Lecture 15: Potassium balance and Renal K+ transport

Question 1

What is the physiologic role of potassium?

Answer 1

1. Maintenance of cell volume
2. Regulation of intracellular pH
3. Function of enzymes
4. DNA and protein synthesis
5. Resting cell membrane potential
6. Neuromuscular excitability
7. Cardiac conduction
8. Vascular tone

Question 2

What are the normal values of K in ECF and ICF?

Answer 2

3500-4500 meQ in ICF

3.5-5 mEq in plasma but 50-60 total K in a normal 70 kg adult

Question 3

How much K do we usually intake? Excrete?

Answer 3

Intake = 60-100 mEq/day
Excretion = 50-90 in urine and 10 in stool

Question 4

What are the two types of potassium balances to consider?

Answer 4

1. Internal potassium balance = the distribution of potassium between ECF and ICF
2. External potassium balance = balance between potassium intake and excretion

Question 5

What is PlasmaK a function of?

Answer 5

A function of intern AND external K balance

Hyperkalemia: K>5 mmol/L
Hypokalemia: K<3.5 mmol/L

Question 6

How does the body handle an acute K load?

Answer 6

1. First translocates K+ into cells (takes up 75%+ of K load)
2. over time, there is an increase in cumulative renal excretion of K+ above baseline

Question 7

How does K excreted compare to K filtered?

Answer 7

K excreted > K filtered because K can be secreted in the nephron

Question 8

What happens to body when K intake is limited (opposite of acute K load)?

Answer 8

Body retains more renal K but this process takes SLOWLY
-days to a week
Thus, body can become K deficient over the time it takes to adjust

Question 9

What is the relationship between change in total body K and plasma K concentration?

Answer 9

It is much easier for body to handle potassium deficit than an acute potassium load
If you look at the units, you can see that the TBK (most of which is intracellular) does a tremendous job at keeping plasma K (y-axis) from dropping too much
Point of graph: in order to drop 2 mEq of plasma K, you need to contend with -900 mEq of intracellular TBK that will be released from the cells to compensate/keep the plasma volume from dropping further
-thus it is hard to decreased K plasma or get hypokalemic
On the other hand, it is easy to get HYPERkalemic, as you see that an increase of +4 plasma K happens rather quickly, slopewise in the right side of the graph (validates question right above)

Question 10

What happens to cell if one intakes 50 mEq of K?

Answer 10

Would increase plasma K by potentially lethal 7.5 mEq/L if homeostatic mechanism of internal K balance was not in place

Question 11

What are the determinants of K distribution?

Answer 11

1. the Na/K ATPase is major regulator of internal K balance

Question 12

What are the factors affecting internal K balance?

Answer 12

1. Plasma AK concentration
2. Hormones
   i. insulin
   ii. catecholamines
   iii. aldosterone
   Less important
3. Exercise (muscle breakdown = K release)
4. Plasma tonicity
5. Acid-base balance
6. Cell lysis

Question 13

How does plasma K concentration affect internal K balance?

Answer 13

High plasma K = increase Na/K ATPase activity to enhance cellular K uptake
-this reduces K gradient for efflux

Question 14

What does increased plasma K concentration upregulate?

Answer 14

Upregulates the secretion of
i. insulin
ii. epinephrine
iii. aldosterone
Insulin binds to insulin receptor to upregulate GLUT4 as well as Na/K ATPase…the glucose and K intake are independent from one another
Epinephrine binds to its Beta-2 receptor, upregulating cAMP and ultimate the Na/K ATPase
Aldosterone binds to intracellular MR and increases Na/K activity and leads to greater

Question 15

Why is insulin the first line agent in emergency treatment of life-threatening hyperkalemia?

Answer 15

Because insulin leads to greater potassium uptake into the cells

Question 16

How is a patient with diabetes at risk for hyperkalemia?

Answer 16

If cells are not sensitive to insulin, then they can’t take up the K when there is hyperkalemia
-thus patients with diabetes can be said to have impaired potassium tolerance

Question 17

What effects can beta2-agonist drugs have on the treatment of hyperkalemia?

Answer 17

Beta-2 agonists used to treat asthma can stimulate the Na/K ATPase and increase K cellular uptake to counteract hyperkalemia

Question 18

How does ECF hypertonicity affect internal K balance?

Answer 18

Increases K movement from ICF to ECF in two ways

1. Water diffuses out into ECF due to osmolarity gradient and pulls K along due to solvent drag
2. less water inside the cell = greater K concentration = more K efflux if K channel is open

Question 19

How does plasma K and blood glucose respond in a diabetic?

Answer 19

Plasma K increases with glucose load and doesn’t drop
Glucose in plasma also increases without dropping
Whereas normally, plasma K would drop because insulin increases K+ uptake into the cells

Question 20

What are the effects of acidosis on plasma K?

Answer 20

Increases plasma K
This is because a decrease in intracellular pH will inhibit K uptake
H+ inside the cell will inhibit Na/K ATPase and NKCC2 transporters

Question 21

What are the cellular exchanges taking place for alkalemia and acidemia?

Answer 21

1. Alkalemia = H+ is going out of the cell while K+ is going into the cell = decrease in plasma K
2. Acidemia = H+ is going into the cell while K+ is going out of the cell (or net K+ is staying outside the cell) = increase in plasma K
   Thus H and K move reciprocally to one another

Question 22

What factors affect total body K content?

Answer 22

1. K intake
2. GI K excretion
3. Urinary K excretion (so kidney is primary control point)

Question 23

Where is K reabsorbed in the kidney?

