6. Sodium and Potassium Balance Flashcards
What are the proportions of sodium reabsorbed in the different parts of the nephron?
- PCT - 65%
- Loop - 25%
- DCT - 8%
- Collecting duct - up to 2%
(true at any volume up to the transport maxima)
How is sodium retention increased?
Increased sympathetic activity:
1) Vasoconstriction in afferent arteriole
• reduced GFR
2) Stimulates Na channels in the PCT
• increased Na reabsorption
3) Stimulates the juxtaglomerular apparatus => angiotensin II synthesis
• stimulates Na channels in PCT
• drives aldosterone synthesis
- increases Na and water reabsorption in DTC and collecting duct
- lower concentrated filtrate reaching the juxtaglomerular apparatus, further driving angiotensin II production
How is sodium reabsorption decreased?
• Atrial natriuretic peptide (ANP)
- vasodilator (on afferent arteriole)
- reduced activity of Na uptake channels in PCT, juxtaglomerular apparatus and collecting duct
- less angiotensin II, less aldosterone, less sodium reabsorportion
What stimulates renin synthesis?
- Reduced filtrate Na concentration
- Decreased blood pressure
- Decreased fluid volume
- Increased beta1-sympathetic activity
What is aldosterone and where is it synthesised?
- Steroid hormone
* Zona glomerulosa of adrenal cortex
What does aldosterone do in the nephron?
• Stimulates principal cells of the DCT/cortical collecting duct to:
- increase sodium (and water) reabsorption
- increase potassium secretion
- increase hydrogen secretion
What can an excess of aldosterone lead to?
• Hypokalaemic alkalosis
- more K+ and H+ excreted
- reduced K+ and H+ in blood
- increased pH
How does aldosterone act on a parietal cell?
• Aldosterone binds to intracellular receptors
• Change in conformation - receptor-aldosterone complex moves into nucleus
• Acts as transcription factor on DNA
- increases expression of apical (luminal) Na channel
• Also promotes activity, using regulatory proteins - converted from low to high affinity transporters
• Increased formation of Na/K ATPase pumps
• Positive feedback - increased effect of aldosterone-receptor binding to the DNA
What is Hypoaldosternonism?
- Reduced reabsorption of sodium in the distal nephron
- Increased urinary loss of sodium and water
- ECF volume falls - compensatory increase in renin, angiotensin II and ADH
- Low BP, dizziness and salt craving
- Palpitations (as salt is required for heart function)
What is Hyperaldosteronism?
- Increased reabsorption of sodium in the distal nephron
- Reduced urinary loss of sodium and water
- ECF volume increases - compensatory increase in atrial/brain natriuretic peptide occurs
- Hypertension, muscle weakness, polyuria, thirst
What is Liddle’s Syndrome?
- Autosomal dominant
- Mutation in aldosterone activated sodium channel in principal cells
- Permanently activated channel - increased sodium reabsorption
- Low plasma renin, metabolic alkalosis (hypokalaemia) and hypoaldosteronism
Where are the 2 sets of baroreceptors located?
- Low pressure environment - atria, right ventricle and pulmonary vasculature
- High pressure environment - carotid sinus, aortic arch, juxtaglomerular apparatus (and pulmonary vasculature)
How is a low blood pressure detected and what is the response?
- Baroreceptors on low and high pressure side
- Afferent fibres to the brainstem
- Increased sympathetic activity and ADH release
- Juxtaglomerular cells on high pressure side increases renin release
How is a high blood pressure detected and what is the response?
• Baroreceptors on low pressure side respond to atrial stretch
• Release ANP and BNP
- vasodilation
- inhibition of sodium reabsorption in PCT and CT
- inhibition of renin and aldosterone
- reduced BP
What effect does an expansion in ECF volume have?
- Reduced sympathetic activity - increased GFR, reduced renin
- Reduced ADH production - increased Na and water excretion
- Increased release of ANP
- Direct effect on juxtaglomerular apparatus - reduced renin
What drugs can be used to increase sodium excretion?
- ACE inhibitors
- Osmotic diuretics
- Carbonic anhydrase inhibitors
- Loop diuretics
- K+ sparing diuretics
How does carbonic anhydrase increase sodium reabsorption?
- HCO3- bonds with H+ in the tubular fluid to form H2CO3
- Carbonic anhydrase converts this into H2O and CO2 - these can easily diffuse into PCT cell
- In the cell, they are converted back into H2CO3, which split back into H+ and HCO3-
- H+ moved back into tubular fluid, coupled with Na+ moving into the cell (sodium reabsorption)
- HCO3- diffused freely into ECF, increasing the pH of it
What are K+ sparing diuretics and how do they decrease sodium excretion?
• Diuretics that do not promote the secretion of potassium (effect, not mechanism)
- Aldosterone antagonists (e.g. spironolactone) - prevent aldosterone action of increasing sodium reabsorption in late DCT & cortical collecting duct
- Epithelial sodium channel blockers (e.g. amiloride)
What is hypokalaemia and what can cause it?
- Low plasma potassium (20% hospitalised patients)
* Diuretics, surreptitious vomiting, diarrhoea, genetics (Gitelman’s syndrome - Na/Cl transporter)
What is hyperkalaemia and what can cause it?
- High plasma potassium (1-10% hospitalised patients)
* K+ sparing diuretics, ACE inhibitors, age
In which part of the nephron is K+ secreted?
Distal nephron
