Management of hypokalemia

and hyponatremia

‫ اسراء ابوالعال محمد احمد‬: ‫االسم‬

A3 : ‫سيكشن‬
Hypokalemia:

Potassium is the most abundant intracellular cation. In humans, the intracellular concentration of K+ is
around 150 mEq/l, while the extracellular concentration is 3.5-5 mEq/l.

Hypokalemia is defined as serum potassium concentration < 3.5 mEq/l

The average intake of K+ on a western diet is 60-140 mEq/day. The kidneys excrete 90% of the daily
intake while the remaining 10% is excreted in the stool. The amount excreted in the stool increases in
advanced kidney disease as in patients on dialysis. The extracellular fluid (ECF) potassium content is only
60-80 mEq or about 2% of total body K+, while intracellular K+ content is 3000-4000 meq. The muscles
contain 70% of total body K+, while the liver, the erythrocytes and the bone each contains about 7% .

K+ is exchanged between the ECF and the other compartments (muscle, liver, bone).

Hypokalemia is common in hospitalized and community dwelling subjects. A study in about 5000
community subjects aged 55 years or older (the Rotterdam Study) found hypokalemia in about 2.5%.
The prevalence in women was twice as in men. Hypokalemia was most prevalent in patients on thiazide
diuretics, odds ratio (OR): 7.68 (4.92-11.98), P < 0.001.

A study in about 8000 patients admitted to the emergency department (ED) found hypokalemia in 39%.
Hypokalemia is seen in about 20% of hospitalized patients .

Hypokalemia results from renal or non-renal loss of K+. Intracellular K+ shift will lead to transient
hypokalemia, while inadequate dietary intake is a rare cause of hypokalemia. Inadequate intake is seen
in starvation, dementia, and anorexia.

1-Pseudohypokalemia: Pseudohypokalemia is seen when blood samples containing very high number of
white blood cells (>75 x 109/L) are stored at room temperature. Hypokalemia is the result of K+ uptake
by white blood cells

2- Intracellular potassium shift or redistribution: This is a rare disorder that is seen more commonly in
Asians in association with thyrotoxicosis.

3- Non-renal potassium loss: The most common causes in this category are gastrointestinal such as
diarrhea, vomiting, nasogastric (NG) suctioning, and laxatives.

4-Renal potassium loss: Renal loss of K+ is the most common etiology of hypokalemia. This category
includes medications, hormones, hypomagnesemia, and renal tubular acidosis
Mild hypokalemia can be asymptomatic. Most symptomatic patients have a serum K+ < 3 mEq/l. The
severity of the symptoms is also related to the rate of K+ decline.

Muscle weakness and fatigue are the most common symptoms upon presentation. Both hypokalemia
and hyperkalemia can result in muscle weakness starting in the lower extremities and ascending to the
trunk and upper extremities.

In severe hypokalemia muscle weakness can progress to flaccid paralysis, but this is rare. Some patients
develop muscle cramps. Severe hypokalemia can lead to rhabdomyolysis. Gastrointestinal muscle
involvement can lead to ileus, nausea, vomiting and constipation.

ECG changes in hypokalemia include flat T waves, ST segment depression, and prominent U waves.
Hypokalemia can result in palpitations in addition to ventricular and supraventricular tachyarrhythmias.
Digitalis increases the likelihood of arrhythmias.

Hypokalemia can result in a variety of renal manifestations including polyuria, polydipsia, and
nephrogenic DI. Chronic hypokalemia can rarely result in chronic tubulointerstitial nephritis

When approaching a patient with hypokalemia, remember the following principles [37]: See Figure 3.

1-Obtaining a good history is essential. Vomiting and diarrhea are the most common GI causes, while
diuretic use is the most common renal etiology. The focus of physical exam is on blood pressure, volume
status and musculoskeletal exam.

2-Hypokalemia is diagnosed after ordering an electrolyte panel. Hypokalemia is serum K+ < 3.5 mEq/l or
< 3.5 mmol/l in SI units. Serum magnesium should be checked especially in recalcitrant hypokalemia. K+
replacement and addressing the etiology (such as diarrhea, or diuretic use) is usually sufficient.

