PH166: CLINICAL CHEMISTRY I

ELECTROLYTES
PROF. JEREMIAH TORRICO, RND, MD | APRIL 2022
TABLE OF CONTENTS (Broccoli, cabbage,
I. Introduction to Electrolytes okra)
A. Functions C. OSMOLALITY
V. Bicarbonate
B. Food Sources ● Physical property of a solution based on the concentration of solutes
A. Determination
C. Osmolality ● Expressed as millimoles per kilogram of solvent (w/w)
VI. Calcium
II. Sodium → Osmolality is based on the weight of the solvent, while osmolarity
A. Regulation
A. Regulation is based on volume of the solvent (w/v)
B. Clinical Applications
B. Clinical Applications ● In plasma, it is the parameter to which the hypothalamus responds
C. Determination
C. Determination ● The regulation of osmolality affects the Na+ concentration in plasma
VII. Magnesium
III. Potassium → Na+ and its associated anions account for approximately 90% of
A. Clinical Applications
A. Regulation the osmotic activity in plasma
B. Determination
B. Clinical Applications ● Normal plasma osmolality: 275-295 mOsm/kg of plasma H2O
VIII. Phosphorus
C. Determination → Osmoreceptors in the hypothalamus respond quickly to small
A. Clinical Applications
IV. Chloride changes
B. Determination
A. Clinical Applications → A 1%-2% increase in osmolality causes a fourfold increase in the
B. Determination circulating concentration of Arginine Vasopressin (AVP)
I. INTRODUCTION TO ELECTROLYTES (antidiuretic hormone)
● Electrolytes → 1%-2% decrease in osmolality shuts off AVP production
→ Ions capable of carrying an electric charge 𝑇𝑜𝑡𝑎𝑙 𝑚𝑜𝑙𝑒𝑠 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒 (𝑜𝑠𝑚𝑜𝑙𝑒𝑠)
→ Found in blood, urine, tissues, and other body fluids
𝑂𝑠𝑚𝑜𝑙𝑎𝑙𝑖𝑡𝑦 = 𝑊𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑠𝑜𝑙𝑣𝑒𝑛𝑡 (𝑘𝑔)
● Electroneutrality 𝑇𝑜𝑡𝑎𝑙 𝑚𝑜𝑙𝑒𝑠 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒 (𝑜𝑠𝑚𝑜𝑙𝑒𝑠)
→ Fluid always contains equal number of cations and anions 𝑂𝑠𝑚𝑜𝑙𝑎𝑟𝑖𝑡𝑦 = 𝑉𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝑠𝑜𝑙𝑣𝑒𝑛𝑡 (𝐿)
→ Ensues equilibrium or balance in body
● Dissociation of solutes into charged particles (ions) depends on: Table 2. Reference Ranges for Osmolality
→ Chemical composition of the compound Reference Value
→ Concentration of other charge particles in the medium Serum 275-295 mOsm/kg
A. FUNCTIONS Urine (24 h) 300-900 mOsm/kg
● Volume and osmotic regulation Urine/serum ratio 1.0-3.0
→ Na, Cl, K Random urine 50-1,200 mOsm/kg
● Myocardial rhythm and contractility Osmolal gap 5-10 mOsm/kg
→ K, Ca, Mg Body’s Responses to Changes in Blood Osmolality and Blood
● Important cofactors in enzyme activation Volume
→ Ca, Mg, Zn, K, Cl
● Regulation of ATPase ion pumps
→ Mg
● Neuromuscular excitability
→ K, Ca, Mg
● Production and use of ATP from glucose
→ Mg, PO4
● Maintenance of acid-base balance
→ HCO3, K, Cl, PO4
▪ used to produce buffers
● Replication of DNA and the translation of mRNA
→ Mg
B. FOOD SOURCES
Table 1. Food Sources of Electrolytes
Figure 1. Responses to changes in blood osmolality and blood volume.
Sodium Potassium Chloride
ANP: atrial natriuretic peptide; ADH: antidiuretic hormone; ACE:
Processed foods Green leafy vegetables Seafood angiotensin-converting enzyme. Primary stimuli are shown in boxes.
Cheese (spinace, kale) Seaweeds
Breads Tomatoes Rye ● Hypovolemia or decreased water volume in the body would cause
Cereals Cucumbers Tomatoes less renal perfusion pressure
Sauces Pumpkin Lettuce ● Decreased renal perfusion pressure would stimulate kidneys to
Pickled foods Carrots Celery produce renin
Commercial rice Potatoes and sweet Olives ● Renin would convert angiotensinogen to angiotensin I
Pasta mixes potatoes ● In the lungs, angiotensin I would be converted by
Condiments Banana angiotensin-converting enzyme (ACE) to angiotensin II
Avocado ● Angiotensin II causes vasoconstriction of arteries
Beans and peas → compensate for low blood pressure due to low volume
Milk ● Angiotensin II also stimulates adrenal glands to produce
Yogurt aldosterone
Calcium Magnesium Phosphorus → retain Na+ in the blood and excrete K+ to the urine, leading to
Milk Legumes Milk water retention to counteract hypovolemia
Milk alternatives Nuts Milk products II. SODIUM
Soya Seeds Meat alternatives ● Natrium in Latin
Nuts Fish (beans, lentils, nuts) ● Present in all body fluids
Green leafy vegetables Whole grains Grains → Found in highest concentration in the blood and extracellular fluid

