regulation of potassium and hydrogen ion

potassium

• most abundant intracellular ion (98%)

• concentration in extracellular fluid is important for function of excitable tissues (nerve and muscle)

  • resting membrane potential is directly related to relative K⁺ concentrations

hyperkalemia

high concentration of potassium in the extracellular fluid (> 5 mEq/L)

hypokalemia

low concentration of potassium in the extracellular fluid (< 3.5 mEq/L)

effects of hyper- and hypokalemia

• abnormal rhythms of the heart

• abnormalities of skeletal muscle contraction

effect of hyperkalemia on electrocardiogram (pre cardiac arrest)

• [K⁺] = 4.0 → normal

• [K⁺] = 6.0 → tall T

• [K⁺] = 8.0 = wide QRS

• [K⁺] > 8.0 → sinusoidal → ventricular tachycardia

potassium balance

• input: dietary intake

• output: 90% excreted into urine, 10% excreted into feces/sweat

renal regulation of potassium

• freely filtered at glomerulus

• tubules normally reabsorb most filtered so very little appears in urine

  • net reabsorption 15-99% (normally ~86%)

• can be secreted at cortical collecting cells

  • coupled with Na⁺ reabsorption through diffusion channels

• changes in excretion are mainly due to changes in secretion in the cortical collecting duct

regulation of potassium secretion

• dietary intake

• aldosterone

regulation of K⁺ secretion by dietary intake and aldosterone

1. increased potassium intake

2. increased plasma potassium

   • increased potassium secretion in cortical collecting ducts

3. increased aldosterone secretion from adrenal cortex

4. increased plasma aldosterone

5. increased potassium secretion in cortical collecting ducts

6. increased potassium excretion

regulation of K⁺ secretion by RAA pathway

1. decreased plasma volume

2. increased plasma angiotensin II

3. increased aldosterone secretion from the adrenal cortex

4. increased plasma aldosterone

5. increased sodium reabsorption and potassium secretion in cortical collecting ducts

6. decreased sodium excretion and increased potassium excretion

hyperaldosteronism

• conditions in which aldosterone is released in excess

• most common cause is adenoma of the adrenal gland that produces aldosterone autonomously

• causes increased fluid volume, hypertension, and hypokalemia (severe → muscle weakness)

• renin is suppressed

• metabolic alkalosis is often seen

hydrogen ion regulation

• metabolic reactions are highly sensitive to hydrogen ion concentration of the environment

• concentration of extracellular fluid is tightly regulated

• pH = ~7.4 ([H⁺] = ~40nmol/L)

bicarbonate mass reaction

• CO₂ + H₂O ⇌ H₂CO₃ ⇌ HCO₃^- + H⁺

• first reaction catalyzes by carbonic anhydrase

• bicarbonate ion lost from body = hydrogen ion gained

sources of hydrogen ion gain

• generation of hydrogen ions from CO₂

• production of nonvolatile acids from the metabolism of protein and other organic molecules

• loss of bicarbonate in diarrhea or other nongastric GI fluids

• loss of bicarbonate in urine (only happens in pathological condition)

sources of hydrogen ion loss

• utilization of hydrogen ions in the metabolism of various organic anions

• loss in vomitus

• loss in urine

• hyperventilation (loss of CO₂)

nonvolatile acids

• non-CO₂ acids

• phosphoric, sulfuric, lactic acid

• average net production: 40-80 mmol of H⁺ per day

buffer of hydrogen ion

• any substance that can reversibly bind hydrogen ions

  • H⁺ + buffer^- ⇌ Hbuffer

• temporary measure to maintain [H⁺] = 40 nmol while excess H⁺ is excreted

• major extracellular buffer: CO₂/HCO₃^- system

• major intracellular buffers: phosphates and proteins

ultimate balance of hydrogen ion

• controlled by respiratory system (controlling CO₂) and kidneys (controlling HCO₃^-)

• both systems work together to minimize change of hydrogen ion concentration (pH)

hydrogen ion control via control of HCO₃^-

• low H⁺ concentration → kidneys excrete HCO₃^-

• high H⁺ concentration → kidneys produce new HCO₃^- and add to plasma

• Henderson-Hasselbalch equation shows pH is dependent on log([HCO₃^-] / [CO₂])

renal handling of HCO₃^-

• HCO₃^- excretion = HCO₃^- filtered (+ HCO₃^- secreted) - HCO₃^- reabsorbed

• normally, kidneys reabsorb all filtered HCO₃^- (except in alkalosis)

• H⁺ from original HCO₃^- molecule broken down in tubular epithelial cells secreted by H⁺ pump, H⁺/K⁺-ATPase, or Na⁺/H⁺ antiporter

• 80% reabsorbed in proximal tubule

addition of new HCO₃^- to plasma

• H⁺ secretion and excretion on nonbicarbonate buffers such as phosphate (always functional, limited capacity)

• glutamine metabolism with NH₄⁺ excretion (only in severe acidosis, large capacity)

• together, normally contribute enough new HCO₃^- to the plasma to compensate for hydrogen ions from nonvolatile acids generated in body (40-80 mmol/day)

addition of new HCO₃^- to plasma via nonbicarbonate buffer

• happens only after all the HCO₃^- has been reabsorbed and is no longer available in lumen

• H⁺ is secreted into tubule, where it binds nonbicarbonate buffer (HPO₄^2-)

• HCO₃^- enters interstitial fluid

• buffer bound to H⁺ is excreted

addition of new HCO₃^- to plasma via glutamine metabolism (H⁺ excretion bound to NH₃)

• mainly in proximal tubule

• glutamine is brought into tubular epithelial cells from either ISF or tubule (filtered)

  • if brought in from tubular lumen, pumped with Na⁺

• glutamine metabolized, resulting in NH₄⁺ and HCO₃^-

• HCO₃^- enters ISF

• NH₄⁺ pumped into tubular lumen (Na⁺ antiporter) and excreted