ELECTROLYTES

 These are ions capable of carrying an electric charge

*cations- positively charge anions-negatively charge
 Fluid always contains equal numbers of cations and anions- this balance of charges is referred
to as electroneutrality
 Dissociation of solutes into charged particles (ions) depends on the chemical composition of
the compound and on the concentration of other charged particles in the medium
Distribution:
 40-75% is the average water content of the human body
 Extracellular fluid (ECF)- 1/3 of the total body water
 Intracellular fluid (ICF)- 2/3 of total body water
 60% of the body’s water is inside cells, and the rest is in the bloodstream or tissue fluids
 About 30 liters of fluid passes from the blood to the tissue spaces daily
 Normal plasma is composed of 93% water and 7% solutes
 Water content of plasma is 12% higher than that of whole blood
 Retention of 3 liters of fluid in the tissues will result to edema
 Deficiency of vasopressin (Anti Diuretic Hormone (ADH)) causes 10-20L of water excreted
daily
*Diabetes insipidus
 Sweat contains about 50mmol/L of sodium and 5mmol/L of potassium
 Salt content of the body is the main determinant of the extracellular volume
Functions of electrolytes:
 For volume and osmotic regulation *sodium, chloride, potassium
 For myocardial rhythm and contractility *potassium, magnesium, calcium
 Important cofactors in enzyme activation *calcium and chloride = amylase
 For the regulation of ATPase ion pumps *magnesium
 For neuromuscular excitability *potassium, calcium, magnesium
 For the production and use of ATP from glucose *phosphate, magnesium
 Maintenance of acid-base balance *bicarbonate, potassium, chloride
 Replication of DNA and the translation of mRNA
 Blood coagulation *magnesium, calcium

1. SODIUM
a. Characteristics
i. Major extracellular cation *positively charge
ii. Solute that contributes most to total serum osmolarity
iii. Blood levels of sodium are mainly controlled by aldosterone (promote absorption of
sodium in distal tubule in kidney and also promote excretion of potassium)
iv. Renin-Angiotensin-Aldosterone System (RAAS) produces Angiotensin II which is
responsible for regulating sodium levels and blood pressure
b. Functions
i. Regulates osmolarity and blood volume
 c. Clinical Considerations
CAUSES OF HYPERNATREMIA
*increased amount of sodium
Diabetes insipidus *deficient vasopressin
*excrete increased amount of water
Osmotic dieresis
Loss of thirst
Insensible loss of water
Gastrointestinal loss of hypotonic fluid
Excess intake of sodium
CAUSES OF HYPONATREMIA
*decreased normal value of sodium
Diuretics, potassium depletion
Aldosterone deficiency, ketonuria
Salt-losing nephropathy, vomiting
Diarrhea, excess fluid loss as with burns,
excess sweating or trauma
Syndrome of Inappropriate Anti Diuretic
Hormone (SIADH), excess water intake
Adrenal insufficiency
Reset osmostat
Acute or chronic renal failure
Nephrotic syndrome, hepatic cirrhosis,
congestive heart failure
Pseudohyponatremia (hyperglycemia,
hyperlipidemia, hyperproteinemia)

d. Specimen considerations and patient preparation

i. Serum, plasma, 24-hour urine sample, as well as sweat and CSF can be used as
sample
ii. If plasma is used, lithium and ammonium salts of heparin, as well as lithium
oxalate may be used
iii. Heparin is the anticoagulant of choice
iv. Hemolysis does not cause significant changes but marked hemolysis should be
avoided
e. Methodologies
i. Flame emission photometry
a. Sodium produces yellow color when exposed to flame
b. Sodium emits light at a wavelength of 590nm
c. Dilute sample first to prevent interferences, to prevent atomizer plugging
and to acquire increased sensitivity
d. Dilute sample using high purity water
e. Serum is usually diluted 1:100 or 1:200
f. Lithium or cesium may act as internal standard
ii. Atomic absorption spectrophotometry
iii. Ion-selective electrode (glass aluminum silicate)
f. Values to remember
i. Reference value- 135-145 mmol/L
ii. Conversion factor- mEq/L to mmol/L= 1.0

