Regulation of K+, Ca2+, PO43- and Mg2+ Flashcards
Normal range of EC [K+]:
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
Renal tubular handling of K+
Freely filtered into Bowman’s capsule; c 720 mEq/day at 4 mEq/l plasma K+
K+ handling in different nephron segments:
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
K+ secretion by
principal cells in collecting duct
Five factors affect K+ secretion in collecting duct
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
Situations that alter K+ handling
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
Primary hyperaldosteronism (Conn’s disease):
Aldosterone secreting tumor in adrenal cortex
K+ secretion by collecting duct is inappropriately stimulated
Consequence: hypokalemia
Addison’s disease:
Destruction of adrenals: aldosterone isn’t secreted
Decreased K+ secretion in collecting duct
Consequence: hyperkalemia
Diuretics
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
Osmotic diuretics (e.g. mannitol)
inhibit reabsorption of water and, secondarily, Na+
Carbonic anhydrase inhibitors (e.g. acetazolamide):
inhibit NaHCO3- reabsorption
Diuretics acting in loop of Henle: ‘Loop diuretics’
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
Thiazide diuretics
distal convoluted tubule
Inhibit Na+,Cl- cotransport
Increase Na & Cl excretion as well as K+
Example: hydrochlorothiazide
: ‘Potassium-sparing’ diuretics
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)
Importance of EC Ca2+
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
Some plasma Ca2+ is protein-bound
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
Effect of plasma pH on free [Ca2+]
H+ compete with Ca2+ for binding sites on plasma proteins:
Acidemia: ^ [H+] = ^ plasma free [Ca2+]
Alkalemia: dec [H+] =dec plasma free [Ca2+]
Mechanism of proximal tubular Ca2+ reabsorption
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.
Paracellular Ca2+ Reabsorption in Thick Ascending Limb of Henle’s loop
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?
Physiological control of tubular Ca2+ reabsorption
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+]
PTH inhibits proximal tubular phosphate reabsorption
This effect of PTH increases the amount of phosphate excreted at any given plasma phosphate concentration.
Renal handling of Mg2+
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
Mg2+ handling by nephron
The bulk of the filtered Mg2+ is reabsorbed in the thick ascending limb of Henle’s loop by paracellular movement
Mechanism of Mg2+ reabsorption in thick ascending limb
Magnesium is reabsorbed via the paracellular route. The 6 mV transepithelial potential (lumen positive) is the driving force for Mg2+ reabsorption.
Reasons for K+ shift out of cells IC to EC
Hypokalemia Acidemia Hyperosmolality ischemia/ cell damage Alpha adrenergic agonist Heavy Exercise
Reasons for IC shift of K+ = ec to ic
Hyperkalemia
Alkalemia
Beta adrenergic agonists
insulin
