Flashcards in Lecture 19: Renal Regulation Of Ion Concentrations Deck (23)
Describe extracellular potassium
* Normally precisely regulated at 4.2 mEq/L (±0.3 mEq/L).
* An increase of 3 to 4 mEq/L can lead to cardiac arrhythmias.
* Higher concentrations can lead to cardiac arrest or fibrillation.
* Extracellular fluid contains 2% of total body potassium.
- Note that intake of potassium from a single meal can be as high as 50 mEq.
* Kidneys must adjust potassium excretion rapidly and precisely in response to wide variations in intake.
- Mainly involves distal and collecting tubules.
Describe intracellular potassium
* What is the normal intracellular concentration of potassium ion?
- 140 mEQ/L
* Total amount of potassium in body compartments:
- Extracellular = 4.2 mEq/L x 14 L = 59 mEq
- Intracellular = 140 mEq/L x 28 L = 3920 mEq
- Refer to Figure 29-1.
Describe Major factors responsible for potassium excretion
* Direct influence on distal renal tubules and collecting ducts via increase in extracellular potassium ion concentration.
* Effect of aldosterone secretion on potassium excretion:
- Increase in extracellular potassium stimulates increase in aldosterone secretion.
What are the main sites of potassium reabsorption and secretion?
- Proximal tubule
- Ascending limb of Henle
- Late tubule
- Collecting duct
- See Slides 9-10
See slide 11 for Mechanisms of potassium secretion and sodium reabsorption and secretion by principal cells.
Note that potassium secretion by principal cells is stimulated by potassium concentration and aldosterone.
Describe the Effect of plasma aldosterone concentration and extracellular potassium ion concentration on rate of urinary potassium excretion.
See Slide 12
Describe the Effect of extracellular fluid potassium ion concentration on plasma aldosterone concentrations.
See Slide 13
Note that small changes in potassium concentration cause large changes in aldosterone secretion by adrenals.
Describe Mechanisms by which high potassium intake raises potassium excretion.
See Slide 14
- Direct influence on kidneys via high potassium concentration.
- Indirect via aldosterone secretion.
Describe the Effect of large changes in potassium intake on extracellular fluid potassium concentration under normal conditions.
See Slide 15
- Blockage of aldosterone system impairs regulation of potassium concentration.
Describe the Relationship between flow rate in cortical collecting tubules and potassium secretion and the effect of changes in potassium intake.
See Slide 16
- Conditions that cause an increase in tubular flow rate:
- Volume expansion
- High sodium intake
--Note: High K+ diet greatly enhances effect of increased tubular flow rate to increase K+ secretion
- Some diuretics
-- Note that high potassium intake greatly increases the potassium secretion rate even at low tubular flow rates.
Describe the Effect of high sodium intake on renal excretion of potassium
See slide 18
- Note that increased sodium intake decreases aldosterone secretion and, therefore, potassium excretion.
- However, Increased sodium intake also increases GFR and decreases proximal tubular reabsorption of sodium. This leads to an increase in distal tubular flow rate and increase in potassium excretion.
- Therefore, High sodium diet leads to little change in potassium excretion.
- Compare a high sodium/low potassium diet with a low sodium/high potassium diet. (See page 395)
Describe parathyroid hormone's (PTH) effect on maintaining a constant extracellular concentration of calcium
* About 50% of total plasma calcium is in the ionized form.
- Ionized has biological activity at cell membranes.
* Changes in plasma pH on calcium binding:
-- Less calcium is bound to the plasma proteins
-- More calcium is bound to the plasma proteins.
* A large amount of calcium excretion occurs in the feces; therefore, GI tract is important in calcium homeostasis.
* Almost all the calcium in the body is stored in the bone.
* PTH is one of the most important regulators of bone uptake and release of calcium.
* Parathyroid glands are directly stimulated by low calcium levels.
- Increase secretion of PTH.
Describe calcium reabsorption with regards to the effects of PTH and in the proximal tubule
* PTH effects (See Figure 29-11):
- Stimulates bone reabsorption
- Stimulates activation of vitamin D
-- Note that calcium is filtered and reabsorbed but not secreted.
