Electrolytes
Electrolytes
• Substances that dissociate in water into a
cation (positively charged ion) and an anion
(negatively charged ion)
• Carry a charge or dissociate into charged
species.
• The degree of dissociation of an electrolyte
– Affinity of the anion for a H+.
– The weak dipole forces of water that interact with
the anion and cation
Electrolytes
• Strong electrolytes
– Dissociate totally
• Weak electrolytes,
– Partial dissociation
– The concentration of each component can be
determined from the equilibrium equation
•
The activity of each species rather than concentration should be employed in the equilibrium equation.
• Na+ is the major extracellular cation, with a
concentration of ~140 meq L-1 (mM);
• K+ is the major intracellular cation
• The major extracellular anions are CI- and
HC03 • Major intracellular anions are inorganic
phosphate, organic phosphates, and proteins.
• Composition
of the Body
Fluid
• The ionic composition depend on
– Volume and degree of hydration of cells
• Total cation equals total anion concentration
in the different fluids.
• There is a osmotic equilibrium between the
cells and their extracellular fluid
Electrolytes
• Physiological electrolytes
– include Na+, K+, Ca2+, Mg2+, CI-, HCO3- ,H2PO4- ,HPO2-, and
SO42- and some organic anions, such as lactate.
• Major electrolytes
– Na+, K+,CI-, and HCO3– Primarily as free ions
• Function
– Water homeostasis
• Maintenance of osmotic pressure and water distribution in the
various body fluid compartments
– Maintenance of pH, proper heart and muscle function,
oxidation-reduction reactions, and as cofactors for
enzymes.
POTASSIUM
• K+ is the major intracellular cation
• In tissue cells, its average concentration is 150
mmol/L
• The body requirement for K+ is satisfied by a
dietary intake of 50 to 150 mmol/day.
• Potassium absorbed from the gastrointestinal
tract is rapidly distributed, with a small
amount taken up by cells and most excreted
by the kidneys.
• The kidneys respond almost immediately to K+
loading with an increase in K+output
• Unlike the prompt response of the tubules to
conserve Na+ in deficit states, it can take up to
1 week for the tubules to reduce K+ excretion
to 5 to 10mmol/day.
Control of Renal Excretion of
Potassium
• 10% in the stool
• 90% of the daily K+ intake (60- 100 mEq) is
excreted in the urine
– (70-80%) reabsorbed by active and passive
mechanisms in the proximal tubule
– In the ascending limb of Henle's loop, K+ is
reabsorbed together with Na+ and CI– Secreted in the distal tubules
• Na+-K+ exchange mechanism.
• K+excreted in the urine is largely what has been
secreted into the cortical collecting duct
• aldosterone can also directly stimulate Na+-K+ATPase and ROMK activities
• increased expression of ENaC on the luminal
membrane.
(renal outer medullary K channel) ROMK
Control of potassium secretion at the cortical collecting duct
(renal outer medullary K channel) ROMK
• The normal ratio of intracellular K+ /
extracellular K+ is about 30
• Control of Transcellular Flux of Potassium
– Transmembrane elearical gradients cause diffusion
of cellular K+ out of cells and Na+ into cell
– the Na+- K+ pump, which reverses this process, is
stimulated by insulin and catecholamines
Control of transcellular movement of
potassium.
• Alkalosis, insulin, and beta-2-agonists can
cause hypokalemia by stimulating Na+-K+ATPase activity
• Inhibition of the K+ channel by barium,
resulting in inhibition of K+ efflux from the cell
• Vomiting hypokalemia
– K+ loss in the urine
• Vomiting causes metabolic alkalosis
– Renal excretion of bicarbonate leads to renal K+wasting
• Cells can act as buffers
– In acidosis,cells take up H+ions in exchange for
K+ions
– In alkalosis, cells extrude H+ions in exchange for
K+ions.
• Effect of acidosis and alkalosis on transcellular
K+flux
– Depends on the pH
– type of anion that accumulates.
• Metabolic acidosis causes greater K+ efflux
than respiratory acidosis.
