CLINICAL CHEMISTRY 2

Electrolytes

I. Introduction
 Ions capable of carrying an electric charge
 Two types of Ions:
A. Anions B. Cations
 Carry (-) charge and move toward the anode  Carry (+) charge and move toward the cathode
 E.g. Cl-, HCO3-, PO4-  E.g. Na+, K+, Mg2+, Ca2
 Functions of Electrolytes
1. Volume and osmotic regulation (Na+, Cl-, K+) 5. Regulation of ATPase ion pumps (Mg2+)
2. Myocardial rhythm and contractility (K+, Mg2+, Ca2+) 6. Acid-base balance (HCO3-, K+, Cl-)
3. Neuromuscular Excitability (K+ ,Mg2+, Ca2+) 7. Production and use of ATP from glucose (Mg2+, PO4-)
4. Cofactors in enzyme activation (Mg2+, Ca2+, Zn2+)

II. Water
A. Introduction
 40-75% of body weight
 Function Transport nutrients to the cells and Removes waste products
 Location: ICF: 2/3 E CF: 1/3 Intravascular (25%) and interstitial fluid (75%)
B. Osmolality:
• Concentration of ions is maintained by: 1. Passive Transport
• Passive movement of ions across a membrane
2. Active Transport
• Requires energy to move ions across a membrane
• ATPase-dependent ion pumps
i. Definition: Conc. of solutes per Kg of solvent (millimoles/kg)
ii. Regulation
a. Thirst Sensation • Response to consume more fluids
• Prevents water deficit
b. Arginine vasopressin hormone (AVP) • Antidiuretic Hormone (ADH)
• ↑ rea sorptio of ater i kid e s
• Suppressed in excess H2O load
• Activated in water deficit
c. Renin-angiotensin-aldosterone • ↑ Na+ retention, aldosterone release, vessel constriction
system
d. Atrial natriuretic Peptide (ANP) • ↑ Na+ excretion in the kidney
e. Glomerular Filtration Rate (GFR) • ↑ / ol. e pa sio a d ↓ / ol. depletio
iii. Determination
Any substance dissolve in a solvent will:
• ↓ freezing point by 1.858°C • ↓ freezing point by 1.858°C
• ↑ boiling point by 0.52°C • ↑ boiling point by 0.52°C
Main contributors are Na, Cl, Urea and Glucose
Distribution of Body Water in Adult
Compartment (%) of Body Weight (%) of Total Body H2O
Extracellular
Plasma 5 8
Interstitial 15 25
Intracellular 40 67
Total Body Water 60 100

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II. Electolytes

A. Sodium (Na+)

i. Description and Regulation

 The most abundant cation
in the ECF
 Major Extracellular cation
 Na+, K+ -ATPase ion pump
moves 3 Na+ ions out of the
cell in exchange for 2 K+ ions
 Plasma concentration depends in renal regulation
a. Intake of water  Thirst
b. Excretion of water  AVP ↑ H2O reabsorption)
c. The blood volume status • A giote si II ↑ aldostero e
• Aldostero e ↑ Na+ reabsorption in kidney)
• ANP ↑ Uri ar Na + Excretion )

ii. Clinical Applications

Causes of Hypo atre ia (↓ Na+) Causes of Hyper atre ia (↑ Na+)
. ↑ Sodiu (Na+) Loss . ↑ Water Rete tio 1. Excess Water Loss 2. Decreased Water Intake
a. Hypoaldosteronism a. Renal failure a. Diabetes insipidus a. Old/Infant/Mentally Impaired
b. K+ Deficiency b. SIADH b. Profuse sweating 3. Increased Intake or Retention
c. Diuretic Use c. Nephrotic syndrome c. Severe burns a. Cushing Syndrome
d. Salt-losing nephropathy d. Chronic heart failure b. Hyperaldosteronism
e. Severe Burns e. Hepatic cirrhosis c. Hypertonic Salt Solution

iii. Determination of Sodium

Specimen Methods
a. Serum, Plasma (heparin and oxalate) a. FES
b. False ↑ ith arked he ol sis b. AAS
c. ISE (Glass ion-exchange membrane)