3-If the etiology of hypokalemia is unclear, a 24 h urine collection for K+ is helpful. If hypokalemia is due
to GI loss, the kidneys will preserve K+ and 24 h urine K+ is < 30 meq. In patients with renal loss of K+, 24
h urine K+ is ≥ 30 meq. If a 24 h urine collection is not feasible, the ratio of urine K+ to urine creatinine is
obtained in a random specimen

4-Some patients require further testing such as urine electrolytes (including urine Na+, K+, Cl-, Ca2+, and
Mg2+), thyroid function tests, plasma renin activity, and plasma aldosterone level .

5-In case of GI loss, patients with diarrhea or laxative abuse usually have low HCO3-, while patients with
vomiting usually have high HCO3-.

6-If diuretic abuse is suspected, urine diuretic screen is ordered. A clue to diuretic abuse is inconsistent
values of random urine K+/Cr (high while taking a diuretic, and low hours after the last diuretic dose)
-Patients with serum K+ in the range of 3.0-3.5 mEq/l are usually treated with oral K+ salts as long as
they can take oral medications. Patients with serum K+ < 3 mEq/l may require IV K+ especially in
emergencies such as arrhythmias, rhabdomyolysis and respiratory failure. In many situations both PO
and IV K+ salts are used.

-IV replacement of K+ is appropriate for patients with ECG changes, and in hypokalemia associated with
diabetic ketoacidosis (DKA) or the use of digitalis. K+ deficit is about 200-400 mEq for every 1 mEq/l drop
in K+, but the actual amount varies among individuals.

-Most patient are treated with potassium chloride (KCl). KCl is widely available in multiple forms
(extended release (ER) tablets, capsules, liquid, and IV). KCl works quickly and is the preferred agent
especially in patients with concomitant metabolic alkalosis. In those patients, replenishment of Cl- is
paramount. Cl- stays mostly in the extracellular compartment.

-Intravenous KCl should be given at a rate that does not exceed 10 mEq/h. A higher rate up to 20 mEq/h
is a consideration in emergency situations such as cardiac arrhythmias, telemetry monitoring is required.

-Administration of IV KCl should be done through a central venous catheter if available. IV KCl can cause
phlebitis, and many patients find the infusion painful. It is preferable to give intravenous KCl in 0.9 NS
(usually 20 mEq KCl in 100 ml of 0.9 NaCl). Giving IV KCl in a dextrose solution may stimulate insulin
release and potentially aggravate hypokalemia.

-Potassium chloride salt substitutes are a good source of oral K+. They contain about 13.6 mEq/g. K+
containing foods are appropriate for chronic management of mild hypokalemia. There are not effective
for emergency treatment because the amount needed for correction is large, and potassium in diet is K+
citrate or phosphate which is less effective compared to KCl as explained above. Bananas are a good
source of K+. They contain about 1 mEq/cm. Therefore, one needs to eat 2 large bananas to get 40 mEq
of K+. Examples of foods that are high in K+ include: dried fruits (dates, figs, prunes), spinach, broccoli,
kiwis, mangos, oranges, tomatoes, avocados, bananas, milk, raisins, and lima beans [20].

-Potassium sparing diuretics [50] may be appropriate for the chronic management of hypokalemia
especially in patients who are already on a thiazide or a loop diuretic. Aldosterone receptor antagonists
(spironolactone and eplerenone) may help in the management of patients with advanced heart failure
and in patients with resistant hypertension. Amiloride is well tolerated as well, it blocks the epithelial
sodium channel ENaC in the collecting duct. Triamterene is rarely associated with kidney stones, and the
use of amiloride, eplerenone or spironolactone is preferable.

-Laxatives and diuretics should be stopped if hypokalemia is due to their abuse. Symptomatic treatment
of diarrhea and vomiting is helpful.

