Sodium potassium balance

Question 1

What is the effect of a high sodium diet on body weight?

Answer 1

weight goes up as more water uptake

Question 2

What is the effect of high sodium in diet?

Answer 2

high osmolarity -> increased ECF volume -> high blood volume and blood pressure

Question 3

What is the effect of low sodium in diet?

Answer 3

low osmolarity -> decreased ECF volume -> low blood volume and blood pressure

Question 4

Where is sodium reabsorbed?

Answer 4

PCT - 65%
Descending LoH - 25%
DCT - 8%
CD - UP TO 2%

Question 5

What does increasing increasing glomerular filtration do to sodium reabsorption?

Answer 5

more sodium filtered out of blood and 65% of a larger amount reabsorbed so more reabsorption

Question 6

What is done to increases sodium reabsorption?

Answer 6

1. Increase SNS:
   - Vasoconstrict AA -> reduce GFR and pressure gradient
   - Stimulates reabsorption at PCT
   - Stimulates JGA to release renin
2. 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.

Question 7

What leads to decreased sodium reabsorption?

Answer 7

ANP/Atrial Naturietic Peptide:

Dilates the AA -> increase GFR

Reduces sodium uptake in PCT and CT

Reduces stimulation to JGA

Question 8

How does juxta glomerular apparatus stimulate renin production and where is it?

Answer 8

Reduced sodium detected by macula densa cells
Leads to production of prostaglandin 2, stimulating juxtaglomerular cells to produce renin
AFFERENT ARTERIOLE AND DCT

Question 9

What are the 3 main effects of angiotensin 2?

Answer 9

Stimulate vasoconstriction in the vascular system -> raise BP

Act on PCT to increase sodium reabsorption -> raise BP

Stimulate adrenal cortex to create aldosterone

Question 10

What stimulates and inhibits renin production?

Answer 10

stimulates

• low blood pressure
• low fluid bolume
• sympathetic system

inhibits

• high blood pressure
• high fluid volume
• ANP

Question 11

What is aldosterone?

Answer 11

Steroid hormone synthesised and secreted from the adrenal cortex in response to angiotensin 2, decrease in BP or decrease in osmolarity of ultrafiltrate

Question 12

What does aldosterone stimulate?

Answer 12

• more sodium reabsorption

- more potassium and hydrogen ion secretion

Question 13

What is the effect of too much aldosterone?

Answer 13

hypokalemic alkalosis

Question 14

Aldosterone mechanism of action

Answer 14

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

Question 15

What are the effects of aldosterone inside of the cell?

Answer 15

Upregulate production of apical sodium transporters and activity

Upregulate production of basolateral Na+/K+-ATPase

Upregulate regulatory proteins

Question 16

Diseases of aldosterone

Answer 16

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

Question 17

What is Liddle’s syndrome?

Answer 17

Inherited disease of high blood pressure
Mutation in aldosterone activated sodium channel so it is always open
Results in sodium retention and hypertension

Question 18

Where are baroreceptors found and what pressures do they work under?

Answer 18

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

Question 19

What is ANP and its actions?

Answer 19

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)

Question 20

What do baroreceptors on the low pressure and high pressure side do to counteract pressure changes?

Answer 20

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

Question 21

What do diuretic drugs do?

Answer 21

They reduce BP

Question 22

What does ACE inhibitors do?

Answer 22

ACE Inhibitors reduce BP by reducing Ang-II production -> less aldosterone, less vasoconstriction and less reabsorption directly at PCT.

Question 23

Give examples of diuretic drugs and where they work

Answer 23

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

Question 24

How do osmotic diuretics work?

Answer 24

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

Question 25

How do carbonic anhydrase inhibitors work?

Answer 25

Less carbonic anhydrase -> less protons -> indirect inhibition of proton pump -> thus less sodium reabsorption via transporter -> less water reabsorption

Question 26

How do loop diuretics work?

Answer 26

Directly blocks the triple Symporter (soidum, chloride and potassium) -> less sodium reabsorption -> less water reabsorption

Question 27

How do thiazides work?

Answer 27

Directly blocks Na+/Cl- co-transporter -> less sodium reabsorption -> less water reabsorption.

Question 28

What is the main intracellular ion?

What are its effects extracellularly when too high/low?

Answer 28

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)

Question 29

What happens after a meal with high K+?

Answer 29

After a meal, insulin (and aldosterone/adrenaline) mediates uptake of potassium into cells
Sodium/potassium ATPase uptake into cells

Question 30

How much potassium is absorbed in the PCT, LoH and amount excreted in urine?

Answer 30

60-70% absorbed in PCT
20% in LoH
Amount in urine varies from 1-80% of filtered load

Question 31

What is potassium secretion stimulated by?

Answer 31

• high plasma conc of K+
• High aldosterone
• high tubular flow rate
• high plasma pH

Question 32

Potassium disorders

Answer 32

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

Question 33

Where does K+ secretion occur?

Answer 33

principal cells of CD

Question 34

What is normal plasma osmolarity and the determinant?

Answer 34

Normal plasma osmolarity is 285-295 mosmol/L and maintained by volume changes -mainly sodium affects it as main component of plasma

Question 35

Potassium secretion

Answer 35

Secretion mediated by sodium/potassium ATPase into cell and then out via potassium channel into lumen
Occurs via 2 methods:
- aldosterone
- tubular flow

Question 36

What are the two methods via which potassium is secreted

Answer 36

• 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.