01-07 Potassium Flashcards
hormonal regulation of [K+]
—w/in mins: insulin, epi; w/in hrs: aldo
—cause muscle, liver, bone and RBCs to uptake excess K+ in serum via upreg of Na+/K+-ATPase, Na+/K+/2Cl- and Na+/Cl-
—∆s in serum [K+] ∆ the rate of secretion of these hormones
INSULIN: most import; pts w/ DM have ↑er [K+] rise s/p eating than non-DM pts; used in tx of hyperkalemia
EPI: ↑ uptake via β2; α → release
—β-blocker can be slow absorption of K+ into cell s/p meal
ALDO: slower but acts to both ↑ cell uptake and urinary excretion
—Addisonian crisis (low aldo) → hyperkalemia
Acid-Base and K+
—In METABOLIC (i.e. usu. not resp) acidosis → hyperkalemia b/c cells uptake H+ and secrete K+ to maintain electroneutrality
Effect of Plasma osmolality on [K+]
hyper-omolarity (e.g. ↑ [glucose]) → hyperkalemia
—hypertonic plasma shrinks cells ↑ intracell [K+] creating gradient for more K+ to leave cell
—also solvent drag (H2O pulls K+ w/ it)
—double-whammy for diabetics b/c of decr levels of/sensitivity to insulin which also leads to hyperkalemia
10mOsm ↑ → 0.4-0.8 ↑ [K+]
Effect of cell lysis on [K+]
—trauma, burns, tumor lysis syndrome and rhabdo all ↑ [K+]
—ulcers → bleed → RBCs lyse → reabsorb K+ in GI tract
Effect of exercise on [K+]
exercise releases K+ from muscles
—can be up to 2.0mEq/L w/ vigorous exercise
—only problematic in: β-blockers, renal failure, d/o affecting release of epi, aldo or insulin (Addison’s, DM, etc.)
filtering of K+
freely filtered b/c no protein bound
—can also be secreted
PT handling
—67% reabsorbed here (constant fraction of filtered load)
LoH handling
—20% reabsorbed here (constant fraction of filtered load)
DCT and CT/CD handling
—where?
—by what mech?
—resorbs AND secretes
—regulated by aldo, serum [K+] and, to a lesser extent ADH
—∆s in tubular flow rate and acid-base imbalances can ∆ K+ handling but in non-homeostatic ways
SECRETION: The Principal Cell
—first basolateral Na+/K+ ATPase moves K+ into princ. cell
—second, K+ diffuses out through channels into tubular fluid
REABSORPTION: The Intercalated Cell
—H+/K+-ATPase (Exchanger)
[IMAGE]
Mechanism of [K+] regulation of [K+]
∆s: —speed of Na+/K+-ATPase —electrochecmical gradient —aldosterone secretion —flow rate
Mechanism of Aldo regulation of [K+]
∆s:
—expresion of basolater Na+/K+-ATPase
—expression of ENaC both directly and indirectly via (SGK1 and CAP1)
—the permeability of the apical membrane by ∆ing # of channels
—takes ~24hrs b/c its effect on K+ is initially cancelled by ↑ Na+ reabsorption → decr H2O delivery to distal nephron
Regulation of aldosterone secretion
↑: A2 and hyperkalemia
↓: natruetic peptides (e.g. ANP) and hypokalemia
Mechanism of ADH regulation of [K+]
—stimulates K+ secretions by DCT/CD basically by ∆ing intracellular [Na+] altering electrochem gradient
—makes up for the decreased flow it causes, so there is constant urinary K+ excretion despite ∆s in water handling
Effect of tubular flow rate on K+
Tubular flow rates bend 1° cilia on principal cells ↑ing [Ca2+]intracell → depolarizes apical membrane → K+ channels activated
—↑ flow → ↑ K+ secretion
Effect of ∆ing pH on [K+]
acidosis: HYPERkalemia —inhibits basolateral Na+/K+-ATPase —reduces permeability of apical membrane alkalosis: HYPOkalemia —opposite above
When acidosis is chronic, kidney can once again secrete K+ b/c of alterations in tubular flow 2°to ↓ed
Effect of glucocorticoids on [K+]
glucocorticoids ↑ K+ secretion → HYPOkalemia
—↑ GFR → ↑ flow rate → ↑ K+ secretion
—stimulate Sgk1
Hyperkalemia 101: —[K+] cut-off? —How common? —Severity? —Symptoms?
– Serum [K+] > 5 mEq/L
– Relatively uncommon
– Often life-threatening: severity depends on speed of ∆ in serum [K+]
– Often asymptomatic: 1st sx may be cardiac arrest
Clinical Manifestations of HYPERkalemia
—S/Sx
—EKG ∆s?
—Mechanism for these ∆s?
