K+ in the Kidney

K+ in the Kidney

1. in a normal diet we consume far to much potassium

   • body has to deal with this in some way = excretion

2. the nephron

   • low potassium - absorption of K+ into bones
   • normal or high potassium - more secretion of potassium

3. conc. ICF = 150mM and ECF = 4mM

   • maintained in a very close range - above 5mM = hyperkalemia and below 3.5mM = hypokalemia
     • body tries to maintain a net balance of 0

4. why is the conc of K+ important?

   • High ICF conc.
     • maintain cell volume - pump action
     • regulation of pH
     • control of enzyme function
     • control DNA and protein synthesis
     • control of growth and cell proliferation
   • Low ECF conc.
     • maintain steep K+ gradient across membrane
     • maintain potential of cells
     • Low levels of K+ prevents problems with excitation and contraction
       • Action potential firing
       • Muscle contraction
       • Cardiac rhythmicity

5. Physiological role of K+

   • cell volume maintenance
     • Low K+ = cell shrinkage
     • High K+ = cell swelling
   • intracellular pH regulation
     • low K+ = cell acidosis
     • high K+ = cell alkalosis
   • enzyme function
   • DNA/ protein synthesis
     • lack of K+ results in reduction of protein synthesis = stunted growth

6. roles of transmembrane K+ ratio

   • resting membrane potential
     • reduced K+ inside to outside - depolarization
     • increased K+ inside to outside - hyperpolarization
   • neuromuscular activity
     • low plasma K+ - muscle weakness, paralysis, vasodilation and respiratory failure
     • high plasma K+ - conduction disturbances, arrhythmia and fibrillation
   • cardiac activity
     • low K+ - slow conduction of pacemaker cells, arrhythmia
     • High K+ - conduction disturbances, arrhythmia and fibrillation
   • Vascular resistance
     • Low K+ - vaso-constriction
     • high K+ - vaso-dilation

7. K+ and the heart

   • high conc. = heart fibrillation and death
   • low conc. = low T wave, high U wave

8. overall K+ homeostasis - daily intake = excreted, net = 0

   • most K+ excreted via urine
     • when intake is greater than excreted amount we have a + balance
     • when intake is less than excreted we have a - balance
   • how does body respond to changes in K+
     • extracellular renal function - increase K+ uptake into cells
     • increase pump function and secrete more K+
     • intracellular renal function - regulation of reabsorption and secretion of K+ along nephron - occurs after several hours
     • extra renal affects of EPO,insulin, aldosterone
       • more sodium out, more potassium in
       • EPO released from chromatin cells form the adrenal medulla increases Na+ K+ ATPase activity
       • insulin released from beta cells
       • aldosterone released from zone glomerulosa cells from adrenal cortex

9. intra-renal effects - GFR x K+ plasma = daily filtered load

   • depends on diet - increase in K+ in diet, increase in K+ filtered load
   • low diet of K+ reabsorption
     • proximal tubule
       • paracellular pathway
       • apical K+ channels
       • NKCC2
         • sets up voltage across membrane
       • 67% reabsorbed
         • minimal secretion to lumen
     • thick ascending limb
       • NKCC2
       • 20% reabsorbed
       • paracellular pathway
     • distal tubule
     • collecting duct
       • reabsorption: intercalated cells (30%)
         • K+/H+ exchanger
         • pH important
       • Na+ reabsorption and K+ section principle cells (70%)
         • aldosterone is important
         • ENaC
         • K+ Cl- co transporter
     • low K+ = low flow rate, low/no secretion
   • normal or increased K+
     • secretion
       • distal tubule
       • collecting duct
       • excreted in urine
       • secretion- high plasma K+, action of aldosterone
         • when we have high K+ we see different things occurring in all areas of the body - lungs, liver, adrenal glands, heart and kidney
         • if we increase plasma K+ we stimulate the adrenal cortex to release aldosterone
           • Aldosterone
             • Late distal tubule and collecting duct
             • ROMK1 is important
             • ENaC activity - cell more positive and lumen more negative
             • increase in Na+ K+ ATPase activity on BL membrane
               • entry of Na+ makes cell potential more positive = driving force for K+ exit across apical membrane (secretion)
                 • increase pump function and therefore increase K+
             • Increase Na+ K+ Activity
               • change in electrochemical gradient - aldosterone is secreted
                 • K+ permeability increases and K+ is secreted
         • Activation of Na+ K+ ATPase - increases intracellular K+
           • increases K+ secreted across apical membrane - collecting duct and late distal tubule
     • reabsorption
       • proximal tubule
       • thick ascending limb
     • secretion is high compared to single flow rate

10. Summary

    • K+ homeostasis is crucial for survival - ICF = 150mM and ECF = 4mM
    • Hormones effect tubular flow rate in K+ secretion
    • various segments of nephron involved in reabsorption and secretion
    • K+ can be transported into tissues