Potassium, Pi, Ca, Mg balance

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Revision as of 19:34, 17 April 2011

• started here on 03/29/11.

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.
• 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).

• 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.

Renal regulation of Pi

The importance of Pi

Kidneys filter, reabsorb, secrete, and excrete Pi

Renal regulation of Ca

The importance of Ca

Kidneys filter, reabsorb, secrete, and excrete Ca