Renal and muscle regulation of potassium Flashcards
1
Q
Potassium homeostasis
A
- After being absorbed in GI, K is sequestered into muscle to prevent plasma [K] from going up too much
- Muscle will release k when levels are low
- There is a narrow range of [k] for ECF (3.5-5 mM)
- When there is hypokalemia the membranes hyper polarize (larger K gradient-> more leaves the cell)
- When there is hyperkalemia the membranes depolarize (less gradient -> more K is retained in cell)
2
Q
Mechanism of distribution
A
- Na/K ATPase allows for K accumulation in the cell
- K channels continuously leak K into ECF
- Insulin stimulate K uptake into cells (mostly muscle) by increasing the ATPase activity (this is preserved even in T2 diabetes)
- Catecholamines: during exercise there can be transient hyperkalemia as the K effluxes from muscle, so the muscles must reuptake the ECF K. Catecholamines increase ATPase activity to do this (muscles also eventually lose less K with exercise training)
- Tissue breakdown releases K into ECF which will need to be cleared by muscle or kidney
3
Q
Hyper vs hypokalemia
A
- During hypokalemia there is a shift in K from ICF to ECF, by decreasing the ATPase activity (same amount leaving, but less coming in) and by reducing K secretion in the distal nephron (reduced number of ROMK)
- Also during hypokalemia the colon reduces fecal K by absorbing more and the nephron reabsorbs more K by increasing H/K ATPase activity
- During hyperkalemia (tissue breakdown, injury), the kidneys secrete more and reabsorb less K
- Colon increases fecal K by absorbing less, and the muscle will increase the ATPase activity to sequester more
4
Q
Relationship btwn K and H+
A
- Since both are positive ions they will compete for negative charges within the cell and displace each other
- This means at high levels of one the other will be displaced and its levels will subsequently rise
- Acidosis and hyperkalemia are often seen simultaneously (but it depends on acute or chronic acidosis, as chronic can lead to hypokalemia), and alkalosis and hypokalemia are often simultaneous
5
Q
Renal handling of K 1
A
- In PT: there is reabsorption of 2/3rds of filtered K (mech not clear), but reabsorption of K is proportional to reabsorption of Na in PT (opposite is true in cortical collecting duct)
- LOH: 20% of filtered K is reabsorbed by NKCC
- CCD (and DT) is where K regulation occurs, as it can change K excretion via either reabsorbing K in CCD or secreting K in CCD (usually secretion unless hypokalemic)
6
Q
Renal handling of K 2
A
- On a normal K diet, 20% of the filtered load is excreted thus there is net secretion in CCD
- On a K rich diet up to 80% of filtered load is excreted, thus there is an increase in net secretion in CCD
- On a low K diet only 1% of filtered load is excreted, so there is net reabsorption in CCD
7
Q
Principal cells (in CCD) handling of K secretion 1
A
- Primary site of secretion, via ROMK channels
- The K secretion is driven by ENaC sodium reabsorption in multiple ways, and this is influenced by how much Na is reabsorbed before the CCD
- The K gradient favors secretion (high [K] inside cell, low [K] in lumen) and the apical membrane is more permeable to K than the basolateral membrane so most of it is secreted
- The electrical gradient will help facilitate more K secretion when Na reabsorption increases
8
Q
Principal cells (in CCD) handling of K secretion 2
A
- When Na amount in CCD lumen increases more is brought in by ENaC, this depolarizes the cell and increases the electrical gradient favoring K secretion to repolarize the cell
- Even when Na levels in lumen are not elevated, the overall electrochemical gradient favors K secretion
- During K depletion ROMK channels retract from the apical membrane to decrease K secretion (are not degraded and are ready to be re-inserted)
- During high K diet more ROMK channels are inserted to increase K secretion
9
Q
Intercalated cells in CCD handling of K secretion 1
A
- Primary site of K reabsorption in CCD
- Since the electrochemical gradient favors secretion there must be active reabsorption
- Apical H/K ATPase facilitates reabsorption of K for secretion of H
- There are flow sensitive channels that are activated to secrete K when Na levels are high in CCD lumen (less Na reabsorbed before CCD)
10
Q
Intercalated cells in CCD handling of K secretion 2
A
- During hypokalemia there is a decrease in apical K channels and an increase in H/K ATPase activity leading to increased reabsorption
- During hyperkalemia there is increased flow sensitive K channel abundance leading to more secretion
- Also during hyperkalemia there is tissue kallekrein secreted from connecting tubule cells to deactivate H/K ATPase
11
Q
Factors causing increased K secretion (principal cells) 1
A
-Increased K in ICF (can be from alkalosis) or decreased K in tubule fluid (TF) increased gradient for secretion
-Increased Na in TF increases ENaC activity and thus increases electrochemical (EC) gradient favoring K secretion
Increasing Na delivery to CCD by increasing flow does the same as above
12
Q
Factors causing increased K secretion (principal cells) 2
A
- Increased HCO3- (poorly reabsorbed anion) in TF means a larger EC gradient for K secretion (cell gets depolarized so wants to secrete K to repolarize)
- Decreased Cl- in the TF of CCD means there are more poorly reabsorbed anions in the TF and has the same affect as above
- All of these factors can lead to hypokalemia due to excess K excretion
13
Q
ENaC inhibitors on K
A
- Decreased Na reabsorption by ENaC decreases EC gradient driving K secretion
- Therefore ENaC inhibitors can cause hyperkalemia
- ENaC inhibitors = K sparing diuretics
14
Q
Factors affecting volume flow and K secretion 1
A
- Diuretics that act before collecting ducts (LOH and PT) will increase volume flow to CCD (increases Na delivery)
- This leads to more activity of ENaC and increased K/H+ secretion
- Therefore these diuretics can cause alkalosis and hypokalemia
- Genetic diseases: LOF mutations of NKCC (bartters syndrome) or LOF mutations in NCC of DT (gitelmans) both increase volume flow to CCD and cause hypokalemia and alkalosis by activating ROMK and H ATPase (from ENaC activity, same as above)
15
Q
Factors affecting volume flow and K secretion 2
A
- Aldosterone: increases Na/K ATPase and Na transport by ENaC thus leading to hypokalemia and alkalosis
- Contraction alkalosis: chronic decrease in ECFV stimulate chronicly high aldo levels causing hypokalemia and alkalosis
- K rich meal: high plasma K leads to dephosphorylation of NKCC and decreases Na reabsorption in LOH and increases ENaC activity
- This leads to increased secretion of K and there is also net secretion of Na
