Electrolytes

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Electrolytes

• Part 1

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Electrolytes

• Electrolytes are ions capable of carrying an
  electricl charge
• Anions (-) ? Anode
• Cations () ? Cathode
• Major cations of the body
• Na, K, Ca2 Mg2
• Major anions of the body
• Cl-, HCO3-, HPO4-2 SO4-2

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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

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• 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-)

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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

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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

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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

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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.

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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.

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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

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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

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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.

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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.

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Angiotensin converting enzyme (ACE)
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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

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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

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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.

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Osmolal Gap

• 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
  ß-hydroxybutyrate)

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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.

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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 (atrial natriuretic peptide).

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Nephron
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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

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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.

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Hyponatremia
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Hypernatremia

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

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Sodium determination

• Methods
• Flame emission spectrophotometry
• Atomic absorption spectrophotometry
• Ion Selective electrode

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Atomic absorption spectrophotometry
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Ion Selective electrode
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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

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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

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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.

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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.

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Hypokalemia

• Decrease of serum potassium below 3.5 mmol/l

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Hyperkalemia

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

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Potassium determination

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

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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.

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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.

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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

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Chloride shift
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Hypochloremia

• Hypochloremia lt 98 mmol/l

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Hypercholremia

• Hypercholremia gt 109 mmol/l

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Assay

1. Coulometric titration (ref. method)
2. Ion selective electrode