1. CLINICAL CHEMISTRY
ELECTROLYTES

2. 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.

3. Chapter KEY TERMS Anion Anion Gap Cation Active transport Diffusion
Electrolyte
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

4. 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

5. 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- )

6. 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

7. 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.

8. 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)

9. Electrolytes

10. 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

11. 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.

12. 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

13. Electrolytes
Laboratory assessment of body hydration is often by determination of osmolality and specific gravity of urine

14. 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

15. 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

16. Electrolytes Osmolality another term: concentration of solute / kg
reported as mOsm / kg
another term:
Osmolarity - mOsm / L - not often used

17. Electrolytes Determination
2 methods or principles to determine osmolality
Freezing point depression
(the preferred method)
Vapor pressure depression
Also called ‘dewpoint’

18. 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

19. 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 units difference
(measured – calculated = 10 to 15)

20. 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

21. Electrolytes Decreased osmolality Diabetes insipidus ADH deficiency
Because they have little / no water re-absorption, produce 10 – 20 liters of urine per day

22. Electrolytes Osmolality normal values Serum – 275-295 mOsm/Kgm
24 hour urine – mOsm/Kgm
urine/serum ratio –
Osmolal gap < mOsm (depending on author)

23. 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

24. Electrolytes Anions – have a negative charge - move toward the anode
Cl– (1st) most abundant extracellular anion
HCO–3 – (bicarbonate) second most abundant extracellular anion

25. Electrolytes
Phosphate is sometimes discussed as an electrolyte, sometimes as a mineral.
HPO / H2PO-4
when body pH is normal, HPO-24 is the usual form 80 % of time)

26. Electrolyte Summary cations (+) anions (-) Na 142 K 5 Ca 5 Mg 2
154 mEq/L
anions (-)
Cl 105
HCO
HPO4-2 2
SO4-2 1
organic acids 6
proteins 16
154 mEq/L

27. 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

28. 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

29. 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.

30. Sodium (Na) Aldosterone From the (adrenal cortex) Functions
promote excretion of K
in exchange for reabsorption of Na

31. Sodium (Na) Sodium normal values Serum – 135-148 mEq/L
Urine (24 hour collection) – mEq/L

32. 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.

33. 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

34. 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

35. 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 )

36. 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

37. 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)

38. Sodium (Na)
Note:
Increased lipids or proteins may cause false decrease in results. artifactual/pseudo-hyponatremia

39. Sodium (Na) Sodium determination direct measurement
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)

40. 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.

41. 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)

42. 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)

43. Potassium (K) Regulation Diet Kidneys easily consumed (bananas etc.)
Kidneys - responsible for regulation. Potassium is readily excreted, but gets reabsorbed in the proximal tubule - under the control of ALDOSTERONE

44. Potassium (K) Potassium normal values Serum (adults) – 3.5 - 5.3 mEq/L
Newborns slightly higher – mEq/L
Urine (24 hour collection) – mEq/L

45. Hypokalemia Effects Decrease in K concentration
neuromuscular weakness & cardiac arrhythmia

46. 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

47. 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 )

48. 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

49. Hyperkalemia Causes Tissue breakdown ( RBC hemolysis )
Addison’s - hypo- adrenal; hypo- aldosterone

50. Specimen Collection:Potassium
Non-hemolyzed serum
heparinized plasma
24 hr urine.

51. Potassium (K) Determination
Ion-selective electrode (valinomycin membrane)
insensitive to H+, & prefers K X over Na+
Flame photometry
- K λ 766 nm

52. 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

53. 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.

54. Chloride ( Cl - ) Normal values Serum – 100 -110 mEq/L
24 hour urine – mEq/L
varies with intake
CSF – mEq/L

55. Hypochloremia Decreased serum Cl loss of gastric HCl
salt loosing renal diseases
metabolic alkalosis;
increased HCO3- & decreased Cl-

56. Hyperchloremia Increased serum Cl dehydration (relative increase)
excessive intake (IV)
congestive heart failure
renal tubular disease
metabolic acidosis
decreased HCO3- & increased Cl-

57. Specimen Collection: Chloride
Serum
heparinized plasma
24 hr urine
sweat

58. Chloride ( Cl - ) Determination Amperometric/Coulometric titration
involves titration with silver ions.

59. Chloride ( Cl - ) Mercurimetric titration of Schales and Schales
Precipitate protein out - 1 st step
Titrate using solution of mercury
Hg 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

60. Chloride ( Cl - ) Colorimetric Procedure suitable for automation
Chloride complexes with mercuric thiocyanate
forms a reddish color proportional to amt of Cl in the specimen.

61. 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

62. Chloride ( Cl - ) CSF chloride
NV = mEq/L (higher than serum)
Often CSF Cl is decreased when CSF protein is increased, as often occurs in bacterial meningitis.

63. 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

64. bicarbonate ion (HCO3- )
Total plasma CO2 =
HCO H2CO3- + CO2
HCO3- (carbonate ion) accounts for 90% of total plasma CO2
H2CO3- carbonic acid (bicarbonate)

65. bicarbonate ion (HCO3- )
Regulation:
Bicarbonate is regulated by secretion / reabsorption of the renal tubules
Acidosis : ↓ renal excretion
Alkalosis : ↑ renal excretion

66. 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

67. bicarbonate ion (HCO3- )
CO2 Transport forms
8% dissolved in plasma
dissolved CO2
27% carbamino compounds
C02 bound to hemoglobin
65% bicarbonate ion
HCO carbonate ion

68. bicarbonate ion (HCO3- )
Normal values
Total Carbon dioxide (venous) mmol/L
includes bicarb, dissolved & undissociated H2CO3 - carbonic acid (bicarbonate)
Bicarbonate ion (HCO3–) – mEq/L

69. 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 95% of the buffering capacity of plasma

70. 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

71. 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

72. Electrolyte balance
Anion gap – an estimate of the unmeasured anion concentrations such as sulfate, phosphate, and various organic acids.

73. 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.

74. Electrolyte balance Causes in normal patients Increased AG –
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

75. PLASMA OSMOALITY 275 - 295 mOsmol / kg CALCIUM 8.5 – 10.0 mg/dL
Normal Ranges
SODIUM – 145 mEq/L
POTASSIUM – 5.0 mEq/L
CHLORIDE – 110 mEq/L
CO – mEq/L
ANION GAP meq / L
PLASMA OSMOALITY mOsmol / kg
CALCIUM – mg/dL
IONIZED Ca – mg/dL
MAGNESIUM – mEq/L
PHOSPHATE – mg/dL
LACTATE – mgl/dl

76. 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 )

77. Electrolyte Links