3. •Is serum potassium level an
accurate estimate of total body
potassium?
No.
The majority of potassium is
distributed in the intracellular fluid
(ICF) compartment, with only
approximately 2% of the total body
potassium in the extracellular fluid
(ECF) compartment.
4. Alterations in serum potassium can
result from transcellular potassium
shift between ECF and ICF
compartments or
From actual changes in total body
potassium.
5. •When does serum potassium
level falsely estimate total body
potassium?
Transcellular potassium shifts
between ECF and ICF
compartments can have profound
effects on serum potassium.
6. Buffering of the ECF compartment,
with reciprocal movement of
potassium and hydrogen across
the cell membrane, can result in
A rise in serum potassium in the
case of acidemia and a fall in
serum potassium in the case of
alkalemia.
7. Two important hormones that are
known to drive potassium into the ICF
compartment are insulin and
catecholamines.
The classic example of how serum
potassium falsely estimates total
body potassium is a patient with
diabetic ketoacidosis.
8. Insulin deficiency and acidemia
cause potassium to shift to the ECF
compartment so that serum
potassium may be normal or high
despite profound total body
potassium depletion
(due to osmotic diuresis and
hyperaldosteronemic state).
9. Only after proper treatment of
insulin deficiency
and acidosis
the total body potassium depletion
become apparent.
10. •Why is tight regulation of serum
potassium concentrations so
critical?
Although a small fraction of total body
potassium is in the ECF compartment, changes
in ECF
potassium, either by compartmental shifts or by
net gain or loss, significantly alter the ratio of
ECF to ICF potassium, which determines the
cellular resting membrane potential.
11. As a consequence, small
fluctuations in ECF potassium
can have profound effects on
cardiac and neuromuscular
excitability.
12. •Estimate the total body
potassium deficit
It is difficult to predict accurately the
total body potassium deficit on the basis
of serum potassium, but in
uncomplicated potassium depletion a
useful rule of thumb is as follows:
For each 100 mEq potassium deficit,
the fall in serum potassium level is
0.27 mEq/L.
13. Thus, for a 70-kg patient, serum
potassium of 3 mEq/L reflects
A 300- to 400-mEq deficit
Whereas potassium of 2 mEq/L reflects
a 500- to 700-mEq deficit.
In patients with acid-base
disorders, this rule of thumb is not
accurate because of shifts in
compartmental potassium.
14. Relationship between potassium
and magnesium
Magnesium depletion typically occurs after
diuretic use, sustained alcohol consumption,
or diabetic ketoacidosis.
Magnesium depletion can cause
hypokalemia that is refractory to oral or
intravenous (IV) potassium chloride therapy
because severe magnesium depletion
causes renal potassium wasting through
undefined mechanisms.
15. Relationship between potassium
and magnesium
In the setting of severe magnesium
and potassium depletion,
magnesium and potassium must
be replaced simultaneously.
16. Magnesium regulates activity of
the renal outer medullary
potassium (ROMK) channel.
Intracellular magnesium is inversely
proportional to the open renal outer
medullary potassium ROMK channel pore.
Therefore low intracellular magnesium
causes more renal outer medullary
potassium ROMK channels to open,
allowing more K+ efflux into the urine.
17. Magnesium is also closely related
to sodium-potassium-adenosine
triphosphatase (Nat,K+- ATPase)
Possibly explaining failure to retain
intracellular potassium in
hypomagnesemia.
18. Factors important in K+ balance
K+ is mostly intracellular cation.
Of 3500 mEq of total body potassium
only approximately
60 mEq is in the extracellular
compartment.
Dietary K+ must be rapidly shifted from
the vascular space into cells
(internal K+ balance)
before excretion by kidneys and GI
tract (external balance).
19. Internal balance is primarily
regulated by insulin
Whereas external balance is
regulated by kidneys (85%) and
gastrointestinal (GI) tract (15%).
20. Factors that dictate urine
potassium excretion
Key factors influencing potassium
secretion include adequate sodium
delivery to the distal nephron
and Increased
Aldosterone action
{ Na retention and K+
excretion }.
21. Causes of hypokalemia
Redistribution
lntracellular potassium redistribution or
shift can be caused by
Metabolic alkalosis, increased
insulin availability, increased B-
adrenergic activity, and periodic
paralysis
(Classically associated with
thyrotoxicosis).
22. GI loss
Diarrhea or poor K+ intake.
Renal loss
Diuretics, vomiting, and states of
mineralocorticoid excess (e.g.,
primary hyperaldosteronism,
Cushing disease, European
licorice ingestion, and
hyperreninemia).
23. Increases in distal sodium delivery in
the setting of high plasma
aldosterone levels
(due to lower blood volume)
result in increases in urinary
potassium and subsequent
Hypokalemia.
24. Other causes
Include hypomagnesemia and familial
hypokalemic alkalosis syndromes
(Bartter and Gitelman syndromes)
Low intake
Poor oral intake or total parenteral
nutrition with inadequate potassium
supplement.
