ELECTROLYTES Women have lower average water content than men as

Electrolytes are ions capable of carrying an electric a result of a higher

charge. fat content .

- Wateristhesolventforallprocesses
- Theyareclassifiedasanionsor in the human body.
cations based on the type of charge
they carry. These names were • transports nutrients to cells, • determines cell volume by
determined years ago based on how its transport into and out of cells, • removes waste products
the ion migrates in an electric field. by way of urine • acts as the body's coolant by way of
sweating
Anions have a negativecharge
and move toward the anode
Cations migrate in the directionof
the cathode because of their Intracellular fluid (ICF)
positive charge. is the fluid inside the cells and accounts
for about two thirds of total body water.

Electrolytes are an essential component

Extracellular fluid (ECF)
in numerous processes, including:
accountsfortheother one third oftotal
body water and can be subdivided into the
1. Volume and osmotic regulation
intravascular extracellular fluid (plasma) and the
(sodium [Na*], chloride [CI], potassium [K]);
interstitial cell fluid that surrounds the cells in the
2. Myocardial rhythm and contractility (K,
tissue.
magnesium [Mg2], calcium [Ca2]);
3. Cofactors in enzyme activation (e.g.,
- Normalplasmaisabout93%water,
Mg2, Ca2, zinc [Zn2]);
4. Regulation of adenosine with the remaining volume occupied by lipids and
triphosphatase (ATPase) ion pumps (Mg2); 5. Acid-base balance proteins.
(bicarbonate [HCO3], K, CI);
6. Blood coagulation (Ca2, Mg2); 7. Neuromuscular The concentrations of ions within cells and in plasma are
excitability (K, Ca2, maintained both by energy-consuming active transport
Mg2); and the processes and by diffusion or passive transport processes
8. Production and use of ATP from
glucose (e.g., Mg2, phosphate [PO4]).

Water

The average water content of the human body varies from

40% to 75% of total body weight, with values declining
with age and especially with obesity.
Regulation - Decreasedlevelsmaybecaused
by increased Na+ loss, increased water
The plasma Na+ concentration depends greatly on the retention, or water imbalance.
intake and excretion of water

• Three processes are of primary Importance: • Increased Na+ loss in the urine can occur with:

- decreasedaldosteroneproduction,
(1) the intake of water in response to thirst, as stimulated - certaindiuretics(thiazides),
or suppressed by plasma osmolality; (2) the excretion of - withketonuria(Na+lostwith ketones), or
water, largely affected by arginine vasopressin (AVP) release
in response to changes in either blood volume or - salt-losingnephropathy(withsome
osmolality; and (3) the blood volume status, which affects renal tubular disorders).
Nat excretion through aldosterone, angiotensin Il, and ANP
(atrial natriuretic peptide). •K+ deficiency also causes Na+ loss
because of the inverse relationship of the
two ions in the renal tubules.

• Prolonged vomiting or diarrhea or severe burns

can result in Na+ loss.
• The kidneys have the ability to conserve or excrete large
amounts of Na+ +, depending on the sodium content of the
ECF and the blood volume.

- 60% to 75% of filtered Na+ is

reabsorbed in the proximal tubule
- Some Na+ is also reabsorbed in the loop and distal
tubule and (controlled by aldosterone) exchanged
for K+ in the connecting segment and cortical
collecting tubule.

Clinical Applications

Hyponatremia

• Hyponatremia is defined as a
serum/plasma sodium level less than 135 mmol/L.

- Hyponatremiaisoneofthemost
common electrolyte disorders in hospitalized
and nonhospitalized patients.
 Na+ concentration in the ECF is much
larger than inside the cells. Because a
small amount of Na+ can diffuse through the cell
membrane, the two sides would eventually reach equilibrium.

- Topreventequilibriumfrom
occurring, active transport systems, such as
ATPase ion pumps, are present in all cells. K+ is
the major intracellular cation. Like Nat, K+
would eventually diffuse across the cell
Active Transport membrane until equilibrium is reached.
- amechanism that requires energy
to move ions across cellular
membranes.
- Forexample,maintainingahigh The Na+, K+ -ATPase ion pump moves
intracellular concentration of K and a high three Na+ ions out of the cell in exchange for two K+ ions
extracellular (plasma) concentration of Na moving into the cell as ATP is converted to ADP.
requires use of energy from ATP in ATPase-
dependent ion pumps.
Because water follows electrolytes across cell
membranes, the continual removal of Nat from the cell
Diffusion prevents osmotic rupture of the cell by also drawing
- thepassivemovementofions water from the cell.
across a membrane.
- Itdependsonthesizeandcharge
of the ion being transported and
on the nature of the membrane through which
it is passing. Therateofdiffusionofvariousions
-
also may be altered by physiologic
and hormonal processes.