B. Potassium (K+)

i. Description and Regulation iii. Determination of Potassium

 Major Intracellular cation 1. Aldosterone • Specimen
 Regulation of neuromuscular ↑ K+ excretion in urine) a. Serum, Plasma (heparin)
excitability, contraction of 2. Na+, K+ -ATPase pump b. False ↑ ith he ol sis
heart, ICF volume, H+ conc. (↓ fu tio ↓ ellular e tr ) c. 24 hour urine
• ↑ K+, ↑ ell e ita ility (↑ fu tio ↑ ellular e tr ) • Methods
(muscle weakness) 3. ↑ ith e er ise, dia etes a. FES
• ↓ K+ , ↓ ell e ita ilit mellitus and cell breakdown b. AAS
(arrhythmia/paralysis) c. ISE (valinomycin membrane)
ii. Clinical Applications
Causes of Hypokalemia (↓K+) Causes of Hyperkalemia (↑K+)
1. GI Loss 3. Renal Loss 1. Decreased Renal Excretion 3. Cellular Shift
a. Vomiting a. Diuretics a. Renal Failure a. Acidosis
b. Diarrhea b. Renal Tubular Acidosis b. Hypoaldesteronism b. Muscle/cellular injury
c. Gastric suction c. Cushi g’s s dro e . Addiso ’s Disease c. Chemotherapy / Leukemia
d. Laxatives d. Hyperaldosteronism 2. Increased Intake 4. Artifactual
2. Cellular Shift - e. Hepatic cirrhosis a. Oral/IV – K+ replacement a. Hemolysis, Thrombocytosis
↑ K+ uptake 4. Decreased Intake b. Prolonged tourniquet
a. Alkalosis
b. Insulin Overdose

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C. Potassium (K+)
i. Description and Regulation
 Major Extracellular anion
 Involve in maintaining
Osmolality,blood volume
and electric neutrality
(Chloride shift)
 Rate limiting component
in Na+ reabsorption
ii. Clinical Applications
Causes of Hyperchlore ia (↑Cl-)
1. Excess Loss of HCO3-
a. GI Losses
b. Metabolic acidosis
D. Bicarbonate (HCO3-)
i. Description and Regulation
 2nd Most Abundant anion in
the ECF
 Accounts for more than
80% of total CO2
(Chloride shift)
 Major buffering system
of the blood
ii. Clinical Applications
Metabolic Alkalosis ↑ HCO3-
a. Severe vomiting
b. Hypoventilation
c. Excessive alkali intake
E. Magnesium (Mg)
i. Physiology and Regulation
 2nd Major Intracellular cation
 Neuromuscular conduction
Enzyme cofactor and
ATPase ion pump
 53% (Bone), 46% (muscle,
soft tissues), <1% (Blood)
 Serum: 33% (protein bound),
61% (ionized),5% (complexed
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CLINICAL CHEMISTRY 2
iii. Determination of Potassium
1. Aldosterone • Specimen
↑ K+ excretion in urine) a. Serum, Plasma (lithium heparin)
2. Na+, K+ -ATPase pump b. False ↓ ith arked he ol sis
(↓ fu tio ↓ ellular e tr ) c. 24 hour urine
(↑ fu tio ↑ ellular e tr ) • Methods
3. ↑ ith e er ise, dia etes a. ISE ( Use ion exchange membrane)
mellitus and cell breakdown b. Amperometric-coulometric
(Cotlove Chloridometer)
Ag2+ +2Cl- -> Ag Cl2
Cause of Hypochlore ia (↓Cl-) c. Scales and Schales
2. Excess Loss of Cl- Titration with mercuric nitrate
a. Prolonged Vomiting
b. Aldosterone Deficiency
c. Salt-losing pyelonephritis
iii. Determination of Bicarbonate
1. Aldosterone • Specimen
↑ K+ excretion in urine) a. Serum, Plasma (heparin)
2. Na+, K+ -ATPase pump b. False ↓ if left uncapped
(↓ fu tio ↓ ellular e tr ) ↓6 ol/L per hr
(↑ fu tio ↑ ellular e tr ) • Methods
3. ↑ ith e er ise, dia etes a. Enzyme method
mellitus and cell breakdown
Metabolic acidosis ↓ HCO3-
a. Hyperventilation
1. Parathyroid Hormone (PTH) - ↓ Mg2+
 Promotes Ca + renal reabsorption
2. Aldosterone and thyroxine - ↓ Mg2+
 Promotes Na + renal reabsorption
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 CLINICAL CHEMISTRY 2