S/Sx: muscle weakness EKG ∆s by frequency: —1. Peaked Ts —2. PR prolongation/QRS widening —3. sine wave/asystole Mechanism: —depolarization because [K+]_out is now closer to [K+]_in —Na+ channels become paralyzed —No APs/contractions
Tx for arrythmias 2° to HYPERkalemia
Ca2+ stabilized membrane
Causes of HYPERkalemia by category of distrurbance
INCREASED INTAKE
—problematic only when output decreased
—foods, meds (abx, K+ supplement), salt substitutes
DECREASED OUTPUT
—Decreased GFR
—Hypoaldosteronism (1°, 2° or Hyporeninemic)
—Meds
CELL SHIFT
—e.g. exercise (many others see list card)
SPURIOUS
—pseudohyperkalemia due to cell lysis from improper phlebotomy
Foods high in K+
Potatoes, tomatoes, citrus fruits, melons, milk
How does hypoaldosteronism (or resistance to aldo) effect [K+]? Mechanism?
Lack of aldosterone or aldosterone resistance closes the distal Na+ channel
—Inability to absorb Na+ = inability to generate negative electrical gradient for K+ secretion
Primary Hypoaldosteronism
Adrenal gland damage (Addisonian crisis)
– Autoimmune, shock, sepsis, hemorrhage
– Characterized by hypotension, fatigue, malaise, HYPERKALEMIA, abdominal pain
Congenital
– E.g. 21-hydroxylase (involved in aldo & cortisol synth) deficiency
Heparin – Blocks aldosterone production
2° Hypoaldosteronism
Causes HYPERKALEMIA
Hyporeninemic hypoaldosteronism
– Juxtaglomerular apparatus damage (e.g. from NSAID-induced acute interstitial nephritis)
– Diabetic nephropathy, obstructive uropathy
ACEI / ARB therapy
– ↓ A-II reduces aldosterone production
– Eff arteriolar dilation can ↓ GFR and consequently tubular flow rate
How does Aldosterone Resistance effect [K+]?
What types of Aldosterone Resistance are there?
Mechanism?
¡ALDOSTERONE WASTES K+!
Aldo antagonists – K+ - sparing diuretics
Pseudohypoaldosteronism (PHA) – Post-receptor defects
—AR & AD inherited (AR much worse) mutation in WNK kinase
—opposite of Gitelman’s so tx w/ thiazides
Gitelman Syndrome is like what drug?
thiazide diuretics
Effect of K-sparing diuretics?
Potentially HYPERkalemia
—amiloride and triamterene inhibit ENac
—spirinolactone blocks the MR-receptor
—net effect of both is to block Na+ reabsorption in the distal nephron; there is then no net luminal negative charge so no electrochemical gradient to secrete K+ out of the cell
Effect of NSAIDs on kidney fxn (and therefore K+)?
HYPERkalemia
—Direct: tubular toxin causes interstitial nephritis & decreased renin production
—Indirect: ∆ing arachadonic acid metabolism → ∆s prostaglandin synthesis → dilates EA & constricts AA → ↓ GFR → ↓ tubular flow rate → ↓ K+ secretion
Effect of cyclosporine on kidneys
HYPERkalemia
—Immunosuppressive agent (calcineurin inhibitor)
—Causes renal vasoconstriction
—Can lead to ischemic tubular damage
—Directly reduces renal blood flow
—Decreases both GFR and tubular flow rate
—therefore HYPERkalemia
Bactrim effect on K+
HYPERKALEMIA
Trimethoprim is structurally similar to K+ - sparing diuretics
Blocks the distal Na+ channel (ENaC)
Decreased Na+ absorption decreases the electrical gradient for K+ secretion
List causes of transcellular K+ shifts leading to HYPERKALEMIA
- Acidemia
- Insulin deficiency
- Beta blockade
- Hemolysis / rhabdomyolysis / tumor lysis
- Exercise
- Digitalis toxicity (directly inhibits Na+/K+/ATP-ase activity)
- Hyperosmolarity
Succinylcholine
can cause massive K+ exodus in patients with neuromuscular dysfunction
Cause of pseudohyperkalemia?
1. Severe leukocytosis / thrombocytosis – K+ release from cells – Check PLASMA K+ rather than serum K+ 2. Hemolyzed blood sample 3. Prolonged tourniquet time
TTKG
Transtubular K+ Gradient
—TTKG = (U_K+ x Sosm) / (S_K+ x Uosm)
—Estimate of renal K+ excretion
—Serum / Urine Osmolality corrects for water absorption in the distal tubule
—Typically 8-9;
—above 11 with hyperkalemia
—< 7 in the face of hyperkalemia is highly suggestive of hypoaldosteronism
Tx of Hyperkalemia
Acute interventions for symptomatic hyperkalemia IV calcium Insulin / glucose Albuterol Bicarbonate (only if pt acidotic) Kayexalate (K+-binding resin) Dialysis
When is dialysis indicated in hyperkalemia?
K+ >7 or QRS widening with renal failure or inability to use kayexalate
Ongoing K+ release (GI bleed, tissue necrosis) and refractory hyperkalemia
Failure of above therapies
Order of Rx for acute hyperkalemia?
