clinical chemistry chapter 13

1. 1 CLINICAL CHEMISTRYCHAPTER 13 ELECTROLYTES

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3. 3 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

4. 4 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. 5 Water ( The solvent for all electrolytes ) Intracellular : Inside cells ( ? of body water ) Extracellular : Outside cells ( ? of body water ) Intravascular : Plasma � 93% water Intersititial : Between cells

6. 6 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 ? 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 Interestingly, there seems to be no scientific basis for the 8 glasses of water per day mantra

7. 7 Plasma Sodium accounts for 90 % of plasma osmolality Diabetes insipidus ADH deficiency Without water re-absorption, 10 � 20 liters of urine per day ? Osmolality are concerns for Infants Unconscious patients Elderly

8. 8 Osmolality testing Freezing Point Depression Vapor Pressure Osmolality estimation

9. 9 Renin � Angiotensin � Aldosterone system Regulates blood volume via plasma Sodium ? blood pressure stimulates renin secretion by the renal glomeruli Angiotensinogen Renin Angiotensin I Angiotensin II Aldosterone secretion by adrenal cortex Aldosterone has two effects on blood volume / pressure : Stimulates re-absorption of sodium by the kidneys - Water passively follows sodium, increasing blood volume Aldosterone stimulates vasoconstriction � Increasing blood pressure

10. 10 Sodium ( Na ) Most abundant ( 90 % ) extracellular cation Main contributor to plasma osmolality Na-K ATPase 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 Sodium is regulated by Water intake / Output ( Thirst mechanism / ADH ) Aldosterone Reference range: 135 � 145 meq / l

11. 11 Conditions that cause hyponatremia ( Decreased Na ) Fluid loss ( hypovolemic ) Aldosterone deficiency Diabetes mellitus ( Na is excreted with ketones ) Potassium depletion ( K normally excreted , if none, then Na) No fluid loss Pregnancy Increased volume Water overload , edema Renal failure ( excretion of > 20 mmol urine sodium )

12. 12 Conditions that cause hypernatremia ( ? Na+ ) Excess water loss Sweating Diarrhea Burns Dehydration from inadequate water intake Diabetes insipidus ( ADH deficiency � ? H2O loss ) IV solutions

13. 13 Potassium ( K ) Main intracellular cation Only 2 % of potassium is in the plasma RBCs have high concentrations of potassium Important component of neuromuscular function - ? potassium promotes muscular excitability ? potassium decreases excitability ( paralysis and arrhythmias ) Regulation of potassium is performed by renal secretion / retention in response to various factors Reference Range: 3.5 � 5.0 meq / l

14. 14 Causes of hypokalemia ( decreased K ) Excessive fluid loss ( diarrhea, vomiting, diuretics ) Aldosterone promote Na reabsorption � K is excreted in its place Insulin IVs promote rapid cellular potassium uptake Increased plasma pH ( decreased Hydrogen ion )

15. 15 Causes of hyperkalemia ( Increased potassium ) IV�S Acidosis ( opposite from alkalosis ) Renal disease � impaired excretion Diabetes mellitus Decreased insulin promotes cellular K loss Hyperosomolar plasma ( from ? glucose ) pulls H2O and potassium into the plasma Tissue breakdown ( RBC hemolysis )

16. 16 Chloride ( Cl - ) Main extracellular anion Chloride moves passively with Na+ or against HCO3- to maintain neutral electrical charge Cl usually follows Na ( if one is abnormal, so is the other ) Cl is reabsorbed in the renal proximal tubules. along with sodium. Deficiencies of either one limits the reabsorption of the other. Reference Range: 100 � 110 meq / l

17. 17 Bicarbonate ( HCO3- ) or CO2 2ND most important anion Total plasma CO2 = HCO3- + H2 CO3- + CO2 HCO3- accounts for 90% of Total Plasma CO2 Most important plasma buffer Regulation: Bicarbonate is regulated by secretion / reabsorption of the renal tubules Acidosis : ? renal excretion Alkalosis : ? renal excretion Reference range : 20 � 30 meq / l