• Alkalosis tends to lower serum K+
Causes of Hypokalemia
• Renal loss of K+ is by far the most common
cause of hypokalemia
• Primary hyperaldosteronism
• Secondary hyperaldosteronism
– Increased renin secretion
• Primary
• Secondary
– Renal artery stenosis
• Diuretic therapy
• Banter's syndrome and Gitelman's syndrome.
– Defects in renal salt transport
• Bartter's syndrome
– Defective NaCI reabsorption in the thick ascending
limb of Henle
• Gitelman's syndrome
• Defect in NaCI reabsorption is in the distal convoluted tubule
• Increased delivery of Na+ to the cortical
collecting duct results in hypokalemia.
• Diuretic therapy
– Increase distal delivery of Na+
• Hypokalemia
• Liddle's syndrome
– Increased ENaC activity in the collecting duct
• Increased sodium reabsorption and enhanced
potassium secretion
• Factors that regulate distal tubular secretion
of K+
– Intake of Na+ & K+,plasma concentration of
mineralocorticoids,and acid-base balance.
• Chronic renal failure
– Diminished glomerular filtration rate
• Decrease in distal tubular flow rate
– Retention of K+
• Osmotic diuresis
– Renal K+wasting
• By rapid urine flow
• ADH increases the luminal K+channel activity
Causes of Hyperkalemia
• Digitalis inhibits the Na+-K+-ATPase pump
• Hyperkalemia is almost always due to
impaired renal excretion
• Major mechanisms of diminished renal
potassium excretion:
– Reduced aldosterone or aldosterone
responsiveness, renal failure, and reduced distal
delivery of sodium.
• Heparin therapy
– Inhibits steroid production in the zona
glomerulosa
• Regulation of K+ excretion
– Renal tubular acidosis and metabolic and
respiratory acidoses and alkaloses also affect
renal.
• Potassium concentrations in plasma and
whole blood are 0.1 to 0.7 mmol/L
• Serum 0.2 to 0.5mmol/L
– Higher than those for plasma
– Depends on the platelet count
• Gross hemolysis (>500 mg Hb/dL) can be
expected to raise K+ as much as 30%.
• Preanalytical errors
– If a whole blood specimen is chilled before separation
• Glucose exhaustion or inhibition of glycolysis by
refrigeration
• Falsely decreased K+value
– Leukocyte count, temperature, and glucose
concentrations
• Skeletal muscle activity
– Clenches fist repeatedly.
• Reference Intervals
– Serum of adults varyfrom 3.5 to 5.1 and 3.5 to 5.0
mmol/L
• For plasma, frequently cited intervals are 3.5
to 4.5 and 3.4 to 4.8 mmol/L for adults.
• Cerebrospinal fluid concentrations are -70% of
plasma.
• Urinary excretion of K+ varies with dietary intake
• In severe diarrhea, gastrointestinal loss may be
as much as 60mmollday.
• Methods for the Determination of Sodium and
Potassium
– AAS, FES(
), or spectrophotometric
methods
– Most laboratories now use ISE
Flame Emission Spectrophotometry
• Spectrophotometric Methods
– Based on enzyme activation
– Those that detect the spectral shift produced
when either Na+ or K+ binds to a macrocyclic
chromophore
– Fluorescent sensors.
• The most common causes
pseudohyponatremia or pseudohypokalemia
– Hyperlipidemia and hyperproteinemia.
– In severe hypoproteinemia, the effect works in
reverse
• Falsely high
– Depends on method of analysis
– Due to altered plasma water fraction
CHLORIDE
• Major extracellular anion
• Plasma and interstitial fluid concentrations of
~103 mmol/L
• The largest fraction of the total inorganic anion
concentration of ~154 mmol/L
• Together,sodium and chloride represent the
majority of the osmotically active constituents of
plasma.
