MLAB 2401: CLINICAL CHEMISTRY

1. MLAB 2401:CLINICAL CHEMISTRY WATER BALANCE & ELECTROLYTES Part Two 1

2. Electrolytes Electrolytes Substances whose molecules dissociate into ions when they are placed in water. Osmotically active particles Classification of ions: by charge CATIONS (+) In an electrical field, move toward the cathode Sodium (Na), Potassium (K), Calcium(Ca), Magnesium(Mg) ANIONS (-) In an electrical field, move toward the anode Chloride(Cl), Bicarbonate, PO4, Sulfate 2

3. 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. 3

4. 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 4

5. Electrolyte Panel Panel consists of: sodium (Na) potassium (K) chloride (Cl) and CO2 (in its ion form = HCO3- ) 5

6. Analytes of the Electrolyte Panel Sodium (Na)� the major cation of extracellular fluid Most abundant (90 %) extracellular cation Diet Easily absorbed from many foods 6

7. Function: Sodium 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 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 7

8. 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. 8

9. Reference Ranges:Sodium Serum 136-145 mEq/L or mmol/L Urine (24 hour collection) 40-220 mEq/L 9

10. Sodium Urine testing & calculation: 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. 10

11. Disorders of Sodium Homeostasis Hyponatremia: < 136 mmol/L Causes of: Increased Na+ loss Increased water retention Water imbalance Hypernatremia:> 150 mmol/L Causes of: Excess water loss Excess intake/retention Decreased water intake 11

12. Hyponatremia Increased Na+ loss Aldosterone deficiency Addison�s disease ( result in decreased 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 12

13. Hyponatremia Increased water retention Dilution of serum/plasma Na+ Renal failure Nephrotic syndrome Congestive heart failure 13

14. Hyponatremia Water imbalance Excess water intake Chronic condition 14

15. Sodium Note: Increased lipids or proteins may cause false decrease in results. This would be classified as artifactual/pseudo-hyponatremia 15

16. Clinical Symptoms of Hyponatremia Depends on the serum level Can affect GI tract Neurological Nausea, vomiting, headache, seizures,coma 16

17. Hypernatremia Excess water loss resulting Sweating Diarrhea Burns Inadequate water intake Diabetes insipidus 17

18. Hypernatremia Increased intake/retention Excessive IV therapy Decreased water intake Elderly Infants Mental impairment 18

19. Clinical Symptoms of Hypernatremia Involve the CNS Altered mental status Lethargy Irritability Vomiting Nausea 19

20. Specimen Collection: Sodium Serum (sl hemolysis is OK, but not gross) Heparinized plasma Timed and random urine Sweat GI fluids Liquid feces (would be only time of excessive loss) 20

21. Analytes of the Electrolyte Panel 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-K pump exchanges 3 Na for 1 K Diet easily consumed by food products such as bananas 21

22. Function: Potassium Critically important to the functions of neuromuscular cells Controls heart muscle contraction Promotes muscular excitability Decreased potassium decreases excitability (paralysis and arrhythmias) 22

23. Regulation of Potassium Kidneys Responsible for regulation. Potassium is readily excreted, but gets reabsorbed in the proximal tubule - under the control of ALDOSTERONE Diet 23

24. Reference Ranges: Potassium Serum (adults) 3.5 - 5.1 mEq/L or mmol/L Newborns 3.7 - 5.9 mEq/L Urine (24 hour collection) 25 - 125 mEq/L 24

25. Disorders of Potassium Homeostasis Hypokalemia < 3.5 mmol/L Causes of: GI loss Renal Loss Cellular Shift Decreased intake Hyperkalemia >5.1 mmol/L Causes of Decreased renal excretion Cellular shift Increased intake Artifactual 25

26. Hypokalemia GI loss Excessive fluid loss ( diarrhea, vomiting, diuretics ) Increased Aldosterone promote Na reabsorption � K is excreted in its place 26

27. Hypokalemia Renal Loss Nephritis, renal tubular acidosis, hyperaldosteronism, Cushing�s Syndrome Cellular Shift Alkalosis, insulin overdose Decreased intake 27