25. Clinical manifestations of
hypokalemia
By depressing neuromuscular
excitability, hypokalemia leads to
muscle weakness, which can
include quadriplegia and
hypoventilation.
Severe hypokalemia disrupts cell
integrity, leading to
rhabdomyolysis.
26. Among the most important
manifestations of hypokalemia are
cardiac arrhythmias
including paroxysmal atrial tachycardia
with block, atrioventricular dissociation,
first- and second-degree atrioventricular
block with Wenckebach periods, and
even
Ventricular tachycardia or fibrillation.
28. Drugs causing hypokalemia
The most common drugs are diuretics:
loop diuretics, thiazides, and
acetazolamide.
Penicillin and penicillin analogs (e.g.,
carbenicillin, ticarcillin, piperacillin) also
cause renal potassium wasting that is
mediated by various mechanisms, including
delivery of nonreabsorbable anions to the
distal nephron, which results in potassium
trapping in the urine.
29. Drugs causing
hypokalemia
Drugs that damage renal tubular
membranes such as amphotericin,
cisplatin, and aminoglycosides cause
renal potassium wasting even in
the absence of decreases in glomerular
filtration rate (GFR).
30. Diagnostic approach to a patient
with hypokalemia
After eliminating spurious causes (such as
leukocytosis), the diagnosis of true
hypokalemia can be approached on the basis
of urine potassium concentration, systemic
acid-base status, urine chloride level, and
blood pressure .
Urine potassium excretion is best measured
by a 24-hour urine collection.
31. A spot urine potassium concentration
can also be measured (less accurate, but
easier to obtain thus most commonly
obtained) with a value of < 15 mEq/L
indicating extrarenal loss (poor oral
intake, GI loss, intracellular shift) and a
value of >15 mEq/L indicating renal
potassium wasting.
32. Low urine osmolality can interfere with
interpretation of isolated urine potassium by
diluting the urinary K+ concentration.
•Why is serum K+ often low in patients
with myocardial infarction or acute
asthma?
Both conditions are associated with
activation of the sympathetic nervous
system.
B2-Adrenergic activation results in
transcellular shift of K+.
33. Treatment hypokalemia in the
setting of K+ depletion
Oral replacement is the safest route, and
administration of doses of up to 40 mEq
multiple times daily is allowed.
In most cases, potassium chloride is
used because metabolic alkalosis and
chloride depletion often accompany
hypokalemia, such as in patients who
are taking diuretics or who are vomiting.
34. In these settings, coadministration of chloride
is important for correction of
both the metabolic alkalosis and hypokalemia.
In other settings, potassium should be
administered with other salt preparations.
For example, in metabolic acidosis,
replacement with potassium bicarbonate or
bicarbonate equivalent (e.g., potassium
citrate, acetate, or gluconate) is
recommended to help alleviate the acidosis.
35. Persons who abuse alcohol or who
have diabetes with ketoacidosis
often have concomitant phosphate
deficiency and should receive some
of the potassium in the form of
potassium phosphate.
36. Treatment of hypokalemia in
patients requiring loop diuretics
Positive K+ balance is important in patients
requiring loop diuretics because hypokalemia
is arrhythmogenic.
Increases in dietary K+ and or K+
supplements are often inadequate.
Amiloride (Na+ channel inhibitor) and
spironolactone or eplerenone
(mineralocorticoid receptor antagonist) are
used.
37. Treatment of hypokalemia in
patients requiring loop diuretics
Consider measuring 24-hour K+ excretion,
then adjusting the dose of these
agents to account for intake.
The usual K+ intake is 40 to 80 mEq1day.
38. Treatment of hypokalemia in the
setting of periodic paralysis
In both familial and nonfamilial periodic
paralysis (e.g., from thyrotoxicosis),
hypokalemia can be life threatening.
Oral propranolol (nonselective B-
blocker) at the dose of 1-2 mg/kg is an
effective treatment to treat an acute
attack of thyrotoxic periodic paralysis.
39. •When is IV potassium
replacement necessary? What are
the risks?
In life-threatening situations such as severe
weakness, respiratory distress, cardiac
arrhythmias, and rhabdomyolysis, or in
situations when oral administration is not
possible, potassium must be replaced
intravenously.
Infusion rates in the intensive care unit should
be limited to 20 mEq/hr to prevent the
potentially catastrophic effect of a potassium
bolus to the heart.
40. •What are the circumstances
requiring special care in monitoring
potassium replacement?
Patients with defects in potassium excretion
(e.g., renal failure, use of potassium-sparing
diuretics or angiotensin-converting enzyme
[ACE] inhibitors) must have their serum
potassium concentrations monitored frequently
when potassium is being replaced to prevent
overcorrection.
41. Patients who are receiving digitalis therapy
and have hypokalemia are prone to having
serious cardiac arrhythmias (especially in
overdose situations) and must be treated
urgently.
Patients with significant magnesium
deficiency have renal potassium wasting
and often must have their magnesium
levels corrected before therapy for
hypokalemia is initiated.
