Renal regulation of K, Ca, Mg Flashcards
K concentrations
-cells are very sensitive to changes in K concentrations
-increases in levels (hyperkalemia) can cause cardiac arrest, decreases (hypokalemia) can also be critical
Normal plasma K levels
4.2 mEq/L
-if increased more than 3-4 mEq/L can cause cardiac arrest
Extracellular vs. intracellular K levels
Extracellular: 2%
Intracellular: 98%
Steps to K adjustments
1.Transport K between extra and intracellular K stores (fast response)
2. Adjusting the changes in plasma K concentrations is by renal excretion (slow response)
Insulin release
-causes shift of K into the cell
Aldosterone impact on K
-shifts K into the cells
Beta-adrenergic stimulation
-shifts K into the cells
-Epi increases K uptake
Alkalosis
shifts K into the cells
Acidosis
-shifts K out of cells
-due to reduction of Na/K pump function
Cell lysis
-shift K out of cells
-occurs due to severe muscle injury
Strenuous exercise
-shift K out of the cells
-due to skeletal muscles will release K
Increased extracellular fluid osmolarity
-shift K out of cells
-due to cells becoming dehydrated and intracellular K goes up and cells will send K out
What effects K+ excretion?
1.filtration rate- decreased GFR will lead to hyperkalemia
2. Tubular reabsorption (mainly proximal tubules)
3. K secretion in late distal and collecting tubules (important for day-to-day adjustments)
>principle cells important for secretion. If intake of K is high, K secretion increases even more than the filtered amount
K Excretion
-Secretion by principle cells which make up the majority of epithelial cells in late distal and collecting tubules
Steps of K excretion
- Uptake from interstitium into the cells by Na/K pump
- Diffusion of K into the lumen (membrane is permeable to K by using K channels)
Factors of K excretion
-Na/K pump
-concentration gradient
-permeability of luminal membrane
Factors affecting K secretion
1.Increased extracellular K
2.Increased aldosterone
3.increased tubular flow rate
4.acidosis (increased extracellular H+)
Increased extracellular K
-important factor and works very quickly when plasma concentration of K is increased
-3 mechanisms:
1.stimulates Na/K pump, moves K into epithelial cells and diffusion into tubules
2.Reduces leakage of intracellular K to the interstitium
3.stimulates aldosterone secretion and K secretion
Increased aldosterone
-aldosterone enhances the function of Na/K
-increases permeability of apical cell membrane of K
-extracellular concentrations of K and aldosterone have a positive feedback loop
Increased tubular flow rate
-occurs when volume expansion, high Na intake, treatment with diuretics
-when high tubular flow rate, secreted K is quickly flushed and net K secretion is stimulated
-important when Na intake is high. High Na causes less aldosterone release and less K secretion, but since the tubular flow rate is increased, more K secretion is stimulated which helps to excrete excess K
Acidosis
-short term: reduces K secretion because Na/K pump is inhibited
-chronic: increases K secretion because Na, Cl, water reabsorption is reduced and tubular flow increases and leads to more K secretion
Extracellular K and aldosterone feedback loop
1.Increased extracellular K signals more aldosterone release
2.More aldosterone increases K excretion
3.More K excretion reduces extracellular K and that reduces aldosterone
Calcium normal concentration `
2.4mEq/L
Hypocalcemia vs. hypercalcemia
-Hypo= reduced nerve and muscle excitability
-Hyper= suppresses neuromuscular excitability and may cause cardiac arrhythmia
3 forms of calcium in plasma
1.calcium ions (50% active form)
2.Protein-bound (40%)
3.Non-ionized form (10%)
Calcium storage
-99% stored in bone, 1% inside cells, 0.1% in extracellular fluid
Dietary calcium excreted
-90% excreted in feces
Acidosis impact on calcium
Acidosis reduces the binding of calcium to plasma proteins
Parathyroid hormone regulation of calcium
1.Stimulates bone reabsorption
2.Activates vitamin D and interstitial reabsorption of calcium
3.Directly increases renal calcium reabsorption
Calcium excretion, filtration and reabsorption distributions
-calcium is not secreted by kidneys so:
Excretion rate=filtration -reabsorption
Filtration: all ionized calcium
Reabsorption: 99% (65% proximal, 25-30% in loop of Henle, 4-9% in distal and collecting tubules)
**kidneys regulate plasma calcium concentrations by adjusting reabsorption
Calcium reabsorption in proximal tubules
80% paracellular (dissolved in water)
20% transcellular reabsorption
**independent of parathyroid hormone
Mechanism of transcellular calcium reabsorption
-transcellular within the proximal tubules
1.diffusion at apical membrane due to electrochemical gradient (calcium channels)
2. Calcium pumps at the basolateral membrane
3. Calcium-sodium counter transport at basolateral membrane (3Na in, 1Ca out)
Calcium reabsorption in loop of Henle
-only in thick ascending limb
-50% paracellular (diffusion due to the more positive charge in the lumen)
-50% transcellular (regulated by PTH)
Calcium reabsorption in distal tubules
-mainly active transport
-mechanisms similar to those in proximal tubules
-affected by PTH and vitamin D (both stimulate calcium reabsorption)
How does calcium excretion change when there is increased volume or arterial pressure?
With increased volume or arterial pressure:
-sodium and water reabsorption is reduced and since calcium reabsorption in proximal tubules is dependent on water reabsorption, calcium reabsorption will be reduced too
What is the effect of phosphate on calcium reabsorption?
Phosphate increases PTH and therefore, increases
calcium reabsorption
Magnesium storage
-50% in bones
-49% in cells
-1% in extracellular fluid
-more than half the Mg in plasma is bound to proteins
Mg excretion
-Mg intake is usually high, and kidneys need to excrete about half of absorbed Mg
>10-15% of filtered Mg is excreted
How is Mg regulated?
-regulation mainly by adjusting the reabsorption
Distribution of Mg reabsorption
Loop of Henle: 65%
Proximal Tubules: 25%
What increases Mg excretion?
-increased extracellular Mg
-increase extracellular Ca
-increases extracellular volume
Phosphate excretion
-follows an overflow pattern. The phosphate transport max is 0.1 mM/min so there is usually a higher intake so there is continued urine phosphate excretion
Phosphate reabsorption distribution
Proximal tubules: 75-80%
Distal tubules: 10%
How much phosphate is excreted?
10%
Reabsorption of Phosphate in proximal tubules
-transcellular transfer by co-transport of Na
Phosphate change of transport maximum
-a low phosphate intake leads to increased transport maximum over time
Regulation of phosphate
regulated by PTH
>PTH decreases the transport maximum of phosphate and therefore increases its excretion
