K+ regulation

Question 1

Intracellular v. Extracelluar Na and K conc:

Answer 1

Intracellular: [K] = 110, [Na] = 10

Extracellular: [K] = 4, [Na] = 140

Na/K atpase controls the concentrations

Question 2

K+ Channel

Answer 2

All cells have one or more K+ channel

Each has 4 subunits, there are 70 genes= tons of possibilities

Membrane potential is largely determined by K

Question 3

Where does K+ come from?

Answer 3

The diet- it’s found in almost all foods

Question 4

When K+ is absorbed, what are the levels in the plasma and why does this pattern occur?

Answer 4

You eat, absorb K+, plasma K+ goes up, then plasma K+ comes back to normal

It goes up as it’s absorbed

It goes back down because of

(1) redistribution– goes into the cells
(2) urinary excretion – mainly the kidney, also colon, and sweat

Question 5

What three things affect K+ redistribution?

Answer 5

pH

• acidosis: less rapid uptake into the cell
• alkalosis: more rapid uptake into the cell

insulin:

• diabetes: less rapid uptake of + into the cells
• insulin: stimulates uptake of K+ into the cells

Beta blockers

• beta blockers: less rapid uptake into the cells
• beta agonist: more K+ uptake into the cell

Question 6

How does K+ get in the urine?

Answer 6

K+ is freely filtered in the glomerulus

Then most of it is reabsorbed in the proximal tubule and TALH

What appears in the urine is actively secreted by the distal tubule and collecting duct

Question 7

What is the role of the principal cells in K+ secretion?

Answer 7

• *Principal cells** of collecting duct are aldosterone responsive –> affects Na absorption
• more aldosterone –> more Na reabsorption

Na is asorbed by Epithelial Na Channel (ENaC) –> transports Na into the cell then it’s pumped out by the Na/K ATPase into the blood
- when it does this, the lumen of the tubule becomes negative with respect to the blood (makes sense bc Na+ is flowing from lumen to blood)

K+ channels on the luminal membrane allow K+ to be secreted

Coupling between Na reabsorption and K+ secretion: more Na+ that’s absorbed –> more K+ secretion

H, K ATPase: can absorb K+ when you have extreme diet/ very low K+ but this does not normally play a role at all!

Question 8

What is the driving force for K+ secretion?

Answer 8

1. Concentration gradient
2. Transepithelial membrane potential

Question 9

What are the 2 main K+ channels that control K+ secretion?

Answer 9

ROMK

BK

Question 10

How does aldosterone control K+ secretion?

Answer 10

It affects both the ROMK and BK channels- changes the activity of them

Present in the principal cells of collecting duct

Question 11

BK channel: where is it?

Answer 11

On the flagella of principal cells (tickling them with a pipette opens them & changes the membrane potential of the cell)

Aldosterone sensitive

Question 12

Mutations in the flagella can lead to what type of kidney dz?

Answer 12

Cystic kidney disorders

Question 13

What factors affect K+ secretion/reabsorption?

Answer 13

Aldosterone

Urine flow rate

pH

Question 14

How does aldosterone affect K+ secretion/reabsorption?

Answer 14

Increases K+ secretion

Hypoaldosteronism i.e. ACEI or ARB’s –> can develo hyperkalemia bc you don’t have as much K+ secretion

Question 15

How does flow rate affect K+ secretion?

Answer 15

Increased flow rate –> increased secretion

Question 16

What can affect flow rate?

Answer 16

Diuretics – can increase flow rate –> increased K+ secretion

Low flow rate: CHF, oliguric htn

Question 17

What can cause hypokalemia?

Answer 17

1. intake: only if severely reduced
2. redistribution: alkalosis, insulin infusion, beta-agonists in asthma
3. increased loss:
   - non renal: diarrhea, sweat
   - renal: increased flow rate, hyperaldosteronism, drugs - amphotericin B

Question 18

What can cause hyperkalemia?

Answer 18

1. intake: only in the presence of acidosis/renal failure
2. redistribution: acidosis, diabetes, beta-blockers
3. decreased loss: mainly renal
   - decreased urine flow rate, hypoaldosteronism- ACEI, ARB’s, drugs - ENaC blockers, interstitial renal dz

Question 19

What are the clinical manifestations of hypokalemia?

Answer 19

Muscle weakness, can eventually lead to paralysis

Cardiac arrhythmias: t wave becomes flatter, heart blocks

All of this is due to severe hyperpolarization so repolarization is very difficult

Question 20

Clinical manifestations of hyperkalemia

Answer 20

Membrane is more depolarized –> easier to open the Ca channels –> increased contractility of the heart

Question 21

How do you treat hyperkalemia?

Answer 21

Acutely: insulin and glucose –> increased uptake of K+ into the cell

Question 22

What is Barter’s syndrome?

Answer 22

Mutations in thick ascending loop of Henle: either in the

1. NKCC channel (furosemide sensitive cotransport or Na K and 2Cl’s)
2. ROMK channel
3. CLC-Kb: chloride channel

Leads to:

• chronic volume depletion: bc you’re not reabsorbing bc the transporters dont work!
• high renin & high aldo
• hypokalemia (or if it’s a ROMK mutation, hyperkalemia)
• metabolic alkalosis