Answer 23

80% in proximal tubule
10% in thick ascending loop of Henle
Regardless of how much K is excreted, these percentages stay pretty much constant

Question 24

What is the control point of K excretion/reabsorption?

Answer 24

Step 4, the collecting tube (since steps 1 and 2 are pretty much constant)

Question 25

Where is K secreted the most in the nephron?

Answer 25

In the initial collecting tubule (ICT)

20-180% can be secreted

Question 26

How is potassium processed in the proximal tubule?

Answer 26

Most of the K+ reabsorption is through paracellular diffusion and solvent drag
There is a potassium channel on apical membrane but there is minimal secretion to lumen
Reabsorption is proportionate to fluid reabsorption
There is also a small positive transepithelial difference the farther you are down the lumen due to water reabsorption early in the tubule

Question 27

How is K handled in descending LoH? Ascending LoH?

Answer 27

Descending = secrete K into the tubular lumen from the interstitium, driven by high K permeability and high medullary K concentration
Ascending = K moves OPPOSITE to the way it moves in descending = K moves from lumen into medulla, thereby allow K to accumulate K in medullary interstitium

Question 28

How is K handled in the TAL?

Answer 28

Active K reabsorption
Apical NKCC2 co transporter (secondary active)
Passive K reabsorption
-due to positive lumen charge so electrogenic gradient, K can travel paracellularly
Some K gets secreted back out to lumen through ROMK2 transporter

Question 29

What portions of the nephron secrete K?

Answer 29

According to slide 24, the DCT, specifically the proximal part of collecting duct
According to slide 26, specifically the principal cells of the cortical and outer medullary tubules are responsible for K secretions

Question 30

What happens to K excretion during a state of K deprivation?

Answer 30

Suppression of distal nephron K secretion
Enhanced K reabsorption
Only 1-3% gets filtered in urine

Question 31

How does the delivered load of K change to the distal nephron change in K normal, K loading, K deprivation?

Answer 31

In all three states, the K delivered to distal nephron is the SAME

Question 32

What are the two types of cells in collecting duct and what are their roles in K handling?

Answer 32

Principal cells = 70% of collecting duct = K secretion

Alpha intercalated cells = 30% of distal nephron = K reabsorption

Question 33

What mediates K reabsorption in alpha intercalated cells?

Answer 33

1. HK ATPase

2. basolateral K channel for K efflux from cell

Question 34

What mediates K secretion in principal cells?

Answer 34

Apical K channels

K/Cl cotransporter in apical membrane

Question 35

What determines the difference in transepithelial voltage in collecting ducts (as shown above)?

Answer 35

A function of Na reabsorption through amiloride-sensitive Na channels (the ENaC in DCT)

Question 36

What is amiloride?

Answer 36

Potassium-sparing diuretic
Blocks ENaC in the distal collecting tubule
Leads to loss of Na without depleting K

Question 37

What are factors affecting distal nephron K secretion?

Answer 37

1. K intake and plasma K concentration
2. Aldosterone
3. Distal tubule Na delivery and flow
4. Anions in tubular fluid

Question 38

What does aldosterone do to renal K excretion?

Answer 38

Promotes more excretion as the plasma K increases
More aldosterone = more K excretion at a given plasma level
Stimulates the ENaC, the ROMK and the Na/K ATPase at the level of the principal cells of the collecting duct

Question 39

What happens to the basolateral membrane area of principal cells with administration of aldosterone?

Answer 39

Hyperplasia of basolateral membrane area

Question 40

How does flow rate affect renal K excretion?

Answer 40

Directly proportional
Higher the flow rate, the higher the K secretion rate and urinary excretion rate
Significance: so if you have a high salt diet, you increase flow rate, which would increase K excretion
-that’s why one treatment for hypokalemia is restricting salt intake to decrease flow rate

Question 41

What is the mechanism through which flow rates affects K secretion?

Answer 41

Faster flow = faster the K+ is washed away in the lumen = replaced with K free fluid from more proximal nephron segments = more of a favorable gradient for longer
If flow rate is slow, K+ does not get removed quickly so there is less of gradient for a shorter period of time

Question 42

What happens to potassium secretion when there is volume expansion or contraction?

Answer 42

Volume expansion will have offsetting effects on K secretion
i. more volume expansion = less aldosterone = less K secretion
BUT
ii. more volume expansion = more distal flow = more K secretion
So the two cancel out
In volume contraction, greater aldosterone levels and less distal flow will cancel out and lead to normal K secretion

Question 43

Why do patients with hyperaldosteronism get hypokalemia with administration of diuretics?

Answer 43

Because you are taking away one of the factors that maintain normal K secretion
Aldosterone upregulates ROMK channel activity (as well as the rest of the channels in principal cells)
Diuretics = greater distal flow = greater K secretion
Thus greater distal flow + aldosterone = two conditions that both upregulate K secretion

Question 44

How does tubular fluid composition affect distal tubular K secretion?

Answer 44

If Na is paired with a permeable anion (like Cl-) then K will secrete at normal rates
If Na is paired with an more impermeable anion (like SO42-), then K will secrete more because the lumen will be more negative
-lumen is more negative because the negative charge is not being taken up from the lumen as fast

Question 45

What does giving a poorly reabsorble anion that is part of a diuretic?

Answer 45

The poorly reabsorbable anion will (like sulfate) will make the lumen more negative, thereby promoting more K+ secretion
Thus more negative lumen = more K secretion

Question 46

What is the primary site of external K balance regulation?

Answer 46

The primary site of regulation of external balance is the principal cell, modulated by aldosterone, K, delivery of Na, Cl, anions and tubular fluid