- Indirectly increases tubular calcium reabsorption
* Reabsorption in proximal tubule:
- About 99% of filtered calcium is reabsorbed:
-- About 65% is reabsorbed in the proximal tubule mostly through paracellular route
-- About 20% is reabsorbed in the proximal tubule mostly through transcellular route:
--- Electrochemical gradient
--- Basolateral calcium-ATPase and sodium-calcium countertransporter
Describe calcium reabsorption in the loop of henle
* Restricted to thick ascending limb
- 50% through paracellular route
-- Passive diffusion and slight positive charge of tubular lumen
- 50% via transcellular route stimulated by PTH
Describe calcium reabsorption in the distal tubule, and factors that regulate tubular calcium reabsorption
* Reabsorption in distal tubule:
- Almost entirely via active transport:
- Calcium-ATPase pump in basolateral membrane
- Stimulated by PTH
* Factors that regulate tubular calcium reabsorption:
- ↑ levels PTH (Decreases calcium excretion)
- ↑ Plasma concentration of phosphate (Decreases calcium excretion)
- ↑ Metabolic alkalosis (Decreases calcium excretion)
- Refer to Table 30-2
- See Figures 30-11 and 30-12
- See slides 25-26
Describe phosphate excretion
* Controlled by overflow mechanism:
- Phosphate transport maximum for reabsorption = 0.1 mM/min
- [phosphate] < 0.1 → all filtered phosphate is reabsorbed
- [phosphate] > 0.1 → excess is secreted
- 75-80% reabsorbed in proximal tubule:
-- Transcellular pathway
- 10% reabsorbed in distal tubule
* Role of PTH in reabsorption:
- PTH promotes bone reabsorpon →
-- ↑ [phosphate] in extracellular fluid
- PTH → ↓transport maximum for phosphate by renal tubules →
-- Greater loss of phosphate in urine
Describe the maintenance of a Constant Extracellular Concentration of Potassium
* Extracellular fluid potassium concentration normally is maintained at 4.2 ± 0.3 mEq/L.
* Only 2% of the total body potassium is in the extracellular fluid.
* Kidneys must be able adjust potassium excretion rapidly.
Describe the role of insulin, aldosterone, and catecholamines on the regulation of extracellular potassium
- Stimulates potassium uptake by cells
- Increases potassium uptake by cells
-- Hypokalemia: Excess secretion of aldosterone (Conn’s syndrome)
-- Hyperkalemia: Deficiency in aldosterone secretion (Addison’s disease)
- Stimulates active reabsorption of Na+ by principal cells via Na+─K+─ATPase pump
- ↑ Permeability of luminal membrane for K+
- ↑ Extracellular K+ → aldosterone secretion
- β-adrenergic stimulation (epinephrine):
-- Stimulates potassium uptake by cells
- β-adrenergic receptor blockers → hyperkalemia
Describe other factors that regulate extracellular potassium
* Metabolic acidosis → ↑[extracellular K+]
- ↑[H+] → reducon in acvity of Na+─K+─ATPase pump → decrease in cellular uptake of K+
* Metabolic alkalosis → ↓[extracellular K+]
* Cell lysis (Hyperkalemia)
* Strenuous exercise (Hyperkalemia)
* Increased extracellular fluid osmolarity (Hyperkalemia)
What are 3 Processes that Determine Renal Potassium Excretion
* Rate of potassium filtration:
- Normal = 180 L/day X 4.2 mEq/L = 756 mEq/day
* Rate of potassium reabsorption:
- 65% in proximal tubule; 25-30% in loop of Henle
* Rate of potassium secretion
Describe principle cells
* Found in late distal tubule and cortical collecting tubules
- 90% of cells in these regions
* Secrete potassium:
- Na+─K+─ATPase pump in basolateral membrane
- Passive diffusion of K+ into tubular lumen
* Control of K+ secretion:
- Activity of Na+─K+─ATPase pump
- Electrochemical gradients
- Permeability of luminal membrane
* Factors that stimulate K+ secretion:
- ↑Extracellular fluid K+ concentration
-- Stimulates Na+─K+─ATPase pump
-- ↑ Potassium gradient from ECF to cellular fluid
-- Stimulates aldosterone secretion
- ↑ aldosterone
- ↑ tubular flow rate
Describe intercalated cells
* Reabsorb K+ during K+ depletion:
- Possibly through a H+─K+─ATPase pump
- Secrete H+ into tubular lumen