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Electrolytes. Part 1. Cathode. Anode. Electrolytes. Electrolytes are ions capable of carrying an electricl charge Anions: (-) → Anode Cations: (+) → Cathode Major cations of the body Na + , K + , Ca +2 & Mg +2 Major anions of the body Cl - , HCO 3 - , HPO 4 -2 & SO 4 -2.

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electrolytes2

Cathode

Anode

Electrolytes
  • Electrolytes are ions capable of carrying an electricl charge
    • Anions: (-) → Anode
    • Cations: (+) → Cathode
  • Major cations of the body
    • Na+, K+, Ca+2 & Mg+2
  • Major anions of the body
    • Cl-, HCO3-, HPO4-2 & SO4-2

M. Zaharna Clin. Chem. 2009

essential component in numerous processes
Essential Component in Numerous processes
  • Volume and osmotic pressure (Na+, K+, Cl-)
  • Myocardial rhythm and contraction (K+, Mg2+, Ca2+)
  • Cofactors in enzyme activation (Mg2+, Ca2+, Zn2+).
  • Regulation of ATPase ion pump (Mg2+)
  • Acid/Base balance (pH) (HCO3-, K+, Cl-)
  • Coagulation (Mg2+, Ca2+)
  • Neuromuscular (K+, Mg2+, Ca2+)

The body has complex systems for monitoring and maintaining electrolyte concentrations

M. Zaharna Clin. Chem. 2009

slide4

Maintenance of water homeostasis is vital to life for all organisms

  • Maintenance of water distribution in various body fluids is a function of electrolytes (Na+, K+, Cl- & HCO3-)

M. Zaharna Clin. Chem. 2009

water
Water
  • Average water content of human body is 40-75% of total body weight.
    • Solvent for all body processes
    • Transport nutrients to cells
    • Regulates cell volume
    • Removes waste products → urine
    • Body Coolant → sweating
  • Water is located in intracellular and extracellular compartments

M. Zaharna Clin. Chem. 2009

water6
Water
  • Normal plasma ~ 93 % H2O, the rest is mixture of Lipids and proteins.
  • Concentration of ions within the cells and plasma is maintained by:
      • Energy consumption: Active transport
      • Diffusion: Passive transport
  • Maintaining conc. of electrolytes affect distribution of water in compartments
  • Most membranes freely permeable to water
  • Conc. of ions on one side affect flow of water across the membrane

M. Zaharna Clin. Chem. 2009

osmolality
Osmolality
  • Physical property of a solution based on the concentration of solutes per kilograms of solvent. (mOsm/Kg)
  • Sensation of thirst & arginine vasopressin hormone (AVP) [formerly, Antidiuretic hormone (ADH)] are stimulated by hypothalamus in response to increased blood osmolality
    • Thirst → more water intake
    • AVP → increase water absorption in kidney

M. Zaharna Clin. Chem. 2009

clinical significance
Clinical Significance
  • Osmolality is the parameter to which hypothalmus responds to maintain fluid intake.
  • The regulation of osmolality also affects the Na+ concentration in plasma
    • 90% of osmotic activity in plasma
  • Another process affects Na+ concentration is regulation of blood volume.

M. Zaharna Clin. Chem. 2009

clinical significance9
Clinical significance
  • To maintain normal plasma osmolality (275-295 mOsm/Kg) hypothalamus must respond quickly to small changes
    • 1-2% increase in osmolality: 4 fold increase in AVP secretion.
    • 1-2% decrease in osmolality: shuts off AVP secretion.
  • Renal water regulation by AVP and thirst play important roles in regulating plasma osmolality.
    • Renal water excretion is more important in controlling water excess,
    • whereas thirst is more important in preventing water deficit or dehydration.
  • Consider what happens in several conditions.

M. Zaharna Clin. Chem. 2009

water load
Water Load
  • Excess intake of water lower plasma osmolality
  • Kidney is important in controlling water excess
  • AVP and thirst are suppressed
  • Water is not reabsorbed, causing a large volume of dilute urine to be excreted
  • Hypoosmolality and hyponatremia usually occur in patients with impaired renal excretion of water

M. Zaharna Clin. Chem. 2009

water deficit
Water deficit
  • As a deficit of water, plasma osmolality begins to increase
  • Both AVP secretion and thirst are activated.
  • Although AVP contributes by minimizing renal water loss, thirst is the major defense against hyperosmolality and hypernatremia.
  • A concern in infants, unconscious patients, or anyone who is unable to either drink or ask for water

M. Zaharna Clin. Chem. 2009

regulation of blood volume
Regulation of blood volume
  • Blood volume essential in maintaining blood pressure and ensure perfusion to all tissue and organs.
  • Regulation of both sodium & water are interrelated in controlling blood volume
  • Renin-angiotensin-aldosterone: system of hormones that respond to decrease in blood volume and help maintain the correct blood volume.

