

ELECTROLYTES I Both the sensation of thirst and antidiuretic hormone secretion

are stimulated by hypothalamus in response to an increase in
Ions capable of carrying an electric charge
osmolality of blood.
Cations – positive charge and move toward the cathode
Anions – negative charge, move toward the anode
Measurement of plasma, or serum and urine osmolality
 Serum osmolality is 92% due to electrolytes (e.g. sodium, chloride,
Functions
bicarbonate) and 8% due to proteins, glucose, and urea.
 Volume and osmotic regulation
 Normal Values within 285-319
 Myocardial rhythm and contractility
 Calculations (either) (serum osmolality)
 Cofactors in enzyme activation
o = 1.86 Na + glucose/18 + BUN/2.8
 Regulation of adenosine triphosphate
o = 2 Na = glucose/20 + BUN/3
 Acid-base balance
 Blood coagulation
Clinical significance of Osmolality
 Neuromuscular excitability
 Parameter to which the hypothalamus responds
 Osmolality affects the Na concentration in plasma
Water:
 Regulation of blood volume
 Average water content: 40-75% of the total body weight.
 To maintain a normal plasma osmolality, osmoreceptors in the
 Solvent of all processes in the human body
hypothalamus respond quickly to small changes in osmolality
 Transports nutrients
 A 1-2% increase in osmolality causes a four-fold increase in the
 Removes waste products by way of urine circulating concentration of ADH
 Acts as the body’s coolant  A 1-2% decrease in osmolality shuts off ADH production
o located in both intracellular and extracellular compartments.
 Renal water excretion is more important in controlling water
excess, whereas thirst is more important in preventing water
Intracellular fluid deficit or dehydration
 Fluid inside the cells and accounts for about 2⁄3 of the total body
water Water load
 Excess intake (polydipsia) - lower osmolality
Extracellular fluid
 Both ADH and thirst are suppressed
 Accounts for the other 1⁄3 of total body water o Absence of ADH
 Intravascular (plasma)  Dilute urine to be excreted
 Interstitial (surrounds the cells in the tissue)  10 L to 20 L
o Hyposmolality and hyponatremia usually occurs only in
EXTRA CELLULAR FLUID PHYSICAL PROPERTIES patients with impaired renal excretion of water
 2 important properties are ECF osmolality and ECF volume
Water Deficit
ECF Osmolality  As a deficit of water begins to increase plasma osmolality, both
 Regulated by the levels of sodium and associated anions (e.g. Cl, ADH secretion and thirst are activated
HCO3), glucose, urea and proteins  Thirst is the major defense against hyperosmolality and
 Of these solutes, sodium is the major determinant of plasma hypernatremia
osmolality. Note that of the different fluid compartments only  Hypernatremia rarely occurs in a person with normal throat
plasma is accessible for analysis mechanism and access to water (except infants, unconscious
 When there is pure water loss, an increase in the ECF Osmolality patients)
occurs  Osmotic stimulation of thirst progressively diminishes in people
 This triggers the following physiological responses who are older that age 60 years old.
o Antidiuretic hormone (ADH) or vasopressin (released by thr
posterior pituitary) via hypothalamic osmoreceptors Regulation of Blood Volume:
o Stimulation of the hypothalamic thirst center  Adequate blood volume is essential to maintain BP and ensure
o Redistribution of water from the intracellular fluid good perfusion to all tissues and organs
compartment  The renin-angiotensin-aldosterone system responds primarily to a
decrease blood volume
 Normal plasma is about 93% water, with the remaining volume  Renin is secreted near the glomeruli in response to decrease in
occupied by lipids and proteins renal blood flow
 Maintenance of ion concentration  Renin converts angiotensinogen to angiotensin I, which will
o Active transport - is a mechanism that requires energy to becomes angiotensin II
move ions across cellular membranes
o Passive transport - depends on the size and charge of the ion Angiotensin II
being transported  Vasocontstriction
 The concentration of ions and proteins on one side of the  Secretion of aldosterone
membrane or another will influence the flow of water across a Atrial natriuretic peptide, release from myocardial atria in response to
membrane volume expansion, promotes sodium excretion in the kidney