Sodium (Na+)

Na+ is the most abundant cation in the

ECF, representing 90% of all extracellular cations, and
largely determines the osmolality of the plasma.
- A normal plasma osmolality is approximately 295
mmol/L, with 270
mmol/L being the result of Nat and associated anions.
Hypernatremia

• Increased serum Na+ concentration, results from

- excesslossofwaterrelativeto
sodium loss, decreasedwaterintake,or
-
- increasedsodiumintakeor
retention.
Potassium (K+)
• Hypernatremia may result from loss of
water in diabetes insipidus, either because the kidney • The major intracellular cation in the body, with a
cannot respond to concentration 20 times greater
AVP (nephrogenic diabetes insipidus) or inside the cells than outside • Only 2% of the body's
because AVP secretion is impaired. total K+ circulates in the plasma.
• Functions of K+ in the body include • regulation of
Diabetes insipidus is characterized by copious neuromuscular excitability, • contraction of the heart, •
production of dilute urine (3-20 L/day). ICF volume, • H+ concentration

• Water loss through the skin and by breathing

(insensible loss) accounts for about 1 L of water loss
per day in adults.
Regulation

• The kidneys are important in the regulation of K+ balance.

- Theproximaltubulesreabsorb
nearly all the K+.
- Undertheinfluenceofaldosterone,
additional K+ is secreted into the urine in
exchange for Na+ in both the distal tubules and
the collecting ducts.

- The distal nephron is the

principal determinant of urinary K+
excretion.
• Exercise
- K+ is released from cells during
exercise, which may increase plasma K+ by 0.3-
1.2 mmol/L(mild to moderate exercise ) 2 to 3
mmol/L (exhaustive exercise) .
 - Forearm exercise during
venipuncture can cause erroneously
high plasma K+ concentrations.

• Hyperosmolality
- Hyperosmolality, as with uncontrolled
diabetes mellitus, causes water to diffuse from
the cells, carrying K+ with the water, which
leads to gradual depletion of K+ if kidney
function is normal.

• Cellular Breakdown
- Cellular breakdown releases K+ into the ECF.
Examples are severe trauma, tumor lysis
- syndrome, and massive blood transfusions.

Clinical Applications
Clinical Applications
Hypokalemia
Hyperkalemia
• Plasma K+ concentration below the
• Patients with hyperkalemia often have an underlying
lower limit of the reference range.
disorder, such as renal insufficiency, diabetes mellitus, or
• Hypokalemia can occur with Gl or urinary loss of K+ or
metabolic acidosis. • The most common cause of hyperkalemia
with increased cellular uptake of K+.
in hospitalized patients is due to therapeutic K+
administration. • In diabetes mellitus, insulin deficiency
- GllossoccurswhenGlfluidislost promotes cellular loss of K+. Hyperglycemia also contributes
through vomiting, diarrhea, gastric suction, by producing a hyperosmolar plasma that pulls water and
or discharge from an intestinal K+ from cells, promoting further loss of K+ into the plasma.
• Various drugs may cause hyperkalemia, especially in
- IncreasedK+lossinthestoolalso patients with either renal insufficiency or diabetes mellitus.
occurs with certain tumors, malabsorption,
cancer therapy (chemotherapy or radiation
therapy), and large doses of laxatives.

• Renal loss of K+ can result from kidney disorders such

as K*-losing nephritis and renal tubular acidosis (RTA).

- InRTA,astubularexcretionofK+
These drugs include:
decreases, K+ excretion increases.
captopril (inhibits angiotensin converting enzyme),
nonsteroidal anti-inflammatory agents (inhibit Clinical Applications
aldosterone), spironolactone (K+ -sparing diuretic),
digoxin (inhibits Cl - K* pump), cyclosporine (inhibits Cl disorders are often a result of the same causes that
renal response to aldosterone), heparin therapy disturb Na levels because Cl passively follows Na. There
(inhibits aldosterone secretion) are a few exceptions.

