01-07 Potassium

Question 1

hormonal regulation of [K+]

Answer 1

—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

Question 2

Acid-Base and K+

Answer 2

—In METABOLIC (i.e. usu. not resp) acidosis → hyperkalemia b/c cells uptake H+ and secrete K+ to maintain electroneutrality

Question 3

Effect of Plasma osmolality on [K+]

Answer 3

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+]

Question 4

Effect of cell lysis on [K+]

Answer 4

—trauma, burns, tumor lysis syndrome and rhabdo all ↑ [K+]

—ulcers → bleed → RBCs lyse → reabsorb K+ in GI tract

Question 5

Effect of exercise on [K+]

Answer 5

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.)

Question 6

filtering of K+

Answer 6

freely filtered b/c no protein bound

—can also be secreted

Question 7

PT handling

Answer 7

—67% reabsorbed here (constant fraction of filtered load)

Question 8

LoH handling

Answer 8

—20% reabsorbed here (constant fraction of filtered load)

Question 9

DCT and CT/CD handling
—where?
—by what mech?

Answer 9

—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]

Question 10

Mechanism of [K+] regulation of [K+]

Answer 10

∆s:
—speed of Na+/K+-ATPase
—electrochecmical gradient
—aldosterone secretion
—flow rate

Question 11

Mechanism of Aldo regulation of [K+]

Answer 11

∆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

Question 12

Regulation of aldosterone secretion

Answer 12

↑: A2 and hyperkalemia

‪↓‬: natruetic peptides (e.g. ANP) and hypokalemia

Question 13

Mechanism of ADH regulation of [K+]

Answer 13

—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

Question 14

Effect of tubular flow rate on K+

Answer 14

Tubular flow rates bend 1° cilia on principal cells ↑ing [Ca2+]intracell → depolarizes apical membrane → K+ channels activated
—↑ flow → ↑ K+ secretion

Question 15

Effect of ∆ing pH on [K+]

Answer 15

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

Question 16

Effect of glucocorticoids on [K+]

Answer 16

glucocorticoids ↑ K+ secretion → HYPOkalemia
—↑ GFR → ↑ flow rate → ↑ K+ secretion
—stimulate Sgk1

Question 17

Hyperkalemia 101:
—[K+] cut-off?
—How common?
—Severity?
—Symptoms?

Answer 17

– 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

Question 18

Clinical Manifestations of HYPERkalemia
—S/Sx
—EKG ∆s?
—Mechanism for these ∆s?

Answer 18

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

Question 19

Tx for arrythmias 2° to HYPERkalemia

Answer 19

Ca2+ stabilized membrane

Question 20

Causes of HYPERkalemia by category of distrurbance

Answer 20

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

Question 21

Foods high in K+

Answer 21

Potatoes, tomatoes, citrus fruits, melons, milk

Question 22

How does hypoaldosteronism (or resistance to aldo) effect [K+]? Mechanism?

Answer 22

Lack of aldosterone or aldosterone resistance closes the distal Na+ channel
—Inability to absorb Na+ = inability to generate negative electrical gradient for K+ secretion

Question 23

Primary Hypoaldosteronism

Answer 23

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

Question 24

2° Hypoaldosteronism

Answer 24

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

Question 25

How does Aldosterone Resistance effect [K+]? What types of Aldosterone Resistance are there? Mechanism?

Answer 25

¡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

Question 26

Gitelman Syndrome is like what drug?

Answer 26

thiazide diuretics

Question 27

Effect of K-sparing diuretics?

Answer 27

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

Question 28

Effect of NSAIDs on kidney fxn (and therefore K+)?

Answer 28

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

Question 29

Effect of cyclosporine on kidneys

Answer 29

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

Question 30

Bactrim effect on K+

Answer 30

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

Question 31

List causes of transcellular K+ shifts leading to HYPERKALEMIA

Answer 31

1. Acidemia 2. Insulin deficiency 3. Beta blockade 4. Hemolysis / rhabdomyolysis / tumor lysis 5. Exercise 6. Digitalis toxicity (directly inhibits Na+/K+/ATP-ase activity) 7. Hyperosmolarity

Question 32

Succinylcholine

Answer 32

can cause massive K+ exodus in patients with neuromuscular dysfunction

Question 33

Cause of pseudohyperkalemia?

