CLINICAL CHEMISTRY� ELECTROLYTES

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.

1. CLINICAL CHEMISTRYCLINICAL CHEMISTRY
ELECTROLYTESELECTROLYTES
1
By
SATHISHKUMAR G
([email protected])

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.
2

3. 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
3

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
4

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- )
5

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
6

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.
7

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)
8

9. Electrolytes
9

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
10

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.
11

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
12

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

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
14

15. Electrolytes
Osmolality -
"­ osmolality stimulates two responses
that regulate water
–Hypothalamus stimulates the sensation of
thirst
–Posterior pituitary secrets ADH
•( ADH increases H
2O re-absorption by renal
collection ducts )
•In both cases, plasma water increases
15

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

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

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
18

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

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
20

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

22. 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 < 10-15 mOsm (depending on
author)
22

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
23

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
24

25. Electrolytes
•Phosphate is sometimes discussed as
an electrolyte, sometimes as a
mineral.
–HPO
-2
4
/ H
2
PO
-
4

–when body pH is normal, HPO
-2
4
is the
usual form (@ 80 % of time)
25

26. Electrolyte Summary
•cations (+)
•Na 142
•K 5
•Ca 5
•Mg 2
•154 mEq/L
•anions (-)
•Cl 105
•HCO3- 24
•HPO4-22
•SO4-2 1
•organic acids 6
•proteins 16
» 154 mEq/L
26

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
27

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
28

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.
29

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

31. Sodium (Na)
•Sodium normal values
–Serum – 135-148 mEq/L
–Urine (24 hour collection) – 40-220
mEq/L
31

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.
32

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
33

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
34

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 …­ H
2
O loss )
35

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
36

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)
37

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

39. 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)
39

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.
40

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)
41
1
20
=
OUTSIDE
INSIDE

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)
42

43. 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
43

44. 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
44

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

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
46

47. Causes of hypokalemia
•Increased plasma pH ( decreased Hydrogen ion )
47
K
+
moves into RBCs to preserve electrical balance,
causing plasma potassium to decrease.
( Sodium also shows a slight decrease )
H
+
K
+
RBC

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
↑
H
2
O and potassium into the plasma
48

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

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

51. Potassium (K)
•Determination
–Ion-selective electrode (valinomycin
membrane)
• insensitive to H+, & prefers K+ 1000
X over Na+
–Flame photometry
•- K λ 766 nm
51

52. Chloride ( Cl
-
)
•Chloride - the major anion of extracellular
fluid
–Chloride moves passively with Na
+
or against
HCO
3
-
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
52

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.
53

54. Chloride ( Cl
-
)
•Normal values
–Serum – 100 -110 mEq/L
–24 hour urine – 110-250 mEq/L
• varies with intake
–CSF – 120-132 mEq/L
54

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

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

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

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

59. 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
59

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.
60

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
61

62. 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.
62

63. bicarbonate ion (HCO
3
-
)
•Carbon dioxide/bicarbonate –
–* the major anion of intracellular fluid
–2
nd
most important anion (2
nd
to Cl)
•Note: most abundant intra-cellular
anion
•2
nd
most abundant extra-cellular
anion
63

64. bicarbonate ion (HCO
3
-
)
•Total plasma CO
2
=
HCO
3
-
+ H
2
CO
3
-
+ CO
2
–HCO
3
-
(carbonate ion) accounts for
90% of total plasma CO
2
–H
2
CO
3
-
carbonic acid (bicarbonate)
64

65. bicarbonate ion (HCO
3
-
)
•Regulation:
–Bicarbonate is regulated by
secretion / reabsorption of the
renal tubules
–Acidosis : renal excretion
↓
–Alkalosis : renal excretion
↑
65

66. bicarbonate ion (HCO
3
-
)
•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
⇋ →
66

67. bicarbonate ion (HCO
3
-
)
CO
2
Transport forms
–8% dissolved in plasma
•dissolved CO2
–27% carbamino compounds
•C02 bound to hemoglobin
–65% bicarbonate ion
•HCO3- - carbonate ion
67

68. bicarbonate ion (HCO
3
-
)
•Normal values
–Total Carbon dioxide (venous) – @ 22-
30 mmol/L
•includes bicarb, dissolved & undissociated
H2CO3 - carbonic acid (bicarbonate)
–Bicarbonate ion (HCO3–) – 22-26 mEq/L
68

69. bicarbonate ion (HCO
3
-
)
•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
69

70. bicarbonate ion (HCO
3
-
)
•Significance
–The bicarbonate ion (HCO–3) is the
body's major base substance
–Determining its concentration provides
information concerning metabolic
acid/base
70

71. bicarbonate ion (HCO
3
-
)
•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
71

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

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.
73

74. 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
74

75. Normal Ranges
SODIUM 135 – 145 mEq/L
POTASSIUM 3.5 – 5.0 mEq/L
CHLORIDE 100 – 110 mEq/L
CO
2
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
75

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 “COPlasma “CO
22” = Dissolved CO” = Dissolved CO
2 2 + H + H
2 2 COCO
33 + HCO + HCO
33
--
•Chloride is usually a passive follower of Sodium to maintain electrical Chloride is usually a passive follower of Sodium to maintain electrical
chargecharge
•Sodium and Potassium usually move opposite each otherSodium and Potassium usually move opposite each other
•Parathyroid Hormone ( PTH ) secretion secretion increases plasma calcium , ,
increases plasma magnesium and and decreases phosphatedecreases phosphate
•Acidosis is associated with ­ Potassium ( Alkalosis with ¯ Potassium )
•Most electrolytes are measured by Ion Selective Electrodes ( ISE )
76

77. 77
Thank you