M. Zaharna Clin. Chem. 2009

regulation of blood volume13
Regulation of blood volume
  • Changes in blood volume detected by receptors in:
    • the cardiopulmonary circulation ,
    • carotid sinus,
    • aortic arch
    • and glomerular arterioles
  • They activate effectors that restore volume by:
    • appropriately varying vascular resistance,
    • cardiac output,
    • and renal Na and H2O retention.

M. Zaharna Clin. Chem. 2009

slide14

Angiotensin converting enzyme (ACE)

M. Zaharna Clin. Chem. 2009

regulation of blood volume16
Regulation of blood volume
  • Other Factors effecting blood volume:
    • Atrial natriuretic Peptide (ANP) → sodium excretion → ↓ blood volume
    • Volume receptors → release of AVP → conserve water → ↑ blood volume
    • Glomerular filtration rate (GFR) ↑ in volume expansion and ↓ in volume depletion

M. Zaharna Clin. Chem. 2009

determination of osmolality
Determination of Osmolality
  • Serum or urine sample (plasma not recommended due to the use of anticoagulants)
  • Based on properties of a solution related to the number of molecules of solutes per kilogram of solvent such as:
    • Freezing point
    • Vapor pressure

M. Zaharna Clin. Chem. 2009

determination of osmolality18
Determination of Osmolality
  • Freezing Point Osmometer:
  • Standardized method using NaCl reference solution.
  • Specimen is supercooled to -7ºC, to determine freezing point.
  • ↑ osmolality causes depression in the freezing point temp.
  • More solutes present the longer the specimen will take to freeze.

M. Zaharna Clin. Chem. 2009

osmolal gap
OsmolalGap
  • Osmolal gap is the difference between the measured osmolality and the calculated one.

Osmolal Gap= measured osmolality - calculated osmolality

  • The osmolal gap indirectly indicates the presence of osmotically active substances other than sodium, urea or glucose. (ethanol, methanol or β-hydroxybutyrate)

M. Zaharna Clin. Chem. 2009

sodium
Sodium
  • Most abundant extracellular cation- 90%
  • Major function is maintaining the normal water distribution & osmotic pressure of plasma
  • Role in maintaining acid-base balance (Na+, H+ exchange mechanism)
  • Normal range Serum: 136-145 mmol/L
  • ATPase ion pump: the way the body moves sodium and potassium in and out of cells.
  • 3 Na+ out of the cell for every 2 K + in and convert ATP to ADP.

M. Zaharna Clin. Chem. 2009

regulation of sodium balance
Regulation of Sodium Balance
  • Plasma Na+ concentration depends:
    • on the intake and excretion of water
    • and, on the renal regulation of Na+
  • Three processes are of primary importance:
    • intake of water in response to thirst (p. osmolality)
    • the excretion of water (AVP release)
    • the blood volume status, which affects Na+ excretion through aldosterone, angiotensin II, and ANP (atrialnatriuretic peptide).

M. Zaharna Clin. Chem. 2009

regulation of sodium balance24
Regulation of Sodium Balance
  • 70 % of sodium that is filtered is reabsorbed in proximal tubules.
  • Remainder occurs in the ascending loop of Henle (without water absorption) & DCT under regulation of Aldosterone
  • Renin-Angiotensin system
  • Atrial natriuretic Peptide (ANP) → sodium excretion

M. Zaharna Clin. Chem. 2009

hyponatremia
Hyponatremia
  • Defined as a serum/plasma level less than 135 mmol/L.
  • One of the most common electrolyte disorders in hospitalized and non-hospitalized patients
  • Levels below 130 mmol/L are clinically significant.

