Potassium, Pi, Ca, Mg balance
From Iusmphysiology
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- started here on 03/29/11.
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K, Pi, Ca, and Mg Balance
Objectives
- Discuss the amount of potassium in the body and its distribution.
- Define hypokalemia and hyperkalemia.
- Indicate how the following factors affect the distribution of potassium between intracellular and extracellular fluids: Na+/K+-ATPase activity, plasma pH, insulin, epinephrine, plasma osmolality, tissue trauma, infection, and hemolysis.
- Identify the sites of K+ reabsorption and secretion along the nephron and collecting duct system.
- Draw a cell model for K+ secretion by a cortical collecting duct principal cell.
- Explain how the following affect potassium excretion: dietary potassium intake, mineralocorticoids (aldosterone), acid-base disturbances, excretion of poorly reabsorbed anions, and sodium excretion (tubule fluid flow rate).
- Explain how the kidneys keep maintain phosphate and calcium balance.
- Indicate the important sites of reabsorption of phosphate and calcium along the nephron.
- State the effects of parathyroid hormone (PTH) on tubular reabsorption of phosphate, tubular reabsorption of calcium, renal synthesis of 1,25-dihydroxy vitamin D3, and bone resorption.
- Identify the major site of magnesium reabsorption along the nephron.
Renal potassium regulation
- Note that potassium input is from diet and output is via feces and urine.
- Note that potassium movement within compartments is regulated: ECF, intercellular fluid, bone / connective tissue, trancellular fluid (CSF, etc.).
The importance of Potassium
- Potassium is important for several physiological reasons.
- Potassium affects the volume of cell as it is the primary osmolyte that gets moved across cellular membranes.
- Potassium affects excitability as it is the dominant ion in determining the transmembrane potential.
- Potassium affects pH (acid-base) balance.
- Potassium affects cell metabolism as it is involved in tissue growth and repair.
- In a healthy male, 89% of the body's K is intracellular, 8% is in bone / cartilage, 2% is in the ECF, and 1% is transcellular (CSF, etc.).
- A normal plasma K is 3.5-5 mEq / L; anything above or below is hyper- / hyper-kalemia.
- Note that hyperkalemia reaching 7 mEq / L is dangerous and 10-12 mEq / L of potassium is usually fatal via cardiac arrhythmia / arrest.
Movement of K between ICF and ECF
- There are many reasons K moves out of cells: low ECF pH, digitalis, O2 lack, hyperosmolality, hemolysis, infection, ischemia, and trauma.
What's the difference between O2 lack and ischemia?
- There are several reasons K moves in to cells: elevated ECF pH, insulin, epinephrine.
- Clinically, hyperkalemia can be treated with sodium-bicarbonate (IV) which will push K into cells by alkalinizing the ECF (that is, elevating the ECF pH).
- Hyperkalemia can also be treated with insulin + glucose (IV) as increased insulin drives K in to cells.
Kidneys filter, reabsorb, secrete, and excrete K
- Recall that we filter 180 L of plasma each day.
- Potassium (K) is normally maintained at 4 mEq / L.
- For comparison, recall that Na is maintained at 140 mEq / L.
- About 90 mEq of potassium are excreted each day (about 12.5% of the potassium filtered).
- Recall that only 0.9% of the Na filtered each day is excreted.
- Potassium (K) is normally maintained at 4 mEq / L.
- The kidneys excrete 90% of our daily intake of potassium.
K reabsorption within the nephron
- As with Na, most of the secretion / regulation of K occurs at the collecting duct.
- Just as only about 10-15% of the water of filtrate makes it to the collecting duct, only about 5% of the K of filtrate makes it to the collecting duct.
- 70% of filtered K is reabsorbed in the PCT (like Na).
- 25% of filtered K is reabsorbed in the LoH.
- Recall that the descending branch is permeable to water and solute in both directions.
- Recall that the ascending branch is impermeable to water and actively reabsorbs Na (actively pumps Na out of the filtrate).
- When plasma K levels are low, the collecting duct and continue reabsorption until only 1% of filtered K remains in the filtrate.
- When plasma K levels are high, the collecting duct can secrete K such that the filtrate contains 150% as much K as was filtered.
- Recall that normal physiological state results in 15% of the filtered load being excreted in the urine.
K secretion at the collecting duct
- The main site for regulated K secretion is the principal cells of the collecting duct.
- Recall that the principal cells of the collecting duct use ENaC and Na-K ATPase to regulate Na reabsorption.
- In a similar manner, principal cells use their basolateral Na-K ATPase to drive up the intracellular K concentration and their apical K channels to allow the K to flow into the filtrate via electrochemical gradient.
- So, just as the Na-K ATPase moves Na and K in opposite directions, the channels on the membrane allow them to flow opposite directions (out of and into the filtrate, respectively).
- So, principal cells respond to elevated K via their basolateral Na-K ATPase and apical K channel.
K reabsorption at the collecting duct
- The main site for regulated K reabsorption is the type A intercalated cells of the collecting duct.
- Recall that type A and type B intercalated cells of the collecting duct regulate blood pH by secreting H+ and reabsorbing HCO3- (type A cells) or secreting HCO3- and reabsorbin H+ (type B cells).