Trans # 11 Group A: Surname, Surname, Surname 1 of 10

● Major extracellular cation ▪ Drinking too much water
● One of the most readily available electrolytes nowadays → Water imbalance
● Good food preservative ● Can also be classified according to serum/plasma osmolality:
→ Dehydrate food products making them last long → Low osmolality
● Can increase blood pressure → Normal osmolality
→ Sodium attracts water: higher sodium in blood → increase water → High osmolality
retention → increased volume → increased blood pressure ● Symptoms
Functions → depend on serum level
● Major contributor of osmolality → 125-130 mmol/L
● Has a central role in maintaining the normal distribution of water in ▪ GI symptoms
the body and osmotic pressure in the ECF compartments → <125 mmol/L
→ Water status of a person is not dependent on the amount of water ▪ Nausea, vomiting, muscular weakness, headache, lethargy,
on the body but on the amount of sodium ataxia
● Helps in controlling the blood pressure ▪ Severe hyponatremia can lead to muscle twitching and
● Proper functioning of muscles and nerves seizures, coma, and death
→ <120 mmol/L for 48 or less (acute hyponatremia)
Table 3. Reference Ranges for Sodium ▪ considered a medical emergency
Reference Value ● Treatment
Serum, plasma 135-145 mmol/L → correction of either water loss / Na+ loss in excess of water loss
Urine (24 h) 40-220 mmol/d, varies with diet
Cerebrospinal fluid 135-150 mmol/L
A. REGULATION
● Plasma concentration depends on the intake and excretion of
water
● Obtained from food and drink and lost primarily in sweat and urine
● Regulated by the kidneys
● Kidneys maintain a consistent level of sodium in the body by
adjusting the amount excreted in the urine
→ Natriuretic peptides
▪ hormones that can increase the amount of of sodium in urine
→ Aldosterone
▪ hormones that can decrease the amount of of sodium in urine
→ Antidiuretic hormone (ADH) or Vasopressin (AVP)
▪ hormone that prevents water losses
→ Controlling thirst
▪ Even 1% increase in blood sodium would stimulate thirst

Figure 3. Activities in the Brain during Hyponatremia

● Brain is very sensitive to water balance, thus sodium (Na+) levels
must be maintained
● Normonatremia
→ balance of osmolality in ECV and ICV
→ no net movement or equilibrium of water between ECV and ICV
● Hyponatremia
→ Low levels of sodium (Na+) outside the brain cells (ECV)
▪ imbalance: more water (H2O) than sodium (Na+)
→ More solute (Na+) inside the brain cells (ICV)
→ Water enters the brain cells = excess water in the brain forming
edema
▪ could lead to derangement of brain structure and function
Figure 2. Hormones acting in a nephron. − causing seizure, lethargy, coma, and death
● Three important processes in the regulation of sodium: ● Major Causes:
1. Intake of water in response to thirst → Increased Na+ Loss
2. Excretion of water ▪ Kidney problems
3. Blood volume status ▪ Hypoadrenalism
● Abnormal blood sodium levels ▪ Potassium deficiency
→ When the level of sodium in the blood changes, the water content ▪ Diuretic use
in the blood also changes ▪ Ketonuria
→ Can result to: ▪ Salt-losing nephropathy
▪ Dehydration - too little fluid ▪ Prolonged vomiting or diarrhea
▪ Edema - too much fluid ▪ Severe burns
B. CLINICAL APPLICATIONS → Increased Water Retention
▪ Renal failure
Hyponatremia ▪ Nephrotic syndrome
● <135 mmol/L ▪ Hepatic cirrhosis
● <130 mmol/L: clinically significant ▪ Congestive heart failure
● Most common electrolyte disorder → Water Imbalance
● Caused by: ▪ Excess water intake
→ Increased Na+ loss ▪ Syndrome of inappropriate arginine vasopressin hormone
→ Increased water retention secretion (SIADH)

