Sodium and Potassium balance Flashcards
if there are 2900 mmosmoles of something in 10 L, what will it’s osmolarity be
290mosmol/L
Describe the effect of a high sodium diet on body weight
High Na+, more water retained
Therefore volume of ECF increases to keep osmolarity constant and thus weight increases due to more fluid and will also increase BP
What are the effects of an increase in mmosmoles of a substance in solution
Number of mosmoles in ECF rises (i.e. the solute concentration rises) - volume of the ECF rises - concentration of the ECF remains stable.
What are the effects of changing sodium levels
Increased dietary sodium Increased osmolarity (but the body can’t let this happen Increased ECF volume Increased blood volume and pressure
Where is Na+ reabsorbed
§ 65% sodium reabsorbed at the PCT, ~25% in the ascending limb of LoH, 8% at the DCT and up to 2% in the collecting duct.
What happens as you increase GFR
§ If you increase the GFR, the sodium reabsorption goes up but this is as you filter more so you reabsorb more (same percentage reabsorbed).
Therefore more sodium is excreted
More in DCT
Describe how we can increase sodium reabsorption
- Increase SNS:
a. Vasoconstrict AA - reduce GFR.
b. Stimulates reabsorption at PCT.
c. Stimulates JGA to release renin. - Low tubular sodium at the JGA -releases renin à converts angiotensinogen to angiotensin I - ACE mediates AT-1 to angiotensin II:
a. Stimulates release of aldosterone:
i. Stimulates reabsorption at CT and DCT.
b. Stimulates reabsorption at PCT.
Describe decreased sodium reabsorption
- ANP/Atrial Naturietic Peptide:
a. Dilates the AA - increase GFR.
b. Reduces sodium uptake in PCT and CT.
c. Reduces stimulation to JGA.
Describe the production of angiotensin 2
Liver makes angiotensinogen
JGA makes renin which converts angiotensinogen into angiotensin 1
ACE converts Angiotensin 1 into angiotensin 2
What are the effects of angiotensin 2
o Stimulate vasoconstriction in the vascular system - raise BP.
o Act on PCT to increase sodium reabsorption - raise BP (increased water reabsorption- increasing ECF)
o Stimulate adrenal cortex to create aldosterone.
What stimulates renin release
Decreased BP
Decreased fluid volume
increased beta sympathetic activity
opposite inhibits
Describe aldosterone
Steroid hormone
Synthesised and released from the adrenal cortex
Released in response to Angiotensin ll,
decrease in blood pressure (via baroreceptors)
decreased osmolarity of ultrafiltrate
What does aldosterone stimulate
Increased Sodium reabsorption (principal cell)
(controls reabsorption of 35g Na/day)
Increased Potassium secretion (principal cell)
Increased hydrogen ion secretion (intercalated cell)
What does an aldosterone excess lead to
leads to hypokalaemic alkalosis
More K+ and H+ excreted
How does aldosterone work
Steroid hormone
Diffuses through plasma membrane
Binds to type 1 Intracellular receptors
Heat shock protein dissociates
Receptors (with aldosterone attached) form homodimer
Homodimer translocated to the nucleus where it modifies transcription.
Describe the effects of the transcription of this homodimer
Increased expression of transcription factors, regulatory proteins and transport machinery
Induces expression of the apical Na channel of the collecting duct, and probably also promotes its activity (via a protein activator)
induces formation of Na-K-ATPase pumps (increased transcription of the corresponding mRNA)
induces formation of Na-K-ATPase pumps (increased transcription of the corresponding mRNA)
Regulatory proteins will increase the opening of these channels- more Na+ leaves
Describe hypoldosteronism
§ Hypoaldosteronism – less sodium reabsorption - ECF volume falls (hypotension).
o INCREASED renin, Ang-II and ADH (VP).
o Dizziness, hypotension, salt craving and palpitations.
Describe 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
Describe 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
Where are baroreceptors found in the heart
Heart:
o Atria – LOW pressure.
o Right ventricle – LOW pressure.
Where are baroreceptors found in the vasculature
o Pulmonary vasculature – LOW pressure.
o Carotid sinus – HIGH* pressure.
o Aortic arch – HIGH* pressure.
o JGA – HIGH* pressure.