Osmolality
 A physical property of a solution, which is based on the
concentration of solutes per kilogram of solvent
Determination of Osmolality  Chloride maintains electric neutrality in two ways:
 Specimen = serum or urine o Sodium is reabsorbed along with chloride in the proximal
 Plasma = anticoagulant (interference) tubules
 Osmometer o Chloride shift
 Osmolal gap = difference between the measured osmolality and
calculated osmolality BICARBONATE
 Presence of osmolality active substances other than Na, Urea and  2nd most abundant anion in the ECF
glucose  Accounts for mor than 90% of the total CO2
 Ethanol, methanol, ethylene glycol, lactate or beta-  Due to being the largest fraction of total CO2, total CO2
hydroxybutyrate measurement is indicative of bicarbonate measurement
 Major component of the buffering system in the blood
SODIUM  Diffuses out of the cell in exchange for chloride to maintain ionic
 Most abundant cation in the ECF (90%) charge neutrality within the cell (chloride shift)
 Major contributor of plasma osmolality
 Sodium concentration in the ECF is much larger than inside cells Regulation
 In the kidneys, 85% of the bicarbonate ion is reabsorbed by the
Regulation of sodium proximal tubules, with 15% being reabsorbed by the distal tubules
 sodium concentration depends greatly on the intake and excretion
of water and, to a somewhat lesser degree, the renal regulation of MAGNESIUM
sodium  4th most abundant cation in the body
 2nd most abundant intracellular ion
Hormones  Average human contains 24g of magnesium
Aldosterone  Approx. 53% of the body magnesium is found in the bone, 46% in
 Promotes absorption of Na in the distal tubule muscles and other organs and soft tissue, and less than 1% in
 Promotes sodium retention and K excretion serum and RBCs
Atrial natriuretic peptide  Present in serum (duhh)
 Endogenous antihypertensive agent secreted from the cardiac o 1/3 is bound to protein
atria o 2/3 – 61% exists in free or ionized state and about 5% is
 Block aldosterone and renin secretion, and inhibits the action of complexed with other ions, such as phosphate and citrate
angiotensin II and vasopressin  Free ion that is physiologically active in the body
 Essential cofactor or more than 300 enzymes
POTASSIUM
 Major intracellular cation Regulation
 Only 2% of the body’s total K circulates in plasma  The overall regulation of the body magnesium is controlled largely
 Single most important analyte in terms of an abnormality being by the kidney, which reabsorbs magnesium in deficiency states of
immediately life threatening readily excretes excess magnesium in overload states
 Function:
1. Heart contraction  PTH - increases the renal reabsorption of Mg and enhances the
2. Neuromuscular excitability absorption of magnesium in the intestine
3. ICF volume regulation  aldosterone and thyroxine - increase the renal excretion of
magnesium
 Elevated plasma potassium decreases the resting membrane
potential of the cell (increase muscle excitability) leading to CALCIUM
muscle weakness  Essential for myocardial contraction
 Hyperkalemia = paralysis or fatal cardiac arrhythmia  Ionized calcium - proportional to the amplitude of heart
 Hypokalemia = decrease cell excitability by increasing the RMP contraction
 The heart may cease to contract in extreme cases of either  Protein-bound and citrate-bound calcium - no effect
hyperkalemia or hypokalemia  Decreased ionized calcium - neuromuscular irritability (tetany)
 Affects the hydrogen concentration ion concentration in the blood  Regulators:
o PTH
Regulation of Potassium o Vit D
 The kidneys are important in the regulation of potassium balance o Calcitonin
 Aldosterone
 Insulin and catecholamines promote cellular entry of potassium Parathyroid hormone
 Stimulated by a decrease in ionized calcium
CHLORIDE  PTH secretion is stopped by an increase in ionized calcium
 Major extracellular anion  Activates the process known as bone resorption
 Involved in maintaining osmolality, blood volume and electric  Conserves calcium by increasing tubular reabsorption
neutrality  Stimulates renal production of active vitamin D
 Chloride ingested in the diet is almost completely absorbed by the
intestinal tract
 Chloride ions are then filtered out by the glomerulus and passively
reabsorbed, in conjunction with sodium, by the proximal tubules
 Excess chloride is excreted in the urine and sweat.
 Excessive sweating stimulates aldosterone secretion, which acts
on the sweat glands to conserve sodium and chloride vitamin D
  Two types: ergosterol (provitamin D2) and 7-dehydrocholesterol  Helpful as a form of quality control for the analyzer used to
(provitamin D3) measure electrolytes
 Obtained either in the diet or from exposure of skin to sunlight  Consistently abnormal anion gaps in serum from healthy persons
 Increases calcium absorption in the intestine may indicate an instrument problem
 Enhances the effect of PTH on bone resorption
 Equation 1
o AG = sodium – (chloride + bicarbonate)
o Ref range: 7-16 mmol/L
 Equation 2
o AG = (sodium + potassium) – ( chloride + bicarbonate)
o Ref range: 10-20 mmol/L