- Start w/ IV Ca++ if EKG changes
- Insulin/glucose or albuterol once stabilized
- Add bicarbonate if acidotic
- Give first dose of kayexalate immediately
- Plan for repeat kayexalate PRN based on initial K+ level (10g / 0.1mEq K+ above 6)
- Stop offending medications and optimize renal function
Rx for chronic hyperkalemia
—Low K+ diet counseling almost always required
—Avoid provoking meds (NSAIDS, ACEI,
ARB, K+-sparing diuretics)
—Frequently seen in hypoaldosterone states
—Assess volume status and BP:
— Fludrocortisone as long as no HTN or fluid overload
— Furosemide if fludrocortisone is contraindicated
—K binding resins
Hypokalemia 101: —[K+] cut-off? —How common? —Severity? —Symptoms?
– Serum [K+] < 3.5 mEq/L
– Probably the most common electrolyte disorder
– Rarely life-threatening
– Frequently symptomatic
Clinical manifestations of HYPOkalemia
Muscle weakness ( ↑ membrane excitability) Cardiac arrhythmias (∆ed RMP and repolarization) Metabolic alkalosis (HypoK+ induces H+ secretion) Nephrogenic D.I.
Causes of HYPOkalemia by category of distrurbance
- Decreased Intake (rare)
- Increased Losses
—Renal
—GI
—Miscellaneous - Transcellular Shifting
- Spurious
Effect of hypomagnesemia on K+?
hypomagnesemia often co-occurs to HYPOkalemia
—mechanism unsure
—have to correct Mg to get K right
Bartter’s syndrome
Mutation in Na+/K+/2Cl- pump in LoH —behave like LOOP diuretics —five variants —more rare than Gitelman's Causes: —HYPOkalemia —hypomagnesemia —volume depletion —metabolic alkalosis
Gitelman’s syndrome
Mutation in Na+/Cl- co-transporter in DCT —behave like THIAZIDES Causes: —hypokalemia —metabolic acidosis
MORE COMMON; FEWER ADVERSE EFFECTS
Bartter’s vs. Gitelman’s
[IMAGE]
Liddle’s Syndrome
Activating mutation in ENaC —behave OPPOSITE AMILORIDE/TRIAMTERENE —Pseudohyperaldosteronism: aldo-sensitive Na+ channel in DCT always active Causes: —HYPOkalemia —severe (vol overload) HTN —low serum renin and aldosterone
GI Losses of K+ — A discussion of mechanisms
Diarrhea/laxative abuse
—some direct K+ loss in fluid
—likely vol depl → ↑ aldo → renal K+ wasting
—vomit → H+ loss → ↑ [HCO3-] to be excreted → tubular lumen more +ly q’ed → less K+ reabsorbed/more excreted b/c it wants to stay in that lumen
Miscellaneous K Losses
Dialysis
– Peritoneal Dialysis removes more K+ than HD
Plasmapheresis
– Plasma is removed and often replaced with albumin
Excessive sweat
– 5-10 mEq/L K+ in sweat
High volume peritoneal drainage
List causes of transcellular K+ shifts leading to HYPOKALEMIA
—↑ insulin (causes K+ to shift into cells; insulin overdose, IV insulin for DKA), rarely: insulinoma)
—adrenergic excess (pheo, β2 agonists for COPD,
—alkalemia
——anxiety (both alkalemia and adrenergic)
—re-feeding syndrome (insulin is secreted whilst total body K+ is low AND rapid cell growth)
—↑ RBC/tumor/etc. prod (esp leukemias; folate/B12 repletion, epo; depletes K+)
—periodic paralysis
Alkalemia effect on K+ (Mechanism)
—High blood pH shifts K+ into cells
—kidney attempts to correct alkalemia by excreting HCO3-
—Bicarbonaturia leads to urinary K+ wasting as K+ remains in the urine to balance the charge of HCO3-
Periodic Paralysis
—genetic, recurrent, severe hypokalemia that causes paralysis
—M=F; presents 20-30 y/o;
—can be triggered by exercise, stress, or eating
—Asian males: presents w/ thyrotoxicosis
What causes spurious HYPOkalemia?
Severe leukocytosis
– Cellular uptake of K+ in tube
– Avoided by rapid refrigeration and sample processing
Hypertension with unprovoked hypokalemia is ______ until proven otherwise!
hyperaldosteronism / RAS
Work-up for HYPOkalemia
—History / Physical
— – GI fluid loss, meds (diuretics, laxatives)
—Electrolytes, Mg++, urine pH, 24-hour UK
—Urine diuretic screens, stool laxative
—Metabolic alkalosis + low urine K+ with hypokalemia is _______ until proven otherwise
vomiting / diuretic abuse
Management of HYPOkalemia
—correct alkalosis, if possible
—give K+ IV w/o dextrose (would cause insulin release → worsened hypokalemia)
—K+ sparing diuretics
—EKG + q1-2hr K+ measurements when giving IV K+
—dialysis when severe