- Hyperchloremiamayalsooccur
when there is an excess loss of HCO, as a result
of GI losses, RTA, or metabolic acidosis.

- Hypochloremiamayalsooccurwith excessive loss of Cl

from prolonged vomiting, diabetic ketoacidosis,
aldosterone deficiency, or salt- losing renal diseases
such as pyelonephritis.

Bicarbonate (HCO3- )

• Bicarbonate is the second most abundant

anion in the ECF. • Total CO, comprises the

- bicarbonateion(HCO3-)
Chloride (Cl-)
HCO3 accounting for more than 90% of
the total CO2, at physiologic pH.
• Chloride (CI) is the major extracellular anion. • It is
Because HCO3- composes the largest
involved in maintaining osmolality, blood volume, and
fraction of total CO2, total CO2,
electric neutrality. • Cl ingested in the diet is almost
measurement is indicative of HCO3
completely absorbed by the intestinal tract.
measurement.

- Clisthenfilteredoutbythe
- carbonicacid(H2CO3),
glomerulus
- dissolvedCO2,
- Reabsorbed,inconjunctionwith
Nat, by the proximal tubules.
• HCO3- is the major component of the
- ExcessClisexcretedintheurine
buffering system in the blood.
and sweat.
Carbonic anhydrase in RBCs converts CO2, and increased pCO2, as a result of compensation by
H20 to carbonic acid, which dissociates into H+ hypoventilation.
and HCO3-
- Typicalcausesofmetabolic alkalosis
include severe vomiting, hypokalemia, and
CO2 + H20 <-CA→ H2СО3 <-CA→ H+ + НСО3- excessive alkali intake.
CA, carbonic anhydrase

Reference Ranges:
Regulation Carbon dioxide, venous 23 to 29 mmol/L (plasma,serum)

• Most of the HCO3 in the kidneys (85%) is

reabsorbed by the proximal tubules, with 15% being Magnesium ( Mg2+ )
reabsorbed by the distal tubules. • In alkalosis,
with a relative increase in HCO3- compared to CO2, • Magnesium (Mg2+) is the fourth most abundant cation in
the kidneys increase excretion of HCO3- into the the body and second most abundant intracellular ion. • The
urine, carrying along a cation such as Na. average human body (70 kg) contains 1 mole (24 g) of Mg2+.
• Approximately 53% of Mg2+ 2 in the body is found in bone,
46% in muscle and other organs and soft tissue, and less
than 1% is present in serum and red blood cells. Of the Mg2+
- ThislossofHCO,fromthe body helps present in serum, about one third is
correct pH. bound to protein, primarily albumin.
• Among the responses of the body to acidosis is
an increased excretion of H+ into the urine.

Clinical Application • The role of Mg2+ in the body is widespread.

• Acid-base imbalances cause changes in HCO3- - Essentialcofactorofmorethan300

and CO2 levels. enzymes, including those important in
glycolysis, transcellular ion transport,
• A decreased HCO3- may occur from metabolic neuromuscular transmission, synthesis of
acidosis as HCO3- combines with H to produce carbohydrates, proteins, lipids, and nucleic acids,
CO2 ,which is exhaled by the lungs. and release of and response to certain
Thetypicalresponseto metabolic acidosis is hormones.
compensation
- by hyperventilation, which
lowers pCO2,.
Regulation

• The small intertine may absorb 20%-65% of the dietary

• Elevated total CO2, concentrations occur in Mg2+, depending on the need and intake. • The overall
metabolic alkalosis as HCO3- is retained, often regulation of body Mg* is controlled largely by the kidney.
with
 - Henle'sloopisthemajorrenal
regulatory site, where 50%-60% of filtered

- Mg2+isreabsorbedinthe
ascending limb. In addition, 2%-5% is reabsorbed
in the distal convoluted tubule.

- TherenalthresholdforMg2+is
approximately 0.60-0.85 mmol/L (1.46-2.07
mg/dL).
• Mg2+ regulation appears to be related to that of Ca2+
and Na.
- Parathyroidhormone(PTH)
increases the renal reabsorption of Mg2+ and
enhances the absorption of Mg2+ in the
intestine. However, changes in ionized Ca2+ have
a far greater effect on PTH secretion.
Aldosteroneandthyroxine apparently have the
- opposite effect of PTH in the kidney, increasing
the renal excretion of Mg2+.