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 ▪ Pseudohyponatremia → Decreased water intake, or
● Classifications of Hyponatremia by Osmolality → Increased Na+ intake or retention
Table 4. Classifications of Hyponatremia by Osmolality ● Less common
Low Osmolality Normal Osmolality High ● In persons who may be thirsty but who are unable to ask for or
Osmollality obtain water, e.g. Comatose/bedridden patients
● Chronic hypernatremia in alert patient
Increased Increase non-sodium cations Hyperglycemia
→ Indicative of a hypothalamic disease since there’s no response
sodium loss
to thirst
Increased water Lithium excess Mannitol
● Causes:
retention infusion
→ Dehydration from not drinking enough fluids
● diuretic
→ Diarrhea
● decrease
→ Kidney dysfunction
pressure/
→ Diuretics
total body
→ Excessive sweating
water
→ Hormonal imbalance
● act like
▪ low ADH
glucose
▪ low aldosterone
Increased gamma globulins-cationic → Diabetes insipidus
(multiple myeloma) ▪ copious production of dilute urine (3 to 20L/day)
Severe hyperkalemia ▪ frequent urination
Severe hypermagnesemia → Excess ingestion of salt
Severe hypercalcemia → Administration of hypertonic solutions of Na+
Pseudohyponatremia ● Measurement of urine osmolality is used to evaluate the cause of
Hyperlipidemia hypernatremia
Hyperproteinemia ● Classifications of Hypernatremia by Urine Osmolality
Pseudohyperkalemia (due to in vitro Table 5. Classifications of Hypernatremia by Urine Osmolality
hemolysis <300 mOsm/kg 300-700 mOsm/kg >700 mOsm/kg
Pseudohyponatremia Diabetes insipidus Partial defect in AVP Loss of thirst
● Fake low sodium levels in the blood due to technical misreading release or response to AVP
● Reduction of serum sodium concentration by a systematic error in Osmotic diuresis Insensible loss of water
measurement (breathing, skin)
● Hyperlipidemia: presence of excess lipids in serum GI loss of hypotonic
→ Sodium ions look less concentrated fluid
→ No sodium ions are dissolved in lipids Excess intake of
sodium

● Symptoms: usually involve the CNS; almost the same with

hyponatremia
→ Altered mental status
→ Lethargy
→ Irritability
→ Restlessness
→ Seizures
→ Muscle twitching
→ Hyperreflexia
→ Fever
Figure 4. Hyperlipidemia → Nausea or vomiting
● If the absolute amount of sodium in a given volume of serum is → Difficult respirations
determined (flame photometry), this value is divided by the sample → Increased thirst
volume to get the concentration ● >160 mmol/L sodium levels is associated with a mortality rate of
→ Falsely low value of sodium can be obtained since part of this 60-75%
sample volume is lipid that has no sodium ● Treatment is directed at correction of the underlying condition
→ Hypernatremia must be corrected gradually because too rapid
Hypernatremia can induce cerebral edema and death (brain is too sensitive)
● High sodium levels in the blood ▪ Recommended rate of decrease:12 mmol/L per 24 hours
● Sodium level: > 145 mmol/L
C. DETERMINATION
● Specimen:
→ Serum
→ Plasma (suitable anticoagulants: lithium heparin, ammonium
heparin, or lithium oxalate)
→ Urine (24h)
→ Sweat
● Methods
→ Ion-Selective Electrode (ISE) is the most routinely used
→ Atomic Absorption Spectrophotometry (AAS)
→ Flame Emission Spectrophotometry (FES)