ii. Clinical Applications

Causes of Hypomagnesemia (↓Mg+) Cause of Hypo ag ese ia ( ↓ Mg+) - ↑ Excretion
1. Reduced Intake 2. ↓ Absorption 4. Renal 5. Endocrine
a. Poor diet/starvation a. Malabsorption synd. a. Tubular disorders, a. Hyperparathyroidism
b. Prolonged Mg+- deficient IV b. Diarrhea Pyelonephritis b. Hyperaldosteronism
3. Others c. Vomiting b. Glomerulonephritis c. Hyperthyroidism
a. Excess lactation d. Laxative 6. Drug Induced d. Hypercalcemia
b. Pregnancy a. Furosemide, Thiazide e. Diabetic ketoacidosis
b. Gentamicin, Cyclosporin
c. Digitales and Digoxin
Causes of Hyper ag ese ia (↑ Mg 2+ ) iii. Determination of Magnesium
a. ↓ E retio , Re al failure • Specimen
b. Hypoparathyroidism a. Serum, Plasma (lithium heparin), 24 hr urine
c. Hypoaldosteronism b. He ol sis ause False ↑
e. Bone carcinoma and bone metastases • Method
a. Calmagite Mtd. Mg2+ + CalmagiteReddish-violet (532nm)
b. Formazen Dye Mtd. Mg2+ + DyeColored complex (660 nm)
c. Methylthymol blue Mtd. Mg2+ + ChromogenColored complex
d. Titan Yellow Serum TCA filtrate+titan yellowRed cmpd.

F. Calcium (Ca+2)

i. Physiology and Regulation

 For muscle contraction and blood coagulation Factors affecting Ca+2 level in blood:
 99% in bone and teeth and 1% in blood and ECF 1. Bone resorption Cause ↑ Ca+2 in blood
 Calcium in the blood is distributed as PTH mobilizes Ca+2 from the bone
1. Ionized Unbound/ free, physiologically active 2. Bone deposition Cause ↓ Ca+2 in blood
45% of Total Calcium Calcitonin inhibits PTH and Vit.D
2.Protein bound Bound to protein (E.g. albumin)/40% 3. Intestinal absorption Vitamin D ↑ Ca+2 in the intestine
3. Complex Ca+2 Bound to anions
(E.g. HCO3-, PO4- & lactate)/15%
Causes of Hypocalcemia Cause of Hypercalcemia
(↓ Ca+) (↑ Ca+)
a. Hypoparathyroidism a. Hyperparathyroidism
b. Hypo/hypermagnesemia b. Malig a ↑PTHrP
c. Hypoalbuminemia c. ↑ Vita i D
d. Acute pancreatitis d. Thiazide diuretics
e. Vitamin D deficiency e. Prolonged immobilization
e. Rhabdomyolysis

iii. Determination of Calcium

• Specimen
a. Serum, Plasma (Dry lithium heparin), 24 hr urine b. Hemolysis cause False ↑
• Method
a. AAS, ISE d. Clark and Collip (Redox Titration method)
b. Ortho-cresolphthalein complexone (CPC) e. Ferro and Ham (Precipitation with Chloranilic acid)
c. Alizarin, Arsenzo III dye, Methyl phenol blue

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 CLINICAL CHEMISTRY 2

F. Phosphate

i. Physiology and Regulation

 Major Intracellular anion
 Component of phospholipids, nucleic acids, creatine phosphate and ATP
 80% - bone, 20% - soft tissues, 1% - serum/plasma
 GH ↓ re al e retio of phosphate

ii. Clinical Applications

Causes of Hypophosphate ia (↓ PO4-) Cause of Hyperphosphate ia (↑ PO4-)
a. Hyperparathyroidism a. ↑ I take
b. Vitamin D Deficiency b. ↑ release of cellular phosphate
c. ↑ breakdown of cells
iii. Determination of Sodium
Specimen Methods
Serum, Plasma (lithium heparin), 24 hour urine Ammonium phosphomolybdate comp.(340nm)
He ol sis ause False ↑ Fiske-Subbarow Method (Final product: Molybdenum blue)

G. Lactate

i. Description and Regulation

 Indicator of severity of O2 deprivation (hypoxia)
 Li er o erts la tate a k to glu ose Glu o eoge esis

ii. Clinical Applications

Hypoxic Conditions (Type A)
a. Lactate Acidosis
b. Shock, MI, Severe CHF
c. Pulmonary edema, severe blood loss
Lactate Acidosis
Metabolic Origin (Type B)
a. Diabetes Mellitus, Liver disease
b. Toxins (ethanol, methanol or salicylate poisoning)

IV. Anaion Gap

• Mathematical approximation of difference between the concentration of unmeasured cations & unmeasured anions
• (Na+) – (Cl- + HCO3-)
• 7-16 mEq/L
• ↑ A io gap
• ↑ u easured a io s
• Uremia
• Ketoacidosis
• Lactic acidosis
• ↑i easured atio s
• Hypernatremia
• ↓ A io gap
• ↓ u easured a io s
• Hypoalbuminemia
• ↑ i u easured atio s:
• Hypermagnesemia
• Hypercalcemia

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