• Involved in
– Maintenance of water distribution, osmotic pressure,
and anion-cation balance
CHLORIDE
• Erythrocytes is 45 to 54mmol/L
• intracellular fluid of most other tissue cells it is
only ~ 1 mmol/L
• The most abundant anion
– In both gastric and small and large intestinal
secretions
• Passively reabsorbed, along with Na+, in the
proximal tubules.
• Thick ascending limb of the loop of Henle, Cl- is
actively reabsorbed
CHLORIDE
• Loop diuretics such as furosemide and
ethacrynic acid inhibit the chloride pump.
• Surplus Cl- is excreted in the urine and is also
lost in the sweat
• Methods for Determination of Chloride in
Body Fluids
• Mercurimetric titration,spectrophotometry,
coulometric-amperometric titration, or, most
commonly today, ISE.
CHLORIDE
• Congenital hypochloremic alkalosis
– Hyperchloridorrhea
• (increased excretion of Cl- in stool)
– With almost no CI- being found in urine
• Reference Intervals
– the serum or plasma
• from 98 to 107mmol/L to 100 to 108mmol/L.
– Spinal fluid Cl• ~15% higher than in the serum.
• Urinary excretion of Cl– Varies with dietary intake, 110 to 250 mmol/day
BICARBONATE
• HCO3- and CO2 are the major buffers of the
body
• All body buffers are in equilibrium with
protons (H+)
– H+ effects the ratio of HCO3-/PCO2
• pH is typically expressed as a function of this ratio
• Increased ratio
– pH increases
• Alkalosis
• Decreased ratio
– pH decreases
• Acidosis
• Alkalosis
– Metabolic
• Increase in HCO3-
– Respiratory
• Decrease in PCO2
BICARBONATE
• Total carbon dioxide is measured most often
in automated analyzers
– Acidification of a serum or plasma sample and
measurement of the carbon dioxide released by
the process, or by alkalinization and measurement
of total bicarbonate.
• Blood gas analysis
BICARBONATE
• Under certain conditions of collection and
specimen handling
– Specimen should be rapidly processed and promptly
analyzed
• Either serum or heparinized plasma may be
assayed.
• Usual specimen is venous blood
• Most accurate when the assay is done
immediately after opening the tube and as
promptly as possible after collection and
centrifugation of the blood in the unopened tube.
BICARBONATE
• The first step in automated methods is
acidification or alkalinization of the sample.
• Acidifying the sample converts the various
forms of CO2 in plasma to gaseous CO2
• Alkalinizing the sample converts all CO2 and
carbonic acid to HCO3-
BICARBONATE
• The gaseous CO2 diffused across a silicone
membrane into a recipient solution buffered at
pH 9.2 and containing the pH indicator
phenolphthalein. The change in color over the
baseline was determined by a photometer
• Electrode based
– The released gaseous CO2 after acidification is
determined by a PCO2 electrode
• Enzymatic methods
– The specimen is first alkalinized to convert all CO2 and
carbonic acid to HCO3-
Reference Intervals
• Instrument dependent
SODIUM
• Represents approximately 90% of the ~ 154
mmol of inorganic cations per liter of plasma
– Responsible for almost one half the osmotic
strength of plasma.
• Ultimate regulators of the amount of Na+ (and
thus water)
– Kidneys
Mechanisms of sodium reabsorption at different
nephron segments
Classification of Hyponatremia by Pathogenesis
Hyponatremia
• Drugs:
– arginine vasopressin and its analogs,sulfonylureas,
tricyclic antidepressants, clofibrate
• Emesis
• Endocrine causes: glucocorticoid deficiency
and myxedema
Hypernatremia
• Serum sodium levels > 145 mEq/L.
• Increased effective plasma osmolality and hence with a
reduced cell volume.
• Hypernatremia
– Sodium retention
– Water loss
• Physiological defense against hyponatremia is
increased renal water excretion
• Physiological defense against hypernatremia is
increased water drinking in response to thirst.
– Sensitive to a few mEq/L increase
Causes of Hypernatremia
• Excess gain of sodium
– administration of hypertonic sodium bicarbonate
• Treatment of lactic acidosis.
• Volume-mediated activation of sodiumretaining mechanisms