28. Mechanism of hypokalemia Increased plasma pH ( decreased Hydrogen ion ) 28

29. Clinical Symptoms of Hypokalemia Neuromuscular weakness Cardiac arrhythmia Constipation 29

30. Hyperkalemia Decreased renal excretion Renal disease Addison�s disease Hypoaldosteronism Cellular Shift Such as acidosis, chemotherapy, leukemia, muscle/cellular injury Hydrogen ions compete with potassium to get into the cells 30

31. Hyperkalemia Increased intake Insulin IVs promote rapid cellular potassium uptake Artifactual Sample hemolysis Prolonged touniquet use Excessive fist clenching 31

32. Clinical Symptoms of Hyperkalemia Muscle weakness Tingling Numbness Mental confusion Cardiac arrhythmias Cardiac arrest 32

33. Specimen Collection:Potassium Non-hemolyzed serum heparinized plasma 24 hr urine 33

34. Analytes of the Electrolyte Panel Chloride (Cl-) 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 34

35. Function: Chloride Body hydration/water balance Osmotic pressure Electrical neutrality 35

36. Regulation of Chloride 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. 36

37. Reference Ranges: Chloride Serum 98 -107 mEq/L or mmol/L 24 hour urine 110-250 mEq/L varies with intake CSF 120 - 132 mEq/L Often CSF Cl is decreased when CSF protein is increased, as often occurs in bacterial meningitis. 37

38. Determination: Chloride Specimen type Serum Plasma 24 hour urine CSF Sweat Sweat Chloride Test Used to identify cystic fibrosis patients Increased salt concentration in sweat Pilocarpine= chemical used to stimulate sweat production Iontophoresis= mild electrical current that stimulates sweat production

39. Disorders of Chloride Homeostasis Hypochloremia Decreased blood chloride Causes of : Conditions where output exceeds input Hyperchloremia Increased blood chloride Causes of: Conditions where input exceeds output 39

40. Hypochloremia Decreased serum Cl loss of gastric HCl salt loosing renal diseases metabolic alkalosis increased HCO3- & decreased Cl- 40

41. Hyperchloremia Increased serum Cl dehydration (relative increase) excessive intake (IV) congestive heart failure renal tubular disease metabolic acidosis decreased HCO3- & increased Cl- 41

42. Specimen Collection: Chloride Serum Heparinized plasma 24 hr urine Sweat 42

43. Analytes of the Electrolyte Panel Carbon dioxide/bicarbonate (HCO3-) the major anion of intracellular fluid 2nd most abundant anion of extracellular fluid Total plasma CO2= HCO3- + H2CO3- + CO2 HCO3- (bicarbonate ion) accounts for 90% of total plasma CO2 H2CO3- (carbonic acid) 43

44. Function:Bicarbonate ion 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 44

45. Regulation ofBicarbonate ion Bicarbonate is regulated by secretion / reabsorption of the renal tubules Acidosis : ? renal excretion Alkalosis : ? renal excretion 45

46. Regulation of Bicarbonate ion 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 46

47. Reference Range:Bicarbonate ion Total Carbon dioxide (venous) 23-29 mEq/L or mmol/L includes bicarb, dissolved & undissociated H2CO3 - carbonic acid (bicarbonate) Bicarbonate ion (HCO3�) 22-26 mEq/L or mmol/L 47

48. Specimen Collection: Bicarbonate ion heparinized plasma arterial whole blood fresh serum Anaerobic collection preferred 48

49. Electrolyte balance Anion gap � an estimate of the unmeasured anion concentrations such as sulfate, phosphate, and various organic acids. 49

50. Electrolyte Summary 50 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

51. Electrolyte balance Calculations Na - (Cl + CO2 or HCO3-) Reference range: 7-16 mEq/L Or (Na + K) - (Cl + CO2 or HCO3-) Reference range: 10-20 mEq/L 51

52. Anion Gap 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 52

53. References Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins. http://thejunction.net/2009/04/11/the-how-to-authority-for-donating-blood-plasma/ http://www.nlm.nih.gov/medlineplus/ency/article/002350.htm Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson . 53