meal with high K+?
After a meal, insulin (and aldosterone/adrenaline) mediates uptake of potassium into cells
Sodium/potassium ATPase uptake into cells
How much potassium is absorbed in the PCT, LoH and amount excreted in urine?
60-70% absorbed in PCT
20% in LoH
Amount in urine varies from 1-80% of filtered load
What is potassium secretion stimulated by?
- high plasma conc of K+
- High aldosterone
- high tubular flow rate
- high plasma pH
Potassium disorders
Hypokalaemia
Causes include:
- Diuretics, vomiting, diarrhoea, genetics (Gitelman’s Syndrome - mutation in Na/Cl transporter in distal nephron)
Hyperkalaemia
Causes include:
- K+ sparing diuretics, ACE inhibitors, elderly
Where does K+ secretion occur?
principal cells of CD
What is normal plasma osmolarity and the determinant?
Normal plasma osmolarity is 285-295 mosmol/L and maintained by volume changes -mainly sodium affects it as main component of plasma
Potassium secretion
Secretion mediated by sodium/potassium ATPase into cell and then out via potassium channel into lumen
Occurs via 2 methods:
- aldosterone
- tubular flow
What are the two methods via which potassium is secreted
- Aldosterone stimulates:
Apical sodium transporter so more sodium into cells
Basolateral sodium/potassium ATPase so more sodium out and potassium in
Apical Potassium transporter so the potassium can leave - Flow stimulates the primary cilia on apical side -> activates PDK1 -> increases cytosolic Ca2+ -> up-regulates apical K+ channels.