Answer 33

``` 1. Severe leukocytosis / thrombocytosis – K+ release from cells – Check PLASMA K+ rather than serum K+ 2. Hemolyzed blood sample 3. Prolonged tourniquet time ```

Question 34

TTKG

Answer 34

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

Question 35

Tx of Hyperkalemia

Answer 35

``` Acute interventions for symptomatic hyperkalemia IV calcium Insulin / glucose Albuterol Bicarbonate (only if pt acidotic) Kayexalate (K+-binding resin) Dialysis ```

Question 36

When is dialysis indicated in hyperkalemia?

Answer 36

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

Question 37

Order of Rx for acute hyperkalemia?

Answer 37

1. Start w/ IV Ca++ if EKG changes 2. Insulin/glucose or albuterol once stabilized 3. Add bicarbonate if acidotic 4. Give first dose of kayexalate immediately 5. Plan for repeat kayexalate PRN based on initial K+ level (10g / 0.1mEq K+ above 6) 6. Stop offending medications and optimize renal function

Question 38

Rx for chronic hyperkalemia

Answer 38

—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

Question 39

``` Hypokalemia 101: —[K+] cut-off? —How common? —Severity? —Symptoms? ```

Answer 39

– Serum [K+] < 3.5 mEq/L – Probably the most common electrolyte disorder – Rarely life-threatening – Frequently symptomatic

Question 40

Clinical manifestations of HYPOkalemia

Answer 40

``` Muscle weakness ( ↑‬ membrane excitability) Cardiac arrhythmias (∆ed RMP and repolarization) Metabolic alkalosis (HypoK+ induces H+ secretion) Nephrogenic D.I. ```

Question 41

Causes of HYPOkalemia by category of distrurbance

Answer 41

1. Decreased Intake (rare) 2. Increased Losses —Renal —GI —Miscellaneous 3. Transcellular Shifting 4. Spurious

Question 42

Effect of hypomagnesemia on K+?

Answer 42

hypomagnesemia often co-occurs to HYPOkalemia —mechanism unsure —have to correct Mg to get K right

Question 43

Bartter's syndrome

Answer 43

``` 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 ```

Question 44

Gitelman's syndrome

Answer 44

``` Mutation in Na+/Cl- co-transporter in DCT —behave like THIAZIDES Causes: —hypokalemia —metabolic acidosis ``` MORE COMMON; FEWER ADVERSE EFFECTS

Question 45

Bartter's vs. Gitelman's

Answer 45

[IMAGE]

Question 46

Liddle's Syndrome

Answer 46

``` 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 ```

Question 47

GI Losses of K+ — A discussion of mechanisms

Answer 47

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

Question 48

Miscellaneous K Losses

Answer 48

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

Question 49

List causes of transcellular K+ shifts leading to HYPOKALEMIA

Answer 49

—↑ 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

Question 50

Alkalemia effect on K+ (Mechanism)

Answer 50

—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-

Question 51

Periodic Paralysis

Answer 51

—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

Question 52

What causes spurious HYPOkalemia?

Answer 52

Severe leukocytosis – Cellular uptake of K+ in tube – Avoided by rapid refrigeration and sample processing

Question 53

Hypertension with unprovoked hypokalemia is ______ until proven otherwise!

Answer 53

hyperaldosteronism / RAS

Question 54

Work-up for HYPOkalemia

Answer 54

—History / Physical — – GI fluid loss, meds (diuretics, laxatives) —Electrolytes, Mg++, urine pH, 24-hour UK —Urine diuretic screens, stool laxative

Question 55

—Metabolic alkalosis + low urine K+ with hypokalemia is _______ until proven otherwise

Answer 55

vomiting / diuretic abuse

Question 56

Management of HYPOkalemia

Answer 56

—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