K+ regulation Flashcards
Intracellular v. Extracelluar Na and K conc:
Intracellular: [K] = 110, [Na] = 10
Extracellular: [K] = 4, [Na] = 140
Na/K atpase controls the concentrations
K+ Channel
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
Where does K+ come from?
The diet- it’s found in almost all foods
When K+ is absorbed, what are the levels in the plasma and why does this pattern occur?
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
What three things affect K+ redistribution?
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
How does K+ get in the urine?
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
What is the role of the principal cells in K+ secretion?
- *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!
What is the driving force for K+ secretion?
- Concentration gradient
- Transepithelial membrane potential
What are the 2 main K+ channels that control K+ secretion?
ROMK
BK
How does aldosterone control K+ secretion?
It affects both the ROMK and BK channels- changes the activity of them
Present in the principal cells of collecting duct
BK channel: where is it?
On the flagella of principal cells (tickling them with a pipette opens them & changes the membrane potential of the cell)
Aldosterone sensitive
Mutations in the flagella can lead to what type of kidney dz?
Cystic kidney disorders
What factors affect K+ secretion/reabsorption?
Aldosterone
Urine flow rate
pH
How does aldosterone affect K+ secretion/reabsorption?
Increases K+ secretion
Hypoaldosteronism i.e. ACEI or ARB’s –> can develo hyperkalemia bc you don’t have as much K+ secretion
How does flow rate affect K+ secretion?
Increased flow rate –> increased secretion
What can affect flow rate?
Diuretics – can increase flow rate –> increased K+ secretion
Low flow rate: CHF, oliguric htn
What can cause hypokalemia?
- intake: only if severely reduced
- redistribution: alkalosis, insulin infusion, beta-agonists in asthma
- increased loss:
- non renal: diarrhea, sweat
- renal: increased flow rate, hyperaldosteronism, drugs - amphotericin B
What can cause hyperkalemia?
- intake: only in the presence of acidosis/renal failure
- redistribution: acidosis, diabetes, beta-blockers
-
decreased loss: mainly renal
- decreased urine flow rate, hypoaldosteronism- ACEI, ARB’s, drugs - ENaC blockers, interstitial renal dz
What are the clinical manifestations of hypokalemia?
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
Clinical manifestations of hyperkalemia
Membrane is more depolarized –> easier to open the Ca channels –> increased contractility of the heart
How do you treat hyperkalemia?
Acutely: insulin and glucose –> increased uptake of K+ into the cell
What is Barter’s syndrome?
Mutations in thick ascending loop of Henle: either in the
- NKCC channel (furosemide sensitive cotransport or Na K and 2Cl’s)
- ROMK channel
- 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
