CLINICAL CHEMISTRY
ELECTROLYTES
1
Introduction
– This chapter is largely about the water
and electrolytes ( salts )in your plasma and
how the body manages to keep you from
drying up and blowing away even if you are
in the hot Texas sun and without liquid
drink.
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Chapter KEY TERMS
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Anion
Anion Gap
Cation
Active transport
Diffusion
Electrolyte
Osmolality
Osmolality
Polydipsia
Tetany
ADH
Hypothalamus Gland
Renin - Angiotensin Aldosterone System
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Hyper / Hypo … natremia ,
kalemia, calcemia
Parathyroid Hormone ( PTH )
Acidosis / Alkalosis
Calcitonin
Ion Selective Electrode
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Na = Sodium
K
= Potassium
Cl = Chloride
CO2 = Carbon Dioxide
Ca = Calcium
Mg = Magnesium
PO4 = Phosphate
3
General Objectives
• Define the key terms
• Discuss the factors that regulate each of the electrolytes
• Discuss the physiological functions and clinical significance of
each of the electrolytes
• Discuss ISE and Osmometers
4
Electrolytes
• Electrolytes
– Substances whose molecules dissociate into ions
when they are placed in water.
– CATIONS (+)
ANIONS (-)
• Medically significant / routinely ordered electrolytes
include:
– sodium (Na)
– potassium (K)
– chloride (Cl)
– and CO2 (in its ion form = HCO3- )
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Electrolyte Functions
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Volume and osmotic regulation
Myocardial rhythm and contractility
Cofactors in enzyme activation
Regulation of ATPase ion pumps
Acid-base balance
Blood coagulation
Neuromuscular excitability
Production of ATP from glucose
6
Electrolytes
• General dietary requirements
– Most need to be consumed only in small
amounts as utilized
– Excessive intake leads to increased excretion
via kidneys
– Excessive loss may result in need for
corrective therapy
• loss due to vomiting / diarrhea; therapy required
- IV replacement, Pedilyte, etc.
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Electrolytes
• Water (the diluent for all
electrolytes) constitutes 4070% of total body and is
distributed:
– Intracellular – inside cells
• 2/3 of body water
(ICW)
– Extracellular – outside cells
•
1/3 of body water
– Intravascular – plasma
93% water
» Intrastitial -surrounds the
cells in tissue (ISF)
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Electrolytes
9
Electrolytes
• Ions exist in all of these fluids, but the
concentration varies depending on individual
ion and compartment
• The body uses active and passive transport
principles to keep water and ion concentration
in place
10
Electrolytes
• Sodium has a pulling effect on water
– Na affects extracellular fluids (plasma &
interstitial) equally.
– However, because there is considerably more Na
outside cells than inside, the water is pulled out
of cells into the extracellular fluid.
– Na determines osmotic pressure of extracellular
fluid.
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Electrolytes
• Proteins (especially albumin) inside the
capillaries strongly pulls/keeps water inside
the vascular system
– Albumin provides oncotic pressure.
– By keeping Na & albumin in their place, the
body is able to regulate its hydration.
• When there is a disturbance in osmolality,
– the body responds by regulating water intake,
– not by changing electrolyte balance
12
Electrolytes
• Laboratory assessment of body
hydration is often by determination
of osmolality and specific gravity of
urine
13
Electrolytes
Osmolality • Physical property of a solution based
on solute concentration
– Water concentration is regulated by
thirst and urine output
– Thirst and urine production are
regulated by plasma osmolality
14
Electrolytes
Osmolality •  osmolality stimulates two responses
that regulate water
– Hypothalamus stimulates the sensation of
thirst
– Posterior pituitary secrets ADH
• ( ADH increases H2O re-absorption by renal
collection ducts )
• In both cases, plasma water increases
15
Electrolytes
• Osmolality
– concentration of solute / kg
– reported as mOsm / kg
• another term:
– Osmolarity - mOsm / L - not often
used
16
Electrolytes
• Determination
– 2 methods or principles to determine
osmolality
• Freezing point depression
– (the preferred method)
• Vapor pressure depression
– Also called ‘dewpoint’
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Specimen Collection
• Serum
• Urine
• Plasma not recommended due to
osmotically active substances that can be
introduced into sample
• Samples should be free of particulate
matter..no turbid samples, must centrifuge
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Electrolytes
• Calculated osmolality
– uses glucose, BUN, & Na values
– (Plasma Sodium accounts for 90 % of plasma
osmolality)
• Formula:
– 1.86 (Na) + glucose∕18 + BUN∕2.8 = calculated osmolality
• Osmolal gap = difference between calculated and
determined osmolatity
– Should be less than 10-15 units difference
• (measured – calculated = 10 to 15)
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Electrolytes
• Increase in the difference between
measured and calculated
– would indicate presence of osmo active
substances such as possibly alcohol - ethanol,
methanol, or ethylene glycol or other substance.