Clinical Applications

Hypomagnesemia Clinical Applications

- Hypomagnesemiaismost
frequently observed in hospitalized individuals in Hypermagnesemia
intensive care units or those receiving diuretic
therapy or digitalis therapy. • Hypermagnesemia is observed less frequently than
hypomagnesemia. Causes for elevated serum Mg2+ levels
- Thesepatientsmostlikelyhavean
overall tissue depletion of Mg2+ as a result of
severe illness or loss, which leads to low serum • Renal failure (GFR, 30 mL/min)- the most common is causes
levels. for elevated serum Mg2+ levels
• Hypomagnesemia is rare in
nonhospitalized individuals.
• The most severe elevations are usually a result of the
combined effects of decreased renal function and increased
intake of commonly prescribed Mg2+ -containing
medications, such as antacids, enemas, or cathartics.
Nursing home patients are at greatest risk for this
occurrence.
 regulated and had a mean concentration in humans of
• Hypermagnesemia has been associated with several about 1.18 mmol/L.
endocrine disorders.
- Thyroxineandgrowthhormone • Because decreased ionized Ca2+ impairs myocardial function,
cause a decrease in tubular reabsorption of it is important to maintain ionized Ca2+ at a near normal
Mg2+ and a deficiency of either hormone may concentration during surgery and in critically ill patients.
cause a moderate elevation in serum Mg2+ Decreased ionized Ca2+ concentrations in blood can cause
neuromuscular irritability, which may become clinically
apparent as irregular muscle spasms, called tetany.
- Adrenalinsufficiencymaycausea
mild elevation as a result of decreased renal
excretion of Mg2+

Regulation

• Three hormones, PTH, vitamin D, and calcitonin, are known

to regulate serum Ca2+ by altering their secretion rate in
response to changes in ionized Ca2+ • PTH secretion in blood
is stimulated by a decrease in ionized Ca2+ and, conversely,
PTH secretion is stopped by an increase in ionized Ca2+. PTH
exerts three major effects on both bone and kidney. • In the
bone, PTH activates a process known as bone resorption, in
which activated osteoclasts break down bone and
subsequently release Ca2+ into the ECF. • In the kidneys, PTH
conserves Ca2+ by increasing tubular reabsorption of Ca2+
ions. • Vitamin D 3, a cholecalciferol, is obtained from the
diet or exposure of skin to sunlight. • The active form of
vitamin D increases Ca2+ absorption in the intestine and
enhances the effect of PTH on bone resorption. • Calcitonin,
which originates in the medullary cells of the thyroid
Calcium ( Ca2+) gland, is secreted when the concentration of Ca2+ in blood
increases. • Calcitonin exerts its Ca2+ lowering effect by
• In 1883, Ringer showed that Ca2+ was essential for inhibiting the actions of both PTH and vitamin D.
myocardial contraction. While attempting to study how
bound and free forms of Ca2+ affected frog heart
contraction, McLean and Hastings showed that the
ionized/free Ca2+ concentration was proportional to the
amplitude of frog heart contraction, whereas protein-
bound and citrate-bound Ca2+ had no effect. From this
observation, they developed the first assay for ionized/free
Ca2+ using isolated frog hearts. The investigators were able
to show that blood-ionized Ca2+ was closely
 - Many tumors produce PTH-related
Clinical Applications peptide (PTH-rP), which binds to normal PTH
receptors and causes increased Ca2* levels.
• Although both total Ca2+ and ionized Ca2+ measurements
are available in many laboratories, ionized Ca2+ is usually a
more sensitive and specific marker for Ca2+ disorders.

Hypocalcemia
• When PTH is not present, as with primary
hypoparathyroidism, serum Ca2+ levels are not properly
regulated. Bone tends to "hang on" to its storage pool and
the kidney increases excretion of C2+. • Because
hypomagnesemia has become more frequent in hospitalized
patients, chronic hypomagnesemia has also become
recognized as a frequent cause of hypocalcemia.

Hypomagnesemia may cause hypocalcemia by three

mechanisms:
(1) it inhibits the glandular secretion of PTH across the
parathyroid gland membrane, (2) it impairs PTH action at
its receptor site on bone, and (3) it causes vitamin D
resistance.

