Metabolism of K+, Na+, and Water Flashcards
Potassium in Proximal Tubule
- Freely filtered
- Reabsorbed passively
- 65% in proximal convoluted tubule
Potassium in thick ascending limb
• 25% reabsorbed in thick ascending limb
Potassium in Collecting duct
• Secretion (10-20%) by principal cells
Increased secretion:
o High K+ increases aldosterone release
o High plasma K+ delivery
o Increased tubular flow → K+ is washed away → higher concentration gradient → increased K+ secretion
o Negative charge in lumen
o Increased ECF volume = increased flow but decreased aldosterone
o 10% lost in stool
Causes of hypokalemia
< 20 mmol/24 hours
• Less secretion
• Increases active reabsorption in GI tract
Increased stool losses
• Diarrhea
• Laxative use
Vomiting/Gastric drainage
• Little loss from gastric fluid
• But low plasma volume → increased aldosterone → increased K+ secretion
• Metabolic alkalosis = further K+ loss
Kidney losses of K+
• Increased distal sodium delievery
• Diuretics inhibit Na+ and Cl- reabsorption → increased Na+ delivery to distal nephron
• Result: enhanced tubular K+ secretion
• Low volume state and increased aldosterone → K+ secretion
Mineralocorticoid excess
Poorly reabsorbable anions/Alkaline pH
• HCO3- and poorly reabsorbable anions → generate negative electrical potential
o Ketoanions
o Sulfate
• K+ secretion to achieve electroneutrality
Bartter’s Syndrome
= mutation of transporter in ascending limb
o Effect of hypokalemia, symptoms like patients on loop diuretics (ex: Flurosemide)
Gittelman Syndrome
= mutation of transporter in distal convoluted tubule
o Effect of hypokalemia, symptoms like patients on Thiazide diuretics
Renal Tubular Acidosis Type II or Metabolic alkalosis
- HCO3- not reabsorbed (overwhelmed transport or dysfunction)
- Increased delivery of HCO3- to distal nephron
- Increased K+ secretion to maintain electroneutrality
- Result: Acidosis and hypokalemia
o Renal Tubular Acidosis (RTA) Type I
- Dysfunction causing decreased H+ secretion
- Increased K+ secretion to maintain electroneutrality
- Alkaline urine and hypokalemia
Is the balance of K+ appropriate or inappropriate?
• If not due to kidney problem:
o Conservation occurs over 5-14 days
o Fractional excretion of K+ < 20 mmol/day
• If due to kidney problem
o Fractional excretion of K+ >10%
o Urinary K+ >20 mmol/day
Causes of hyperkalemia
> 5.0 mmol/L
Transcellular shift • Tissue breakdown • Acidosis • Insulin deficiency • Use of beta-blockers
Increased intake
• Would need >150 mmol to overwhelm normal kidney
• IV replacement if rate too quick
Renal failure: AKI: o Low GFR o Decreased distal delivery o Low K+ secretion CKD: o Adapts by increased K+ secretion per nephron o Can’t adapt to acute change in dietary load, medications, stressors
Hypoaldosteronism • Decreased secretion • Primary adrenal insufficiency (Addison’s disease) • Aldosterone antagonists RAAS impairment = medications: o ACE inhibitors o Angiotensin receptor blockers o NSAIDs o K+-sparing diuretics (spironolactone, triamterene, amiloride) Hypo-reninemic hypoaldosteronism o Diabetic nephropathy
Explain the pathophysiologic effects of potassium deficiency on neuromuscular, cardiac, and kidney function.
o Hyperpolarization: increased threshold for AP → increased stimulus needed for AP
• <3.0 = fatigue, malaise, myalgia
• Severe = paralysis and rhabomyolysis
K+ is needed during exercise
• Maintain vasodilation and perfusion to avoid muscle ischemia
Heart: • Hyperpolarization of membrane • Raised threshold for AP • Delayed repolarization of ventricle • ST-depression • U wave • Results: premature ventricular beats, ventricular tachycardia or fibrillation
Metabolic effects:
• Low K+ inhibits insulin release → high glucose levels
Growth retardation/failure to thrive
• Children with Bartter’s Syndrome
Stimulates renin synthesis
• Increased Angiotensin II
• Decreased Aldosterone (low K+ suppresses aldosterone)
Explain the pathophysiologic effects of potassium excess on neuromuscular, cardiac, and kidney function.
o Heart: • Sustained subthreshold depolarization • Delayed depolarization • EKG changes • Tall peaked T wave from enhanced conductance of K+ channels and enhanced repolarization of ventricle • Arrhythmias • Death
Neuromuscular • Skeletal muscle weakness/paralysis Subthreshold depolarization • Activation of sodium channels • Loss of excitability
How to treat hypokalemeia
o Treat underlying cause o Eliminate dietary restriction o Mild (at or slightly below 3.5 mmol/L) = dietary supplementation o More significant = oral or IV replacement • IV at slow rate = 10-20 mmol/hour o If additional hypokalemic alkalosis = KCl a good option • Avoid further bicarb administration (KHCO3) o If hypokalemic metabolic acidosis = K citrate or K bicarb
How to treat hyperkalemia
Restore excitability of cardiac myocyte
• Calcium gluconate or calcium chloride
• Antagonized potassium effect
Shift the K+ into ICF
• Insulin with glucose (works in minutes)
• If acidosis → sodium bicarb
• Beta-2 agonists (takes 30-60 minutes)
Removal of K+
• Via stool = Sodium Polystyrene sulfonate (Kayexalate):
o Cation exchange resin
o Decrease uptake of K+ in gut
o Given with sorbitol to increase bowel movement
• Slower to remove via bowl
Via urine • Enhance urine output • Dialysis o Low K+ concentration in dialysate o High dialysate flow rate
Diagnosis of hyponatremia
What is the measured serum osmolality?
If high → look for an added effective osmole
• High serum osmolality and low serum sodium = water is being brought into ICF
• Ex: hyperglycemia, use of mannitol
If iso-osmolar (normal plasma osmolality but low plasma sodium)
• A substance other than water is taking up volume → plasma sodium appears low
• Ex: massive hyperlipidemia or multiple myeloma
• When measured with ion electrodes (measures against volume of water) = serum sodium is normal
Is the GFR very low? (Is kidney functioning?)
Is the kidney behaving appropriately for having low [Na+]
• What is the urine osmolality?
• Should be low (< 100 mosm/L)
If low = likely diagnoses include:
• Decreased excretion of solute (beer potomania)
• Primary polydipsia
• Reset osmostat
If high (>100 mosm/L) = kidney is behaving inappropriately
If kidney is behaving inappropriately, is there evidence of decreased effective circulating volume?
• Evidence of true volume depletion (diarrhea, vomiting, diuretics) or volume overload (CHF, cirrhosis, nephrotic syndrome)
• Use physical exam and weight to determine if ECV is low
• Other clues:
o Plasma uric acid levels
o Plasma K+
o Asking if patient is thirsty (due to increased angiotensin II)
o Urine lytes ([Na+] and [Cl-])
If there is ADH and no decreased effective circulating volume, are there any known triggers for ADH release present?