Describe how the low pressure side responds to low pressures
Signal through Afferent fibres to the brainstem
Sympathetic activity
ADH release
blood pressure increased
Describe how the low pressure side responds to high pressures
Atrial stretch
ANP and BNP released
Blood pressure decreases
Describe how the high pressure side responds to low pressures
Signal through Afferent fibres to the brainstem
Sympathetic activity
ADH released
BP increases
JGA cells
renin released
What is 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
Describe the relationship between Na+ and blood pressure
Na+ levels determine the ECF volume
Reducing ECF volume reduces BP
Reducing Na+ reabsorption reduces total Na+ levels, ECF volume and BP
What do ACE inhibitors do
ACE inhibitors (lower blood pressure) Effects of the consequent reduction in Angiotensin II and aldosterone levels are not confined to the kidney
Describe osmotic diuretics
§ 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.
List some diuretic drugs
Carbonic anhydrase inhibitors Loop Diuretics: furosemide (blocks triple co-transporter) Thiazides: block Na/Cl co-transport K+ sparing diuretics: amiloride - block Na channels spironolactone – aldosterone antagonist
Describe the action of carbonic anhydrase inhibitors
Less carbonic anhydrase - less protons à indirect inhibition of proton pump - thus less sodium reabsorption (less H+ exchanged for it) - less water reabsorption.
Describe loop diuretics furosemide
Directly blocks the triple Symporter (ascending limb) - less sodium reabsorption - less water reabsorption.
Describe the actions of thiazide in the DCT
Directly blocks Na+/Cl- co-transporter - less sodium reabsorption - less water reabsorption.
What is meant by K+ sparing
Work on distal part of nephron
So no effect on K+
What is important about potassium
Potassium is the main intracellular ion (150 mmol/l), extracellular [K+] = 3-5 mmol/l.
Describe the effects of K+ on excitable membranes
Extracellular K+ has effects on excitable membranes (of nerve and muscle).
High K+ ; depolarises membranes - action potentials, heart arrhythmias.
Low K+ ; heart arrhythmias (asystole).
Describe the response to K+ after a meal
K+ absorption
Plasma conc increases
Insulin, aldosterone and adrenaline stimulate its uptake into tissues
Uptake easy due to Na+/K+ ATPase
Describe potassium uptake into the tube
§ 30% potassium in PCT.
§ 10% potassium in thin ascending loop of LoH.
§ 1-80% potassium in CD – LOTS of secretion into the tubular fluid.
What can stimulate K+ secretion
Increased plasma conc
Aldosterone
Increased tubular flow rate
Increased plasma pH
What will cause K+ to leave the cell
Outside more negative
Inside more positive
Describe potassium secretion in principal cells
§ Secretion mediated by sodium/potassium ATPase and is coupled with sodium absorption into the blood. § Occurs via 2 methods: o Aldosterone stimulates: § Apical Potassium transporter. § Apical sodium transporter. § Basolateral sodium/potassium ATPase.
How does flow increase potassium secretion
Flow stimulates the primary cilia - activates PDK1 - increases cytosolic Ca2+ - up-regulates apical K+ channels.
Describe hypokalaemia
Hypokalemia one of the most common electrolyte imbalances (seen in up to 20% of hospitalised patients)
Diuretics (due to increase tubular flow rates)
Surreptitious vomiting
Diarrhoea
Genetics (Gitelman’s syndrome; mutation in the Na/Cl transporter in the distal nephron)
Describe hyperkalaemia
Common electrolyte imbalance present in 1-10% of hospitalised patients
Seen in response to K+ sparing diuretics
ACE inhibitors
Elderly
Describe the actions of K+ sparing diuretics
less Na+ in
therefore less Na+ out through pump
less k+ in
therefore less K+ out in the tubule
What happens in the macula densa in low Na+ conc
Water leaves macula densa
PGE2 and NO produced- which stimulate the granular cells to release renin (also stimulated by SNS and local hormones)
Not a lot of Na+ comes into cells- low osmolarity- therefore water leaves cells
