Transcript Hypokalemia       CR, 51 y/o woman Na+K+ 2.7 Cl97 CO2Creat 1.0       SC, 33 y/o woman Na+K+ 3.1 Cl98 CO2Creat 0.8 Hypokalemia can only occur for four reasons: Decreased intake  Shift into cells  Extra-renal losses  Renal.

Hypokalemia
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CR, 51 y/o woman
Na+
139
K+
2.7
Cl97
CO2
33
Creat
1.0
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SC, 33 y/o woman
Na+
138
K+
3.1
Cl98
CO2
27
Creat
0.8
Hypokalemia can only occur for
four reasons:
Decreased intake
 Shift into cells
 Extra-renal losses
 Renal losses
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Causes of hypokalemia
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Decreased intake: kidney can conserve to 5-25
mEq K+ daily; normal intake 40-120 daily.
Shift into cells:
 Alkalosis
 Insulin
 Beta
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adrenergic stimuli
Stress
Beta agonists- e.g.: albuterol, ritodrine
Increased potassium entry into
cells:
Hypokalemic periodic paralysis- typically
oriental men with thyrotoxicosis; ?
abnormal Ca++ channel; ? Increased
Na/K atp ase activity.
 Increased rbc uptake, e.g. after treatment
with B12, folate.
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Extra-renal losses of potassium:
Gastrointestinal losses of
potassium
Gastric juice contains 5 – 10 mEq K+/L.
 Intestinal fluids contain 20 – 50 mEq/L
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Hypokalemia from loss of gastric
fluid.
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Loss of hydrogen ion increases plasma
bicarbonate.
Coexisting volume depletion increases
aldosterone secretion.
Increased delivery of bicarbonate to the distal
nephron obligates a cation. In the setting of
increased aldosterone levels, sodium is retained
and potassium excreted.
Potassium loss is most prominent early.
Actual losses in gastric juice are relatively small.
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Diarrheal losses are usually accompanied
by metabolic acidosis
 Villous
adenoma
 Laxative abuse
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Sweat losses- 5 – 10 mEq/L
The kidney and potassium
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Nearly all potassium filtered at the glomerulus is
reabsorbed in the proximal nephron. Urinary
potassium is the result of distal potassium
secretion.
To excrete potassium, the kidney requires an
adequate number of nephrons, aldosterone, and
a circulation adequate to provide adequate distal
delivery of sodium for sodium/potassium
exchange.
Renal losses of potassium
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Diuretics- activate the renin-angiotensinaldosterone cascade.
Primary aldosteronism/increased steroids.
Presentation of a non-resorbable anion distally,
obligating a cation, which will lead to increased
potassium excretion in the presence of
aldosterone.
 Bicarbonate
 Penicillin
derivatives
 Betahydroxybutyrate
Renal losses of potassium
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Renal tubular acidosis
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Proximal, especially with therapy
 Some distal types
 Type IV RTA patients are typically
hyperkalemic
Hypomagnesemia
 Polyuria
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What data do we want to diagnose
the cause of hypokalemia in these
women?
Urinary potassium: 24 hour values better
than spot specimens.
 Aldosterone and renin levels.
 Blood pressure measurements.
 A history.
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Both women had urinary potassium levels
that were elevated.
 Both women had elevated renin and
aldosterone levels.
 Both women had low normal blood
pressures
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Therefore:
Potassium is being lost in the urine.
 Primary aldosteronism is r/o by normal
blood pressures.
 Electrolytes r/o renal tubular acidosis.
 Diuretic abuse?
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C.R.
Admitted with repeated episodes of
hypokalemia, many year history of chronic
edema, treated periodically with lasix,
zaroxolyn, and aldactone. Now
vehemently denies diuretic use.
Subsequent urine positive for furosemide.
S.C.
Low potassium noted during initial lab drawn
with pregnancy. Only medication is
synthroid. No nausea, vomiting, diarrhea.
140 mEq KCl required daily to maintain K+
in the 3.5 range.
Other possibilities?
Bartter’s and Gitelman’s
syndromes
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Bartter’s syndrome is usually diagnosed in
childhood, sometimes associated with growth
and mental retardation. The defect is impaired
NaCl reabsorption in the loop of Henle. Findings
are similar to administration of a loop acting
diuretic:
 Salt
loss leading to volume depletion and activation of
the renin-angiotensin system
 Increased urinary calcium
Bartter’s and Gitelman’s
Syndromes
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3 or 4 types of Bartter’s have been identified:
•
Defects in the luminal Na-K-Cl transporter
• Defects in the luminal potassium channel
• Defects in the basolateral chloride channel
I’ve never seen a patient with Bartter’s syndrome,
although many have been referred.
Gitelman’s syndrome
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Like Bartter’s an autosomal recessive disorder,
but not usually diagnosed early in life.
Findings mimic administration of a thiazide
diuretic: the defect is in the Na-Cl transporter.
Patients may complain of polyuria, cramps.
They do not have hypercalciuria, but typically
have low serum magnesium levels.
Gitelman’s syndrome
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Diagnosis is made by history as well as
lab findings. Lab findings are
indistinguishable from thiazide use:
 Hypokalemia,
hypomagnesemia, increased
renin and aldosterone levels, decreased
urinary calcium.
 Genetic screening?
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1: Clin Nephrol. 2001 Mar;55(3):233-7.Related Articles, Links

Mimicry of surreptitious diuretic ingestion and the ability to make a genetic
diagnosis.
Schepkens H, Hoeben H, Vanholder R, Lameire N.
Department of Internal Medicine, University Hospital Gent, Belgium.
[email protected]
Gitelman's syndrome, also known as "hypocalciuric variant of Bartter's syndrome",
is a cause of chronic hypokalemia and hypomagnesemia in adults. A specific gene
has been found responsible for this disorder, encoding the thiazide-sensitive NaCl
coporter (TSC) in the distal convoluted tubule. We describe a psychiatric patient
with chronic symptomatic hypokalemia and hypomagnesemia whose electrolyte
disturbances were subsequently misdiagnosed as an acute alcohol and
benzodiazepine withdrawal syndrome, as chronic diuretic abuse and as a classical
Bartter's syndrome. Finally, genetic investigation revealed the presence of
mutations in the SLC12A3 gene leading to the proper diagnosis of Gitelman's
syndrome. We emphasize that Gitelman's syndrome should be suspected in every
hypokalemic patient with biochemical resemblance of diuretic ingestion, especially
when repeated toxic screens for diuretics are negative. The ability to make a
molecular-genetic diagnosis can be of practical benefit in confusing clinical settings.
Gitelman’s syndrome: treatment
Potassium
 Magnesium
 Aldactone or amiloride
 ACEI’s
 NSAIDS of no benefit
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S.C.
Continues to require very large doses of
KCl, and is on amiloride.
 Magnesium levels have consistently been
low or low normal.
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General comments about the
treatment of hypokalemia
Think about the cause of the hypokalemia
you are treating? A cellular shift, e.g.
hypokalemic periodic paralysis, will require
a lot less potassium to correct than
hypokalemia from potassium loss.
 Orally or i.v.? Orally is safer; limit i.v.
repletion to 20 mEq./hour except in very
unusual circumstances- then monitor.
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Anticipate: has K+ loss stopped or will it be
ongoing?
Are you giving other drugs that will influence K+
levels? E.g. NSAIDs, ACEIs, ARBs.
Generally, use KCl vs. other preparations.
Followup with repeat levels- consider using the
replacement protocols.