•  Osmolality are concerns for
– Infants
– Unconscious patients
– Elderly
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Electrolytes
• Decreased osmolality
– Diabetes insipidus
• ADH deficiency
• Because they have little / no water reabsorption, produce 10 – 20 liters of urine
per day
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Electrolytes
• Osmolality normal values
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Serum – 275-295 mOsm/Kgm
24 hour urine – 300-900 mOsm/Kgm
urine/serum ratio – 1.0-3.0
Osmolal gap < 10-15 mOsm (depending on
author)
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Electrolytes
• Classifications of ions -
by their charge
– Cations – have a positive charge - in an
electrical field, (move toward the cathode)
• Na+ = most abundant extracellular cation
• K+ = most abundant intracellular cation
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Electrolytes
– Anions – have a negative charge - move
toward the anode
• Cl– (1st) most abundant extracellular anion
• HCO–3 – (bicarbonate) second most
abundant extracellular anion
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Electrolytes
• Phosphate is sometimes discussed as
an electrolyte, sometimes as a
mineral.
– HPO-24 / H2PO-4
– when body pH is normal, HPO-24 is the
usual form (@ 80 % of time)
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Electrolyte Summary
• cations (+)
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Na 142
K
5
Ca
5
Mg
2
154 mEq/L
• anions (-)
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Cl 105
HCO324
HPO4-2
2
SO4-2
1
organic acids 6
proteins
16
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154 mEq/L
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Routinely measured electrolytes
• Sodium –
– the major cation of extracellular fluid outside
cells
– Most abundant (90 %) extracellular cation
– Functions - recall influence on regulation of
body water
• Osmotic activity - sodium determines osmotic activity
(Main contributor to plasma osmolality)
• Neuromuscular excitability - extremes in concentration
can result in neuromuscular symptoms
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Routinely measured electrolytes
• Diet - sodium is easily absorbed
• Na-K
ATP-ase Pump
– pumps Na out and K into cells
• Without this active transport pump, the
cells would fill with Na and subsequent
osmotic pressure would rupture the cells
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Regulation of Sodium
• Concentration depends on:
– intake of water in response to thirst
– excretion of water due to blood volume or osmolality
changes
• Renal regulation of sodium
– Kidneys can conserve or excrete Na+ depending on ECF
and blood volume
• by aldosterone
• and the renin-angiotensin system
– this system will stimulate the adrenal cortex to
secrete aldosterone.
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Sodium (Na)
• Aldosterone
– From the (adrenal cortex)
– Functions
• promote excretion of K
• in exchange for reabsorption of Na
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Sodium (Na)
• Sodium normal values
– Serum – 135-148 mEq/L
– Urine (24 hour collection) – 40-220
mEq/L
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Sodium (Na)
• Urine testing & calculation:
– 1st. Because levels are often increased, a
dilution of the urine specimen is usually
required.
– Then the result from the instrument (mEq/L or
mmol/L) X # L in 24 hr.