Low anion gap

 Rare
 Seen in multiple myeloma (due to high protein)
 Instrument error
CALCITONIN
 Medullary cells of the thyroid Elevated AG
 Secreted when the concentration of calcium in blood increases  Uremia (phosphate retention)
 Inhibits PTH and vitamin D  Ketoacidosis
 Secreted response to hypercalcemic state  Poisoning due to ingestion of methanol, ethyl glycol, salicylate, or
paraldehyde
Distribution  Severe hydration
 99% - part of the bone
 1% - present in blood and other ECF SODIUM
o 45% - free calcium  Most abundant cation in the ECF
o 40% - bound to protein  Represents 90% of all extracellular cations
o 15% - bound to anions  Determines osmolality

PHOSPHATE Regulation:
 Phosphate deficiency can lead to ATP depletion  Plasma Na concentration depends greatly on the intake and
 The concentration of phosphate indirectly affects the release of excretion of water
oxygen from hemoglobin  The intake of water in response to thirst, as stimulated or
 Phosphate in blood may be absorbed in the intestine from dietary suppressed by plasma osmolality
sources, released from cells into blood, and lost from the bone  The excretion of water, largely affected by ADH release in
response to changes in either blood volume or osmolality
 PTH – increases renal excretion of phosphate  The blood volume status, which affects sodium excretion through
 Vitamin D – facilitates absorption in the intestine and aldosterone , angiotensin II and ANP
reabsorption in the kidney
 Growth hormone – decreases renal excreation Hormones affecting Na levels
 Predominant intracellular anion ALDOSTERONE
 About 80% of total body pool of phosphate is contained in bone  It promotes absorption of sodium in the distal tubule
 It promotes sodium retention and potassium excretion
LACTATE
 By product of and emergency mechanism that produces small ATRIAL NATRIURETIC PEPTIDE
amounts of ATP when O2 delivery is severely diminished  It is an endogenous anti-hypertensive agent secreted from the
 Pyruvate – lactate instead of pyruvate to acetyl-CoA cardiac atria
 The release of lactate into the blood has clinical importance  It blocks aldosterone and renin secretion
because the accumulation of excess lactate in blood is an early,  Inhibits the action of angiotensin II and vasopressin
sensitive, and quantitative indicator of severity of O2 deprivation  It causes natriuresis

Regulation HYPERNATREMIA
 The liver is the major organ for removing lactate by converting  Excess water loss
lactate back to glucose by process called gluconeogenesis  Diabetes insipidus
 Renal tubular disorder
Anion Gap  Prolonged diarrhea
 Routine measurement of electrolytes usually involves only  Profuse sweating
sodium, potassium, chloride and bicarbonate  Severe burns
 Difference between unmeasured anions and unmeasured cations  Vomiting
 AG id crested by the concentration difference between commonly  Fever
measure cations (Na and K) and commonly measured anions (Cl  Hyperventilation
and HCO3)
 Useful in indicating an increased in one of the unmeasured anions
in the serum
  Decreased water intake  Addition of water to the precipitate produces a yellow solution
 Increased intake or retention of sodium
o Conn’s disease
o Sodium bicarbonate infusion
o Ingestion of seawater
o Increased oral intake or IV of NaCl

 Hypernatremia - serum sodium level > 145 mmol/L

 Usually results from excessive water loss
 Perspiration and breathing - 1 liter water loss per day
 150-160 (moderate water deficit)
 165 (severe water deficit)
 Chronic hypernatremia - indicative of hypothalamic disease
 Thirst - major defense against hyperosmolality and hypernatremia

HYPONATREMIA
 increased sodium loss
o Diuretic use
 Increased water retention
o Renal failure
o Aldosterone deficiency
o Cancer
o SIADH
o Hepatic cirrhosis
o Primary polydipsia
o CNS abnormalities
o Myxedema

 Most common electrolyte disorder

 Less than 135 mmol/L
 Clinical concern - less than 130
 Urine Na is more than 20 mmol/day - renal loss
 For every 100 mg/dL increase in blood glucose, serum Na
decreases by 1.6 mmol/L
 SIADH - excess water retention
 Symptoms of hyponatremia occurs when the serum level is 125-
130 mmol/L

Pseudohyponatremia
 Caused by system error in measurement
 In vitro hemolysis
 Artifactual hyponatremia - hyperlipidemia and hyperproteinemia

METHODS
1. FEP
2. ION SELECTIVE ELECTRODE - most commonly used mtd.
3. AAS
4. COLORIMETRY

DETERMINATION of SODIUM
 Serum sodium may be measured using emission flam photometry,
atomic absorption spectrophotometry, or ion-selective electrodes
 A colorimetric method called Albanese-Lein is available for sodium
 The test involves combining sodium with zinc uranyl acetate to
produce sodium uranyl acetate precipitate