III. POTASSIUM
Figure 5. Hypernatremia ● Major intracellular cation
● Excess loss of water relative to: ● Comes from fruits and vegetables
→ Na+ loss ● Has a blood pressure-lowering effect
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 → In contrast with sodium that increases blood pressure ▪ Acute leukemia
● Functions: → Cellular shift
→ Regulation of neuromuscular excitability ▪ Alkalosis
→ Contraction of the heart ▪ Insulin overdose
→ ICF volume → Decreased intake
→ H+ concentration ● Symptoms:
● Plasma K+ affects the resting membrane potential (RMP) of the cell → Mild hypokalemia (3-3.4 mmol/L) usually causes no symptoms
(RM is closer to zero), thereby affecting cell excitability → A larger decrease (<3 mmol/L) can cause muscle weakness,
→ Muscle needs potassium to be stimulated cramping, twitches and even paralysis
● Obtained from food and drink and loses it primarily in urine, some in ▪ Abnormal heart rhythms may develop in people who have a
the digestive tract and sweat heart disorder or are taking digoxin even when there is only
● Dietary deficiency or excess is rarely a primary cause of mild hypokalemia
hypo-/hyperkalemia; with a preexisting condition, it only enhances → If hypokalemia lasts for an extended time, kidney problems may
the degree of hypo-/hyperkalemia develop, causing the person to urinate frequently and drink large
Table 6. Reference Values for Potassium amounts of water.
Plasma, Serum 3.5 - 5.1 mmol/L ● Treatment:
● Males: 3.5 - 4.5 → Oral KCl replacement of K+ over several days
● Females: 3.4 - 4.4 → Chronic mild hypokalemia can be corrected simply by including
food with high K+ content (dried fruits, nuts, bran cereals,
Urine (24 h) 25-125 mmol/d
bananas, and orange juice) in the diet
● Highest in newborn children: up to 6.5 mmol/L
Hyperkalemia
A. REGULATION
● High level of potassium in the blood
● Levels are mainly controlled by aldosterone, a hormone produced ● Causes:
by the adrenal glands in the kidneys → Decreased renal excretion
● Three factors that influence the distribution of K+ between cells and ▪ Acute or chronic renal failure (GFR <20 mL/min)
ECF: ▪ Hypoaldosteronism
→ K+ loss frequently occurs whenever the Na+,K+-ATPase pump in ▪ Addison’s disease
the cell membrane is inhibited by conditions such as: ▪ Diuretics
▪ hypoxia − Certain diuretics are potassium-sparing; they induce
▪ hypomagnesemia urination without excreting potassium
▪ digoxin overdose → Cellular shift
→ Insulin promotes acute entry of K+ into skeletal muscle and liver ▪ Acidosis
by increasing Na+, K+-ATPase activity ▪ Muscle/cellular injury
▪ used in hyperkalemia ▪ Chemotherapy
→ Catecholamines: ▪ Leukemia
▪ Epinephrine (β2-stimulator) ▪ Hemolysis
− promote cellular entry of K+ → Increased intake
▪ Propranolol (β-blocker) ▪ Oral or intravenous replacement therapy
→ Artifactual
− impairs cellular entry of K+. ▪ Sample hemolysis
● Exercise causes K+ release from the muscle cells ▪ Thromobocytosis
→ Reversible after several minutes rest because it enters ▪ Prolonged tourniquet use or excessive fist clenching
Na+,K+-ATPase pump → Patients with hyperkalemia often have an underlying disorder,
→ Forearm exercise during venipuncture can cause erroneous high such as renal insufficiency, diabetes mellitus, or metabolic
plasma K+ concentration acidosis, that contributes to hyperkalemia
● Hyperosmolality, as with uncontrolled diabetes mellitus, causes → Cell damage such as rhabdomyolysis and hemolysis, kidney
water to diffuse from the cells carrying K+ with it → gradual depletion failure
of K+ if kidney function is normal ▪ Since potassium is an intracellular cation, any form of cell
● Cellular breakdown releases K+ into the ECF damage can increase potassium.
