PSL301: Kidney - K

• The kidney glomerulus filters approximately 150-170 liters a day (Starling Forces)

  
• The kidney glomerulus filters approximately 600 mmoles liters of sodium a day, K+ 100 mmoles/day

  
• The kidney reabsorbs most of the filtered load and then excretes About 100 mmoles/day K+

  
• Potassium

  (take heart and think about bananas …)
• General comments about potassium

  • General comments about potassium
  • Distribution
  • Nephron function and potassium
  • Regulation
• Typical North American diet 50-100 mmol/d, Early humans may have eaten 300 mmol/d, 100% absorbed from the gut, >90% excreted in urine, Small amount in stool
• Where does potassium come from

  • Dietary potassium = fruits, vegetables
  • Bananas, tomatoes, papayas, avocadoes, raisins, dried fruit, oranges, orange juice, milk
• Potassium Distribution

  56 mmoles of potassium in the ECF (<2%), 4200 mmoles of potassium in the ICF (>98%), 4.0 mmole/L in the ECF, 150 mmole/L in the ICF

  
• Potassium and the Resting membrane Potential

  Leak of potassium out of cells through potassium channels keeps cell interior negatively charged, [K]ecf/[K]icf: a major determinant of cell transmembrane potential gradient (Nernst equation), Resting membrane potential critical for muscle, nerve, cardiac function

  
• Insulin promotes cellular K uptake

  β2-catecholamine receptor activation by adrenaline promotes cell K uptake
• Low ECF Potassium Levels and the RMP

  ↓[K]ecf, ↓[K]ecf/[K]icf, RMP more negative, Cell hyperpolarized

  
• High ECF Potassium Levels and the RMP

  [K]ecf, [K]ecf/[K]icf, RMP more negative, Cell hypopolarized

  
• Clinical consequences

  • Hyperkalemia: Muscle stiffness and weakness, Abnormal ECG, Life-threatening cardiac arrhythmias
  • Hypokalemia: Muscle contraction difficult, Muscle weakness, Promotes cardiac arrhythmias
• A high potassium meal may contain 60 mmol of potassium (equal to ECF content), This could double ECF potassium concentration and cause cardiac arrest, Eating glucose stimulates insulin secretion, Insulin stimulates muscle cell uptake of potassium to prevent lethal hyperkalemia
• Exercise causes muscles to release potassium, Local increase in potassium concentration causes local arterioles to dilate, increasing muscle blood flow, The excess potassium in the ECF is redistributed into resting tissue by increased adrenaline
• Proximal Tubule

  Site of bulk reabsorption of sodium, chloride, water, potassium, bicarbonate (60%), Most important lumenal sodium transport protein is sodium-hydrogen exchanger (NHE3), Very leaky

  
• Thick Ascending Limb of Loop of Henle

  Lumenal transport protein: Na-K-2Cl (NKCC2): potassium reabsorption, Fluid leaving thick ascending limb has almost no potassium
• Almost all of the potassium that is filtered at the glomerulus is re-absorbed, All of the potassium in the urine is secreted in the collecting duct (CD)

  
• Collecting Duct

  Luminal sodium transport protein is epithelial sodium channel (ENaC), Has luminal potassium channels (ROMK and Maxi-K), Less permeable to chloride - lumen negative PD-facilitates potassium secretion, Aldosterone Receptors

  
• Factors regulating potassium secretion

  • Sodium Delivery
  • Tubule Flow rates
  • Lumen negativity
  • Aldosterone

  
• Aldosterone Action on Collecting Duct

  Increases number and open probability of sodium channels, Increases sodium reabsorption, Increases lumen negativity, Increases K secretion

  
• How is K Balance Achieved With Changes in Effective Circulating Volume? Low ECF volume stimulates renin, angiotensin II and aldosterone, Low volume state reduces GFR reduces flow to CCD, Increased aldosterone and reduced flow to CCD counteract each other: normal K excretion. Expanded ECF volume inhibits renin, angiotensin II and aldosterone secretion, Expanded ECF increases GFR, inhibits proximal reabsorption, increases flow to CCD, Low aldosterone and increased CCD flow counteract each other: normal K excretion

  
• Dietary K = urinary K excretion normally, Signal to kidney is change in serum [K], Increased serum [K] →increased excretion, Decreased serum [K] →decreased excretion, 90% of filtered K is reabsorbed in proximal tubule and loop of Henle, Cortical collecting duct regulates K excretion by adjusting K secretion, An important mediator is aldosterone

  
• A 45 year old man with end stage kidney disease undergoes dialysis three time per week, On the weekend he had the stomach flu and diarrhea. Monday morning he felt unwell so went back to bed and missed dialysis. Monday evening he was comatose, When seen in the emergency room: pH 6.92 (7.40), PCO2 40 (40), HCO3 8 (25)