sodium & potassium regulation

Question 1

What is osmolarity? What does it depend on?

Answer 1

Osmolarity is the measure of solute particle concentration in a solution. 1 osmole = 1 mole of dissolved particles per litre. It depends on number of dissolved particles, not size

Question 2

What is normal plasma osmolarity? What dictates the ECF volume?

Answer 2

Normal plasma osm is 285-295mosmol/L. sodium dictates the ECF volume (most prevalent extracellular ion, followed by chloride)

Question 3

What does increased dietary sodium cause?

Answer 3

Increased water intake and retention so increased blood volume & pressure

Question 4

How do we regulate sodium intake when we have normal sodium levels? When we have sodium deprivation?

Answer 4

When normal sodium levels suppress desire for sodium intake by lateral parabrachial nucleus (set of cells respond to serotonin & glutamate) to suppress basal sodium intake. In sodium deprivation increased appetite for sodium driven by GABA & opioids. This is central mechanism, peripheral mechanism is taste. Salt appetitising at small concentrations but unappeitising at large concentrations

Question 5

Where is sodium reabsorbed? How much do we excrete?

Answer 5

Most of sodium reabsorbed in PCT, passively in thin ascending loop, actively in thick ascending loop. Small amounts in DCT and collecting duct. We excrete less than 1% of sodium in tubular system

Question 6

What happens in terms of sodium if we increase blood pressure and thus GFR?

Answer 6

If we increase GFR, more sodium in tubular fluid and thus more excreted. After a point this plateaus

Question 7

What happens when tubular sodium increases?

Answer 7

-DCT cells after loop in close contact with glomerulus. Juxtaglomerular cells have macula densa cells. High tubular sodium, increase uptake of sodium & chloride via triple transporter causes release of adenosine in macula densa cells which triggers extraglomerular mesangial cells to interact with smooth muscle cells on afferent arteriole causing them to contract. This reduces flow into glomerulus, thus less GFR. Leads to reduction in renin too (only short term). This is short term solution

Question 8

What do we do if we want to retain sodium (increase sodium reabsorption)?

Answer 8

Best way is to filter less (so we lose less).

1. Sympathetic activity directly contracts smooth muscle cells on afferent arteriole & stimulates sodium reabsorption in PCT.
2. Stimulated JGA to make renin which leads to angiotensin II production (will stimulate PCT cells to reabsorb sodium).
3. Angiotensin II stimulates adrenal glands to make aldosterone which promotes reabsorption of sodium in DCT and CT.

Question 9

What do we do if want to decrease sodium reabsorption?

Answer 9

Atrial naturieptic peptide ANP released and acts as vasodilator increasing GFR and sodium excretion and reducing uptake in PCT, DCT and CT, and suppresing production of renin by JGA

Question 10

What happens if we have low sodium in the body? How do we fix this?

Answer 10

Low fluid volume so increased β1 sympathetic activity causes contraction of afferent arteriole to reduce GFR. Stimulates production of renin, thus angiotensin II and thus aldosterone. Overall causes vasoconstriction, increase in sodium and water reasborption, increaing fluid volume

Question 11

What happens if we have high sodium in the body? How do we fix this?

Answer 11

High fluid volume and BP suppressed β1 sympathetic activity and causes production of ANP which reduces renin, ANGII and aldosterone preventing sodium,water reabsorption & causing vasodilation

Question 12

Where is aldosterone made and in response to what? What is the function of aldosterone? What is its structure and how does it work? What does it cause?

Answer 12

• Aldosterone made in zona glomerulosa of adrenal cortex in response to low blood pressure (baroreceptors) or angiotensin II.
• It increases sodium reabsorption in DCT and CT in kidney and increases pottasium secretion and hydrogen ion secretion.
• Steroid lipid soluble so passes through membrnae, binds to mineralocorticoid receptor in cytplasma normally bound to CSP90, binds, receptor dimerises, translocated into nucleus, binds to DNA and stimulated produuction of MRNA for genes it controls (sodium channels & sodium/potassium ATPases). Regulatory proteins stimulating activity of these channels expressed too.
• End result is more sodium channels and more active ones.

Question 13

What does hypoaldosteronism cause and why?

Answer 13

Decreased sodium reabsorption, hyponatraemia, ECF volume falls. Dizziness, low BP, salt craving, palpitations. Increased renin, ANGII and ADH in response.

Question 14

What does hyperaldosteronism cause and why?

Answer 14

Increased sodium reabiosprtion, increased ECF volume. Hypertension, wuscle weakness, polyuria, thirst. Hpyokalaemia/hypernatreamia. Increased ANP & BNP in response

Question 15

What is liddle’s syndrome and what does it cause?

Answer 15

Inherited disease of hypertension with mutation in aldosterone activated sodium channel (ENaC) causing it always to be on, increasing sodium reabsorption and therefore hypertension. With normal or low aldosterone levels

Question 16

What do baroreceptors do and where are they (what are they divided into)?