→ E.g. severe trauma, tumor lysis syndrome, massive blood ● Symptoms:
transfusions → ≥8 mmol/L: muscle weakness, tingling, numbness, or mental
→ Ensure immediate testing as prolonged blood storage may cause confusion by altering neuromuscular conduction
lysis of blood that could lead to falsely increased K+ → Severe hyperkalemia can cause abnormal heart rhythms;
→ If the level is very high, the heart can stop beating
B. CLINICAL APPLICATIONS ● Treatment:
Hypokalemia → should be initiated when serum K+ is 6.0-6.5 mmol/L
● Low level of potassium in the blood → Ca2+ provides immediate but short-lived protection to the
● Causes: myocardium against the effects of hyperkalemia
→ Gastrointestinal loss ▪ Counteracts the effects of hyperkalemia to a certain extent
▪ Vomiting → Hemodialysis can be used if other measures fail
▪ Diarrhea ▪ Best intervention is to remove the excess or transfer it to the
▪ Gastric suction intracellular space.
▪ Intestinal tumor → Insulin can promote the movement of potassium towards
▪ Malabsorption intracellular space by activating Na-ADPase
▪ Cancer therapy: chemotherapy, radiation therapy C. DETERMINATION
▪ Large doses of laxatives ● Specimen
→ Renal loss → Sample must be collected carefully to avoid artifactual
▪ Diuretics therapy: thiazides, mineralocorticoids hyperkalemia.
− most common ▪ Coagulation – releases K+ from platelets
− decreases blood pressure by decreasing fluid volume in the ▪ Thrombocytosis - lead to excessive coagulation
body → excessive urination → excretion of potassium ▪ Tourniquet left on the arm too long
▪ Nephritis − Nasisira ang mga muscles → falsely increased levels
▪ Renal tubular acidosis ▪ Excessive exercising of the forearm or fist
▪ Hyperaldosteronism ▪ Improper storage, muscle contraction, and blood cell lysis can
▪ Cushing’s syndrome lead to falsely increased levels
▪ Hypomagnesemia
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 ▪ Serum, plasma (using heparin), urine
− Specimen of choice is blood
● Methods:
→ Ion-Selective Electrode (ISE)
▪ most routinely used
▪ uses valincomycin membrane
→ Atomic Absorption Spectrophotometry
→ Flame Emission Spectrophotometry (FES)
IV. CHLORIDE
● Major extracellular anion
● Chloride concentrations mirror those of sodium –
→ increasing and decreasing for the same reasons
→ direct relationship with sodium
● When there is an acid-base imbalance, blood chloride levels can
change independently of sodium
● Chloride acts as a buffer and helps maintain electrical neutrality at
the cellular level by moving into or out of the cells as needed
→ Two ways that Cl- maintains electrical neutrality:
1. Na+ is reabsorbed along with Cl- in the proximal tubules.
Available Cl- limits Na+ reabsorption.
2. Chloride shift
2.1. CO2 generated by cellular metabolism within the tissue
diffuses out into both the plasma and the red cell.
2.2. In the red cell, CO2 forms carbonic acid (H2CO3), which
splits into H+ and HCO3−.
2.3. Deoxyhemoglobin buffers H+, whereas the HCO3−
diffuses out into the plasma and Cl− diffuses into the red cell
to maintain the electric balance of the cell.
Figure 6. Chloride Shift Mechanism. Retrieved from Torrico (2022).
● After eating, the stomach produces acid (HCl) using the chloride in
blood and so there is usually a slight drop of Cl- level after every
meal
→ Chloride is important in digestion
→ Vomiting excretes HCl; thereby decreases chlorine levels
● Cl- from the diet is almost completely absorbed by the intestinal
tract. Excess Cl- is excreted in the urine and sweat.
→ Common sources are salty food.
A. CLINICAL APPLICATIONS
Hypochloremia
● Low level of chloride in the blood
● Occurs with any disorder that causes:
→ Low blood sodium
→ Congestive heart failure
