Sodium and Potassium Balance

Question 1

Define osmolarity and give its units

Answer 1

Measure of the solute concentration in a solution (osmoles/liter)

Question 2

What does osmolarity depend on?

Answer 2

The number of dissolved particles

Question 3

As the number of dissolved particles increases what happens to osmolarity?

Answer 3

It also increases

Question 4

What is normal plasma osmolarity?

Answer 4

285-295 mosmol/L

Question 5

What is the most prevalent solute in the ECF?

Answer 5

Sodium

Question 6

What is the osmolarity of sodium in the ECF?

Answer 6

140 mmol/L

Question 7

When sodium levels are normal what happens to desire to intake sodium?

Answer 7

Its supressed

Question 8

What structure suppresses or stimulates sodium intake?

Answer 8

Lateral parabrachial nucleus

Question 9

What receptors are involved in suppressing sodium intake?

Answer 9

Serotonin and glutamate

Question 10

What receptors are involved in stimulating sodium intake?

Answer 10

GABA and opioids

Question 11

What are the 2 mechanisms involved in sodium intake? Briefly describe them

Answer 11

Central mechanism- involves lateral parabrachial nucleus

Peripheral mechanism- involves taste

Question 12

How does the peripheral mechanism for sodium intake work?

Answer 12

When we have low levels of salt in our body foods with salt will taste more appetising

Question 13

Where does most sodium reabsorption occur?

Answer 13

PCT (67%)

Question 14

What happens to GFR and renal blood flow as MAP increases

Answer 14

GFR and renal blood flow will increase proportionally to MAP until a certain point but then they will plateau

Question 15

As the BP and amount of sodium entering the nephron increases, what happens in the DCT to reduce perfusion pressure and GFR?

Answer 15

High sodium levels are detected by specialised macula densa cells in the juxtoglomerular apparatus
There is increased sodium/chloride uptake via triple transporter
Adenosine is released from macula densa cells
Detected by extraglomerular mesangial cells
Adenosine also reduces renin production
Promotes afferent SMC contraction
Reduces perfusion pressure and so GFR

Question 16

In the DCT what specialised cells detect high sodium levels?

Answer 16

Macula densa cells in the juxtoglomerular apparatus

Question 17

Where is adenosine released from in the DCT?

Answer 17

From macula densa cells

Question 18

What affect does increased sympathetic activity have on the nephron

Answer 18

Increased contraction of the afferent arteriole
Stimulates sodium uptake by PCT cells
Stimulates cells of the juxtaglomerular apparatus to produce renin, renin leads to angiotensin II production, this stimulates cells of the PCT to take up sodium
Stimulates adrenal glands to produce aldosterone, aldosterone stimulates sodium uptake in the distal DCT and collecting duct

Question 19

What hormone does renin increase production of?

Answer 19

Angiotensin II

Question 20

What effect does angiotensin II have on the PCT?

Answer 20

Stimulates cells to take up sodium

Question 21

What hormone stimulates production of aldosterone?

Answer 21

Angiotensin II

Question 22

How does anti naturietic peptide affect sodium levels?

Answer 22

Reduces sodium movement into the nephron and reduces reabsorption in the PCT, DCT and CD

Question 23

How is sympathetic activity affected when blood pressure falls?

Answer 23

As blood pressure falls, fluid vol falls, which increases beta 1 sympathetic activity

Question 24

How does sympathetic activity affect renin production?

Answer 24

Increases it

Question 25

How does blood pressure falling affect ANP?

Answer 25

Increases ANP

Question 26

How is sympathetic activity affected when blood pressure rises?

Answer 26

As blood pressure rises, fluid vol rises, which decreases beta 1 sympathetic activity

Question 27

What type of hormone is aldosterone?

Answer 27

Steroid

Question 28

Where is aldosterone synthesised and released?

Answer 28

From the adrenal cortex (zona glomerulosa)

Question 29

What is aldosterone released in response to?

Answer 29

Angiotensin ll | Decrease in blood pressure (via baroreceptors)

Question 30

How does angiotensin II specifically increase aldosterone synthesis?