- Recall that intercalated cells (both types) generate H+ and HCO3- via the protein AE1.
- Recall, too, that intercalated cells secrete / reabsorb H+ by way of an apical H+ / K+ ATPase: that is, they burn ATP to exchange H+ / K+ at the apical membrane.
- Type A intercalated cells secrete H+ to balance an acidotic plasma and do so by reabsorbing K+ from the filtrate.
- Therefore type A intercalated cells are the primary location of K reabsorption in the nephron.
- type A intercalated cells respond to aldosterone-induced K loss:
- When mineralocorticoids are found in excess (think aldosteronism), Na is heavily reabsorbed at the collecting duct (think ENaC and Na-K ATPase) at the expense of K.
- Therefore type A intercalated cells attempt to compensate for the aldosterone-triggered K loss by secreting acid in exchange for K.
- This is the mechanism for renal alkalosis compensation.
- Recall that the body can compensate elevated pH (alkalosis) via the lungs (hypoventilation, breath off less CO2) or the kidneys (secrete H+ into the filtrate).
Factors that increase K excretion
- There are several factors that increase K excretion; some are pro-reabsorption effects and some are anti-reabsorption effects.
- Increased dietary K intake increases K excretion:
- As dietary K increases, plasma K will increase.
- As plasma K increases both the adrenal glomerulosa cells and the principal cells of the collecting duct respond.
- Glomerulosa cells of the adrenal glands increase production of mineralocorticoids in response to elevated plasma K.
- Increased amounts of mineralocorticoids leads to increased exchange of Na for K at the collecting duct and therefore increased K excretion.
**Principal cells of the collecting duct will How do principal cells respond to elevated plasma K levels?
- Increased mineralocorticoids increases K excretion:
- Recall that mineralocorticoids generally have a delay of hours before their response because they are steroids that bind intracellular receptors that act as gene expression regulators.
- As mineralocorticoids increase (think aldosterone), more Na is exchanged for K at the collecting duct (ENaC / Na-K ATPase).
- Exchange is increased because the number relevant surface proteins is increased (ENaC, Na-K ATPase, and K channels) and the production of ATP is increased.
- As more K is pumped into the principal cell more will flow into the filtrate by way of electrochemical gradient and K channels
- Increased blood pH increases K excretion:
- As the blood pH rises, the type A intercalated cells (think "aaaaah! too much aaaaacid!") respond by pumping H+ out of the blood into the filtrate in exchange for K+.
- As H+ is pumped into the filtrate (from the type A intercalated cell cytoplasm), K+ is brought into the cytoplasm and then moves into the blood via electrochemical gradient and K channels.
- Note that in acute acidosis the converse occurs: high levels of H+ in the ECF leads type B cells secreting H+ in exchange for K+ from the filtrate and thus K+ excretion is decreased.
- Increased concentration of poorly absorbed anions increases K excretion:
- Recall that an electrochemical gradient occurs over the apical membrane of the epithelial cells that line the nephron tract and that the gradient must be (at least somewhat) charge balanced.
- That is, the electrochemical gradient over the membrane cannot be super large.
- Therefore, if many negatively charged ions exist in the filtrate there must be some positively charged ions present also.
- As the concentration of anions increases, the movement of K out of principal cells increases (that is, K excretion increases).
- Recall that an electrochemical gradient occurs over the apical membrane of the epithelial cells that line the nephron tract and that the gradient must be (at least somewhat) charge balanced.
- Increased Na+ excretion increases K excretion:
- Recall that elevated Na excretion means there is increased flow of filtrate (water follows Na, so if the amount of Na is elevated so is the volume of Na).
- When filtrate volume increases, so does the flow rate (more volume through the same area).
- As the flow rate increases ...?
5) increased Na+ excretion (increased tubule fluid flow rate)
stopped on slide 17.
Potassium excretion deficiency
- Potassium excretion is deficient in Addison's disease and renal failure.
- Recall that aldosterone tells the collecting duct to express ENaC and Na-K ATPase.
- Recall that as Na is reabsorbed via ENaC, it is driven by the Na-K ATPase-generated Na gradient and therefore Na is retained at the expense of K lost to the filtrate.
- Recall that Addison's disease is a deficiency in aldosterone production.
- In renal failure, there is deficient response to aldosterone.
- Poor aldosterone production / response means poor expression of ENaC / Na-K ATPase and poor reabsorption of Na / loss of K.
- Chronic renal failure is defined as GFR < 20 ml / min.
- Note that deficiency in excretion can lead to hyperkalemia.
Potassium excretion excess
- Potassium excretion is elevated by hyperaldosteronism and (most) diuretics:
- When aldosterone is elevated (as in hyperaldosteronism), lots of ENaC is put on the apical membrane of principal cells of the collecting duct and lots of Na-K ATPase activity causes lots of K moved into the cell and thus loss of K into the filtrate via electrochemical pull.
- Similarly, most diuretics decrease Na reabsorption upstream of the collecting duct and thus there is more Na in the filtrate to be reabsorbed by ENaC / Na-K ATPase at the collecting duct and thus lots of K movement into the principal cells and subsequently lots of K loss to the filtrate due to electrochemical gradient.
- Note that excessive potassium excretion will lead to hypokalemia.