▪ Water is not pumped adequately leading to water stasis →
decreases sodium levels
→ Prolonged vomiting or gastric suction
→ Addison disease
→ Emphysema
→ Other chronic lung diseases
● Symptoms: often resembles that of hyponatremia
Hyperchloremia
● High level of chloride in the blood
● Causes:
→ Dehydration
→ Conditions with high blood sodium
▪ Cushing syndrome
▪ Kidney disease, too much base is lost from the body
(producing metabolic acidosis)
▪ Hyperventilation (causing respiratory alkalosis)
● Symptoms: often resembles that of hypernatremia
Reference Values
Table 7. Reference Values for Chloride
Plasma, Serum 98-107 mmol/L
Urine (24 h) 110-250 mmol/d, varies with diet
B. DETERMINATION
● Specimen:
→ Serum or plasma (using lithium heparin)
▪ Serum is preferred
● Methods:
→ Ion-Selective Electrode (ISE) is the most routinely used
→ Mercurimetric Titration (Schales-Schales)
→ Colorimetric method
▪ Uses mercuric thiocyanate and ferric nitrate to form a
red-colored complex measured at 480 nm
→ Amperometric-Coulometric Titration (Cotlove Chloridometer)
▪ coulometric generation of Ag+ which combine with Cl- to
quantitate the Cl- concentration
Figure X. Reaction formula
▪ When all Cl− in a patient is bound to Ag+, excess or free Ag+
is used to indicate the endpoint. As Ag+ accumulates, the
coulometric generator and timer are turned off. The elapsed
time is used to calculate the concentration of Cl− in the
sample.
V. BICARBONATE
● Second most abundant anion in the body
● Its production in the body results from the dissociation of H2CO3
which is produced from the formation of CO2 during metabolism
→ Bicarbonate has a major role in the transport of CO2
● It also works with the other electrolytes (sodium, potassium, and
chloride) to maintain electrical neutrality at the cellular level
→ Bicorbanate can also act as a buffer
● Bicarbonate Test measures the total amount of carbon dioxide (CO2)
in the blood, which occurs mostly in the form of HCO3-
● Measuring bicarbonate as part of an electrolyte or metabolic panel
may help diagnose an electrolyte imbalance or acidosis or alkalosis
→ Ratio of carbonic acid to bicarbonate in the blood is 1:20
→ If bicarbonate levels are increased, there is alkalosis
→ If bicarbonate levels are decreased, there is acidosis
● Lungs and kidneys are the major organs involved in regulating
blood pH through the removal of excess bicarbonate
→ The lungs flush acid out of the body by exhaling CO2
→ The kidneys eliminate acids in the urine and regulate the
concentration of bicarbonate in blood
● Drugs affect bicarbonate levels.
→ Increases bicarbonate levels
▪ Fludrocortisone, barbiturates, bicarbonates, hydrocortisone,
diuretics, and steroids
→ Decreases bicarbonate levels
▪ Methicillin, nitrofurantoin, tetracycline, thiazide diuretics, and
triamterene
● Reference range: 23-29 mmol/L (venous -- plasma, serum)
A. DETERMINATION
Electrolyte Panel
● Measures the blood levels of the main electrolytes in the body:
sodium (Na+), potassium (K+), chloride (Cl-), and bicarbonate
(HCO3-; sometimes reported as total CO2)
● Used to identify an electrolyte, fluid, or pH imbalance (acidosis or
alkalosis)
● Used to investigate conditions such as dehydration, kidney disease,
lung disease or heart conditions
● Ordered when a patient is exhibiting the ff. signs and symptoms: fluid
accumulation (edema), nausea or vomiting, weakness, confusion
and/or irregular heartbeat (cardiac arrhythmias)
● If there is a single electrolyte imbalance, repeat tests may be done to
that particular electrolyte for monitoring until it resolves
● If there is acid-base imbalance, additional test for blood gases may
be ordered
→ Measure the pH, oxygen and carbon dioxide levels in an arterial
blood sample