Answer 30

Promotes synthesis of aldosterone synthase which carries out the final 2 steps in aldosterone synthesis

Question 31

What does aldosterone stimulate?

Answer 31

Sodium reabsorption | Potassium secretion

Question 32

What does aldosterone excess lead to?

Answer 32

Hypokalaemic alkalosis

Question 33

How does aldosterone work?

Answer 33

Binds to mineralocorticoid receptor Aldosterone then binds to HSP90, which causes HSP90 to be removed The mineralocorticoid receptor now dimerises so it can translocate into the nucleus It binds to DNA and stimulates production of mRNAs for genes under its control

Question 34

What genes does aldosterone help upregulate?

Answer 34

The gene for the sodium channel in the collecting duct | The sodium potassium ATPase

Question 35

What occurs physiologically in hypoaldosteronism?

Answer 35

Reabsorption of sodium in the distal nephron is reduced Increased urinary loss of sodium ECF volume falls Increased renin, Ang II and ADH

Question 36

What are some symptoms of hypoaldosteronism?

Answer 36

Dizziness, low BP, salt craving, palpitation

Question 37

What occurs physiologically in hyperaldosteronism?

Answer 37

Reabsorption of sodium in the distal nephron is increased Reduced urinary loss of sodium ECF volume increases (hypertension) Reduced renin, ang II and ADH

Question 38

What are some symptoms of hyperaldosteronism?

Answer 38

High blood pressure, muscle weakness, polyuria, thirst

Question 39

What is Liddle's syndrome?

Answer 39

Looks like hyperaldosteronism | An inherited disease of high blood pressure.

Question 40

What occurs physiologically in Liddle's syndrome?

Answer 40

Mutation in the aldosterone activated sodium channel. Channel is always ‘on’ Results in sodium retention, leading to hypertension

Question 41

Where are baroreceptors that detect low BP located?

Answer 41

Atria Right ventricle Pulmonary vasculature

Question 42

Where are baroreceptors that detect high BP located?

Answer 42

Carotid sinus Aortic arch Juxtaglomerular apparatus

Question 43

What is the response of the low pressure side baroreceptors to high pressure?

Answer 43

Atrial strech | ANP and BNP are released

Question 44

What is the response of the low pressure side baroreceptors to low pressure?

Answer 44

Reduced firing Signals sent via afferent fibres to brainstem Sympathetic activity increased and ADH released

Question 45

What is the response of the high pressure side baroreceptors to low pressure?

Answer 45

Reduced firing Signals sent via afferent fibres to brainstem Sympathetic activity increased and ADH released Reduced firing also detected by JGA cells so renin is released

Question 46

How do ANP and BNP affect water loss?

Answer 46

They increase it

Question 47

Where is ANP made?

Answer 47

Atria

Question 48

What stimulates ANP release?

Answer 48

Atrial strech

Question 49

What are the actions ANP?

Answer 49

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

Question 50

What is the mechanism of action of ACE inhibitors?

Answer 50

Block the angiotensin converting enzyme which inhibits the conversion of angiotensin I to angiotensin II

Question 51

Do ACE inhibitors cause vasodilation or vasocnstriction?

Answer 51

Vasodilation

Question 52

What effect do ACE inhibitors have in the kidney?

Answer 52

Reduced Na+ reuptake in the PCT | Increased Na+ in the distal nephron

Question 53

What effect do ACE inhibitors have in the adrenals?

Answer 53

Reduced aldosterone (this results in reduced Na+ uptake in the CCT and increased Na+ in the distal nephron)

Question 54

Where in the nephron do osmotic diuretics work?

Answer 54

PCT and descending limb of LOH

Question 55

Where in the nephron do carbonic anhydrase inhibitors work?

Answer 55

PCT

Question 56

Where in the nephron do loop diuretics work?

Answer 56

Thick ascending limb of the LOH

Question 57

Where in the nephron do thiazides work?

Answer 57

DCT

Question 58

Where in the nephron do K+ sparing diuretics work?

Answer 58

Collecting duct

Question 59

Where in the nephron do aquaretics work?

Answer 59

Distal collecting duct

Question 60

How does carbonic anhydrase activity affect Na+ levels?