M. Zaharna Clin. Chem. 2009

hyponatremia26
Hyponatremia

M. Zaharna Clin. Chem. 2009

hypernatremia
Hypernatremia
  • Hypernatremia: increased sodium concentration > 145 mmol/l
  • Result of excess water loss in the presence of sodium excess, or from sodium gain

M. Zaharna Clin. Chem. 2009

sodium determination
Sodium determination
  • Methods:
    • Flame emission spectrophotometry
    • Atomic absorption spectrophotometry
    • Ion Selective electrode

M. Zaharna Clin. Chem. 2009

atomic absorption spectrophotometry
Atomic absorption spectrophotometry

M. Zaharna Clin. Chem. 2009

ion selective electrode
Ion Selective electrode

M. Zaharna Clin. Chem. 2009

potassium
Potassium
  • Major intracellular cation
  • 20 X greater concentration in the cell vs. outside.
  • 2% of the bodies potassium circulates within the plasma.
  • Function:
    • Regulates neuromuscular excitability
    • Hydrogen ion concentration
    • Intracellular fluid volume

M. Zaharna Clin. Chem. 2009

effects on cardiac muscle
Effects on Cardiac muscle
  • Ratio of K+ intracellular & extracellular is important determinant of resting membrane potential across cell membrane
  • Increase plasma potassium; decreasing the resting membrane potential, increase excitability, muscle weakness
  • Decrease extracellular potassium; decrease excitability

M. Zaharna Clin. Chem. 2009

potassium role in hydrogen concentration
Potassium Role in Hydrogen Concentration
  • In hypokalemia (low serum K+),
  • As K+ is lost from the body, Na+ and H+ move into the cell.
  • The H+ concentration is, therefore, decreased in the ECF, resulting in alkalosis.

M. Zaharna Clin. Chem. 2009

regulation of potassium
Regulation of potassium
  • The kidneys are important in the regulation of K+ balance.
    • Initially, the proximal tubules reabsorb nearly all the K+.
    • Then, under the influence of aldosterone, K+ is secreted into the urine in exchange for Na+ in both the distal tubules and the collecting ducts.
    • Thus, the distal tubule is the principal determinant of urinary K+ excretion.
  • Most individuals consume far more K+ than needed; the excess is excreted in the urine but may accumulate to toxic levels if renal failure occurs.

M. Zaharna Clin. Chem. 2009

hypokalemia
Hypokalemia
  • Decrease of serum potassium below 3.5 mmol/l

M. Zaharna Clin. Chem. 2009

hyperkalemia
Hyperkalemia
  • Increase potassium serum levels > 5 mmol/l
  • Associated with diseases such as renal and metabolic acidosis

M. Zaharna Clin. Chem. 2009

potassium determination
Potassium determination

Assay method:

  • Ion selective Electrode
  • a valinomycin membrane is used to selectively bind K+

M. Zaharna Clin. Chem. 2009

chloride
Chloride
  • Major extracellular anion
  • Cl– is involved in maintaining:
    • osmolality,
    • blood volume,
    • and electric neutrality.
  • In most processes, Cl– ions shift secondarily to a movement of Na+ or HCO3–.
  • Cl– ingested in the diet is Completely absorbed by the intestinal tract.

M. Zaharna Clin. Chem. 2009

chloride39
Chloride
  • Cl– ions are filtered out by the glomerulus and passively reabsorbed, in Conjuction with Na, by the proximal tubules.
  • Excess Cl– is excreted in the urine and sweat.
  • Excessive sweating stimulates aldosterone secretion, which acts on the sweat glands to Conserve Na and Cl–.

M. Zaharna Clin. Chem. 2009

electric neutrality
Electric Neutrality
  • Sodium/chloride shift maintains equilibrium within the body.
    • Na reabsorbed with Cl in proximal tubules.
    • Chloride shift
  • In this process, carbon dioxide (CO2) generated by cellular metabolism within the tissue diffuses out into both the plasma and the red cell.
  • In the red cell, CO2 forms carbonic acid (H2CO3), which splits into H+ and HCO3- (bicarbonate).
  • Deoxyhemoglobin buffers H+, whereas the HCO3- diffuses out into the plasma and Cl- diffuses into the red cell to maintain the electric balance of the cell

M. Zaharna Clin. Chem. 2009

hypochloremia
Hypochloremia
  • Hypochloremia: < 98 mmol/l

M. Zaharna Clin. Chem. 2009

hypercholremia
Hypercholremia
  • Hypercholremia: > 109 mmol/l

M. Zaharna Clin. Chem. 2009

assay
Assay
  • Coulometric titration (ref. method)
  • Ion selective electrode

M. Zaharna Clin. Chem. 2009