2. POTASSIUM
a. Characteristics
i. Major intracellular cation
b. Functions
i. Involved in proper transmission of nerve impulses
ii. Important for contraction of the heart- abnormal levels of potassium can lead to altered
electrocardiographic patterns
 c. Clinical Considerations
CAUSES OF HYPERKALEMIA CAUSES OF HYPOKALEMIA
Decreased renal excretion GI loss
 Acute or chronic renal failure  Vomiting, diarrhea, gastric
 Hypoaldosteronism;addison’s suction
disease  Intestinal tumor,
 Diuretics Malabsorption
Increased intake  Cancer therapy-
 Oral or IV potassium chemotherapy, radiation
replacement therapy therapy
Cellular shift  Large doses of laxatives
 Acidosis, muscle/cellular injury Decreased intake
 Chemotherapy Renal loss
 Leukemia (increased WBC)  Diuretics- thiazides,
 Hemolysis mineralocorticoids
Prolonged tourniquet use or excessive  Nephritis, renal tubular
fist clenching acidosis
 Hyperaldosteronism;
Cushing’s syndrome
 Hypomagnesemia
 Acute leukemia
Cellular shift
 Alkalosis, insulin overdose

d. Specimen considerations and patient preparation

i. Serum or plasma can be used; plasma/serum must be separated from the cells quickly
to prevent potassium from shifting from RBCs to serum
ii. Heparin is the anticoagulant of choice
iii. Whole blood samples for potassium determination should be stored at Room
Temperature
iv. No to prolonged tourniquet application; excessive fist clenching and hemolysis
e. Methodologies
i. Flame emission photometry
a. Potassium produces violet color when exposed to flame
b. Potassium emits light at a wavelength of 768nm
c. Dilute sample first to prevent interferences, to prevent atomizer plugging
and to acquire increased sensitivity
d. Dilute sample using high purity water
e. Serum is usually diluted 1:100 or 1:200
f. Lithium or cesium may act as internal standard
ii. Atomic absorption spectrophotometry
iii. Ion-selective electrode (valinomycin membrane)
f. Values to remember
i. Reference values- 3.4-5.0 mmol/L
g. Conversion factor- mEq/L to mmol/L
3. CHLORIDE
a. Characteristics
i. Major extracellular anion *negatively charge
ii. Chloride is the counterion of sodium - a counterion is an ion that accompanies an ionic
species in order to maintain electric neutrality
 b. Functions
i. Maintains water balance, osmotic pressure, and anion-cation balance in the
extracellular fluid
ii. Responsible for chloride shift - an exchange mechanism between chloride and
bicarbonate across the membrane of RBCs
c. Clinical Considerations
HYPERCHLOREMIA HYPOCHLOREMIA
Excess loss of bicarbonate Prolonged vomiting, diabetic ketoacidosis,
Renal tubular acidosis aldosterone deficiency
Metabolic acidosis Salt-losing renal diseases (pyelonephritis)
High serum bicarbonate (compensated
respiratory acidosis or metabolic alkalosis)

d. Specimen considerations and patient preparation

i. Serum, plasma, whole blood, 24-hour urine and sweat can be used as sample
ii. Lithium heparin is the anticoagulant of choice
iii. Marked hemolysis should be avoided
e. Methodologies
i. Ion-selective electrode
a. Most commonly used
b. Using an ion exchange membrane selective for chloride ions
c. Membrane used is a combination of silver wire coated with AgCl
ii. Amperometric-coulometric titration
a. Principle of cotlove chloridometer
b. Uses coulometric generation of silver ions which combine with chloride to
quantitate chloride concentration
c. Excess silver ions, which were not bound to chloride is used to indicate
endpoint
iii. Mercuric titration
a. Principle of Schales and Schales method
b. Based on the reaction of chloride ions to mercuric ions to form mercuric
chloride
c. Blood containing bromide leads to positive error
d. Excess mercuric ions are then made to react with diphenylcarbazone in
order to form violet-blue color
iv. Colorimetric method (method of Skeggs)
a. Uses mercuric thiocyanate and ferric nitrate to form ferric thiocyanate,
which is a reddish colored complex with a peak absorbance at 480nm
f. Values to remember
i. Reference values- serum:98 to 107mmol/L
ii. Conversion factor- mEq/L to mmol/L= 1.0
4. CALCIUM
a. Characteristics
i. 99% of calcium is found in bones and teeth; 1% is found in the blood
ii. Calcium in the blood exists in three forms
a. Free calcium= 50%
b. Complexed calcium= 10%
c. Protein bound= 40%
iii. 1g/dL decrease in albumin causes 0.8mg/dL decrease in total calcium
 iv. Calcium levels are altered by blood pH
*alkalosis lowers calcium, acidosis increases calcium
v. Calcium is absorbed in ileum (small intestine) at acid pH
vi. Calcium level in the blood is controlled by parathyroid hormone, calcitonin and
vitamin D
vii. Low levels of parathyroid hormone lead to low serum calcium and high serum
phosphorous level *inverse relationship
*parathyroid hormone and calcium = directly proportional
*parathyroid hormone and phosphorous = indirectly proportional
viii. Low vitamin D leads to low serum calcium and increased calcium and phosphorous
in feces
ix. Has reciprocal or inverse relationship with phosphate
b. Functions
i. Contributor to structure of bone and teeth
ii. Coagulation (calcium is coagulation factor IV) *bind calcium
iii. For proper contraction of heart muscles
iv. Activator to enzymes
v. Neurotransmission regulator
c. Clinical Considerations
HYPERCALCEMIA HYPOCALCEMIA
Primary hyperparathyroidism (most Primary hypoparathyroidism
common PTH-mediated hypercalcemia) Severe hypomagnesemia
Familial hypocalciuric hypercalcemia Longstanding hypercalcemia
Ectopic secretion of PTH by neoplasms Pseudohypoparathyroidism
Malignancy associated (most common Vitamin D deficiency, chronic renal failure,
non-PTH mediated hypercalcemia) renal tubulopathies, Fanconi’s syndrome
Vitamin D intoxication, thyrotoxicosis Mutations of vitamin D receptor
Hypoadrenalism, immobilization with Hypoalbuminemia, acute pancreatitis
increased bone turnover Rhabdomyolysis
Milk-alkali syndrome, sarcoidosis, multiple Tetany
myeloma

