CLINICAL CHEMISTRY

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CLINICAL CHEMISTRY

• ELECTROLYTES

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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

• Anion
• Anion Gap
• Cation
• Active transport
• Diffusion
• Electrolyte
• Osmolality
• Osmolality
• Polydipsia
• Tetany
• ADH
• Hypothalamus Gland
• Renin - Angiotensin - Aldosterone System

• Hyper / Hypo natremia , kalemia, calcemia
• Parathyroid Hormone ( PTH )
• Acidosis / Alkalosis
• Calcitonin
• Ion Selective Electrode
• Na Sodium
• K Potassium
• Cl Chloride
• CO2 Carbon Dioxide
• Ca Calcium
• Mg Magnesium
• PO4 Phosphate

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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

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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

• 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

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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 40-70 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
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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

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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

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Electrolytes

• Laboratory assessment of body hydration is often
  by determination of osmolality and specific
  gravity of urine

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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

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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

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Electrolytes

• Osmolality
• concentration of solute / kg
• reported as mOsm / kg
• another term
• Osmolarity - mOsm / L - not often used

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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
  re-absorption, produce 10 20 liters of urine
  per day

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Electrolytes

• Osmolality normal values
• Serum 275-295 mOsm/Kgm
• 24 hour urine 300-900 mOsm/Kgm
• urine/serum ratio 1.0-3.0
• Osmolal gap lt 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
• HCO3 (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
  (_at_ 80 of time)

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Electrolyte Summary

• cations ()
• Na 142
• K 5
• Ca 5
• Mg 2
• 154 mEq/L

• anions (-)
• Cl 105
• HCO3- 24
• HPO4-2 2
• SO4-2 1
• organic acids 6
• proteins 16
• 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 lt 135 mmol/L
• Increased Na loss
• Aldosterone deficiency
• Addisons 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 gt 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 Addisons

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Specimen Collection Sodium (Na)

• serum (sl hemolysis is OK, but not gross)
• 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-hyponatre
  mia

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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 ? 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)

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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 (Cushings 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
• IVS 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 )
• Addisons - hypo- adrenal hypo- aldosterone

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Specimen CollectionPotassium

• 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 ? 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

• 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 HCO3

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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) _at_ 22-30 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 _at_ 95 of the buffering capacity of
  plasma

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bicarbonate ion (HCO3- )

• Significance
• The bicarbonate ion (HCO3) 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.
• methods
• 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
• Increased AG
• uncontrolled diabetes (due to lactic keto
  acids)
• severe renal disorders
• Decreased AG -
• a decrease AG is rare, more often it occurs when
  one test/instrument error

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• Normal Ranges
• SODIUM 135 145 mEq/L
• POTASSIUM 3.5 5.0 mEq/L
• CHLORIDE 100 110 mEq/L
• CO2 20 30 mEq/L
• ANION GAP 10 - 20 meq / L
• PLASMA OSMOALITY 275 - 295 mOsmol / kg
• CALCIUM 8.5 10.0 mg/dL
• IONIZED Ca 4.5 5.5 mg/dL
• MAGNESIUM 1.2 2.1 mEq/L
• PHOSPHATE 2.5 4.5 mg/dL
• LACTATE 0.5 17.0 mgl/dl

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ELECTROYTE TOP 10

• ? 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
  HCO3-
• Chloride is usually a passive follower of Sodium
  to maintain electrical charge
• Sodium and Potassium usually move opposite each
  other
• Parathyroid Hormone ( PTH ) secretion
  increases plasma calcium , increases plasma
  magnesium and decreases phosphate
• Acidosis is associated with ? Potassium (
  Alkalosis with ? Potassium )
• Most electrolytes are measured by Ion Selective
  Electrodes ( ISE )

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Electrolyte Links
http//www.nlm.nih.gov/medlineplus/ency/article/00
2350.htm http//www.thirdage.com/health/adam/ency
/article/002350.htm