Regulation of K+, Ca2+, PO43- and Mg2+

Question 1

Normal range of EC [K+]:

Answer 1

3.5-5.0 mEq/l
Hyperkalemia: > 5.0 mEq/l
Hypokalemia: < 3.5 mEq/l
EC [K+] affects resting membrane potential and excitability of muscle and nerve tissue
Results: changes in cardiac function, ECG changes

Question 2

Renal tubular handling of K+

Answer 2

Freely filtered into Bowman’s capsule; c 720 mEq/day at 4 mEq/l plasma K+

Question 3

K+ handling in different nephron segments:

Answer 3

67% reabsorbed in proximal tubule
20% reabsorbed in thick ascending limb of Henle’s loop (Na+,K+,2Cl- cotransport)
Physiological control exerted in collecting duct
Principal cells: either reabsorb or secrete K+, depending on body’s K+ balance

Question 4

K+ secretion by

Answer 4

principal cells in collecting duct

Question 5

Five factors affect K+ secretion in collecting duct

Answer 5

Extracellular K+ concentration
Na+ reabsorption: negative luminal voltage ‘attracts’ K+
Luminal fluid flow rate: dilution of secreted K+
Extracellular pH: K+ and H+ exchange across cell membranes
Aldosterone: Stimulates K+ secretion in collecting duct

Question 6

Situations that alter K+ handling

Answer 6

Most classes of diuretics increase Na+ and volume delivery to late distal tubule and collecting duct, which increases K+ secretion and may result in hypokalemia

Low-sodium diet: less Na+ delivery to late distal tubule, collecting duct  less K+ secretion, excretion  may cause hyperkalemia

Question 7

Primary hyperaldosteronism (Conn’s disease):

Answer 7

Aldosterone secreting tumor in adrenal cortex
K+ secretion by collecting duct is inappropriately stimulated
Consequence: hypokalemia

Question 8

Addison’s disease:

Answer 8

Destruction of adrenals: aldosterone isn’t secreted
Decreased K+ secretion in collecting duct
Consequence: hyperkalemia

Question 9

Diuretics

Answer 9

Drugs that increase urine excretion by inhibiting tubular solute and water reabsorption (increasing excretion)
Purpose: to help eliminate excess volume to treat volume overload disorders (e.g. edema, congestive heart failure)
Several different diuretic classes exist, which act in different nephron segments by different mechanisms

Question 10

Osmotic diuretics (e.g. mannitol)

Answer 10

inhibit reabsorption of water and, secondarily, Na+

Question 11

Carbonic anhydrase inhibitors (e.g. acetazolamide):

Answer 11

inhibit NaHCO3- reabsorption

Question 12

Diuretics acting in loop of Henle: ‘Loop diuretics’

Answer 12

Examples: furosemide (lasix), bumetanide (bumex) ethacrynic acid
Inhibits Na+,K+,2Cl- cotransporter by competing for Cl-
Increase total RBF and dissipates high solute concentration of medullary interstitium
Lessens water reabsorption in descending limb of Henle’s loop, medullary collecting duct
Powerful: require careful medical supervision

Question 13

Thiazide diuretics

Answer 13

distal convoluted tubule
Inhibit Na+,Cl- cotransport
Increase Na & Cl excretion as well as K+
Example: hydrochlorothiazide

Question 14

: ‘Potassium-sparing’ diuretics

Answer 14

Collecting duct
Inhibit Na+ reabsorption, K+ secretion
Often used in combination with other diuretic classes that increase K+ excretion
Examples: amiloride, triamterene (block Na+ channels); spironolactone (aldosterone antagonist)

Question 15

Importance of EC Ca2+

Answer 15

Affects activity of excitable tissues: nerve, muscle, myocardium
Ca2+ can dampen action potentials by blocking Na+ channels
Low EC Ca2+ can produce hypocalcemic tetany
Ca2+ is required for neuromuscular transmission
Myocardium: EC Ca2+ can affect contractile strength
Enzyme cofactor; component of bone; cellular signaling; blood clotting

Question 16

Some plasma Ca2+ is protein-bound

Answer 16

Total plasma [Ca2+] c. 4.5-5 mEq/l (c. 2.5 mM)

45% is bound to plasma proteins; free plasma [Ca2+] c. 1.2-1.5 mM. Only free Ca is biologically active

Question 17

Effect of plasma pH on free [Ca2+]

Answer 17

H+ compete with Ca2+ for binding sites on plasma proteins:

Acidemia: ^ [H+] = ^ plasma free [Ca2+]
Alkalemia: dec [H+] =dec plasma free [Ca2+]

Question 18

Mechanism of proximal tubular Ca2+ reabsorption

Answer 18

Note: The same transcellular mechanisms of Ca2+ reabsorption operate in the distal tubule (major site of PTH & Vitamin D regulation of Ca2+ excretion), but paracellular Ca2+ reabsorption does not occur there.

Question 19

Paracellular Ca2+ Reabsorption in Thick Ascending Limb of Henle’s loop

Answer 19

Paracellular reabsorption of Ca2+, via channels in the tight junctions is driven by the ~6 mV transepithelial potential. What effect will loop diuretics have on this process?

Question 20

Physiological control of tubular Ca2+ reabsorption

Answer 20

Control exerted in thick ascending limb of Henle’s loop, distal convoluted tubule
Reabsorption stimulated by parathyroid hormone (PTH), calcitriol (vit. D3), calcitonin
Decreased plasma [Ca2+] induces cells in parathyroid gland to secrete PTH
Overall effect of PTH: increase EC [Ca2+]

Question 21

PTH inhibits proximal tubular phosphate reabsorption

Answer 21

This effect of PTH increases the amount of phosphate excreted at any given plasma phosphate concentration.

Question 22

Renal handling of Mg2+

Answer 22

Mg2+ is carried in plasma in 3 forms:
60%: Free Mg2+
20%: Complexed with inorganic, small organic anions
20%: Bound to plasma proteins
About 2 g Mg2+ filtered into nephrons each day

Question 23

Mg2+ handling by nephron

Answer 23

The bulk of the filtered Mg2+ is reabsorbed in the thick ascending limb of Henle’s loop by paracellular movement

Question 24

Mechanism of Mg2+ reabsorption in thick ascending limb

Answer 24

Magnesium is reabsorbed via the paracellular route. The 6 mV transepithelial potential (lumen positive) is the driving force for Mg2+ reabsorption.

Question 25

Reasons for K+ shift out of cells IC to EC

Answer 25

Hypokalemia 
Acidemia 
Hyperosmolality 
ischemia/ cell damage
Alpha adrenergic agonist 
Heavy Exercise

Question 26

Reasons for IC shift of K+ = ec to ic

Answer 26

Hyperkalemia
Alkalemia
Beta adrenergic agonists
insulin