d. Specimen considerations and patient preparation

i. Serum, heparinized plasma, or 24-hour urine sample may be used
ii. Lithium heparin is the preferred; no to EDTA, oxalate and citrate
iii. Samples should be collected anaerobically
iv. For 24-hour urine calcium, sample should be acidified using 6M HCl (1mL of HCl
per 100mL of urine)
v. For assays that are subject to interference with magnesium, magnesium can be
removed by adding 8-hydroxyquinoline
e. Methodologies
i. Orthocresolphthalein complexone (Hitachi and Dimension *machine)
a. A calcium chelator; produces reddish complex with absorbance at 570-
578nm
b. The sample is first diluted with acid to release protein-bound and
complexed calcium
c. Organic base is used to buffer the reaction and to produce an alkaline pH
ii. Arsenazo III (Vitros and Synchron *machine)
a. Binds calcium to produce an intense purple complex
b. pH of reaction is maintained at 6.0
c. imidazole is used to buffer the reaction
 d. interference from most biological pigments is reduced by measuring the
calcium-dye complex near 650nm
e. reagent is more stable than that of cresolphthalein-complexone

iii. atomic absorption spectrophotometry

a. calcium compounds in a flame dissociate into free calcium atoms
b. free atoms absorb light of a characteristic wavelength
c. lanthanum is used to bind phosphate that might instead bind the calcium
and cause falsely low result
iv. Clark Collip precipitation method
a. Classic method that measures oxalic acid as the end product
b. Critical points: washing the calcium oxalate precipitate; titration of oxalic
acid with KMnO4 at 70ºC
v. Ferro Ham chloroanilic acid precipitation method
a. Precipitation of calcium with chloroanilic acid
vi. Compleximetric
a. removal of calcium by EDTA
vii. Ion-selective electrode
a. Uses a liquid-membrane electrode with an ion-selective carrier such as
dioctyphenyl phosphate
f. Values to remember
i. Reference values
Child Adult
Total calcium 2.20-2.70mmol/L 2.15-2.50mmol/L
Ionized calcium 1.20-1.38mmol/L 1.16-1.32mmol/L

24-hour urine- 2.50-7.50mmol/day

ii. Conversion factor- mg/dL to mmol/dL= 0.25
5. MAGNESIUM
a. Characteristics
i. Second most abundant intracellular cation (after potassium)
ii. Fourth most abundant cation in the body
iii. 50% of magnesium in the body is found in the bones; around 25% is in the muscle
iv. Exists in the blood in 3 forms:
a. Free magnesium= 55%
b. Complexed magnesium= 15%
c. Protein bound= 30%
b. Functions
i. Contributor to bone structure
ii. For muscle contraction and heart rhythm
iii. Activator to enzymatic reactions
c. Clinical Considerations
HYPERMAGNESEMIA HYPOMAGNESEMIA
Acute or chronic renal failure Poor diet; prolonged magnesium-deficient
Hypothyroidism IV therapy, chronic alcoholism;
Hypoaldosteronism pancreatitis, vomiting, diarrhea
Hypopituitarism Laxative abuse
Antacids Hyperparathyroidism, Hyperaldosteronism
Enemas Ketoacidosis, diuretics, excess lactation
Cathartics Pregnancy, tubular disorders
 Dehydration Glomerulonephritis, pyelonephritis
Bone carcinoma/ bone metastasis tetany