Hypercalcemia Phosphate
• Primary hyperparathyroidism is the main cause of
• Found everywhere in living cells, phosphate compounds
hypercalcemia.
participate in many of the most important biochemical
- Hyperparathyroidism,orexcess
processes.
secretion of PTH, may show obvious clinical signs
or may be asymptomatic.
- Thegeneticmaterials
deoxyribonucleic acid (DNA) and ribonucleic acid
• The second leading cause of hypercalcemia is
(RNA) are complex phosphodiesters.
associated with various types of malignancy, with
hypercalcemia sometimes being the sole biochemical
- Mostcoenzymesareestersof
marker for disease.
phosphoric or pyrophosphoric acid.
- Themostimportantreservoirsof
biochemical energy are ATP,
 creatine phosphate, and Hyperphosphatemia
phosphoenolpyruvate.
• Phosphate deficiency can lead to ATP depletion, which is • Patients at greatest risk for hyperphosphatemia are those
ultimately responsible for many of the clinical symptoms with acute or chronic renal failure. • An increased intake of
observed in hypophosphatemia • Vitamin D acts to increase phosphate or increased release of cellular phosphate may
phosphate in the blood. also cause hyperphosphatemia. • Because they may not yet
have developed mature PTH and vitamin D metabolism,
neonates are especially susceptible to hyperphosphatemia
- VitaminDincreasesbothphosphate caused by increased intake, such as from cow's milk or
absorption in the intestine and phosphate laxatives.
reabsorption in the kidney.

• Growth hormones can affect circulating

concentrations of phosphate.
- Incasesofexcessivesecretionor
administration of growth hormone, phosphate • Increased breakdown of cells can sometimes lead to
concentrations in the blood may increase hyperphosphatemia,
because of decreased renal excretion of
phosphate. • severe infections, • intensive
exercise, • neoplastic disorders, •
intravascular hemolysis
Clinical Applications
-Because immature lymphoblasts have about four times
Hypophosphatemia the phosphate content of mature lymphocytes, patients
with lymphoblastic leukemia are especially susceptible to
• Hypophosphatemia occurs in about 1% to 5% of hospitalized hyperphosphatemia.
patients. • The incidence of hypophosphatemia increases to
20% to 40% in patients with the following disorders: diabetic
ketoacidosis, chronic obstructive pulmonary disease (COPD),
asthma, malignancy, long-term treatment with total
parenteral nutrition (TPN), inflammatory bowel disease,
anorexia nervosa, and alcoholism. • The incidence increases
to 60% to 80% in ICU patients with sepsis. • Hypophosphatemia
can also be caused by

Lactate

- increasedrenalexcretion,aswith • Lactate is a by-product of an emergency mechanism that

hyperparathyroidism, and produces a small amount of ATP when oxygen delivery is
- decreasedintestinalabsorption,as severely diminished.
with vitamin D deficiency or antacid use
• Pyruvate is the normal end product of glucose metabolism
(glycolysis). The conversion of pyruvate to lactate is
activated when a deficiency of oxygen leads to an
accumulation of excess NADH.

• Normally, sufficient oxygen maintains a favorably high

ratio of NAD to NADH. Under these conditions, pyruvate is
converted to acetyl-coenzyme A (CoA), which enters the
citric acid cycle and produces 38 moles of ATP for each mole
of glucose oxidized.

• Under hypoxic conditions, acetyl-CoA formation does not

occur and NADH accumulates, favoring the conversion of
pyruvate to lactate through anaerobic metabolism. As a
result, only 2 moles of ATP are produced for each mole of
glucose metabolized to lactate, with the excess lactate Clinical Applications
released into the blood.
• Measurements of blood lactate are useful for metabolic
monitoring in critically ill patients, for indicating the
severity of the illness, and for objectively determining
• This release of lactate into blood has clinical importance patient prognosis.
because the accumulation of excess lactate in blood is an
early, sensitive, and quantitative indicator of the severity of
oxygen deprivation.

• There are two types of lactic acidosis:

- TypeA is associated with hypoxic
conditions, such as shock, myocardial
infarction, severe congestive heart failure,
pulmonary edema, or severe blood loss. Type B is
of metabolic origin, such as with diabetes
- mellitus, severe infection, leukemia, liver or
renal disease, and toxins (ethanol, methanol, or
salicylate poisoning).