18. 18 HCO3- ( CO2 ) testing Acid reagent converts HCO3 CO2 CO2 diffuses thru a permeable membrane and into a solution CO2 HCO3- + H+ pH meter measures the change in H+ which is related to the HCO3

19. 19 Magnesium ( Mg +2 ) 2ND most abundant intracellular cation 90 % of Mg is in bones and other tissues ( 1 % in RBCs ) ? is bound to albumin ? is ionized ( active form ) 5% is bound to other ions Common enzyme activator Regulated by parathyroid hormone ( PTH ) Decreased plasma Mg stimulates secretion of PTH PTH increases renal retention and GI absorption of magnesium Reference range : 1.2 - 2.1 meq / l

20. 20 Causes of hypomagnesemia ( ? Mg ) Diuretics ( loss in excess urine ) Diabetes Renal / GI disease ? aldosterone Causes of hypermagnesemia ( ? Mg ) Magnesium sulfate is used to stop labor contractions

21. 21 Calcium ( Ca +2 ) 99 % of calcium is associated with bone tissue Only 1 % of body calcium is in the plasma 45 % ionized ( active form ) 40 % protein bound 15 % bound to other compounds Critical component of cardiac function ? ionized calcium inhibits cardiac function ? ionized calcium causes tetany Regulation Decreased plasma ionized Ca stimulates release of PTH ) PTH increases renal reabsorption of Calcium PTH stimulates Vitamin D synthesis Vitamin increases GI absorption of Calcium and release of calcium from the bone

22. 22 Calcitonin ( from the thyroid gland ) inhibits PTH and Vitamin D activity Causes of hypocalcemia Hypoparathyroidism Vitamin D deficiency Causes of hypercalcemia Hyperparathyroidism Open Heart Surgery Reference range : 8.5 - 10.0 mg / dl

23. 23 Phosphate ( PO4 ) Plasma phosphate originates from diet and bone Multiple functions DNA Coenzymes ATP 2,3-DPG Regulation PTH decreases plasma phosphate ( increases renal excretion ) Vitamin D and Growth Hormone increase renal reabsorption Reference range : 2.5 - 4.5 mg / dl

24. 24 Causes of hypophospatemia ( ? phosphtate ) Ketoacidosis IV�s Antacids Causes of hyperphosphatemia ( ? phosphate ) Renal failure Infant over comsumption of milk Cellular catabolism ( leukemia )

25. 25 Summary of Calcium, Magnesium and Phosphate Regulation

26. 26 Lactate By-product of ATP synthesis in O2 poor cells Liver converts lactate to glucose ( gluconeogenesis ) Sensitive indicator of oxygen deprivation and prognosis Specimen Grey top ( inhibits glycolysis ) on ice Perform testing ASAP

27. 27 Anion Gap Anion Gap is the difference between unmeasured cations and anions Example : Na = 140 K = 4.0 Cl = 100 CO2 = 25 Anion Gap = 19 Low anion gaps may indicate instrument error High anion gaps are associated with acidosis Reference Range : 10 - 20 meq / L

28. 28 Ion Selective Electrodes ( ISE ) are utilized for the measurement of many electrolytes Sodium ( Na ) Potassium ( K ) Chloride ( Cl ) Calcium ( Ca ) Lithium ( Li ) ISE�s are electrochemical cells with the following components Reference Electrode Measurement Electrode Ion sensitive membranes

29. 29 ISEs Reference electrode conducts electrical current at a known potential Sample electrodes have membranes that are selectively sensitive to the effects of a particular ion � This electrode is placed in contact with the patient�s plasma Selective membranes can be made from special glass, plastics or liquids A measurement of the electrical potential between the reference and sample electrode allows for measurement of the effects of the patient�s cation or anion

30. 30 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

31. 31 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 )

32. 32 Electrolyte Links