Answer 60

Leads to more Na+ reabsorption

Question 61

How does carbonic anhydrase activity affect urine pH?

Answer 61

Make it more acidic

Question 62

How do carbonic anhydrase inhibitors lead to less Na+ reabsoption?

Answer 62

Blocking carbonic anhydrase means less h2co3 is produced Less dissociation into H+ and Hco3- Less H+ produced, less co transport of H+ out of the cell and less Na+ in

Question 63

How do loop diuretics lead to reduced water reabsorption?

Answer 63

They are triple transporter Inhibitors Reduced Na+ reuptake in the LOH Increased Na+ in the distal nephron

Question 64

How do thiazide diuretics lead to reduced water reabsorption?

Answer 64

They block sodium chloride uptake transporter Reduced Na+ reuptake in the DCT Increased Na+ in the distal nephron

Question 65

What other marked effect do thiazide diuretics have?

Answer 65

They increase calcium reabsorption

Question 66

How do potassium sparing diuretics lead to reduced water reabsorption?

Answer 66

They are inhibitors of aldosterone function (e.g. spironolactone) They bind to the mineralocorticoid receptor and block its function This will reduce sodium reuptake in the distal nephron

Question 67

What is the main intracellular ion?

Answer 67

K+

Question 68

What does extracellular K+ affect?

Answer 68

Excitable membranes of nerve and muscle

Question 69

What does high K+ cause?

Answer 69

Membrane depolarisation, can lead to heart arrhythmias

Question 70

What does low K+ cause?

Answer 70

Heart arrhythmias (asystole)

Question 71

What are potassium levels in the ECF?

Answer 71

Low

Question 72

Why does the body usually have to reduce potassium levels?

Answer 72

There is potassium in almost all food so levels are usually high

Question 73

How are potassium levels reduced?

Answer 73

Potassium is taken into tissues, this is promoted by insulin (and a bit by aldosterone and adrenaline)

Question 74

What hormone promotes uptake of K+ into tissues?

Answer 74

Insulin mainly, aldosterone and adrenaline a bit

Question 75

What is the mechanism of potassium uptake into tissues?

Answer 75

Insulin stimulates the sodium proton exchanger This leads to more sodium in the tissue cells Sodium conc is reduced via sodium potassium ATPase bringing more potassium into the cell

Question 76

Where is potassium reabsorbed in the nephron?

Answer 76

Mainly the DCT and a bit in the TAL of the LOH

Question 77

What happens to potassium in the DCT and CD when levels are normal and when they are depleted?

Answer 77

When levels are normal it is secreted into the tubular fluid | When levels are low it is reabsorbed

Question 78

How much potassium is usually excreted in the urine?

Answer 78

15-80% of what entered the filtrate

Question 79

What stimulates potassium secretion in the DCT and CD?

Answer 79

Increased plasma [K+] Increased aldosterone Increased tubular flow rate Increased plasma pH

Question 80

How is potassium secreted in principal cells?

Answer 80

Via Na+/K+ ATPase

Question 81

How does tubular flow affect K+ secretion?

Answer 81

As tubular flow increases, cilia are more stimulated Cilia stimulate PDK1 PDK1 increases calcium conc in the cell via uptake This opens potassium channels and allows more secretion

Question 82

How common is hypokalaemia?

Answer 82

One of the most common electrolyte imbalances (seen in up to 20% of hospitalised patients)

Question 83

What are some causes of hypokalaemia?

Answer 83

Inadequate dietary intake (too much processed food) Diuretics (due to increase tubular flow rates) Surreptitious vomiting Diarrhoea Genetics (Gitelman’s syndrome)

Question 84

What is Gitelman's syndrome?

Answer 84

Mutation in the Na/Cl transporter in the distal nephron

Question 85

How common is hyperkalaemia?

Answer 85

Common electrolyte imbalance present in 1-10% of hospitalised patients

Question 86

What response can commonly cause hyperkalaemia?

Answer 86

K+ sparing diuretics

Question 87

What can cause hyperkalaemia?

Answer 87

ACE inhibitors

Question 88

Who is hyperkalaemia often seen in?

Answer 88

Elderly Severe diabetics Those with kidney disease