d. Specimen considerations and patient preparation

i. Serum, lithium heparinized-plasma or 24-hour urine may be used
ii. Oxalate, EDTA and citrate should not be used ; no to hemolysis
iii. 24-hour urine should be acidified with HCl
e. Methodologies
i. Colorimetric method
a. Calmagite (Hitachi and Synchron)
a. A naphthol sulfonic acid derivative
b. Formazen dye (Vitros)
a. Colored complex at 660nm
c. Methyl-thymol blue (Dimension, DuPont aca)
ii. Dye-lake method
a. Titan yellow dye (Clayton yellow/thiazole yellow)
iii. Fluorometry
a. Magnesium reacts with the reagent 9-hydroxy-5-quinoline sulfonic acid or
calcein to form a fluorescent compound
iv. Atomic absorption spectrophotometry
a. Reference method
v. Ion-selective electrode
f. Values to remember
i. Reference value- 0.63-1.0 mmol/L
ii. Conversion factor- mEq/L to mmol/L= 0.5
6. PHOSPHATE
a. Characteristics
i. Intracellular anion; most phosphorus is in the form of phosphate
ii. Most serum phosphate are inorganic; most phosphorus inside the cell is organic
iii. Phosphate metabolism is controlled by PTH, calcitonin and vitamin D
iv. Exists in the blood in 3 forms
a. Free phosphate= 55%
b. Complexed phosphate= 35%
c. Protein bound= 10%
b. Functions
i. Serves as a buffer
ii. Serves as part of energy molecules like ATP
c. Clinical Considerations
HYPERPHOSPHATEMIA HYPOPHOSPHATEMIA
Renal failure Infusion of dextrose solution
Increased breakdown of cells Use of antacids
(intravascular hemolysis) Alcohol withdrawal
Neoplastic disorders (lymphoblastic Poor diet
leukemia) Vomiting
Intensive exercise, severe infections ketoacidosis
d. Specimen considerations and patient preparation
i. Serum, lithium heparin-plasma or 24-hour urine sample may be used
ii. Oxalate, EDTA and citrate should not be used
iii. No to hemolysis
iv. Diurnal variation- highest levels are found in late morning; lowest in the evening
e. Methodologies
 i. Fiske-Subarrow method
a. Uses molybdate reagent
f. Values to remember
i. Reference values
a. Serum/plasma a. (neonate) 1.45-2.91mmol/L
b. (child) 1.45-1.78mmol/L
c. (adult) 0.87-1.45mmol/L
ii. Conversion factor for phosphorus- mg/dL to mmol/L= 0.323
7. LACTATE
a. Characteristics
i. By-product of an emergency mechanism that produces small amount of ATP when
oxygen delivery is severely diminished; activated when there is a deficiency of
oxygen
ii. ATP can be produced when glucose is metabolized to lactate, under anaerobic
metabolism
b. Specimen considerations and patient preparation
i. Do not use tourniquet
ii. No hand exercise before or during collection
iii. Heparinized whole blood must be delivered on ice and plasma must be quickly
separated *LAB -Lactate, Ammonia, Blood Gas = ice specimen
c. Methodologies
i. Enzymatic method; lactate oxidase and peroxidase reaction
ANION GAP
 Difference between unmeasured anions and unmeasured cations
 Useful in indicating an increase in one or more of the unmeasured anions in the serum
 Serves as a form of quality control for the analyzer used to measure these electrolytes
 Formula:
o AG= Na - (Cl+ HCO3)
o AG= (Na + K) - (Cl+ HCO3)
 Reference values:
o 7-16 mmol/L or 10-20mmol/L
 Clinical significance of anion gap
o Increased AG
 Uremia/renal failure, ketoacidosis, poisoning due to ingestion of toxic substances like methanol,
ethanol, ethylene glycol poisoning or salicylate; lactic acidosis; severe dehydration; instrument
error
o Decreased AG
 Rare; Hypoalbuminemia; severe hypercalcemia; patients with multiple myeloma;
instrument error