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Clinical Features: Sodium
• Hyponatremia: < 135 mmol/L
– Increased Na+ loss
• Aldosterone deficiency
– Addison’s disease (hypo-adrenalism, result in ➷
aldosterone)
• Diabetes mellitus
– In acidosis of diabetes, Na is excreted with
ketones
• Potassium depletion
– K normally excreted , if none, then Na
• Loss of gastric contents
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Hyponatremia
• Increased water retention
– Dilution of serum/plasma Na+
– excretion of > 20 mmol /mEq urine
sodium)
• Renal failure
• Nephrotic syndrome
• Water imbalance
– Excess water intake
– Chronic condition
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Hypernatremia
• Excess water loss resulting in dehydration
(relative increase)
– Sweating
– Diarrhea
– Burns
– Dehydration from inadequate water intake,
including thirst mechanism problems
– Diabetes insipidus
• (ADH deficiency … H2O loss )
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Hypernatremia
• Excessive IV therapy
• comatose diabetics following
treatment with insulin. Some Na in
the cells is kicked out as it is
replaced with potassium.
– Cushing's syndrome - opposite of
Addison’s
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Specimen Collection:
Sodium (Na)
• serum (sl hemolysis is OK, but not gross)
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heparinized plasma
timed urine
sweat
GI fluids
• liquid feces (would be only time of
excessive loss)
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Sodium (Na)
Note:
• Increased lipids or proteins may
cause false decrease in results.
artifactual/pseudo-hyponatremia
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Sodium (Na)
• Sodium determination
– Ion-selective (specific) electrode
• Membrane composition = lithium aluminum silicate glass
• Semi-permeable membrane allows sodium ions to cross
300X faster than potassium and is insensitive to
hydrogen ions.
• direct measurement
– where specimen is not diluted
– gives the truest results
– systems that dilute the sample give lower
results (called dilutional effect)
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Sodium (Na)
– Flame emission spectrophotometry (flame
photometer)
• Na emits λ 589 nm (yellow)
• Use internal standard of lithium or cesium
• Possible for a dilutional error to occur in some
flame photometer systems, but literature does
not dwell on it.
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Routinely measured
electrolytes
• Potassium
(K)
– the major cation of intracellular fluid
• Only 2 % of potassium is in the plasma
• Potassium concentration inside cells is 20 X
greater than it is outside.
• This is maintained by the Na pump,
(exchanges 3 Na for 1 K)
INSIDE
20

OUTSIDE
1
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Potassium
(K)
• Function – critically important to the
functions of neuromuscular cells
– Critical for the control of heart
muscle contraction!
• ↑ potassium promotes muscular
excitability
• ↓ potassium decreases excitability
(paralysis and arrhythmias)
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Potassium
(K)
• Regulation
– Diet
• easily consumed (bananas etc.)
– Kidneys
• Kidneys - responsible for regulation.
Potassium is readily excreted, but gets
reabsorbed in the proximal tubule - under
the control of ALDOSTERONE
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Potassium
(K)
• Potassium normal values
– Serum (adults) – 3.5 - 5.3 mEq/L
– Newborns slightly higher – 3.7 - 5.9
mEq/L
– Urine (24 hour collection) – 25 - 125
mEq/L
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Hypokalemia
• Decrease in K concentration
• Effects
• neuromuscular weakness & cardiac
arrhythmia
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Causes of hypokalemia
– Excessive fluid loss ( diarrhea, vomiting,
diuretics )
– ↑ Aldosterone promote Na reabsorption … K
is excreted in its place (Cushing’s syndrome
= hyper aldosterone)
– Insulin IVs promote rapid cellular potassium
uptake
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Causes of hypokalemia
• Increased plasma pH ( decreased Hydrogen ion )
RBC
H+
K+
K+ moves into RBCs to preserve electrical balance,
causing plasma potassium to decrease.
( Sodium also shows a slight decrease )
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Hyperkalemia
• Increased K concentration
• Causes
– IV’S or other increased intake
– Renal disease – impaired excretion
– Acidosis (Diabetes mellitus )
• H+ competes with K+ to get into cells & to be
excreted by kidneys
• Decreased insulin promotes cellular K loss
• Hyperosomolar plasma (from ↑ glucose) pulls
H2O and potassium into the plasma
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Hyperkalemia
• Causes
– Tissue breakdown ( RBC hemolysis )
– Addison’s - hypo- adrenal; hypoaldosterone
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Specimen Collection:Potassium
• Non-hemolyzed serum
• heparinized plasma
• 24 hr urine.
