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?
Clinical manifestations of low Na+
[Na+] < 125 Meq/L
Brain swells Mild: • Headache • Nausea Severe: • Disorientation • Confusion • Obtundation • Seizures • Focal neuro. Deficits Death: cerebral herniation
Causes of Hypernatremia
(when [Na+] > 145 meq/L
• Almost never develops if someone has adequate access to water and has an intact thirst mechanism
o Need abnormal water loss AND cause of abnormal water intake
• Always associated with hyperosmolarity
• Major cause = Diabetes insipidus
Central DI:
• Neurosurgergy
• Trauma to brain
• Various infections affecting posterior pituitary
Nephrogenic DI (ADH ineffective) • Lithium • Hypokalemia • Hypercalcemia • Interstitial diseases of kidney
Treatment of Volume contraction (loss of Na+ and Cl-):
Give back Na+ and Cl-
o Usually as isotonic fluids (stays within ECF)
o Ex: Lactated Ringers or 0.9% normal saline
• Other solutions (1/2 NS, ¼ NS) exist
• Important: if volume depleted = first threat to life is loss of volume
o Always try to give isotonic fluids if possible
Treatment of Volume overload (overload of Na+ and Cl-)
• Remove Na+ and Cl-
Treatment of Edema • Edema = increase in total body sodium content Removal of extra sodium requires: o Decreased intake o Increased output (via diuretics)
Explain what controls the secretion of antidiuretic hormone.
• Factors that increase ADH secretion:
o Increases in ECF osmolality > 280 mOsm/kg (sensed by hypothalamic osmoreceptors)
o Decreases in actual effective intravascular fluid volume (sensed by carotid sinus)
• Factors that decrease ADH secretion:
o Increases in atrial natriuretic peptide levels
o Alcohol intake
Explain how the kidneys make dilute or concentrated urine.
Proximal tubule
o 65% of filtered water is reabsorbed
Na+ reabsorption:
• Early proximal tubule: via Na+/HCO3- reabsorption coupled with Na+-glucose-amino acid reabsorption
• Later part of proximal tubule: Na+ reabsorbed with Cl-
o All reabsorption = iso-osmotic
Ascending limb
o Impermeable to water; permeable to salt
o Separates solute (NaCl) from water
o Uses countercurrent mechanism to create hypertonic medulla
o Involved in dilution of urine directly and concentration indirectly
Distal tubule
o Impermeable to water; permeable to salt
o Urine osmolality decreases to 100 mosm/L
o If inhibit this segment → problems with diluting capacity without affecting concentration (medullary interstium)
Collecting duct
o 0-10% water load is excreted
o Regulates minute-to-minute control of water excretion
• Usually most important in pathogenesis of hyponatremia
Dependent on ADH:
• ADH increases permeability to water and urea
• Activates Vasopressin 2 Receptor → PKA → cAMP → insertion of water channels (Aquaporin type II)
• Increases urine osmolality
o Final osmolality is dependent on urea and sodium
o Urine osmolality can vary between 50 to 1200 mosm/L
Describe the clinical conditions that are associated with excess or decreased antidiuretic hormone secretion.
Stimuli for release:
Osmolality: 1% change → ADH release
• Max ADH action happens with only a 15 mosm/L rise in osmolality
Decreased effective circulating volume
• Most potent stimulus
• Water reabsorption “normalizes” perceived hypovolemia
• Comes at expense of osmolality and serum sodium concentration
Seen in people with low effective circulating volume:
• Diarrhea
• Vomiting
• Heart failure
• Cirrhosis
Non-physiologic stimuli Neurological conditions & Pulmonary diseases • Clinically called SIADH Others: • Nausea • Pain • Various drugs
Synergistic activity of diuretics
-loops and thiazides
= useful in severe edema, ascites, or HF
o Thiazides and loops (NOT K-sparers) = ideal synergists with ACE-I’s and ARB’s
o Thiazides “equalize” racial differences in responsiveness to other drugs (ACE-I)
o Diuretics blunt long-term counter-regulatory mechanism evoked by body to respond to low arterial BP
o Na+ depletion reduces vascular responsiveness to vasoconstrictors
Drug interactions with diuretics
• Lithium (to treat manic depressive psychosis; other psychiatric disorders)
o Thiazides decrease renal lithium excretion → raise lithium levels
o Need to decrease lithium dose by about 1/3 and monitor carefully
• NSAIDs (aspirin, ibuprofen, indomethacin)
o Decrease antihypertensive effectiveness of diuretics
• Digitalis
o Increased tendency to cause cardiac arrhythmias due to hypokalemia from thiazides and loops
• Antibiotics
o Loops exaggerate toxic effects on ear or kidneys of some drugs (gentamycin, tobramycin, amphotericin)
o Amphotericin B can increase K+ loss by diuretics
• Diabetes treatment
o Antagonized by glucose elevating effects of thiazides and loops