Answer 16

Measure blood pressure. Low pressure side of CV system (atria, right ventricle, pulmonary vasculature). High pressure - carotid sinus, aortic arch, JGA.

Question 17

What happens when low pressure side of baroreceptors detect low pressure and high pressure respectively?

Answer 17

Low pressure - less baroreceptor firing - signal brainstem to increase sympathetic acitivity & ADH release. High pressure - more baroreceptor atrial stretch - ANP, BNP released (vasodilative)

Question 18

What happens when high pressure side of baroreceptors detects low pressure?

Answer 18

Less baroreceptor firing, signal to brainstem to increase symp activity and ADH release, and JGA to release renin

Question 19

What is atrial natriuretic peptide ANP? Where is it made? When is it released? What does it cause?

Answer 19

Small peptide made in atria. Released in response to atrial stretch (high pressure). Causes vasodilation or renal & other vessels. Inhibits sodium reabsorption in PCT and CT. inhibits renin & aldosteone release. Reduced BP

Question 20

What does volume expansion cause?

Answer 20

Decreased symp activity, increase in ANP and BNP.

Question 21

What does volume contraction cause?

Answer 21

Increased symp activity, increase in AVP, renin, ANGII, aldosterone

Question 22

What happens to water reabsorption if increase osmolarity (sodium) in tubular fluid and why?

Answer 22

Water requires a gradient to be reabsorbed. High tubular sodium means there is no greadient (no hyperosmotic medullary interstitium) so less water can be reasborbed.

Question 23

How do ACE inhibitors work? What are the results?

Answer 23

Reduce angiotensin conversion to ANGII so causes vasodilation, which decreases blood pressure, increases sodium in distal part of nephron so less gradient for water reabsorption.reduced aldosterone so less sodium reabsorption. Results in vasodilation, lower blood pressure, decreased water reasborption

Question 24

How do carbonic anhydrase inhibitors work? Where? Results?

Answer 24

Block production of protons from carbon dioxide so less proton exhange with sodium, and therefore less sodium reabsorbed. Reduce sodium reabsorption at PCT, increasing sodium in distal nephron so less water reabsorbed.

Question 25

How do loop diuretics work? Where? Results?

Answer 25

Inhibit triple transporter (sodium/chloride/potassium transporter) in thick ascending limb, so more sodium reaches distal nephron and less water reabsorbed

Question 26

How do thiazide diuretics work? Where? Results?

Answer 26

Block sodium/chloride reabsorption transporter in DCT. Decreased water reabsorption and increased calcium reabsorption

Question 27

How do potassium sparing diuretics work?

Answer 27

Inhibitors of aldosterone function(block mineralocorticoid receptor) eg. spironolactone

Question 28

Where is potassium usually in the body?

Answer 28

Intracellular ion.

Question 29

What are the extracellular effects of potassium? High potassium effects? Low potassium effects?

Answer 29

Extracellular potassium affects excitable membranes on nerves and muscles. High potassium cases depolarisation of membanes causing AP & heart arrythmias. Low potassium causes heart arrythmias and asystole

Question 30

When we eat potassium and it gets absorbed what happens? How does this potassium become intracellular?

Answer 30

Potassium in most foods, absorbed, increases extracellular potassium. Stimulated to go into tissues by insulin, aldosteone/adrenaline. Insulin stimulates sodium/proton exchanger increasing sodium going into cells. To get sodium out sodium/potassium ATPase used, brining potassium into cells

Question 31

Under normal conditions where and how is potassium excreted and reabsorbed in the kidney? How much is excreted?

Answer 31

Normally kidney reabsorbs potassium in PCT, thick ascending loop triple transporters. In DCT and CCD secretion of potassium leading to 50-80% being excreted.

Question 32

If potassium depleted what does the kidney do?

Answer 32

If potassium depleted we can reabsorb potassium in DCT and CCD

Question 33

What stimulated potassium secretion?

Answer 33

Potassium secretion stimulated by increased plasma potassium, adlosterone, tubular flow rate and plasma pH

Question 34

Where does potassium secretion happen and how?

Answer 34

In principal cells. Increased plasma potassium so increased activity of sodium/potassium ATPase and potassium moves into cell (secreted)

Question 35

How does increase in flow affect potassium secretion and why?

Answer 35

Distal cells have primary cilia. Increase in flow means cilia stimulate PDK1 that increases calcium concentration in cell, stimulating opening of potassium channels allowing potassium to move out of cell (be secreted)

Question 36

What can cause hypokalameia?

Answer 36

Inaddequate intake, diuretics (increase tubular flow rate), v omiting, diarrhoea, genetics (gitelman’s syndrome mutation in sodium/chloride transporter in distal nephron)

Question 37

What can cause hyperkalaemia?

Answer 37

Potassium sparing diuretics, ACE inhibitors, elderly, severe disease, kidney disease

Question 38

what is gitelman’s syndrome ?

Answer 38

mutation in sodium/chloride transporter in distal nephron