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 → Evaluate the severity of the imbalance and useful in monitoring ● Helps build and maintain strong bones and teeth
response to treatment and in diagnosing ● Essential for cell signaling and functioning of muscles, nerves, and
● Method: heart.
→ Ion-Selective Electrode → Calcium ions needed for muscle contraction
→ Enzymatic → Any dysregulation or problem can lead to abnormalities in
● Specimen: Serum (preferred) or plasma functions of the muscles including the heart
● Container: ● Also needed for proper blood clotting
→ Gel-barrier tube (preferred) ● Regulated by calcitonin, vitamin D, and parathyroid hormone
→ Red-top tube or green-top (heparin) tube is acceptable if (PTH)
centrifuged within 45 minutes and the serum or plasma is ● Levels are tightly controlled
removed and placed in a tightly-stoppered secondary tube → If too low: calcium can be taken from bone to maintain blood
● Avoid hemolysis calcium levels
Basic Metabolic Panel → calcium in bones is not only for structural purposes but also for
● Also known as Chem 7 storage purposes.
● Set of tests that provides information about the current status of A. REGULATION
patient’s metabolism including: ● PTH released when there is a decrease in calcium in the blood
→ kidney health (test for blood urea nitrogen (BUN), creatinine) → Signals kidneys to stop excreting calcium
→ blood glucose level (test for glucose) → Signals bones to release calcium to blood
→ electrolytes and acid base balance (test for Na+, K+, Cl-, HCO3-) ● Vitamin D3, a cholecalciferol, is converted to
▪ Usually, calcium is also included in electrolytes tested 25-hydroxycholecalfierol (25-(OH)-D3) which becomes
● Panel includes kidney tests, electrolytes and glucose test dihydroxycholecalciferol (1,25(OH)-D3) in kidneys
● Often ordered in ER settings because it can indicate acute problems → increases calcium levels by increasing gastrointestinal absorption
like: of calcium
→ kidney failure → also enhances effect of PTH or bone resorption
→ insulin shock or diabetic coma ● Calcitonin decreases Ca levels by inhibiting both vitamin D and PTH
→ respiratory distress Note. See appendix for figure.
→ heart rhythm changes B. CLINICAL APPLICATIONS
● Specimen: Serum (preferred), can also use plasma,
● Container: gel-barrier tube (preferred), red top tubes, and green top Hypocalcemia
(heparinized) tubes. ● Low levels of calcium in blood
● Blood may be drawn after 10-12 hrs. fasting or random basis in case ● Causes:
of an emergency. → hypoparathyroidism
● Results of tests are evaluated together to look for patterns of a ▪ Not enough PTH produced; no calcium from bones, calcium
disease condition excretion is not stopped
→ hypomagnesemia
Anion Gap → Vitamin D deficiency
● Usually total amount of cations are equal to total amount of anions → kidney dysfunction
● Anion gap is measurement of difference between negatively and → low consumption of calcium
positively charged electrolytes → pancreatitis
● If anion gap is either too high or too low it can be a sign of: ● Symptoms: Usually none, but sometimes can cause tetany, unusual
→ disorder in lungs movement, parang nanginginig yung muscles
→ disorder in kidneys → long term hypocalcemia may develop dry scaly skin, brittle nails,
→ disorder in other organ systems coarse hair
→ ingestion of toxin → extremely low levels may cause:
● Acidosis: Too much acid in blood ▪ tingling
● Alkalosis: Not enough acid in blood ▪ muscle aches
● Presence of anion gap if AG formula is greater than 12 ▪ spasms of the throat muscles
𝐴𝑛𝑖𝑜𝑛 𝐺𝑎𝑝 (𝐴𝐺) = 𝑆𝑜𝑑𝑖𝑢𝑚 − (𝐶ℎ𝑙𝑜𝑟𝑖𝑑𝑒 + 𝐵𝑖𝑐𝑎𝑟𝑏𝑜𝑛𝑎𝑡𝑒) ▪ stiffening and spasms of muscles
▪ seizures
▪ abnormal heart rhythms
Hypercalcemia
● High level of calcium in the blood
● Causes:
→ primary hyperthyroidism
→ too much calcium intake
→ too much vitamin D intake
→ certain bone disorders
→ cancer
→ inactivity (immobilized or paralyzed)
Figure 7. Anion Gap. Retrieved from Torrico (2022). ● Symptoms: constipation, nausea, vomiting, abdominal pain, loss of
● High anion gap means presence of other component that equalizes appetite, dehydration, increased thirst.
anions with cations → Severe hypercalcemia may cause brain dysfunction as
→ Can refer to High Anion Gap Metabolic Acidosis (HAGMA) manifested by:
▪ If you have HAGMA, you may have certain conditions like: ▪ confusion
− uremia ▪ emotional disturbances
− diabetes ▪ delirium
− poisoning with excessive medications like iron, ibuprofen, ▪ hallucinations
isoniazid ▪ coma
− lactic acidosis → One of the most common problems in long term hypercalcemia
VI. CALCIUM are kidney stones.containing calcium
● Most abundant mineral in the body C. DETERMINATION
→ Used for the mineralization of bone that is why it is the most ● Specimen: serum, plasma (should be heparinized (lithium heparin) if
abundant. plasma) anaerobic
● 99% of it found in bones and 1% circulates in blood ● Can be measured as total calcium or ionized calcium
● 50% of blood Ca+ is free and metabolically active, 40% bound to ● Methods:
plasma proteins, 10% complexed to anions
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 → Total calcium ▪ Reference but not routinely done in clinical laboratory
▪ Spectrophotometrically analyzed with metallochromic → Photometric methods on automated analyzers
indicators (orthocresolpthalein complexone and Arsenazo III ▪ uses metallochromic indicators such as calmagite, formazan
are commonly used) yellow dye, magon and titan yellow dye