-If the patient needs administration of both bicarbonate and potassium intravenously, potassium should
be given first because bicarbonate results in intracellular K+
Hyponatremia:

The most common classification system for hyponatremia is based on volume status: hypovolemic
(decreased total body water with greater decrease in sodium level), euvolemic (increased total body
water with normal sodium level), and hypervolemic (increased total body water compared with sodium).

Plasma osmolality has a role in the pathophysiology of hyponatremia. Osmolality refers to the total
concentration of solutes in water. Effective osmolality is the osmotic gradient created by solutes that do
not cross the cell membrane. Effective osmolality determines the osmotic pressure and the flow of
water. Plasma osmolality is maintained by strict regulation of the arginine vasopressin (also called
antidiuretic hormone [ADH]) system and thirst. If plasma osmolality increases, ADH is secreted and
water is retained by the kidneys, thus decreasing serum osmolality. If plasma osmolality decreases, ADH
also decreases, resulting in diuresis of free water and a return to homeostasis.

Symptoms of hyponatremia depend on its severity and on the rate of sodium decline. Gradual decreases
in sodium usually result in minimal symptoms, whereas rapid decreases can result in severe symptoms.
Polydipsia, muscle cramps, headaches, falls, confusion, altered mental status, obtundation, coma, and
status epilepticus may indicate the need for acute intervention. Most patients with hyponatremia are
asymptomatic, and hyponatremia is noted incidentally. Volume status should be assessed to help
determine the underlying cause

The diagnostic workup should include a history and physical examination with specific attention to
cardiac, cancer, pulmonary, surgical, endocrine, gastrointestinal, neurologic, and renal histories.
Diuretics, carbamazepine (Tegretol), and selective serotonin reuptake inhibitors can cause hypovolemia;
therefore, medications should be reviewed. Alcohol and illicit drug use (especially beer and 3,4-
methylenedioxymethamphetamine [“Ecstasy”]) can cause hyponatremia. Athletes should be asked
about training regimens because high endurance activities can lead to hyponatremia.

Laboratory tests include a complete metabolic panel and urinary sodium and creatinine levels. Serum
osmolality and fractional excretion of sodium should be calculated. Measurement of thyroid-stimulating
hormone, urinary uric acid, adrenocorticotropic hormone, plasma cortisol, and brain natriuretic peptide
may be considered in select patients to rule out other causes. The diagnosis of reset osmostat (a
variation of syndrome of inappropriate antidiuretic hormone secretion [SIADH] in which ADH secretion
occurs despite low plasma osmolality) may be aided using fractional excretion of urate (uric acid) in
nonedematous patients who have hyponatremia that does not respond to usual treatment.

Hypovolemic Hyponatremia

There are numerous causes of hypovolemic hyponatremia. Patients typically have signs and symptoms
associated with volume depletion (e.g., vomiting, diarrhea, tachycardia, elevated blood urea nitrogen–
to-creatinine ratio). Urinary sodium levels are typically less than 20 mEq per L unless the kidney is the
site of sodium loss.

Pseudohyponatremia
Pseudohyponatremia occurs when seemingly low sodium levels are actually normal. Causes include
hyperglycemia, hyperproteinemia, mannitol use, or laboratory errors

Hypovolemic Hyponatremia

There are numerous causes of hypovolemic hyponatremia. Patients typically have signs and symptoms
associated with volume depletion (e.g., vomiting, diarrhea, tachycardia, elevated blood urea nitrogen–
to-creatinine ratio).

Treatment of Severe Symptomatic Hyponatremia

Vaptans and tolvaptan [Samsca]) are vasopressin-receptor antagonists approved for the treatment of
hospitalized patients with severe hypervolemic and euvolemic hyponatremia. However, their use in the
management of hyponatremia is controversial. Several trials have demonstrated that vaptans increase
sodium levels in patients with cirrhosis and heart failure.24 In the Efficacy of Vasopressin Antagonism in
Heart Failure Outcome Study with Tolvaptan, patients with hyponatremia and heart failure who
received tolvaptan had an associated reduction in cardiovascular morbidity and mortality, although
there were several confounding variables, and further study is needed.