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Potassium
(K)
• Determination
– Ion-selective electrode (valinomycin
membrane)
• insensitive to H+, & prefers K+ 1000
X over Na+
– Flame photometry
• - K λ 766 nm
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Chloride ( Cl
-
)
• Chloride - the major anion of extracellular
fluid
– Chloride moves passively with Na+ or against
HCO3- to maintain neutral electrical charge
– Chloride usually follows Na (if one is
abnormal, so is the other)
– Function - not completely known
• body hydration
• osmotic pressure
• electrical neutrality & other functions
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Chloride ( Cl
-
)
• Regulation via diet and kidneys
– In the kidney, Cl is reabsorbed in the
renal proximal tubules, along with
sodium.
– Deficiencies of either one limits the
reabsorption of the other.
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Chloride ( Cl
-
)
• Normal values
– Serum – 100 -110 mEq/L
– 24 hour urine – 110-250 mEq/L
• varies with intake
– CSF – 120-132 mEq/L
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Hypochloremia
• Decreased serum Cl
– loss of gastric HCl
– salt loosing renal diseases
– metabolic alkalosis;
– increased HCO3- & decreased Cl-
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Hyperchloremia
• Increased serum Cl
– dehydration (relative increase)
– excessive intake (IV)
– congestive heart failure
– renal tubular disease
– metabolic acidosis
–
decreased HCO3- & increased Cl-
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Specimen Collection: Chloride
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Serum
heparinized plasma
24 hr urine
sweat
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Chloride ( Cl
-
)
• Determination
– Amperometric/Coulometric titration
– involves titration with silver ions.
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Chloride ( Cl
-
)
• Mercurimetric titration of Schales and Schales
– Precipitate protein out - 1 st step
– Titrate using solution of mercury
• Hg +2 + 2 Cl- = HgCl2
– When all chloride is removed, next drop of mercury will
complex with diphenylcarbazone indicator to produce violet
color = endpoint
• a calculation required to determine amt of Cl present by
the amt of Hg used
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Chloride ( Cl
-
)
• Colorimetric
– Procedure suitable for automation
– Chloride complexes with mercuric
thiocyanate
– forms a reddish color proportional to
amt of Cl in the specimen.
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Chloride ( Cl
-
)
• Sweat chloride –
– Remember, need fresh sweat to accurately measure
true Cl concentration.
– Testing purpose - to ID cystic fibrosis patients by
the increased salt concentration in their sweat.
• Pilocarpine iontophoresis
– Pilocarpine = the chemical used to stimulate the sweat
production
– Iontophoresis = mild electrical current that simulates
sweat production
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Chloride ( Cl
-
)
• CSF chloride
– NV = 120 - 132 mEq/L (higher than
serum)
– Often CSF Cl is decreased when CSF
protein is increased, as often occurs
in bacterial meningitis.