▪ Titration of fluorescent calcium complex with EDTA ● Reference range:
▪ Atomic Absorption Spectrophotometry (AAS) → Serum, colorimetric: 0.63-1.0 mmol/L or 1.26-2.10 mg/dL
− Reference method VIII. PHOSPHORUS
▪ Clark and Collip Method (Redox Titration)
● Very important electrolyte, major component of ATP, the energy
→ Ionized calcium
currency of the body
▪ Ion selective electrode (ISE)
● Almost all of phosphorus in the body is combined with oxygen,
● Reference ranges:
forming phosphate
→ Total Ca in serum/plasma
→ If low phosphorus, cannot produce ATP, body cannot do all the
▪ 2.15-2.50 mmol/L (8.6-10.0 mg/dL)
functions it needs to do
→ Ionized Ca
● Majority of the phosphate in the body is uncharged
▪ in serum: 1.15 - 1.32 mmol/L (4.6-5.3 mg/dL)
● 85% of body’s phosphates combine with calcium to help form bones
▪ in plasma: 1.03-1.23 mmol/L (4.1-4.9 mg/dL)
and teeth
VII. MAGNESIUM ● Smaller amounts in muscle and nerve tissue
● Second most abundant intracellular cation ● Rest is found within cells throughout the body
● Fourth most abundant cation in general → Structural use as in phospholipid bi-membranes of cells
● Vital for energy production, muscle contraction, nerve function, and ● Used as a building block for several important substances
maintenance of strong bones → used by cell for energy, cell membranes, and DNA
● Stored in bones and soft tissues ● Regulation:
● In blood → Vitamin D increases phosphate in blood
→ 50% is in free/ionized form → PTH decreases phosphate in blood
→ 30% bound with protein, particularly albumin A. CLINICAL APPLICATIONS
→ 20% is complexed with other anions
● Regulation: Hypophosphatemia
→ Largely controlled by kidney like other electrolytes ● Low levels of phosphorus in the blood
▪ Reabsorbs and excretes Mg2+ as needed. ● Can be either acute or chronic hypophosphatemia
→ Appears to be related to that of Ca2+ and Na+ ● Causes:
→ PTH controls Mg balance in the same way it does Ca balance → Acute:
▪ PTH increases renal absorption and enhances absorption in ▪ severe undernutrition
the intestine − Sudden intake of food forces body to produce more cells
→ Aldosterone and thyroxine (thyroid hormone) also increases renal (hypertrophy) to store energy and the sudden
excretion overproduction depletes available phosphorus in blood
A. CLINICAL APPLICATIONS − Also called refeeding syndrome
▪ diabetic ketoacidosis
Hypomagnesemia ▪ severe alcoholism
● Low levels of magnesium in the blood ▪ severe burns
● Commonly found among ICU patients ▪ sudden drop may lead to abnormal heart rhythm or death
● Causes: → Chronic:
→ Starvation ▪ hyperparathyroidism
▪ Mga hindi kumakain, mga comatose ▪ chronic diarrhea
▪ Malabsorption of nutrients ▪ prolonged use of diuretics
− Such as those with kidney or intestinal problems ▪ prolonged use of large amounts of aluminum containing
▪ Kidneys or intestines excete too much magnesium antacids
● Symptoms: ▪ use of large amounts of theophylline (used to treat asthma)
→ Usually asymptomatic until 0.5mmol/L serum levels ● Symptoms:
→ Nausea → Muscle weakness
→ Vomiting → stupor
→ Sleepiness → weakness
→ Weakness → comatose and death
→ Sometimes manifests as personality changes → weakened bones resulting to pain and fractures
→ Muscle spasms → loss of appetite
→ Tremors
→ Loss of appetite Hyperphosphatemia
→ Severe hypomagnesemia can cause neurologic problems, ● High levels of phosphorus in the blood
particularly seizures, in children ● Very very very very rare except for people with kidney disease who
cannot excrete it
Hypermagnesemia ● Causes:
● High levels of magnesium in blood → diabetes
● Very very uncommon condition ▪ diabetic ketoacidosis,
● Causes: usually only develops when people with kidney failure are → kidney problems
given magnesium salts or magnesium containing drugs like antacids → hypoparathyroidism
(MgOH, magnesium hydroxide) and laxatives → crush injuries
● Symptoms: usually asymptomatic → rhabdomyolysis
→ muscle weakness → sepsis
→ low blood pressure ● Symptoms: Mostly no symptoms unless you have severe kidney
→ impaired breathing failure or dysfunction,
→ Severe hypermagnesemia can cause the heart to stop beating → may combine with calcium to result in hypocalcemia
B. DETERMINATION → May form crystals with calcium in the body (calcification),
● Specimen: non-hemolyzed serum, lithium heparinized plasma, urine including walls of blood vessels (arteriosclerosis)
(24-hour collection) ▪ Arteriosclerosis may lead to more detrimental conditions like
● Methods: heart attack
→ Total serum magnesium is measured mostly through Atomic B. DETERMINATION
Absorption Spectrophotometry, unlike most electrolytes ● Specimen: serum or plasma with lithium heparin

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 → hemolysis should be avoided due to high levels of phosphate in
RBCs
→ Urine (24 hr. collection)
● Methods:
→ Fiske-Subarrow method
▪ Reaction of phosphate with ammonium molybdate
→ reduction of phosphomolybdate to molybdenum blue
▪ measured spectrophotometrically at 600-700nm
→ Enzymatic methods
▪ not used much

Figure 8. Fiske-Subarrow Method. Retrieved from Torrico (2022).

● Reference ranges: 0.78-1.42mmol/L (2.4-4.4 mg/dL)
IX. REFERENCES
● Torrico, J. (2022). Electrolytes [Lecture Slides].

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 APPENDIX

Figure 1. Regulation of Calcium. Retrieved from Torrico (2022).

Figure 2. Spectrophotometric determination of calcium. Retrieved from Torrico (2022).

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