Potassium, Pi, Ca, Mg balance

From Iusmphysiology

• started here on 03/29/11.

Contents 1 K, Pi, Ca, and Mg Balance 1.1 Objectives 1.2 The importance of Potassium 1.3 Movement of K between ICF and ECF 1.4 Renal potassium regulation 1.4.1 Kidneys filter, reabsorb, secrete, and excrete K 1.4.2 K reabsorption within the nephron 1.4.3 K secretion at the collecting duct 1.4.4 K reabsorption at the collecting duct 1.4.5 Factors that increase K excretion

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.

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.

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.).

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.
• 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 to H+ moving into the intercalated

• 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

4) increased excretion of poorly reabsorbed anions

5) increased Na+ excretion (increased tubule fluid flow rate)

• 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 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.