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bicarbonate ion (HCO3- )
• Carbon dioxide/bicarbonate –
– * the major anion of intracellular fluid
– 2nd most important anion (2nd to Cl)
• Note: most abundant intra-cellular
anion
• 2nd most abundant extra-cellular
anion
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bicarbonate ion (HCO3- )
• Total plasma CO2 =
HCO3- + H2CO3- + CO2
– HCO3- (carbonate ion) accounts for
90% of total plasma CO2
– H2CO3- carbonic acid (bicarbonate)
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bicarbonate ion (HCO3- )
• Regulation:
– Bicarbonate is regulated by
secretion / reabsorption of the
renal tubules
– Acidosis :
↓ renal excretion
– Alkalosis :
↑ renal excretion
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bicarbonate ion (HCO3- )
• Kidney regulation requires the enzyme
carbonic anhydrase - which is present in
renal tubular cells & RBCs
carbonic anhydrase
carbonic anhydrase
Reaction: CO2 + H2O ⇋ H2CO3 → H+ + HCO–3
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bicarbonate ion (HCO3- )
CO2 Transport forms
– 8% dissolved in plasma
• dissolved CO2
– 27% carbamino compounds
• C02 bound to hemoglobin
– 65% bicarbonate ion
• HCO3-
- carbonate ion
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bicarbonate ion (HCO3- )
• Normal values
– Total Carbon dioxide (venous) – @ 2230 mmol/L
• includes bicarb, dissolved & undissociated
H2CO3 - carbonic acid (bicarbonate)
– Bicarbonate ion (HCO3–) – 22-26 mEq/L
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bicarbonate ion (HCO3- )
• Function –
– CO2 is a waste product
– continuously produced as a result of cell
metabolism,
– the ability of the bicarbonate ion to accept a
hydrogen ion makes it an efficient and effective
means of buffering body pH
– dominant buffering system of plasma
– makes up @ 95% of the buffering capacity of
plasma
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bicarbonate ion (HCO3- )
• Significance
– The bicarbonate ion (HCO–3) is the
body's major base substance
– Determining its concentration provides
information concerning metabolic
acid/base
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bicarbonate ion (HCO3- )
• CO2 /bicarb Determination
– Specimen can be heparinized plasma,
arterial whole blood or fresh serum.
Anaerobic collection preferred.
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methods
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Ion selective electrodes
Colorimetric
Calculated from pH and PCO2 values
Measurement of liberated gas
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Electrolyte balance
• Anion gap – an estimate of the unmeasured
anion concentrations such as sulfate,
phosphate, and various organic acids.
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Electrolyte balance
• Calculations
– 1. Na - (Cl + CO2 or HCO3-) =
– NV 8-12 mEq/L
– Or
– 2. (Na + K) - (Cl + CO2 or HCO3-)
NV 7-14 mEq/L
• which one to use may depend on whether K
value is available. Some authors feel that K
value is so small and usually varies little, that
it is not worth including into the formula.
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Electrolyte balance
•
Causes in normal patients
– what causes the anion gap?
– 2/3 plasma proteins & 1/3 phosphate& sulfate ions, along with
organic acids
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Increased AG –
– uncontrolled diabetes (due to lactic & keto acids)
– severe renal disorders
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Decreased AG – a decrease AG is rare, more often it occurs when one
test/instrument error
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Normal Ranges
SODIUM
POTASSIUM
CHLORIDE
CO2
135 – 145
3.5 – 5.0
100 – 110
20 – 30
ANION GAP
10 - 20
PLASMA OSMOALITY
CALCIUM
IONIZED Ca
MAGNESIUM
PHOSPHATE
LACTATE
mEq/L
mEq/L
mEq/L
mEq/L
meq / L
275 - 295
8.5 – 10.0
4.5 – 5.5
1.2 – 2.1
2.5 – 4.5
0.5 – 17.0
mOsmol / kg
mg/dL
mg/dL
mEq/L
mg/dL
mgl/dl
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ELECTROYTE TOP 10
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 Osmolality is detected by the Hypothalamus Gland
Thirst
sensation and secretion of ADH by Posterior Pituitary Gland. ADH
increases renal reabsorption of water
•
 Blood Volume stimulates Renin - Angiotensin - Aldosterone system.
Aldosterone secretion by the Adrenal Cortex stimulates increased renal
absorption of sodium
•
Sodium is the main extracellular cation and contributor to plasma
osmolality
Potassium is the main intracellular cation
Plasma “CO2” = Dissolved CO2 + H2 CO3 + HCO3Chloride is usually a passive follower of Sodium to maintain electrical
charge
Sodium and Potassium usually move opposite each other
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Parathyroid Hormone ( PTH ) secretion increases plasma calcium ,
increases plasma magnesium and decreases phosphate
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Acidosis is associated with  Potassium ( Alkalosis with  Potassium )
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Electrolyte Links
http://www.nlm.nih.gov/medlineplus/ency/article/002350.htm
http://www.thirdage.com/health/adam/ency/article/002350.htm
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